AIDS-Related Eye Disease

AIDS-Related Eye Disease

Annal Meleth

Sapna Gangaputra

H. Nida Sen

As of 2017, over 1.2 million people in the United States and over 37 million people worldwide are infected with the HIV virus. The incidence of HIV infection in the United States fell by 19% from 2005 to 2014. Globally, the incidence fell by 35% between 2000 and 2015.

Up to 75% of affected patients are men and men who have sex with men, and racial minorities are disproportionally affected. The HIV virus itself can cause retinopathy. The more serious ocular manifestations of AIDS are due to opportunistic infections. The incidence of HIV retinopathy and opportunistic ocular infections has decreased significantly with the use of highly active antiretroviral therapy (HAART) or combination antiretroviral therapy (cART).



HIV retinopathy is the most common ocular manifestation of HIV.

Epidemiology and Etiology

• It is characterized by loss of CD4+ T cells.

• It is uncommon if the CD4 >200, but occurs in approximately 50% of patients with a CD4 <50.

• On histopathology, loss of pericytes, narrowing of the capillary lumen, and thickening of the basement membrane are early manifestations of the disease.

• HIV-associated neuroretinal disorder can be found in eyes without any structural abnormalities and is associated with decreased quality of life and increased mortality and visual impairment.


• Cotton wool spots (Fig. 11-1)

• Intraretinal hemorrhages (Fig. 11-2)

• Microaneurysms, capillary nonperfusion, telangiectasis

• Thinning of the peripapillary retinal nerve fiber layer


• The prognosis is almost uniformly good.


Butler NJ, Thorne JE. Current status of HIV infection and ocular disease. Curr Opin Ophthalmol. 2012;23(6):517-522.

Demirkaya N, Wit FW, van Den Berg TJ, et al; AGEhIV Cohort Study Group. HIV-associated neuroretinal disorder in patients with well-suppressed HIV-infection: a comparative cohort study. Invest Ophthalmol Vis Sci. 2016;57(3):1388-1397.

Jabs DA. Ocular manifestations of HIV infection. Trans Am Ophthalmol Soc. 1995;93:623-683.

FIGURE 11-1. HIV retinopathy. There are scattered nerve fiber layer infarcts (cotton wool spots) in this patient with HIV.

FIGURE 11-2. This 48-year-old man with a CD4 count of 22 and viral load of 450,000 copies/mL has a retinal hemorrhage along with nerve fiber layer infarcts.


Cytomegalovirus (CMV) retinitis is the most common ocular opportunistic infection in AIDS, characterized by retinal necrosis and perivascular inflammation.

Epidemiology and Etiology

• The primary risk factor is the degree of immune compromise, especially CD4+ T-cell level and retinal vascular damage. Up to 30% of patients with AIDS developed CMV retinitis in the pre-highly active retroviral therapy (HAART) HAART era, with an incidence of 0.20/person year (PY). There has been a dramatic decrease in the HAART era to 0.36/100 PY.

• The primary cause of vision loss is necrotic damage to the fovea; however, macular edema is frequently associated with visual impairment.

• The primary risk factor is the degree of immune compromise. Patients with a CD4 count <50 cells/µL have more than a fourfold higher risk of developing CMV retinitis compared to patients with CD4 >100 cells/µL.

• CMV retinitis is the most common ocular opportunistic infection in patients with AIDS and is itself an AIDS-defining illness.

• In the pre-HAART era, most patients died within 1 to 2 years after diagnosis. Fortunately, there has been a dramatic decrease in the HAART and combination antiretroviral therapy (cART) era.

• Rhegmatogenous retinal detachments are an important cause of vision loss, developing in approximately 20% of affected patients.


• Peripheral perivascular inflammation with wedge-shaped areas of white granular necrosis that are associated with retinal hemorrhages. It often starts as a single lesion and then spreads outward as granular dots (Figs. 11-3, 11-4, 11-5, 11-6, 11-7, 11-8 and 11-9).

• Old lesions appear as atrophic areas with stippled pigmentation.

• Structural changes include:

  • Epiretinal membrane

  • Cystoid macular edema

• Progression is typically via expansion of existing retinal lesions, which can advance at a rate of up to 250 microns/week. It typically spreads faster anteriorly than posteriorly.

Differential Diagnosis

• Acute retinal necrosis (ARN): ARN starts as multiple lesions in the midperiphery that rapidly progress and is usually associated with vitritis.

• Progressive outer retinal necrosis (PORN)

• Ocular syphilis


• Serial fundus photographs are the gold standard to monitor lesion progression.

• Fluorescein angiography (FA) demonstrates mottled hyperfluorescence of the advancing edge, with no leakage when the lesion is atrophic.

• Autofluorescence often shows hyperautofluorescence at the advancing border.

• Anterior chamber (AC) tap or vitreous tap with polymerase chain reaction (PCR) can be diagnostic.


• Phenotypic and genotypic resistance can occur to ganciclovir, foscarnet, and cidofovir.

  • Resistance is often secondary to mutations in CMV UL97 gene, which phosphorylates ganciclovir, and CMV ULS4 gene, which inhibits CMV DNA polymerase. Owing to differential mutations, ganciclovir-resistant CMV can be susceptible to foscarnet.

• Rate of resistance has declined in the HAART era (from 28% in pre-HAART to ˜9% in the HAART/cART era).

• Blood and vitreous specimens can be directly PCR amplified and sequenced to detect resistance-conferring mutations.


• CMV retinitis is associated with an increase in mortality (9.8 deaths/100 PY), with improved survivals among those with immune recovery.

• Visual outcomes and blindness are improved with modern antiretroviral therapy (HAART or cART), even among those with CD4+ T cells <50/µL, but never reach 0.


Holbrook JT, Colvin R, van Natta ML, Thorne JE, Bardsley M, Jabs DA; Studies of Ocular Complications of AIDS (SOCA) Research Group. Evaluation of the United States public health service guidelines for discontinuation of anticytomegalovirus therapy after immune recovery in patients with cytomegalovirus retinitis. Am J Ophthalmol. 2011;152(4):628-637.

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May 5, 2019 | Posted by in OPHTHALMOLOGY | Comments Off on AIDS-Related Eye Disease
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