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Retinal Artery Occlusions

Central Retinal Artery Occlusion (CRAO)

A central retinal artery occlusion is a blockage of the main artery supplying the retina of the eye. It causes severe, sudden, painless loss of vision. It is not clear how frequently this occurs, but CRAO's are estimated to account for approximately 1 per 10,000 outpatient visits at the Wills Eye Hospital in Philadelphia. Although the abnormality may be seen in children, it is most frequently encountered in older adults. The average age at presentation is in the early sixties.

Men are more frequently affected than women, and there appears to be no predilection for one eye over the other. Bilateral involvement occurs in 1% to 2% of cases. When both eyes are simultaneously affected by retinal artery obstruction, the possibilities of heart valve disease, giant cell arteritis (temporal arteritits), and other vascular inflammations should be strongly considered.

Background

Patients with CRAOs complain of sudden, painless visual loss. Some may have a previous history of transient visual loss (amaurosis fugax) before the actual CRAO.

Clinical features

An abnormal pupillary reaction (afferent pupillary defect, APD) can appear within seconds after obstruction of the retinal vascular system. During the first hour or so after the obstruction, the retina may appear normal, but the abnormal pupillary reaction (APD) will be present.

Initially, the superficial retina becomes edematous except for the central retina (foveola). This is typically described as a "cherry-red spot" due to its appearance. In general, the opacification resolves within 4 to 6 weeks, often leaving a pale optic nerve. Acutely, the retinal arteries are usually thinned. In severe cases, segmentation or "boxcarring" of the blood column can be seen in both the retinal arteries and veins.

Fundus photograph [top] and a frame from a fluorescein angiogram 1 minute and 21 seconds after dye injection [bottom] of a patient with a central retinal artery occlusion. Normally, dye should be visible in the veins by around 20 seconds, and there is still no visible dye indicating very poor blood flow. Note the normal retinal coloring just to the right of the nerve and the surrounding whitening of the retina due to swelling (edema).

Emboli (clots) can be seen within the retinal arterial system in about 20% of eyes with CRAO. The most common variant is the refractile yellow cholesterol embolus (Hollenhorst plaque), which is thought to most commonly originate from atherosclerotic disease in the carotid arteries in the neck. However, the central retinal artery itself can have atherosclerotic plaque, and it too may produce emboli. These cholesterol emboli are often small and may not totally obstruct retinal arteries. They may even occur asymptomatically. Calcium emboli are less commonly seen, but tend to be larger and cause more severe obstructions. They usually arise from diseased cardiac valves.

The vision in eyes with central retinal artery obstruction ranges between counting fingers and light perception in 90% of eyes at the time of initial examination. The presence of an embolus is usually associated with poorer acuity. A few patients are unable to even see light.

Approximately 25% of eyes with a CRAO also have sparing of part of the macular (central) retina. This is due to the presence of a cilioretinal artery. These arteries are usually derived from a different (choroidal) circulation so they are not affected by the retinal artery occlusion. When a cilioretinal artery spares the central retina, the vision may be initially poor, but over a period of weeks improves to 20/50 or better in over 80% of eyes.

Although the incidences of rubeosis iridis and neovascular glaucoma following CRAO have previously been thought to range from 1% to 5%, more recent data suggest that the occurrence of iris neovascularization approaches 15% to 20%. The hypothesis has been advocated that acute central retinal artery obstruction causes rapid inner-layer retinal death, thus preventing the elaboration of an angiogenic factor. However, fluorescein angiographic evidence suggests that the more severe, chronic CRAOs are those that predispose to the development of rubeosis iridis.

Nevertheless, when rubeosis is seen in association with CRAO, the possibility of concomitant ipsilateral carotid artery obstruction should also be considered. Neovascularization of the optic disc or retina, or both, may also occur, although the clinical incidence appears to be lower than that of neovascularization of the iris.

Ancillary Studies

Intravenous fluorescein angiography may reveal a delay in retinal arterial filling, but the most commonly observed fluorescein angiographic sign with CRAO is a delay in arteriovenous transit time (time elapsed from the appearance of dye within the temporal retinal arteries until the major veins in the temporal retinal vascular arcade are completely filled; normal is less than or equal to 11 seconds). Late staining of the optic disc is variable, but staining of the retinal vessels is rare. Complete lack of filling of the retinal arteries is very unusual and probably occurs in less than 2% of cases.

The choroidal vascular bed usually fills normally, although delays of 10 seconds or greater for completed choroidal filling can be seen in about 10% of cases that clinically appear to have CRAO. In the unaffected eye, the choroid begins to fill 1 to 2 seconds before filling of the central retinal artery; it is completelyfilled within 5 seconds of the first observation of dye. Markedly prolonged choroidal filling in the presence of a cherry-red spot should arouse suspicion of ophthalmic or carotid artery obstruction.

It should be remembered that there is a marked propensity for obstructed retinal arteries to reopen with time. Arterial narrowing may persist, but the angiogram with CRAO at varying times after the insult can revert to normal.

Electroretinography characteristically discloses a diminution of the b wave as a result of inner-layer retinal ischemia. The a-wave, which corresponds to photoreceptor function, is generally unaffected. In some cases the study may be normal in the presence of decreased vision, possibly because of the reestablishment of blood flow.

Visual field studies after CRAO commonly demonstrate a remaining temporal island of vision. In the presence of a patent cilioretinal artery, small areas of central field are preserved. Depending upon the degree and extent of obstruction, varied portions of the peripheral field may remain.

Systemic Associations and Etiology

In many instances, it is clinically difficult to ascertain the exact pathophysiologic mechanism(s) responsible for the obstruction. Those that probably account for most cases include emboli, intraluminal thrombosis, hemorrhage under an atherosclerotic plaque, vasculitis, spasm, circulatory collapse, dissecting aneurysm, and hypertensive arteriolar necrosis.

A consideration of the causes of CRAO is intimately related to the associated systemic abnormalities. Systemic arterial hypertension is present in about two thirds of persons with CRAO, and diabetes mellitus in approximately 25%. Cardiac valvular disease is also present in about one fourth. Carotid atherosclerosis, in the form of an ipsilateral stenosis or plaque, is seen in 45% of cases; in about 20% of patients the stenosis is 60% or greater.

Systemic and ocular abnormalities that have been associated with retinal arterial obstruction are listed as follows:

  • Arterial hypertension (via atherosclerotic plaque formation)
  • Carotid atherosclerosis
  • Cardiac valvular disease
  • Rheumatic
  • Mitral valve prolapse
  • Mural thrombus after myocardial infarction
  • Cardiac myxoma
  • Tumors
  • Intravenous drug abuse
  • Lipid emboli
  • Pancreatitis
  • Purtscher's retinopathy (trauma)
  • Loiasis
  • Radiologic studies
  • Carotid angiography
  • Lymphangiography
  • Hysterosalpingography
  • Head and neck corticosteroid injection
  • Retrobulbar corticosteroids
  • Trauma (via compression, spasm, or direct vessel damage)
  • Retrobulbar injection
  • Orbital fracture repair
  • Anesthesia
  • Penetrating injury
  • Drug- or alcohol-induced stupor
  • Coagulopathies
  • Sickle cell disease
  • Homocystinuria
  • Oral contraceptives
  • Platelet and factor abnormalities
  • Pregnancy
  • Ocular conditions associated with retinal arterial obstruction
  • Prepapillary arterial loops
  • Optic disc drusen
  • Increased intraocular pressure (with sickling hemoglobinopathy)
  • Collagen-vascular diseases
  • Systemic lupus erythematosus
  • Polyarteritis nodosa
  • Giant cell arteritis
  • Other associations
  • Ventriculography
  • Fabry's disease
  • Sydenham's chorea
  • Migraine
  • Hypotension
  • Fibromuscular hyperplasia
  • Optic neuritis
  • Orbital mucormycosis

Each of these may affect the retinal vasculature. The site of the pathologic process determines whether the obstruction will be a CRAO, a branch retinal artery obstruction, a cilioretinal artery obstruction, an ophthalmic artery obstruction, or a cotton-wool spot. In some instances there is overlap between the mechanisms for an accompanying disease entity. It must also be noted that the list may well not be complete.

The causes of retinal arterial obstruction in children and in adults under the age of 30 years are often quite different from those in older adults. Although carotid artery atherosclerosis can be seen in the thirties, it is extremely unusual for it to cause retinal arterial obstruction before this age. Entities in this group that are more commonly associated with arterial obstructive disease include migraine, coagulation abnormalities, trauma, cardiac disorders, sickling hemoglobinopathies, and ocular anomalies such as optic nerve drusen and prepapillary arterial loops.

The finding of a retinal arterial obstruction merits a complete systemic workup to look for etiologic factors. Associated systemic abnormalities can be found in approximately 90% of patients.

Long-term survival appears to be decreased in persons with CRAO; this probably also applies to persons with retinal branch artery obstruction and ophthalmic artery obstruction. Lorentzen found a survival time of 5.5 years in people with CRAO, as compared with an expected survival of 15.4 years in an age-matched population.

Treatment

At the same time that ocular therapy is given, a systemic workup should be initiated to look for the cause of the CRAO. Unfortunately, a satisfactory treatment regimen for improving vision in eyes with CRAO is lacking. Numerous therapeutic modalities have been attempted, but none has proved particularly efficacious as of this writing. In addition, since many eyes are given some form of therapy, the natural history concerning vision is not clearly defined.

Anterior chamber paracentesis has been advocated when the CRAO is less than 24 hours old. Although irreversible retinal damage has been shown to occur after 90 to 100 minutes of complete CRAO in the subhuman primate model, such total obstruction is generally not seen clinically in humans. Augsburger and Magargal noted at least a three-line improvement in vision in 35% of eyes at 1 month after the acute event, when a paracentesis was performed early. This maneuver produces a sudden decrease in intraocular pressure, with the hope that the perfusion pressure behind the obstruction will push on an obstructing embolus. The technique can be performed at the slit lamp with topical cocaine anesthesia, and 0.1 to 0.4 mL of aqueous is removed with a 25-gauge or smaller needle. Intravenous acetazolamide may also be used to induce a relatively rapid decrease in intraocular pressure.

Ocular massage may be attempted via in-and-out movement with a Goldmann contact lens or digital pressure. Repeated pressure for 10 to 15 seconds, followed by a sudden release, has been recommended. The technique may produce retinal arterial dilation, with the hope of improving perfusion. Russell was able to demonstrate a 16% increase in retinal arterial diameter, probably secondary to autoregulation, when the intraocular pressure was raised to 60 mmHg. When a sudden increase in intraocular pressure was followed by a sudden drop, Fytche and associates showed an 86% increase in volume of flow.

The use of an oxygen-carbon dioxide mixture (95% O2, 5% CO2) has been applied systemically in some cases. Despite the fact that higher oxygen concentration may lead to retinal arterial vasoconstriction, it has been demonstrated that inspiration of 100% O2 can produce a normal partial pressure of oxygen (PO2) at the retinal surface via diffusion from the choroid in the face of CRAO; clinically the visual function may also improve. Carbon dioxide, on the other hand, is a retinal vasodilator that can produce increased blood flow. The rationale for using both together is readily apparent.

Other modalities that have been applied include retrobulbar injection of vasodilators, such as papaverine and tolazoline, or systemic administration of these drugs. A possible pitfall with retrobulbar injection is the inducement of a retrobulbar hemorrhage, which could further compromise retinal arterial flow. Watson has described a technique of injecting fibrinolytic agents through the supraorbital artery and has demonstrated some improvement in about half of the eyes with CRAO in his series. The technique theoretically delivers over 100 times the concentration of an agent to the central retinal artery that could be obtained via an intravenous injection of the same dose. Systemic anticoagulants are generally not employed for treatment of CRAO.

In our institution, giant cell arteritis accounts for about 2% of cases of CRAO. Despite this low figure, an erythrocyte sedimentation rate should be obtained to screen for the disease in each case involving an elderly patient in whom emboli are not readily apparent. If the disease is suspected, aggressive corticosteroid therapy should be undertaken, since we have seen the second eye become involved within hours.

Branch Retinal Artery Occlusion

Ophthalmoscopically, a branch retinal artery obstruction appears as an area of superficial retinal whitening,most prominent in the posterior pole, along the distribution of the blocked vessel. Regions of more intense whitening are often seen at the boundaries of the ischemic retina. These probably occur secondary to blockage of axoplasmic flow in the nerve fiber layer as it reaches the hypoxic retina.

Fundus photographs and early angiogram of a patient with a branch retinal artery occlusion. Note the yellow plaque in the artery over the optic nerve which blocks the dye from entering the eye.

Approximately 57% of retinal arterial obstructions involve the central retinal artery, whereas branch retinal arteries account for 38% and cilioretinal artery obstructions represent 5% of the total. Well over 90% of branch retinal artery obstructions involve the temporal retinal vessels. It is uncertain whether the temporal arteries are more commonly affected, or if nasal branch artery obstructions are generally asymptomatic.

The visual acuity prognosis with branch retinal artery obstruction is generally quite good. About 80% of eyes eventually improve to 20/40 or better, although residual field defects generally remain.

Neovascularization of the iris secondary to branch artery obstruction is probably extremely rare. Occasionally, neovascularization of the retina may develop after branch artery obstruction, particularly in patients with diabetes mellitus. Artery-to-artery collateral vessels may develop in the retina and are almost pathognomonic for previous branch artery obstruction.

Since the causes are similar, the workup for patients with branch retinal artery obstruction is the same as that for those with CRAO. Because the visual prognosis is much better than with CRAO, ocular therapeutic measures are generally not undertaken unless most of the perifoveolar capillaries are involved.

Cilioretinal Artery Occlusion

Cilioretinal arteries usually enter on the temporal aspect of the optic disc, separately from the retinal arterial system. With fluorescein angiography, they can be detected in about 32% of eyes. They usually fill concomitantly with the choroidal circulation, 1 to 2 seconds before the appearance of dye within the retinal arterial system.

Cilioretinal artery obstructions appear as areas of superficial retinal whitening along the distribution of these vessels. Three clinical variants can be seen: (1) isolated cilioretinal artery obstruction, (2) cilioretinal artery obstruction with central retinal vein obstruction, and (3) cilioretinal artery obstruction with ischemic optic neuropathy.

Isolated cilioretinal artery obstruction generally has a good visual prognosis. Ninety percent of affected eyes improve to 20/40 or better vision, while 60% return to 20/20. This variety accounts for over 40% of cases of cilioretinal artery obstruction.

Cilioretinal artery obstruction with central retinal vein obstruction occurs with the same frequency as does isolated cilioretinal artery obstruction and also constitutes just over 40% of the total group. The venous obstructions are generally nonischemic and usually do not lead to neovascular glaucoma. Vision loss is determined more by the venous component than by the cilioretinal artery obstruction. Seventy percent of eyes eventually achieve 20/40 vision or better. The reasons for this association are uncertain. It is possible that optic disc swelling resulting from the venous obstructive disease, reduced cilioretinal perfusion pressure, or both, may lead to the arterial compromise.

In contrast to the first two groups, vision is generally poor (20/400 to no light perception) in eyes with ischemic optic neuropathy and cilioretinal artery obstruction; the degree of involvement by optic neuropathy appears to be the main determinant of vision. Since both abnormalities are manifestations of posterior ciliary artery insufficiency, it is not surprising that they may occur concurrently. This variant makes up about 15% of the total group of cilioretinal artery obstructions.

The systemic workup for cilioretinal artery obstruction is the same as that for CRAO. Ocular therapeutic measures are generally not undertaken for isolated cilioretinal artery obstruction or cilioretinal artery obstruction in association with central retinal vein obstruction, since treatment is not particularly effective and the natural course of the disease is relatively good. For cases associated with ischemic optic neuropathy, the possibility of underlying giant cell arteritis should be considered and ruled out via erythrocyte sedimentation rate and by temporal artery biopsy in some cases.

Ophthalmic Artery Occlusion

Approximately 5% of patients with what appears to be a CRAO have, in reality, an acute ophthalmic artery obstruction. A number of clinical features and ancillary studies that help to differentiate between the two are listed. In most instances it is difficult to tell whether the ophthalmic artery itself is obstructed or if there are, instead, separate, but simultaneous, obstructions of the retinal and posterior ciliary circulations.

The history with acute ophthalmic artery obstruction is generally one of abrupt visual loss. Although the visual acuity is usually no light perception, exceptions may occur. We have seen one man with ophthalmic artery obstruction in whom the vision improved from light perception to 20/30 over a several-day period, presumably because of amelioration of the obstructing insult.

Examination of the anterior segment is generally unremarkable with acute ophthalmic artery obstruction. Despite the marked ocular ischemia, rubeosis iridis has not been noted after this entity, although only a limited number of cases have been reported. Acutely, the intraocular pressure averages approximately 4 mmHg lower on the affected side, but the same phenomenon can also be seen with CRAO alone.

Funduscopy generally reveals intense retinal opacification, resulting from inner and outer retinal ischemia, that may extend beyond the posterior pole. A cherry-red spot is absent, because of choroidal compromise and probable retinal pigment epithelial or choroidal opacification, or both, in about 40% of eyes. In the remainder, some degree of a cherry-red spot can be seen. It is presumed that the choroidal hypoperfusion may have improved or been insufficient to produce an acute infarction of the retinal pigment epithelium and outer retina in these instances. A cherry-red spot may be initially absent, but then appear over a several-day period as choroidal perfusion improves.

Over a period of weeks the retinal whitening resolves, and changes develop in the retinal pigment epithelium as a result of choroidal vascular compromise. This pigmentary disturbance is not seen after central retinal artery obstruction alone. Severe optic atrophy usually also ensues.

Fluorescein angiography reveals impairment of retinal vascular and choroidal flows. Staining at the retinal pigment epithelial level may also be seen. Since both the inner and outer retinal layers are ischemic, electroretinography usually discloses a corresponding diminution or absence of the b and a waves.

The causes of acute ophthalmic artery obstruction are generally similar to those seen with CRAO (see outline above). Two unusual causes that can be seen are orbital mucormycosis, which induces a vasculitis within the ophthalmic artery, and inadvertent retrobulbar injection into optic foramen. Ocular treatment is generally ineffective for this entity, and the visual prognosis is usually grim.

Combined Central Retinal Artery and Vein Occlusion

Richards has nicely elucidated the entity of combined obstructions of the central retinal artery and central retinal vein. Persons having this condition usually present with acute visual loss and have fundus features suggestive of both types of obstruction. The retina in the posterior pole demonstrates superficial retinal opacification with a cherry-red spot, while the optic disc is swollen and numerous intraretinal hemorrhages are present. The retinal veins may also be engorged.

The visual prognosis is generally extremely poor in these eyes, but occasionally spontaneous improvement can be seen. One third or more of affected eyes progress to rubeosis iridis and neovascular glaucoma.

Systemic workup should include an evaluation for those abnormalities associated with acute CRAO. Retrobulbar injection has been noted to cause combined central retinal artery and vein obstruction, presumably as a result of injection within the optic nerve sheath or direct damage to the central retinal artery and vein.