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

项目摘要 视力丧失在被诊断为晚期艾滋病毒疾病的人中很常见(CD4200Cells/L) 患有中枢神经系统(CNS)感染，如隐球菌或结核脑膜炎。疾病的流行 作为可逆性视力丧失原因的巨细胞病毒视网膜炎与眼的终末器官的关系 疾病和CMV病毒血症在非洲的特点很差。我们的长期目标是发展更好的 与低收入和中等收入国家相关的眼科保健指南和机构能力 艾滋病毒/艾滋病的高负担。 R21项目的具体目标是确定生活在乌干达人中CMV视网膜炎的患病率 因脑膜炎症状而住院的艾滋病患者。该项目旨在确定新的 智能手机技术可以在这些环境中扩大高质量眼科评估的覆盖范围。 此外，我们还想评估在身体不同部位检测到的病毒是否可以预测 眼部巨细胞病毒终末器官疾病的发展或严重程度。 具体目标1.确定艾滋病毒相关性住院患者中巨细胞病毒视网膜炎的患病率 全科医生使用移动式非散瞳眼底显像检查脑膜炎，并比较 受过训练的眼科医生检查的诊断准确性。 我们假设未被检测到的巨细胞病毒视网膜炎占视力损害的一部分 患有艾滋病毒相关性脑膜炎的人，否则被认为是不可逆转的。使用远程眼科技术- 基于非散瞳眼底成像，综合医院的医生将能够准确地筛查和 与训练有素的乌干达眼科医生相比，检测CMV视网膜炎的准确性毫不逊色 与艾滋病毒相关的脑膜炎。 特定目标2.确定基线血浆CMV DNA浓度与CMV视网膜炎的相关性 通过临床检查或玻璃体体液病毒检测作出诊断(仅适用于已故患者)。 我们假设基线血浆中可检测到的巨细胞病毒DNA可以预测巨细胞病毒视网膜炎和 与玻璃体液中的CMV DNA相关，这是疾病活动/严重程度的标志。 总体而言，这项计划将提高我们对巨细胞病毒视网膜炎在我们人群中的流行率的了解，以及 促进未来的研究，以对抗艾滋病毒相关性脑膜炎患者视力丧失的可逆原因。 我们还致力于深化和扩大眼科、内科和内科之间的合作研究能力 乌干达各地研究地点的医学和微生物学部门。

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.