STUDY AND TREATMENT OF RETINOPATHY ASSOCIATED WITH AIDS

HIV感染者的眼部传染病导致视力丧失 在某些情况下，大约30%的患者完全失明。 这主要是由于感染性病毒性视网膜炎。 另外还有按 视网膜微血管病变导致70 - 100%的多发性视网膜梗死 艾滋病患者;这最近被证明会导致一种较温和的形式， 视力丧失 这项补助金是一个有竞争力的更新，重点是四个 视网膜疾病的各个方面：流行病学，病理生理学，诊断 模式和新疗法。 第一个目标是进一步阐明 HIV感染者视网膜疾病的流行病学特征和危险因素 感染的病人。 这里的重点是视网膜微血管病变， 以及巨细胞病毒视网膜炎 病毒学、免疫学和其他数据将 收集了一组特征明确的HIV阳性个体， 参加了7500万美元的UCSD HIV神经行为研究， 中心 感染性和微血管疾病的病理生理学 将通过使用新的 电生理和心理物理测试，并通过前瞻性 问题研究 我们将确定视力丧失的性质和程度 与视网膜微血管疾病和脑梗死相关 内视网膜（棉絮斑）。 有风险因素的患者研究 CMV视网膜炎的治疗和并发症将包括研究，以确定 发生CMV视网膜炎的CD4阈值及其与CMV的相关性 CNS疾病。 其他研究将包括以下风险因素： 发生视网膜脱离，似乎影响20 - 25%的眼睛 CMV视网膜炎 病理生理学的实验室研究将 包括对整个安装视网膜共焦免疫显微镜检查 以及艾滋病患者视网膜组织的PCR研究， 进一步的病毒和其他病因（细胞因子相关的损伤）。 尝试 提高感染性视网膜病变患者的诊断能力 疾病将包括PCR的灵敏度和特异性的研究， 眼液和组织的培养及相关技术. 尸体解剖和临床资料。 最后， 感染性视网膜炎及其并发症的治疗包括随机 激光预防视网膜脱离的临床试验， 联合膦甲酸和更昔洛韦治疗和随机试验， 视网膜脱离患者的两种手术修复技术。 在实验室中，我们将继续进行玻璃体内注射的研究 长效抗CMV化合物，其中之一（HPMPC）已被证明是 在疱疹性视网膜炎动物模型中高度有效， 适合于通过玻璃体内注射治疗患者， 不频繁的间隔（每月一次）。

Ocular infectious disease in HIV infected individuals causes vision loss and in some cases total blindness in approximately 30% of patients. This is largely due to infectious viral retinitis. In addition, a retinal microvasculopathy causes multiple retinal infarctions in 70-100% of AIDS patients; this has recently been shown to cause a milder form of vision loss. This grant is a competitive renewal and focuses on four aspects of retinal disease: Epidemiology, Pathophysiology, Diagnostic modalities and New Therapies. The first goal is to further elucidate epidemiologic aspects and risk factors for retinal disease in HIV infected patients. The emphasis here is on retinal microvasculopathy as well as CMV retinitis. Virologic, immunologic and other data will be gathered on a cohort of well characterized HIV positive individuals enrolled in the 75 million dollar UCSD HIV Neurobehavioral Research Center. The pathophysiology of infectious and microvascular disease will be elucidated through a combination of clinical testing using new electrophysiological and psychophysical testing, and by prospective studies. We will determine the nature and extent of vision loss associated with retinal microvascular disease and infarctions of the inner retina (cotton wool spots). Studies of patients with risk factors for and complications of CMV retinitis will include studies to determine CD4 threshold for developing CMV retinitis and associations with CMV disease of the CNS. Additional studies will include risk factors for developing retinal detachment which appears to affect 20-25% of eyes with CMV retinitis. Laboratory investigations into pathophysiology will include confocal immunomicroscopic examination of whole mounted retina as well as PCR studies of retinal tissue from AIDS patients to elucidate further viral an other etiologies (cytokine related damage). Attempts to improve diagnostic abilities in patients with infectious retinal disease will include studies of the sensitivity and specificity of PCR, cultures and related techniques on ocular fluids and tissues obtained at autopsy as well as from clinical material. Finally, new approaches to therapy of infectious retinitis and its complications include randomized clinical trials of laser prophylaxis to prevent retinal detachment and combination foscarnet and ganciclovir therapy and a randomized trial of two surgical repair techniques for patients with retinal detachments. In the laboratory, we will pursue our studies of intravitreal injections of long acting anti-CMV compounds, one of which (HPMPC) has proven to be highly effective in an animal model of herpetic retinitis and which may be suitable for therapy in patients by intravitreal injection at infrequent intervals (once monthly).