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，约30%的患者完全失明。 这在很大程度上是由于传染性病毒性视网膜炎。此外，a 视网膜微血管病变导致70%-100%的多发性视网膜梗塞 艾滋病患者；这最近被证明导致一种较温和的形式的 视力丧失。这笔赠款是一次竞争性续签，重点是四个 视网膜疾病方面：流行病学、病理生理学、诊断学 模式和新疗法。第一个目标是进一步澄清 HIV视网膜疾病的流行病学特征和危险因素 被感染的病人。这里的重点是视网膜微血管病变，如 还有巨细胞病毒视网膜炎。病毒学、免疫学和其他数据将 聚集在一群特征良好的艾滋病毒阳性者身上 参加加州大学圣迭戈分校价值7500万美元的艾滋病毒神经行为研究 中心。感染性和微血管疾病的病理生理学 将通过结合使用新的临床测试来阐明 电生理和心理物理测试，并通过预期 学习。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塞有关 视网膜内侧(棉花点)。对有危险因素患者的研究 巨细胞病毒视网膜炎的原因和并发症将包括研究以确定 巨细胞病毒视网膜炎发生的CD4阈值及其与巨细胞病毒的关系 中枢神经系统疾病。其他研究将包括以下风险因素 发生视网膜脱离，似乎影响到20%-25%的眼睛 患有巨细胞病毒视网膜炎。对病理生理学的实验室研究将 包括对整个安装视网膜进行共聚焦免疫显微镜检查 以及艾滋病患者视网膜组织的聚合酶链式反应研究 进一步的病毒和其他原因(与细胞因子相关的损害)。尝试 提高感染性视网膜病变患者的诊断能力 疾病将包括对聚合酶链式反应的敏感性和特异性的研究， 关于眼液和组织的培养和相关技术，请访问 尸检以及临床材料。最后，采取新的方法来 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 磷甲酸钠和更昔洛韦联合治疗的随机对照试验 视网膜脱离患者的两种手术修复技术。 在实验室里，我们将继续研究玻璃体内注射 长效抗CMV化合物，其中之一(HPMPC)已被证明是 在疱疹病毒性视网膜炎的动物模型中非常有效，可能 适用于玻璃体腔内注射的患者 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).