Identifying CMV Retinitis as a Reversible Cause of Vision Loss in Persons with HIV-associated Meningitis

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Project Summary Vision loss is common in persons diagnosed with advanced HIV disease (CD4<200 cells/L) presenting with central nervous system (CNS) infections, such as cryptococcal or TB meningitis. The prevalence of cytomegalovirus (CMV) retinitis as a reversible cause of vision loss and the relationship of end-organ eye disease and CMV viremia is poorly characterized in Africa. Our long term objective is to develop improved guidelines and institutional capacity for ophthalmologic care relevant to low and middle income countries with high burdens of HIV/AIDS. The specific objective of this R21 project is to determine the prevalence of CMV retinitis in Ugandans living with AIDS who are hospitalized with symptoms of meningitis. The project is designed to determine if new smartphone technology could expand the reach of high quality ophthalmologic evaluations in these settings. We additionally want to assess if detectable virus in different compartments of the body could predict the development or severity of CMV end-organ disease in the eye. Specific Aim 1. Determine the prevalence of CMV retinitis in hospitalized persons with HIV-associated meningitis using mobile non-mydriatic fundus imaging by general physicians and compare the diagnostic accuracy to trained ophthalmologist examinations.  We hypothesize undetected CMV retinitis accounts for a proportion of the vision impairment seen in persons with HIV-associated meningitis that is otherwise thought irreversible. Using tele-ophthalmology- based non-mydriatic fundus imaging, general hospital physicians will be able to accurately screen and detect CMV retinitis with non-inferior accuracy as compared to trained ophthalmologists in Ugandans with HIV-associated meningitis. Specific Aim 2. Determine how baseline plasma CMV DNA concentrations correlate with CMV retinitis diagnosis made by either clinical exam or vitreous humor virus detection (in deceased patients only).  We hypothesize detectable CMV DNA in baseline plasma predicts the presence of CMV retinitis and correlates with CMV DNA in vitreous humor, which is a marker of disease activity/severity. Overall, this project will improve our understanding of the prevalence of CMV retinitis in our population and promote future research to combat reversible causes of vision loss in persons with HIV-associated meningitis. We also aim to deepen and expand the collaborative research capacity among ophthalmology, internal medicine, and microbiology departments at research sites throughout Uganda.