Bilateral central retinal artery occlusion as presenting manifestation of human immunodeficiency virus infection.

A 30-year-old male with bilateral acute visual loss presented with retinal edema in the posterior pole and peripapillary region with extensive retinal hemorrhages. Fluorescein angiography revealed delayed arterial filling in the right eye and absent arterial filling in the left eye, suggesting bilateral central retinal artery occlusion. Systemic evaluation revealed a history of chronic low-grade fever and generalized lymphadenopathy. HIV (ELISA) was positive, and other systemic comorbidities were ruled out. Cervical lymph node biopsy stained positive for acid-fast bacilli, with large areas of necrosis, palisaded by epithelioid cell granulomas, macrophages, and multinucleated giant cells, suggesting lymph node tuberculosis. Despite antiretroviral and antitubercular therapy, he developed optic atrophy at 4 weeks.

The spectrum of HIV retinopathy frequently includes microvascular occlusions and rarely involves large retinal vessels, affecting veins more commonly than arteries.[1] The largest series on retinal vascular occlusions in HIV reported a single case of central retinal artery occlusion (CRAO) among 2484 patients studied retrospectively.[2] Few isolated case reports have described CRAO in diagnosed cases of HIV infection.[34]

The risk profile for retinal artery occlusion includes a number of cardiovascular factors. While certain systemic and ocular factors predispose to central retinal vein occlusion (CRVO), the risk profile of a combined CRAO and CRVO differs and involves a number of systemic comorbidities in the form of various cardiovascular risk factors.[5] We report a case where bilateral CRAO was the presenting manifestation of HIV infection.

Case Report

A 30-year-old male presented with bilateral, painless loss of vision (left followed by right eye) for 3 weeks. The visual acuity was counting fingers at 1 m in both eyes with normal intraocular pressures. The anterior segment was unremarkable in both eyes. Fundus examination revealed retinal edema of the posterior pole and peripapillary region with scattered hemorrhages in all quadrants of both eyes [Fig. 1a and b]. Fluorescein angiography (FA) revealed delayed arterial filling with cilioretinal artery sparing in the right eye and absence of arterial filling in the left eye, suggestive of bilateral CRAO [Fig. 1c and d]. A secondary CRVO was considered due to the presence of extensive retinal hemorrhages. A prompt hematology, cardiology, and rheumatology consultation was sought. Systemic evaluation revealed a history of low-grade fever (since 4 months) and generalized lymphadenopathy. Hemogram, chest X-ray, blood culture, coagulation profile, serum electrolytes, renal/liver function tests, ultrasound abdomen, carotid Doppler, and two-dimensional echocardiography were normal. Antinuclear antibody, antineutrophil cytoplasmic antibody, Treponema pallidum hemagglutination assay, antiphospholipid antibody, serum homocysteine, hepatitis B surface antigen, anti-hepatitis C virus, and cytomegalovirus (CMV) IgM antibody were nonreactive. C-reactive protein (20 mg/ml) and erythrocyte sedimentation rate (40 mm/1st h) were elevated. HIV was positive by ELISA. Histopathological examination of cervical lymph node biopsy showed large areas of necrosis, peripherally palisaded by well-formed epithelioid cell granulomas, macrophages, and multinucleated giant cells. Stain for acid-fast bacilli was positive, suggestive of lymph node tuberculosis (TB). The CD4+ T-lymphocyte count was 450 cells/μL. The patient was started on antiretroviral therapy, along with antitubercular therapy. Visual acuity at 4 weeks of follow-up was hand movements in both eyes, with optic disc pallor and resolving hemorrhages.

Figure 1

Wide-field fundus photographs of the right eye (a) and the left eye (b) showing retinal edema of the posterior pole and peripapillary region, scattered retinal hemorrhages in all quadrants and retinal arteries narrowing. Fluorescein angiography in the right eye (c) revealed delayed arterial filling with small island of macular perfusion and absent retinal perfusion in the left eye (d)

Discussion

A combined CRAO and CRVO involves a number of systemic comorbidities in the form of various cardiovascular risk factors such as arterial hypertension, diabetes mellitus, hypercholesterolemia, coagulation disturbances, chronic smoking, hyperuricemia, and systemic vasculitis.[5] Although not completely understood, the retinal vascular abnormalities in HIV infection have been attributed to focal retinal ischemia, elevated fibrinogen, erythrocyte aggregation, reduced perifoveal blood flow, degeneration in the blood vessels, deposition of circulating immune complexes, presence of HIV within retinal endothelial cells, and a higher resistive index in the central retinal artery.[678] These factors precipitate the development of thrombi in HIV-infected patients. Further, an increased risk of atherosclerosis in HIV has been linked to genetic predisposition, virus-induced vasculitis and as a complication of highly active antiretroviral therapy. When compared with HIV-negative individuals of the same age, the retinal macrovascular occlusions in HIV-positive patients are more common and potentially blinding.[2] While CRVO is most common of these, it has not been reported with simultaneous CRAO in HIV-infected patients. Biswas et al. have reported CRVO due to herpes zoster as the initial presentation in an acquired immunodeficiency syndrome (AIDS) patient.[9] A combined hemi-CRVO with branch retinal artery occlusion in HIV was reported by Dunn et al.[2] A simultaneous CRAO with CRVO may occur secondary to infections, inflammations, or trauma. Our patient had a combined bilateral CRAO and CRVO with sparing of cilioretinal artery in the right eye. It is difficult to say if the closed loop circulation or compressive arteriopathy arising from CRVO led to CRAO in our patient. The presence of cilioretinal artery sparing (which is derived from choroidal circulation) in the right eye of our patient may indicate CRAO as the primary event, accompanied by hemodynamic alterations producing hemorrhagic retinopathy manifesting as CRVO. Furthermore, the absence of optic disc edema and venous tortuosity indicate less likelihood of CRVO as the initiating event. A stasis of axoplasmic flow, as known in HIV retinopathy, may have been widespread enough to cause CRVO-like retinopathy in the presence of CRAO. In our patient, fundus FA in both eyes was suggestive of CRAO. In the presence of widespread retinal hemorrhages in all quadrants, we believe that CRVO probably occurred as a secondary phenomenon rather than a simultaneous CRVO as it is difficult to comment upon the latter due to the absence of venous tortuosity. Development of immune complexes by the opportunistic infection agent was postulated in the pathogenesis of a simultaneous branch retinal artery and vein occlusion in a patient with AIDS and CMV retinitis.[10]

None of the systemic (hypertension, extraocular thrombotic disease, sickle cell trait, cardiovascular disease, hemophilia) or ocular (background HIV retinopathy, hypertensive retinopathy, diabetic retinopathy, myopic degeneration, optic nerve drusen) associations of retinal macrovasculopathy in HIV patients, as described by the previous reports, was present in our patient.[234] It is difficult to say whether generalized lymphadenopathy (tubercular) in our patient was directly linked to the combined CRAO and CRVO. A combined vasculopathy has also been attributed to optic nerve inflammation.[11] Wen et al. from China reported a case of combined CRVO with CRAO in HIV suggesting it as a part of systemic vascular disease in AIDS.[12] No association of retinal vascular occlusion with antiphospholipid syndrome was found in our HIV-infected patient, consistent with literature review.[2]

Occlusive retinal vasculitis is a well-known feature of ocular TB, with or without an underlying systemic TB infection, usually involving the veins. Arterial occlusion is extremely rare, with extraocular (pulmonary or miliary) TB and CRAO (or CRVO) existing in the same patient, besides other rare inflammatory (syphilis, periarteritis nodosa, and temporal arteritis) associations with CRAO. Since no perivascular sheathing/infiltrates were seen in our patient, we believe that the presence of tuberculous lymphadenopathy is probably coincidental and not associated with retinal vascular occlusions.

As thrombophilia (heritable or acquired) is a major risk factor for retinal vascular occlusions, these patients are at an increased risk of developing deep vein thrombosis, pulmonary embolism, or large-vein thrombosis at other sites.[13] CRAO in HIV-infected patients differs from that in non-HIV individuals in occurring at a much younger age and not being associated with carotid vascular disease.[2]

Conclusion

Visual loss is generally poor, consistent with the natural course. As CRAO requires prompt evaluation for systemic diseases, HIV screening should be included in the baseline workup of young adults presenting with such an ophthalmic emergency.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.