Branch Retinal Artery Occlusion (BRAO) 

Updated: Sep 18, 2018
Author: Rishabh C Date, MD; Chief Editor: Hampton Roy, Sr, MD 

Overview

Background

The central retinal artery, a branch of the ophthalmic artery, enters the eye through the optic disc and divides into multiple branches to perfuse the inner layers of the retina. A branch retinal artery occlusion (BRAO) occurs when one of these branches of the arterial supply to the retina becomes occluded. Examples are shown in the images below.

Color fundus photo of right eye with inferior bran Color fundus photo of right eye with inferior branch retinal artery occlusion from a platelet-fibrin embolus. Retinal whitening surrounding the occluded artery is noted.
Color fundus photo of right eye with inferior bran Color fundus photo of right eye with inferior branch retinal artery occlusion. Courtesy of Vanderbilt Eye Institute.
Color fundus photo of right eye with superior bran Color fundus photo of right eye with superior branch retinal artery occlusion. Courtesy of Vanderbilt Eye Institute.

Pathophysiology

Most commonly, BRAO results from an embolus. Emboli typically originate within vessels upstream where they dislodge and travel within the circulatory system to ultimately become lodged downstream in a vessel with a smaller lumen. The most common include cholesterol emboli from aorto-carotid atheromatous plaques, platelet-fibrin emboli from thrombotic disease, and calcific emboli from cardiac valvular disease. Various other endogenous emboli as well as exogenous emboli and nonembolic causes have been reported.[1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14]

Ischemia of the inner layers of the retina leads to intracellular edema as a result of cellular injury and necrosis. This intracellular edema has the ophthalmoscopic appearance of grayish whitening of the superficial retina. Primate studies have shown that complete occlusion of arterial supply to the retina results in reversible ischemic injury in up to 97 minutes. This may help explain why patients may give a history of transient loss of vision prior to an episode of BRAO. Possibly, these episodes are secondary to emboli transiently becoming lodged, causing temporary occlusions and then reperfusing the retina as the emboli are released.

BRAO is most likely to occur at the bifurcation of an artery because bifurcation sites are associated with a narrowed lumen. In 90% of cases, BRAOs involve the temporal retinal vessels. Whether the temporal retinal vessels are affected more often or whether the nasal retinal vessel occlusions are more often undetected is unclear.

Patients with BRAO have a higher risk for morbidity and mortality secondary to cardiovascular and cerebrovascular disease. A thorough medical workup is indicated for all patients with BRAO, and an etiology can be identified in as many as 90% of patients.

Epidemiology

Frequency

United States

Central retinal artery occlusions (CRAOs) account for 58% of acute retinal artery obstructions, BRAOs account for 38%, and cilioretinal artery occlusions account for 5%.

Mortality/Morbidity

Multiple studies have shown increased mortality in patients with retinal arterial emboli. Increased mortality secondary to fatal stroke has been shown in studies, but the most common cause of death in this population is cardiovascular disease. One study found that acute coronary syndrome occurred 1.72 times more often in patients with retinal artery occlusion than in controls.[15] A10-fold increase in the annual rate of stroke in patients with retinal emboli compared to controls after a follow-up period of 3.4 years was demonstrated in another study.[16] Over a similar period, another study showed a 20% incidence of stroke in patients with retinal artery occlusion.[17]

Regarding mortality, one study found a 3-fold higher risk of 8-year mortality from stroke in patients with documented retinal emboli at baseline compared with patients without emboli. A case series reported that 15% of patients with retinal emboli died within 1 year, and a mortality rate of 54% was shown within 7 years. Given the higher incidence of cardiovascular and cerebrovascular complications in these patients, appropriate subspecialist referrals should be made at the time of diagnosis.

From an ocular standpoint, and in the absence of subsequent retinal artery occlusions, vision usually stabilizes soon after the ischemic event. A rare, long-term ophthalmic complication is neovascularization. The incidence of neovascularization in all retinal artery obstructions is less than 5%. In BRAO, the incidence is even less common. One large study demonstrated a < 1.0% incidence of neovascularization after BRAO.[18] Neovascularization, when it does occur, is more likely in patients with diabetes. Clinical cases have been reported in which neovascular glaucoma developed after BRAO.[19]

Race

One study compared retinal artery occlusions in black and white patients and found that both groups have the same risk factors for retinal arterial occlusive disease.[20] This study also suggested that whites were more likely to have identifiable carotid disease than blacks.

Sex

Among elderly patients, men are 2.5 times more likely than women to have retinal emboli. This correlates with the higher rate of stroke found in men.

Age

Typically, BRAO presents in the seventh decade of life. BRAO due to embolic causes is rare in patients younger than 30 years. Less than 1 per 50,000 outpatient visits to the ophthalmologist are estimated to involve a person younger than 30 years with retinal arterial obstruction. These cases are more likely to be nonembolic causes of retinal arterial occlusions.

Prognosis

Recovery from BRAO is usually very good without treatment; 80-90% of patients improve to a visual acuity of 20/40 or better. However, some degree of visual field deficit usually persists.

Patient Education

Patients should know that this disorder may serve as a warning of more serious systemic diseases, such as cardiovascular disease or stroke.

For excellent patient education resources, visit eMedicineHealth's Eye and Vision Center and Cholesterol Center. Also, see eMedicineHealth's patient education articles Anatomy of the Eye, High Cholesterol, and Cholesterol FAQs.

 

Presentation

History

Patients with branch retinal artery occlusion (BRAO) typically present with acute, unilateral, painless, partial visual loss. Visual field defects may be central or sectoral. Patients may also be asymptomatic.

Risk factors include smoking, hypertension, hypercholesterolemia, diabetes, coronary artery disease, or history of stroke or transient ischemic attack (TIA). Seventy-five percent of patients have hypertension or carotid occlusive disease.

Patients may give a history of temporary episodes of visual loss (amaurosis fugax) or neurologic loss (TIA). A study showed a prevalence of amaurosis fugax of 14.2% in BRAO.[21]

The physician should ask about any medical problems related to increased risk for embolus formation (eg, heart valve disorders, history of endocarditis, carotid stenosis, coagulopathies, atrial fibrillation), as well as family history of blood clots or clotting disorders. These patients have a significantly higher risk of stroke or cardiovascular events compared with the general population, so appropriate evaluation and referral is necessary.[22]

Physical

Partial visual field deficit may respect the horizontal midline but never the vertical midline.

Funduscopic examination shows retinal whitening along the distribution of the affected artery. The site of obstruction is most often at the bifurcation of the arteries where emboli are most likely to become lodged. Affected retina may be edematous.

Narrowed branch retinal artery, boxcarring, segmentation of the blood columns, cotton-wool spots, and emboli are other possible findings. Emboli are visible in 62% of eyes with a BRAO.

Some of the more common emboli include the following:

  • Cholesterol emboli (also known as Hollenhorst plaques) appear as iridescent, reflective, thin yellow plates. These yellow plates are white rhomboid crystals measuring 10-250 µm in length and less than 3 µm in thickness. They appear yellow on funduscopic examination because of blood showing through their translucent thinness. Digital pressure on the eye can make them turn within the vessel causing them to become more or less visible to the examiner. They usually do not cause occlusion of the artery by themselves because blood can flow around them. However, if they occur in conjunction with platelet-fibrin or if they are large, then they can obstruct arterial blood flow. Because their sources are most likely atheromatous plaques in the aorto-carotid system, even asymptomatic patients need a medical workup.
  • Platelet-fibrin emboli appear as whitish-gray, nonreflective plugs that are mobile. They may appear in "showers" and may pass through without causing an occlusion. They are usually associated with mural thrombus in the carotid artery or cardiac valvular structures.
  • Calcific emboli appear as large, yellowish-white, nonreflective plaques. They more likely are found in the larger arterioles near the optic disc. They are associated with calcified cardiac valves and atheromatous plaques of the carotid artery.

One study demonstrated that attempts to categorize emboli into cholesterol, calcific, or other by funduscopic examination had large intraobserver and interobserver variability.[23] The authors recommended that systemic evaluation not be based on qualitative assessment of the type of emboli.

Auscultation of the heart and carotid arteries and comparison of ophthalmodynamometry may help identify the source of emboli.

Causes

In elderly patients, embolic disease is the most common etiology of a BRAO. In a study of 70 patients with retinal emboli, 40 were found to have cholesterol emboli, 8 platelet-fibrin emboli, 6 calcific emboli, and 1 possible myxomatous embolus.[24] These types of emboli can also be iatrogenically displaced during cardiac angiography, catheterization procedures, or any interventional embolization of any branch of the carotid artery.

Types of emboli (endogenous and exogenous) include the following:

  • Cholesterol – Atheromatous plaques from the aorto-carotid system

  • Platelet-fibrin – Carotid or cardiac thrombosis

  • Calcific - Calcified cardiac valves and atheromatous plaques of the carotid artery

  • Leukoemboli -Vasculitis, Purtscher retinopathy, septic endocarditis

  • Fat emboli - Following long bone fractures

  • Amniotic fluid emboli - Complication of pregnancy

  • Tumors - Atrial myxoma, mitral valve papillary fibroelastoma

  • Talc emboli - Long-term intravenous drug abusers

  • Corticosteroid emboli - Complication of intralesional or retrobulbar steroid injection

  • Air emboli – Following trauma or surgery

  • Synthetic particles – From synthetic materials used in artificial cardiac valves and other vascular procedures; facial dermal filler (Restylane)

  • Interventional embolization material (Onyx) (this has been observed at the current authors’ institution)

    Color fundus photo of left eye with branch retinal Color fundus photo of left eye with branch retinal artery occlusion caused by embolization of ethylene vinyl alcohol copolymer (Onyx), a liquid embolic agent used in the treatment of saccular aneurysms, into the retinal circulation. Courtesy of Vanderbilt Eye Institute.

In younger patients, other more obscure and diverse etiologies are more likely. In patients younger than 30 years with retinal arterial obstruction (RAO), associations have been noted with migraines, coagulation abnormalities, trauma, increased intraocular pressure, optic nerve drusen, oral contraceptives, and other entities, which merit a more comprehensive review. Atheromatous disease is a rare cause of RAO in this age group, and routine carotid angiography for embolic cause is not recommended. Visual prognosis is similar to older patients.

Nonembolic causes of BRAO include the following:

  • Thrombosis -  Atherosclerosis, chemotherapeutic agents, bone marrow transplants
  • Inflammatory conditions - Syphilis, toxoplasma, retinochoroiditis, Behçet disease, Lyme disease, pseudotumor cerebri, Bartonella infection, HIV infection, posterior scleritis, varicella-zoster infection, multifocal retinitis with optic nerve edema, West Nile virus infection, giant cell arteritis
  • Vasospasm - Migraines, cocaine abuse, sildenafil citrate use
  • Coagulopathies -  Sickle cell disease, Hodgkin disease, pregnancy, anemia, platelet and clotting factor abnormalities, protein C, protein S, antithrombin III, factor V Leiden deficiencies, oral contraceptives, homocystinuria, antiphospholipid syndrome, chelation therapy
  • Autothrombosis - From a ruptured arteriolar macroaneurysm
  • Compression - Preretinal arterial loops, vitrectomy surgery, trauma
  • Idiopathic - Syndrome involving recurrent episodes of multiple BRAOs in otherwise healthy individuals, association with Susac syndrome (microangiopathy of brain, retina, and cochlea) in some of patients

Complications

Stroke is a devastating complication of emboli in the arterial circulation.[25]  Few studies report the prospective association between retinal emboli and risk of stroke and stroke mortality. One study reported a 10-fold increase in the annual rate of stroke in patients with retinal emboli compared to controls after a follow-up period of 3.4 years. Another study found a 3-fold higher risk of 8-year mortality from stroke in patients with documented retinal emboli at baseline compared to patients without emboli. A case series reported that 15% of patients with retinal emboli died within 1 year, and a mortality rate of 54% was shown within 7 years.

 

DDx

Differential Diagnoses

 

Workup

Laboratory Studies

Laboratory tests to consider in patients with suspected branch retinal artery occlusion (BRAO) include the following:

  • In patients older than 50 years, consider ordering an immediate erythrocyte sedimentation rate (ESR) to help rule out giant cell arteritis.

  • In patients younger than 50 years or in patients with the appropriate risk factors, consider the following tests to evaluate for coagulopathies: antitreponemal antibody, antiphospholipid antibody, antinuclear antibody, rheumatoid factor, serum protein electrophoresis, hemoglobin electrophoresis, prothrombin time/activated partial thromboplastin time (PT/aPTT), fibrinogen, protein C and S, antithrombin III, and factor V Leiden.

  • A CBC count is obtained to evaluate for anemia, polycythemia, and platelet disorders.

  • Fasting blood sugar, glycosylated hemoglobin, cholesterol, triglycerides, and lipid panel are obtained to evaluate for atherosclerotic disease.

  • Blood cultures are obtained to evaluate for bacterial endocarditis and septic emboli.

Imaging Studies

Acute BRAO or central retinal artery occlusion should be treated as ocular and systemic emergencies, as they can be harbingers for subsequent stroke. Thus, guidelines necessitate urgent imaging and clinical evaluation.[22] Imaging studies are imperative to determine the etiology of the embolus for the purpose of treatment and subsequent prevention of further artery occlusions or stroke.

Two-dimensional or transesophageal echocardiography

Elderly patients and patients with high-risk characteristics for cardioembolic disease warrant medical workup involving either 2-dimensional or transesophageal echocardiography. High-risk characteristics include a history of rheumatic heart disease, mitral valve prolapse, prosthetic valve placement, history of subacute bacterial endocarditis, recent heart attack, intravenous (IV) drug abuse, any type of valvular heart disease (congenital or acquired), detectable heart murmurs, and ECG changes (eg, atrial fibrillation, changes indicating myocardial damage).

Carotid ultrasonography studies and magnetic resonance angiography

Considering the higher incidence of fatal stroke in the elderly population, atherosclerotic disease should be evaluated if no other etiology is obvious.

ECG/Holter monitor

ECG/Holter monitor is used to evaluate for atrial fibrillation.

MRI

MRI can be used to evaluate for additional, possibly occult, vessel occlusions in the brain. In cases of suspected Susac syndrome, MRI may be helpful to look for classic findings in the corpus callosum. Any concern for concurrent stroke symptoms would warrant the appropriate brain imaging and workup, usually guided by neurologic consultation.

Fluorescein angiography

Delayed filling of the affected artery and hypofluorescence in the surrounding retina will be visible immediately after onset of the occlusion. Vessels distal to the site of obstruction may show retrograde filling from surrounding perfused capillaries. Late staining of the vessel walls may be seen.

After resolution of the obstruction, reperfusion can occur, and flow may return to normal. However, narrowing or sclerosis of the affected artery can occur. Artery-to-artery collaterals may form in the retina and are highly suggestive of an old BRAO.

Red-free photograph (before injection of fluoresce Red-free photograph (before injection of fluorescein) of right eye with inferior branch retinal artery occlusion. The red-free photograph greatly accentuates the retinal whitening surrounding the occluded artery.
Fluorescein angiogram of right eye with inferior b Fluorescein angiogram of right eye with inferior branch retinal artery occlusion. Delayed filling of the artery (arrow heads) by the fluorescein is noted.

Optical coherence tomography

Optical coherence tomography (OCT) has been used to demonstrate structural damage of the retinal layers after retinal artery occlusion.[26]

Increased thickening and hyperreflectivity of the inner retinal layers with decreased reflectivity of the photoreceptors and retinal pigment epithelium is often present, which supports the pathophysiology of increasing intracellular fluid within the inner retinal layer. The inner retina, rather than the outer retina, is preferentially affected, because the inner retinal layers receive blood flow from the central retinal artery and its branches, whereas the outer retinal layers are fed by the choroidal vasculature.

One study used OCT to demonstrate the long-term structural results after arterial occlusion. One year after diagnosis of BRAO, the authors found segmental inner retinal layer and peripapillary retinal nerve fiber layer thickness to be reduced. They correlated visual field deficits with OCT thickness and found that a worse functional outcome was associated with a more extensive thinning of the macula and retinal nerve fiber layer.

Another study suggested that spectral domain OCT may be a useful adjunct in the acute phase in characterizing retinal artery emboli, including perfusion characteristics (eg, extent of luminal occlusion) and emboli characteristics and embolus structure (eg, more crystalline in appearance or softer and more conforming to the shape of the vessel lumen).[27]

Optical coherence tomography (OCT) of right eye wi Optical coherence tomography (OCT) of right eye with inferior branch retinal artery occlusion. Cross-section goes through inferior retina to superior retina, capturing the abnormally thickened retina associated with intracellular edema.
Optical coherence tomography (OCT) over time of a Optical coherence tomography (OCT) over time of a branch retinal artery occlusion. Taken 24 hours after symptom onset, A shows an unaffected portion of the macula, while B shows swelling of the inner retina in the area affected by the branch retinal artery occlusion (BRAO). Two weeks later, this swelling/increased thickness is beginning to resolve (C). Two months later, the inner retina has thinned notably, and the inner plexiform layer, inner nuclear layer, and outer plexiform layer are difficult to distinguish from one another. Courtesy of British Journal of Ophthalmology.

Optical coherence tomography angiography

Optical coherence tomography angiography (OCTA) is a newer imaging technique that can noninvasively segment and visualize retinal and choroidal microvasculature. In cases of retinal artery occlusions, OCTA can be used to evaluate the superficial and deep capillary plexuses in the inner retina, which conventional fluorescein angiography is unable to do. While limited, studies of OCTA in retinal artery occlusions have shown perfusion abnormalities in both the superficial and deep plexuses, with the degree of nonperfusion changing as the arterial occlusion process evolves.[28]

OCTA does have limitations, with studies showing that slow-flowing capillaries may not be visible on the angiograms. Thus, nonperfusion on OCTA should be interpreted with caution.[29] While further studies of OCTA are warranted, it may allow for assessment of the extent of macular ischemia and monitoring of vascular flow changes over the course of retinal vascular diseases.

Other Tests

Serial Humphrey visual field testing reveals any field deficits and can be used to monitor the stability or improvement of these deficits.

An electroretinogram (ERG) is of limited usefulness. Findings may be normal. In the case of a large BRAO, it may show loss of oscillatory potential and transient depression of the B wave.

Procedures

Because the prognosis for branch retinal artery occlusion (BRAO) is very good, no interventions usually are taken. In the event of involvement of the perifoveolar capillaries, treatment as for central retinal artery occlusion (CRAO) may be attempted (see Central Retinal Artery Occlusion).

Intra-arterial thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) via a guiding catheter inserted into the femoral artery, placed into the internal carotid artery, and advanced into the ophthalmic artery has been used for CRAO with varying success. This has also been applied to some patients with BRAO with limited benefit compared to conventional forms of therapy or observation. Given the high rate of adverse events (37.1% in the EAGLE study), intra-arterial thrombolysis is not currently recommended in the management of arterial occlusions.[30]

Another procedure that has been attempted for both BRAO and CRAO is transluminal Nd:YAG laser embolysis or TYE. This method relies on the Nd:YAG laser to shatter the embolus, clear the arteriole lumen, and improve perfusion without harming the vessel wall. Potential risks include retina tears, vitreous and retinal hemorrhages, choroidal neovascularization, and epiretinal membrane formation. One study found visual improvement to occur immediately after the embolysis. A meta-analysis suggests possible visual benefit of TYE, especially in patients with poor visual acuity; however, further research is warranted.[31]

Histologic Findings

BRAO causes ischemia to the inner layers of the retina, which causes inner and intracellular edema and a coagulative necrosis.

Eventually, loss of the inner retinal layers occurs, including the nerve fiber layer to the inner nuclear layer.

Because the glial cells have also been destroyed, usually no gliosis is noted.

Histologic evidence of emboli or other etiology may be present.

 

Treatment

Medical Care

Considering the increased rate of mortality, patients with branch retinal artery occlusion (BRAO) should receive a full medical workup with special attention to the cerebrovascular and cardiovascular system. Depending on the findings, carotid endarterectomy or anticoagulation may be indicated. Laboratory workup for coagulopathies should also be performed if no embolic source is found.

Surgical Care

Surgical embolus excision has been described in a few case reports, with the authors reporting good visual outcome and safety.[32, 33] Given the natural history of frequent spontaneous visual improvement and generally good visual outcome in untreated BRAO, further investigation with a randomized controlled trial is likely needed to validate surgical embolus excision as a treatment option in BRAO.

Consultations

Refer to an internist for complete systemic workup.

Prevention

Controlling blood pressure, cholesterol, and diabetes can greatly reduce the risk of atherosclerotic disease.

Smoking cessation can also lower the risk of stroke.

Long-Term Monitoring

Patients should initially be evaluated every 3-6 months to monitor progression.

Ocular neovascularization after BRAO is rare. If neovascularization occurs, panretinal photocoagulation should be performed.

 

Medication

Medication Summary

To prevent stroke, most patients with branch retinal artery occlusion (BRAO) are placed on some form of antiplatelet therapy, such as aspirin, clopidogrel (Plavix), dipyridamole (Aggrenox), and ticlopidine (Ticlid).

Warfarin (Coumadin) is a blood thinner that prevents the blood from clotting. This medication is often used in patients with atrial fibrillation to decrease their risk of stroke.