Multiple extra macular branch retinal vein occlusions in hyperhomocysteinemia

Abstract

Hyperhomocysteinemia is a well-known modifiable risk factor for thromboembolism. Retinal vascular occlusion in patients having hyperhomocysteinemia is a known entity, particularly in young patients. However, multiple extra macular branch retinal vein occlusion (BRVO) is a rare condition, which can be a presentation of this disease. We present a patient who had multiple extra macular BRVO; on complete systemic workup, he was found to have raised homocysteine levels.

Hyperhomocysteinemia is a known risk factor for ocular and systemic vaso-occlusive events.

However, multiple extra macular branch retinal vein occlusion (BRVOs) has not been mentioned in literature with hyperhomocysteinemia.

Case Report

A 45-year-old man presented with a history of blurred vision in his right eye since past 15 days. He was a known case of bronchial asthma since 6 years. On examination, his right eye best corrected visual acuity was 20/20. Anterior segment examination and IOP was normal.

Fundus examination showed multiple cotton wool spots inferior to the papillomacular bundle, extending toward macula with retinal hemorrhages temporal to macula [Fig. 1].

Figure 1.

Color fundus photo showing numerous soft exudates in inferotemporal part extending toward macula in some part, multiple vein constrictions, and occlusions

Red free and fluorescein angiography [Figs. 2 and 3] showed areas of blocked fluorescence due to hemorrhages and multiple BRVOs. Macular perfusion was not affected as foveal avascular zone was normal.

Figure 2.

Fuorescein angiography showing multiple branch retinal vein occlusions

Figure 3.

Asterix and arrows showing partial vein obstructions

Optical coherence tomography [Figs. 3 and 4] showed normal foveal contour and anatomy. Patient underwent complete systemic workup including hemogram with erythrocyte sedimentation rate (ESR), lipid profile, renal function tests, ANA, c-ANCA, p-ANCA, homocysteine levels, coagulation profile (Prothrombin time, APTT, bleeding time, clotting time, protein C and S levels), syphilis serology, echocardiography, and electrocardiogram. Except a raised level of homocysteine (35 μM) (normal range: 5-15 μM), all other levels were within normal limits.

Figure 4.

OCT showing normal anatomy of macula

He was started on anticoagulants and homocysteine lowering agents under guidance of an internist. As macular perfusion was not affected and there was no associated cystoid macular edema, no active ocular intervention was done. He was advised close follow-up for early detection of any further vision threatening vein obstruction.

Discussion

Retinal vein occlusion (RVO) is the second most common sight-threatening retinal vascular disorder after diabetic retinopathy. The incidence of BRVO is generally higher than the incidence of CRVO. Patients with RVO have a higher prevalence of stroke and a greater risk of cardiovascular disease than similarly aged individuals without RVO.[1]

BRVO prevalence has been shown to vary from 0.7% to 1.6%. BRVO is divided into two distinct entities: Major BRVO, when one of the major branch retinal veins is occluded, and macular BRVO, when one of the macular venules is occluded. In 66% of eyes with BRVO, there is occlusion of the major branch in the superotemporal quadrant, followed by 22-43% of eyes with occlusion of the major branch in the inferotemporal quadrant. Major BRVO can be asymptomatic or with visual blurring, usually involving the sector of visual field corresponding to the area of the retina involved. In macular BRVO, there is always a central visual disturbance with normal peripheral vision.[2]

Among all conditions leading to a hypercoagulable state, hyperhomocysteinemia was the commonest cause found in 21.9% patients. Homocysteine is an amino acid derived from methionine, which can be converted into cysteine. The metabolic pathways involving homocysteine require vitamin B₁₂, vitamin B₆, and folate for proper functioning. Various reports on hyperhomocysteinemia depict that arterial as well as venous vessels are involved in the disease.[3]

The rare syndrome of homocystinuria was first described in 1962 among subjects with mental retardation, ocular, and skeletal abnormalities, as well as a high risk of thromboembolism.[4]

Increased plasma homocysteine is associated with both RVO and retinal arterial occlusion, the elevation being greater in the arterial occlusion group. In young patients, RVO is less associated with systemic diseases and is more strongly associated with plasma homocysteine than in older patients.

Atherosclerotic plaques occur in young people with homocystinuria who suffer from premature, aggressive occlusive disease. Plasma concentrations of homocysteine are an independent risk factor for cardiovascular and cerebrovascular disease in the general population.[5]

Mild to moderate elevation of plasma homocysteine is reported as a risk factor for occlusive disease. Specifically, many studies demonstrate hyperhomocysteinemia as an independent risk factor for atherosclerosis in the coronary, cerebral, and peripheral vasculature. The mechanisms by which homocysteinemia damages the blood vessel wall by supporting prothrombotic effects seems to be multifactorial. The various mechanisms reported include homocysteine-induced oxidative stress (redox stress), decreased bioavailability of nitric oxide, altered expression of various thrombotic factors, mutagenic effect on arterial smooth muscle cells, and expression of acute stress-related genes.[6]

Homocysteinemia presenting as multiple extra macular BRVOs has not been cited in literature.[1,2,3,4,5,6,7,8,9]

Patients presenting with such kind of clinical picture should be investigated thoroughly to rule out any modifiable risk factor such as hyperhomocysteinemia to prevent any further vaso-occlusive event.