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Expert Commentary

HIV Neuroretinal Disorder: A New Complication of Accelerated Aging in the Modern Antiretroviral Therapy Era

In this commentary, Mark Jacobson, MD, discusses HIV neuroretinal disorder, a condition that is common (but incompletely studied) in persons with advanced HIV disease and that may be related to immune dysregulation.

Today, long-term survival and morbidity among HIV/AIDS patients receiving effective antiretroviral therapy (ART) is influenced far more by cardiovascular, liver, and kidney disease, as well as non-AIDS-defining cancers, than by AIDS-defining opportunistic infections and malignancies. Another "accelerated disease of aging" seen in persons with HIV may be an ocular condition, HIV neuroretinal disorder (NRD).

Visual function impairment is common among patients with advanced HIV disease, most likely owing to neuroretinal pathology that may result from HIV itself or the immune dysregulation that uncontrolled HIV infection can cause.

The first reports of HIV NRD appeared in the early 1990s, before the modern ART era. Autopsy studies demonstrated loss of the axons that carry nerve impulses from retinal ganglion cells through the optic nerve to the brain, even in specimens without clinically apparent retinal diseases such as cytomegalovirus (CMV) retinitis. At the same time, various forms of vision dysfunction were described among individuals with AIDS who did not have ocular opportunistic infections. For example, in patients with AIDS but without AIDS-defining ocular complications, asymptomatic individuals had normal color contrast sensitivity and visual fields whereas those with more advanced HIV disease had progressive impairment. Some of the abnormalities in visual function correlated with the number of cotton-wool spots detected by dilated ophthalmoscopy, suggesting the underlying pathogenesis might be neuroretinal damage secondary to an HIV-related microangiopathy (a pathogenic mechanism known to contribute to the development of cotton-wool spots).

In the past decade, the multicenter Longitudinal Study of Ocular Complications of AIDS (LSOCA), which opened to enrollment in 1998, has begun to systematically investigate HIV NRD. The first study of NRD to include LSOCA participants examined black/white contrast sensitivity and color vision in 71 HIV-infected patients without ocular opportunistic infections.(1) All these subjects had normal visual acuity, 87% were less than 60 years of age, and 77% had been immuno-restored by ART. Contrast sensitivity and color vision were impaired by more than 2 standard deviations from age-adjusted normal mean values in 7% and 10% of the patients, respectively. Impairments in contrast sensitivity and color vision were not correlated, suggesting they represent different types of neuroretinal pathology.

A larger evaluation of visual function in all 1,351 LSOCA subjects with no major ocular complications was published in 2008.(2) This study demonstrated a significant association between measures of decreasing visual function and indices of the severity of immunosuppression. This cohort, consisting exclusively of patients with a prior clinical AIDS diagnosis, had a median absolute CD4 T-cell count of 180 cells/µL at entry, and 80% were receiving ART. Surprisingly, 39% had visual fields less than the 2.5 percentile of population norms and 12% had black/white contrast sensitivity below this same age-related standard. More recent genetic studies, utilizing stored peripheral blood mononuclear cell (PBMC) specimens, suggest that the risk of developing HIV NRD is associated with polymorphisms in genes known to be important in cytokine and chemokine pathways involved in T-cell activation--a mechanism that appears to underlie other "accelerated diseases of aging" in HIV-infected patients.

In summary, these studies suggest that visual function impairment is common among patients with advanced HIV disease, most likely owing to neuroretinal pathology that may result from HIV itself or the immune dysregulation that uncontrolled HIV infection can cause. Whether these visual abnormalities improve over the course of immune reconstitution with effective ART is still unknown. To date, there is no information on potential therapy for the condition; however, one logical implication of these data is that initiation of ART earlier in the course of HIV disease may prevent NRD.

The author is grateful to Gary Holland, Douglas Jabs, and Jennifer Thorne for helpful discussions about this topic.

References

  1. Shah KH, Holland GN, Yu F, et al; Studies of Ocular Complications of AIDS (SOCA) Research Group. Contrast sensitivity and color vision in HIV-infected individuals without infectious retinopathy. Am J Ophthalmol. 2006 Aug;142(2):284-92.
  2. Freeman WR, Van Natta ML, Jabs D, et al; SOCA Research Group. Vision function in HIV-infected individuals without retinitis: report of the Studies of Ocular Complications of AIDS Research Group. Am J Ophthalmol. 2008 Mar;145(3):453-462.