Key Features

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  Abrupt, painless, severe loss of vision.

  
  
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  Cherry-red spot.

  
  
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  Box-carring of blood flow in the retinal vessels.

  
  
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  Ischemic retinal whitening of the posterior pole.

Associated Features

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  Amaurosis fugax.

  
  
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  Visible embolus (25%).

  
  
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  Carotid artery stenosis (33%).

  
  
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  Giant cell arteritis (5%).

  
  
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  Neovascularization of the iris (18%).

  
  
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  Arterial collaterals on the optic disc.

Key Features

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  Retinal whitening in the territory of the obstructed vessel.

  
  
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  Visible embolus (66%).

  
  
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  Visual field defect that corresponds to the territory of the obstructed vessels.

Associated Features

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  Carotid artery disease.

  
  
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  Cardiac valvular disease.

  
  
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  Cardiac myxoma, long-bone fracture, endocarditis, depot drug injection (rare).

  
  
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  Systemic clotting disorder or vasculitis (rare).

Introduction

Retinal arterial obstructions are divided anatomically into central and branch, depending on the precise site of obstruction. A central retinal artery obstruction occurs when the blockage is within the optic nerve substance itself, and therefore the site of obstruction is generally not visible on ophthalmoscopy. A branch retinal artery obstruction occurs when the site of blockage is distal to the lamina cribrosa of the optic nerve.

Obstructions more proximal to the central retinal artery, in the ophthalmic artery, or even in the internal carotid artery may produce visual loss as well. Ophthalmic artery obstructions may be difficult to differentiate from central retinal artery obstruction. More proximal obstructions usually cause a more chronic form of visual problem—the ocular ischemic syndrome (see Chapter 6.23 ).

The majority of retinal arterial obstructions are either thrombotic or embolic in nature. The potential sources and various types of emboli generally do not differ between central retinal artery obstruction and branch retinal artery obstruction, but a branch retinal artery obstruction is far more likely to be embolic than is a central retinal artery obstruction. It has been determined that over two-thirds of branch retinal artery obstructions are caused by emboli, whereas probably less than one-third of central retinal artery obstructions result from emboli.

The retina has a dual circulation with little to no anastomoses. The inner retina is supplied by the central retinal artery, which is an end artery. The outer retina receives its nourishment via diffusion from the choroidal circulation (see Chapter 6.3 ). Retinal artery obstructions selectively affect the inner retina only.

Because the accompanying visual loss tends to be severe and permanent, it is fortunate that retinal artery obstructions are rare occurrences. As there is a strong association with systemic disease, all patients who suffer retinal artery obstructions should undergo a systemic evaluation.

Epidemiology and Pathogenesis

Central retinal artery obstruction is a rare event—it has been estimated to account for about 1 in 10 000 outpatient visits to the ophthalmologist. The incidence was found to be 1.3 per 100 000, or 1.90 per 100 000 when adjusted for age and sex for the white population in the United States. Men are affected more commonly than women, in a ratio of 2 : 1. The mean age at onset is about 60 years, with a range of reported ages from the first to the ninth decade of life. Right eyes and left eyes appear affected with equal incidence. Bilateral involvement occurs in 1%–2% of cases.

In central retinal artery obstruction, the site of obstruction is not usually visible on clinical examination and, in general, the retrobulbar central retinal artery is too small to image with most techniques. Therefore, the precise cause is speculative. It is currently believed that the majority of central retinal artery obstructions are caused by thrombus formation at or just proximal to the lamina cribrosa. Atherosclerosis is implicated as the inciting event in most cases, although congenital anomalies of the central retinal artery, systemic coagulopathies, or low-flow states from more proximal arterial disease may also be present and render certain individuals more susceptible.

In only 20%–25% of cases are emboli visible in the central retinal artery or one of its branches, suggesting that an embolic cause is not frequent. A more detailed discussion of embolus types is given later in the section on branch retinal artery obstruction. Further indirect evidence against emboli as a frequent cause of central retinal artery obstruction is the 40% or less probability of finding a definitive embolic source on systemic evaluation and the small incidence (approximately 10%) of confirmed associated ipsilateral cerebral emboli in affected patients.

Inflammation in the form of vasculitis (e.g., varicella infection), optic neuritis, or even orbital disease (e.g., mucormycosis) may cause central retinal artery obstruction. Local trauma that results in direct damage to the optic nerve or blood vessels may lead to central retinal artery obstruction. Arterial spasm or dissection rarely produces retinal arterial obstruction. In addition, systemic coagulopathies may be associated with both central and branch retinal artery obstructions.

Other rare causes include radiation retinopathy, emboli associated with depot medication injection around the eye, cosmetic facial injection with filler materials, optic disc drusen, and prepapillary arterial loops. Medical examinations and manipulations (e.g., carotid angiography, angioplasty, chiropractic neck manipulation) rarely result in emboli to the central retinal artery. Although elevated intraocular pressure has been implicated as a cause of central retinal artery obstruction, it is unlikely that intraocular pressure can be raised high enough to block arterial inflow to the eye.

Ocular Manifestations

The hallmark symptom of acute central retinal artery obstruction is abrupt, painless loss of vision. Pain is unusual and suggests associated ocular ischemic syndrome (OIS). Amaurosis fugax precedes visual loss in about 10% of patients. Rarely, in cases associated with arterial spasm, a relapsing and remitting course of visual loss precedes central retinal artery obstruction.

Examination typically reveals a visual acuity of 20/800 (6/240) or worse. Hand motion or light perception vision can occur, but no light perception vision is uncommon except in the setting of an ophthalmic artery obstruction or temporal arteritis. If a patent cilioretinal artery is present and perfuses the fovea, normal central acuity may be present. An afferent pupillary defect on the affected side is the rule. Anterior segment examination is normal except in the setting of concurrent OIS with neovascularization of the iris.

Within the first few minutes to hours after the obstruction, the fundus may appear relatively normal ( Fig. 6.19.1A–B ). Eventually, the decreased blood flow results in ischemic whitening of the retina in the territory of the obstructed artery, which is most pronounced in the posterior pole (where the nerve fiber layer of the retina is thickest). Acutely, the arteries appear thin and attenuated. In severe blockages, both veins and arteries may manifest “box-carring” or segmentation of the blood flow.

The Left Eye of a Healthy 37-Year-Old Man.

The patient had a 3-hour history of visual loss and a visual acuity of 20/60 (6/18). (A) Retinal whitening is very subtle and the retinal vessels appear normal. (B) Fluorescein angiography reveals abnormal arterial filling with a leading edge of dye that confirms central retinal artery obstruction. (C) The same eye 24 hours later. Despite intravenous urokinase, visual acuity dropped to hand movements, and intense retinal whitening with a cherry-red spot is present. Note the interruption in the blood column of the retinal arteries.

A cherry-red spot of the macula is typical and arises in this area because the nerve fiber layer is thin. Transmission of the normal choroidal appearance, therefore, is not diminished, which contrasts distinctly with the surrounding area of intense retinal whitening that blocks transmission of the normal choroidal coloration. Although other conditions may be associated with a macular cherry-red spot ( Box 6.19.1 ), these are usually differentiated easily from central retinal artery obstruction. Splinter retinal hemorrhages on the disc are common, but more extensive retinal hemorrhaging suggests an alternative diagnosis. If pallid swelling is present, temporal arteritis must be ruled out. A patent cilioretinal artery results in a small area of retina that appears normal ( Fig. 6.19.2 ).

A Central Retinal Artery Obstruction.

A prominent cherry-red spot with cilioretinal artery sparing in the papillomacular bundle.

By 6 weeks after the acute event, the retinal whitening typically resolves, the optic disc develops pallor, and arterial collaterals may form on the optic disc. No foveolar light reflex is apparent, and fine changes in the retinal pigment epithelium may be visible. Secondary ocular neovascularization is not uncommon after central retinal artery obstruction and tends to occur around 8 weeks after the obstruction (range 2–16). Iris neovascularization occurs in about 18% of patients, with many of these eyes going on to neovascular glaucoma. Panretinal photocoagulation appears to reduce the risk of neovascular glaucoma moderately. Neovascularization of the optic disc occurs after about 2% of central retinal artery obstruction ( Fig. 6.19.3 ). Vitreous hemorrhage may ensue.

A 26-Year-Old Diabetic Man.

(A) Central retinal artery obstruction caused by a platelet-fibrin embolus. (B) After 3 months, extensive neovascularization of the disc is present.

(Courtesy Larry Magargal, MD.)

Diagnosis and Ancillary Testing

Diagnosis of central retinal artery obstruction is straightforward when diffuse ischemic retinal whitening is present in the setting of abrupt, painless visual loss. Fluorescein angiography may help if the diagnosis is in doubt. A delayed arm-to-retina time with a leading edge of dye visible in the retinal arteries is typical (see Fig. 6.19.1B ). In some cases, it may be minutes before the retinal arterial tree fills with fluorescein. Arteriovenous transit is delayed as well, and late staining of the disc is common. Retinal oximetry may aid in early diagnosis and have utility for follow-up as it can demonstrate the return of blood flow, but this emerging modality requires further clinical testing.

Macular optical coherence tomography (OCT) in the acute phase shows inner retinal thickening with shadowing of the outer retina that can be mistaken for subretinal fluid. When the retinal whitening resolves, OCT reveals severe inner retinal thinning. OCT angiography of prior central retinal artery obstruction demonstrates decreased retinal vascularity and attenuation of vessels in the macula ( Fig. 6.19.4 ). Electroretinography characteristically reveals a decreased to absent b-wave with intact a-wave. Visual fields show a remaining temporal island of peripheral vision. If a patent cilioretinal artery is present, a small intact central island is found as well.

Optical Coherence Tomography Angiography and Corresponding Optical Coherence Tomography Structural B-Scan From an Eye With a Prior Central Retinal Artery Obstruction.

Note the paucity of small retinal vessels in the macula and the attenuation of the large retinal vessels. Structural B-scan shows loss of inner retinal tissue.

Color Doppler imaging is a form of ultrasonography that can help to determine the blood flow characteristics of the retrobulbar circulation. Color Doppler studies of acute central retinal artery obstruction show diminished to absent blood flow velocity in the central retinal artery, generally with intact flow in the ophthalmic and choroidal branches. Color Doppler imaging can be used to detect calcific emboli at the lamina cribrosa and may be used to monitor blood flow changes induced by therapy.

Differential Diagnosis

The differential diagnosis of central retinal artery obstruction is given in Box 6.19.2 .

Systemic Associations

Although systemic diseases commonly are found in patients who suffer from retinal artery obstruction, the true cause and effect may not be clear. About 50%–60% of patients have concurrent systemic arterial hypertension, and diabetes is present in 25%. Systemic evaluation reveals no definite cause for the obstruction in over 50% of affected patients. Potential embolic sources are found in less than 40% of cases.

The most common pathogenetic association uncovered is hemodynamically significant ipsilateral carotid artery disease, which is present in about one-third of affected patients. Carotid noninvasive testing should be considered for all patients who have central retinal artery obstruction, although disease in those younger than 50 years of age is quite rare ( Fig. 6.19.5 ). An embolic source from the heart is present in less than 10% of patients with central retinal artery obstruction, but echocardiography and Holter monitoring should be performed, especially in younger patients. In some cases, transesophageal echocardiography is necessary to reveal embolic sources. In a large, population-based study, subjects with history of retinal artery obstruction were two times more likely to have a stroke than controls.

Acute Central Retinal Artery Obstruction.

Secondary to an embolus at the lamina cribrosa. Note two other emboli in the superior retinal vessels. Ipsilateral carotid artery disease was present.

Even though it is present in less than 5% of cases, it is of paramount importance that temporal arteritis be ruled out in all patients older than 50 years who have a central retinal artery obstruction. An immediate erythrocyte sedimentation rate must be obtained, and if it is elevated or if clinical suspicion exists, corticosteroid therapy and a temporal artery biopsy are considered.

Other rare associated systemic diseases include blood-clotting abnormalities such as antiphospholipid antibodies, protein S deficiency, protein C deficiency, and antithrombin III deficiency. A list of systemic associations for retinal artery obstructions is given in Box 6.19.3 .

Pathology

Histopathological examination shows coagulative necrosis of the inner retina. Acute, early, intracellular edema is followed by complete loss of the inner retinal tissue. Chronically, a diffuse acellular zone replaces the nerve fiber layer, ganglion cell layer, and inner plexiform layer. The outer retinal cells remain relatively intact. Sections of the obstructed central retinal artery may reveal a thrombus or embolus that is often recanalized ( Fig. 6.19.6 ).

Central Retinal Artery Occlusion.

(A) A trichrome-stained section shows an organized thrombus (T) that occludes the central retinal artery within the optic nerve (V, vein). (B) A histological section at the early stage shows edema of the inner neural retinal layers and ganglion cell nuclei pyknosis. Patient had a cherry-red spot in the fovea at time of enucleation.

IM, Internal limiting membrane; IN, inner nuclear layer; NG, swollen nerve fiber and ganglion layers; ON, outer nuclear layer; OP, outer plexiform layer; PR, photoreceptors.

Treatment

No proved treatment exists for central retinal artery obstruction, but treatment strategies center around the following goals:

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  Increase retinal oxygenation.

  
  
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  Increase retinal arterial blood flow.

  
  
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  Reverse arterial obstruction.

  
  
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  Prevent hypoxic retinal damage.

Theoretically, retinal oxygenation can be increased by breathing carbogen (95% oxygen, 5% carbon dioxide). No clinical study indicates efficacy for carbogen therapy, and one retrospective study suggests that it has no beneficial effect. It is rarely used currently.

An increase in retinal arterial blood flow is attempted by lowering intraocular pressure. This is accomplished by ocular massage, paracentesis, and the administration of ocular antihypertensive medications. Medical attempts to dilate retinal arteries or block vascular spasm have been tried as well. Hemodilution, sublingual nitroglycerin, pentoxifylline (oxpentifylline), calcium-channel blockers, and β-blockers have all been used with no proof of efficacy

Reversal of arterial obstruction through the use of anticoagulation or fibrinolytic medications has been reported. To date, the utility of these interventions has not been proved by controlled clinical trials. The only prospective, controlled trial of intra-arterial thrombolysis (EAGLE Study) was unable to show a benefit compared to conventional therapy although the power of the study was low.

Thrombolysis can also be achieved intravenously as per stroke thrombolysis protocol. An interventional case series demonstrated that intravenous tPA with concomitant intravenous heparin resulted in visual improvement of three Snellen lines or more in 50% of subjects if given within 6.5 hours after onset of symptoms. The results of a small, randomized, controlled trial also suggest that intravenous tPA is efficacious only when given within 6 hours of onset of symptoms.

At present, prevention of hypoxic damage to the retina is only theoretically possible. Antioxidant medications (e.g., superoxide dismutase) and N -methyl- d -aspartate (NMDA) inhibitors are two classes of compounds that may accomplish retinal rescue pharmacologically and are under study. Hyperbaric oxygen therapy with hemodilution can also be used.

Cases of central retinal artery obstruction associated with temporal arteritis are treated emergently with high-dose corticosteroids. Without therapy, the risk to the second eye is great. Although the first affected eye rarely recovers, instances exist in which high-dose intravenous methylprednisolone induced visual recovery from central retinal artery obstruction associated with temporal arteritis.

Course and Outcome

Most central retinal artery obstructions result in severe, permanent loss of vision. About one-third of patients experience some improvement in final vision in terms of presentation acuity either with or without conventional treatment. Three or more Snellen lines of improved visual acuity occur in only about 10% of untreated patients.

Experimentally, if an obstruction exists in the primate retina for more than 240 minutes, complete irreversible death of the inner retina occurs. In practice, a rare patient has experienced total spontaneous recovery even after several days of documented visual loss. Spontaneous recovery may be more common in young children.