Retinal Artery Occlusion (RAO)

Background

Retinal artery occlusion (RAO) usually presents as painless loss of monocular vision. Ocular stroke commonly is caused by embolism of the retinal artery, although emboli may travel to distal branches of the retinal artery, causing loss of only a section of the visual field. Retinal artery occlusion represents an ophthalmologic emergency, and delay in treatment may result in permanent loss of vision.

Immediate intervention improves chances of visual recovery, but, even then, prognosis is poor, with only 21-35% of eyes retaining useful vision. Although restoration of vision is of immediate concern, retinal artery occlusion is a harbinger for other systemic diseases that must be evaluated immediately.

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Pathophysiology

Blood supply to the retina originates from the ophthalmic artery, the first intracranial branch of the internal carotid artery that supplies the eye via the central retinal and the ciliary arteries. The central retinal artery supplies the retina as it branches into smaller segments upon leaving the optic disc. The ciliary arteries supply the choroid and the anterior portion of the globe via the rectus muscles (each rectus muscle has 2 ciliary arteries except the lateral rectus, which has 1).

Anatomical variants include cilioretinal branches from the short posterior ciliary artery, giving additional supply to part of the macular retina. A cilioretinal artery occurs in approximately 14% of the population.

Typical funduscopic findings of a pale retina with a cherry red macula (ie, the cherry red spot) result from obstruction of blood flow to the retina from the retinal artery, causing pallor, and continued supply of blood to the choroid from the ciliary artery, resulting in a bright red coloration at the thinnest part of the retina (ie, macula). These findings do not develop until an hour or more after embolism, and they resolve within days of the acute event. By this time, visual loss is permanent and primary optic atrophy has developed. In those with a cilioretinal artery supplying the macula, a cherry red spot is not observed.

See the image below.

View Image

The cherry red spot of central retinal artery occlusion.

An embolism, atherosclerotic changes, inflammatory endarteritis, angiospasm, or hydrostatic arterial occlusion may occlude the retinal artery. The mechanism of obstruction may be obvious from comorbid systemic disease or physical findings. Atrial fibrillation and ipsilateral carotid stenosis are more commonly associated with prolonged visual disturbances.

Animal studies have shown that a retina with completely occluded circulation has irreversible ischemic damage at 105 minutes but may recover at 97 minutes. Complete occlusion of retinal artery circulation in humans is rare with retinal artery disease; thus, retinal recovery is possible even after days of ischemia.

Branch retinal artery occlusion (BRAO) occurs when the embolus lodges in a more distal branch of the retinal artery. BRAO typically involves the temporal retinal vessels and usually does not require ocular therapeutics unless perifoveolar vessels are threatened. The central retinal artery is affected in 57% of occlusions, the branch retinal artery is involved in 38% of occlusions, and cilioretinal artery obstructions occur in 5% of occlusions.^[1]

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Epidemiology

Frequency

United States

Recent estimates put the incidence of retinal artery occlusion at 0.85 per 100,000 per year, with a 10-year cumulative incidence of retinal emboli of 1.5%.^[2]

Mortality/Morbidity

Patients with visualized retinal artery emboli, whether or not obstruction is present, have 56% mortality over 9 years, compared to 27% for an age-matched population without retinal artery emboli. Life expectancy of patients with central RAO (CRAO) is 5.5 years, compared to 15.4 years for an age-matched population without CRAO.

RAO is associated with smoking and cardiovascular disease, with an increased incidence of stroke in patients who have suffered RAO.

Both eyes have an equal incidence of disease, with bilateral involvement in 1-2%.

Sex

Men are affected slightly more frequently than women.

Age

The mean age of presentation of retinal artery occlusion is early in the seventh decade of life, although a few cases have been reported in patients younger than 30 years.

The etiology of occlusion changes, depending on the age at presentation.

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Prognosis

Recovery of useful vision is related directly to the rapidity of treatment and presenting visual acuity.

Studies report that 21% of patients exhibited visual improvement of 6 gradients of visual acuity, 35% exhibited improvement of 3 gradients of visual acuity, while 26% showed no improvement in visual acuity.

Patients that showed improvement had presenting visual acuity of counting fingers and a mean duration of visual loss of 21.1 hours; those that did not improve had presenting visual acuity of hand movement and a mean duration of visual loss of 58.6 hours.

The longest delay to treatment that has been associated with significant visual recovery is approximately 72 hours.

Presence of a cilioretinal artery with foveolar sparing increases improvement of visual acuity.

Branch retinal artery occlusions (BRAOs) are associated with a higher recovery rate (80% of eyes improve to 20/40 or better) than central retinal artery occlusions (CRAOs).

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Patient Education

Patients must understand that the prognosis for visual recovery is poor and that the visual changes are usually a result of a systemic process that needs treatment.

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History

The most common presenting complaint is an acute persistent painless loss of vision. In central artery occlusions, visual loss is central and dense. In branch artery occlusions, visual loss may go unnoticed if only a section of the peripheral visual field space is affected.

A complete visual field defect suggests central retinal artery occlusion (CRAO).

A sectional visual field defect suggests branch retinal artery occlusion (BRAO) and may be an altitudinal defect affecting the upper or lower hemifield but never respecting a vertical axis.

A history of hypertension or diabetes mellitus is elicited in 67% and 25% of patients with CRAO, respectively.

Query about any medical problems that could predispose patients to embolus formation (eg, atrial fibrillation, endocarditis, coagulopathies, atherosclerotic disease).

Prolonged direct pressure to the globe during drug-induced stupor or improper positioning during surgery also may lead to CRAO.

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Physical

Determine the degree of vision loss (eg, no light perception, hand movement, counting fingers); the prognosis for recovery is directly related to initial visual loss.

Document hand movement, finger counts, and visual fields at a standard distance of 1' to 3'. Documentation of distance will provide concise communication with consultants and for standardization of repeated examinations.

Direct the physical examination to evaluate for murmurs, carotid bruits, or other signs of cardiovascular disease.

Funduscopic examination

An afferent pupillary defect (ie, paradoxical dilatation of the pupil when a light is shined from the unaffected eye to the affected eye) may be observed within seconds of the occlusive event.

The cherry red spot and a ground-glass retina are the classic findings but may take hours to develop.

The funduscopic findings typically resolve within days to weeks of the acute event, sometimes leaving a pale optic disc as the only physical finding.

Emboli can be observed in approximately 20% of patients with CRAO.

A dilated funduscopic examination is required to see the pathological signs of RAO.

BRAO presents with whitening of the retina along the distribution of the occluded vessel.

Boxcar segmentation of the blood column is observed most often in BRAO and is a sign of severe occlusion and slowing of circulation.

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Causes

Causes of central retinal artery occlusion (CRAO) vary, depending on the age of the patient. A detailed analysis of comorbid disease is necessary to elucidate the cause of the acute visual loss.

Embolism

Embolism is usually caused by cholesterol, but it can be calcific, bacterial, or talc from IV drug abuse.

It is associated with poorer visual acuity and higher morbidity and mortality than other retinal artery occlusions.

Embolus from the heart is the most common cause of CRAO in patients younger than 40 years.

Amaurosis fugax preceding persistent loss of vision suggests branch retinal artery occlusion (BRAO) or temporal arteritis and may represent emboli causing temporary occlusion of the retinal artery.

Coagulopathies from sickle cell anemia or antiphospholipid antibodies are common etiologies for CRAO in patients younger than 30 years.

Atherosclerotic changes

Carotid atherosclerosis is observed in 45% of CRAO cases, with 60% or more stenosis occurring in 20% of cases.

Atherosclerotic disease is the leading cause of CRAO in patients aged 40-60 years.

Central artery spasm is an additional cause that can lead to occlusion of the vessel.

Inflammatory endarteritis

Occurrence is rare (only 2% of cases).

Suspect inflammatory endarteritis in elderly patients if no other etiology is observed.

Inflammatory endarteritis can affect the second eye within hours if untreated.

Increased intraocular pressure

Increased intraocular pressure (IOP) from glaucoma or prolonged direct pressure to the globe in unconscious patients can precipitate CRAO.

Low retinal blood pressure from carotid stenosis or severe hypotension may lead to CRAO.

Transection of the retinal artery, transection of the optic nerve, or retrobulbar hemorrhage can cause visual loss.

Migraines

Migraines are rare causes of CRAO but are most common in patients younger than 30 years.

Other causes

Other causes of retinal artery occlusion include the following:

• Hydrostatic arterial occlusion
• Moya moya disease
• Thrombophilia
• Carotid dissection

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Complications

Further emboli to brain resulting in CVA

Further emboli to the same or contralateral eye, resulting in further visual loss

Progression of temporal arteritis, resulting in loss of vision to the contralateral eye

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Laboratory Studies

Laboratory studies may be helpful in determining the etiology of central retinal artery occlusion (CRAO) but do not affect ED treatment. These studies may include the following:

• CBC count to evaluate anemia, polycythemia, and platelet disorders
• Erythrocyte sedimentation rate (ESR) for inflammatory endarteritis in the absence of another etiology
• Fibrinogen level, antiphospholipid antibodies, prothrombin time (PT), activated partial thromboplastin time (aPTT), and serum protein for coagulopathies
• Cholesterol, triglycerides, and lipid panel to evaluate for atherosclerotic disease
• Blood cultures for bacterial endocarditis and septic emboli

Sickle cell disease may also cause RAO and may warrant workup for those at risk.

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Imaging Studies

Imaging studies may be helpful in determining the etiology of CRAO but do not affect ED treatment. These studies do not need to be performed emergently in the ED.

Echocardiography is not necessarily an ED test but can be used to evaluate valvular disease, wall motion abnormalities, mural thrombi, and vegetations that may cause septic emboli.

Evaluation of the carotids with carotid Doppler ultrasonography, magnetic resonance angiography (MRA), or computed tomography angiography can be used to evaluate atherosclerotic disease.

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Other Tests

Perform an ECG to evaluate for possible atrial fibrillation (24-hour Holter monitor may be necessary if arrhythmia is suspected but not detected on ECG testing).

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Procedures

See Treatment below for massage and paracentesis.

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Prehospital Care

No specific prehospital treatment is available for retinal artery occlusion. The prognosis for visual recovery is related directly to the promptness in treatment; thus, rapid transport to the ED is essential.

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Emergency Department Care

There are 2 phases of care for patients with RAO. The first phase occurs in the ED and involves rapid detection and treatment of visual loss.

The second phase involves a thorough investigation for the cause of visual loss.No randomized controlled trials to support one treatment modality over any others are underway, but anecdotal reports and case series have suggested many modalities of treatment with varying success. Nonetheless, recent data suggest that these therapies may not be beneficial.^{[3, 4]} In fact, Schrag et al (2015) suggest that classic treatments such as ocular massage and paracentesis may be harmful.^[4]

Ocular massage

Apply direct pressure for 5-15 seconds, then release. Repeat several times.

Increased IOP causes a reflexive dilation of retinal arterioles by 16%.

A sudden drop in IOP with release increases the volume of flow by 86%.

Ocular massage dislodges the embolus to a point further down the arterial circulation and improves retinal perfusion.

Anterior chamber paracentesis

Advocated when visual loss has been present for less than 24 hours

Early paracentesis is associated with increased visual recovery.

Slit-lamp removal of 0.1-0.4 mL of aqueous humor via tuberculin syringe and a 27-gauge needle may decrease IOP to 3 mm Hg.

Decrease in IOP is thought to allow greater perfusion, pushing emboli further down the vascular tree.

Other treatments

See Medication for details and mechanisms of action for medications.

Start timolol early in the treatment of CRAO, as this is readily available in most emergency departments. Acetazolamide and mannitol should also be used when CRAO is suspected because there are few downsides to starting these medications early.

In carbogen therapy (5% carbon dioxide, 95% oxygen), carbon dioxide dilates retinal arterioles, and oxygen increases oxygen delivery to ischemic tissues.

Hyperbaric oxygen (HBO) therapy may be beneficial if initiated within 2-12 hours of symptom onset. Institute treatment with other interventions first; transport to a chamber may usurp precious time. Results from noncontrolled studies have been mixed. A 2001 controlled study in Israel showed a benefit in the treatment group.^[5] In this study, all patients were treated within 8 hours of symptom onset.

Thrombolytics may be useful, but they may not be much help if the embolus is cholesterol, talc, or calcific. While some evidence suggests intra-arterial thrombolytics may be helpful, a 2015 meta-analysis suggests that systemic thrombolytics may be beneficial if given within 4.5 hours of onset.^[4] Research is evaluating the role of thrombolytics in RAO.

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Consultations

Ophthalmologist

Immediate evaluation is imperative for any patient with acute CRAO.

Ophthalmologists can decide with which further treatment (eg, thrombolytics, hyperbaric oxygen, retrobulbar block) to proceed.

Early treatment (< 2 h from onset of symptoms) with HBO may be associated with increased visual recovery, but HBO can be considered if the duration of visual loss is less than 12 hours. Inhalation of 100% oxygen at 2 atm can provide an arterial pO₂ of 1000-1200 mm Hg, resulting in a 3-fold increase in oxygen diffusion distance through ischemic retinal tissues. Some studies show a 40% improvement of 2 or more levels of visual acuity.

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Prevention

Patients should keep their blood pressure under control, lower their cholesterol, avoid IV drugs, and take their medication.

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Long-Term Monitoring

Patients should have serial evaluation of visual acuity by an ophthalmologist.

An ophthalmologist should perform evaluation for subsequent neovascularization of the iris or retina.

If HBO is to be used, several treatments may be necessary.

Patients require urgent follow up for carotid and cardiac evaluation to preclude further central retinal artery occlusion (CRAO) or stroke.

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Further Inpatient Care

Further inpatient care is indicated only if comorbid disease is present.

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Transfer

Transfer to a hyperbaric facility is necessary if hyperbaric oxygen is to be administered.

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Medication Summary

Medical therapy for retinal artery occlusion is directed toward lowering IOP, increasing retinal perfusion, and increasing oxygen delivery to hypoxic tissues. The first goal is accomplished by using the same drugs that are used in acute closed-angle glaucoma. Retinal perfusion may be increased by vasodilatory drugs, increasing arterial pCO₂, or by giving peripheral thrombolytics to remove the offending embolus. Oxygen delivery is improved by breathing higher concentrations of oxygen or with hyperbaric oxygen.

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Acetazolamide (Diamox)

• Dosing, Interactions, etc.

Clinical Context:  Reduces rate of aqueous humor formation by inhibiting enzyme carbonic anhydrase, which results in decreased IOP. Used most frequently as single diuretic agent in acute management of CRAO. Other diuretics may be added if sufficient decrease in IOP not attained.

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Dorzolamide (Trusopt)

Clinical Context:  Used concomitantly with other topical ophthalmic drug products to lower IOP. If more than one ophthalmic drug is being used, administer the drugs at least 10 min apart. Reversibly inhibits carbonic anhydrase, reducing hydrogen ion secretion at renal tubules and increases renal excretion of sodium, potassium bicarbonate, and water to decrease production of aqueous humor.

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Class Summary

Carbonic anhydrase (CA) is an enzyme found in many tissues of the body, including the eye. The reversible reaction it catalyzes involves the hydration of carbon dioxide and the dehydration of carbonic acid.

By slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport, it may inhibit CA in the ciliary processes of the eye. This effect decreases aqueous humor secretion, reducing IOP.

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Mannitol (Osmitrol)

• Dosing, Interactions, etc.

Clinical Context:  Reduces elevated IOP when the pressure cannot be lowered by other means.

Initially assess for adequate renal function in adults by administering test dose of 200 mg/kg IV over 3-5 min. Should produce a urine flow of at least 30-50 mL/h of urine over 2-3 h.

In children, assess for adequate renal function by administering test dose of 200 mg/kg IV over 3-5 min. Should produce a urine flow of at least 1 mL/h over 1-3 h.

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Glycerin (Ophthalgan)

• Dosing, Interactions, etc.

Clinical Context:  Used in glaucoma to interrupt acute attacks. Oral osmotic agent for reducing IOP. Able to increase tonicity of blood until finally metabolized and eliminated by kidneys. Maximum reduction of IOP usually occurs 1 h of glycerin administration. Effect usually lasts approximately 5 h.

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Class Summary

Lower IOP by creating an osmotic gradient between the ocular fluids and plasma (not for long-term use).

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Apraclonidine (Iopidine)

Clinical Context:  Reduces elevated (and normal) IOP, whether accompanied by glaucoma or not. Apraclonidine is a relatively selective alpha-adrenergic agonist that does not have significant local anesthetic activity. Has minimal cardiovascular effects.

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Dipivefrin (AKPro, Propine)

Clinical Context:  Converted to epinephrine in eye by enzymatic hydrolysis. Appears to act by decreasing aqueous production and enhancing outflow facility. Has same therapeutic effect as epinephrine with fewer local and systemic adverse effects. May be used as initial therapy or as adjunct with other antiglaucoma agents for control of IOP.

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Class Summary

Lower IOP mainly by increasing outflow and reducing the production of aqueous humor. The combination of a miotic and a sympathomimetic has additive effects in lowering IOP. Each may be added in rotation after 5-minute intervals until target IOP is reached.

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Pilocarpine ophthalmic (Ocusert Pilo-40, Pilagan, Isopto, Pilostat)

• Dosing, Interactions, etc.

Clinical Context:  Directly stimulates cholinergic receptors in the eye, decreasing resistance to aqueous humor outflow.

Instillation frequency and concentration are determined by patient's response.

If other glaucoma medication also is being used, at bedtime, use gtt at least 5 min before gel.

Patients may be treated with pilocarpine as long as IOP is controlled and no deterioration in the visual fields occurs.

May use alone or in combination with other miotics, beta-adrenergic blocking agents, epinephrine, carbonic anhydrase inhibitors, or hyperosmotic agents to decrease IOP.

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Class Summary

These direct-acting agents used to be considered the first step in the treatment of glaucoma; however, they have now yielded to the beta-blockers. DOC in this category is pilocarpine; a useful adjunctive agent that is additive to the effects of beta-blockers, carbonic anhydrase inhibitors, or sympathomimetics. Individualize dosage and frequency of administration. Patients with darkly pigmented irides may require higher strengths of pilocarpine.

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Prednisone (Deltasone, Orasone, Sterapred)

• Dosing, Interactions, etc.

Clinical Context:  Useful in the treatment of inflammatory and allergic reactions. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

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Class Summary

Used in arterial occlusion only when temporal arteritis is the suspected or if etiology is confirmed.

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Timolol ophthalmic (Timoptic)

• Dosing, Interactions, etc.

Clinical Context:  May reduce elevated and normal IOP, with or without glaucoma, by reducing the production of aqueous humor or by outflow.

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Class Summary

Lower IOP by decreasing the rate of aqueous humor production and possibly outflow. May be more effective than pilocarpine or epinephrine alone and have the advantage of not affecting pupil size or accommodation.

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