DIAGNOSIS AND TREATMENT OF AIDS RELATED OCULAR DISEASE

这个项目的目标是开发改进的方法来 获得性眼部并发症的诊断和治疗 免疫缺陷综合征(艾滋病)。这个项目包括临床 评估新的诊断和治疗方法的试验 与艾滋病相关的眼病患者以及自然病史 巨细胞病毒视网膜炎患者的研究。 巨细胞病毒视网膜炎是最常见的眼内疾病。 艾滋病患者感染后易发生CD4+细胞 计数减少到不到50个细胞/微升。虽然抗巨细胞病毒治疗 使用更昔洛韦、磷甲酸钠或西多福韦最初会导致 视网膜炎失活，疾病进展几乎在所有 由于控制不充分，患者仍在继续治疗 复制中的病毒。最近的研究表明，使用 高效联合抗逆转录病毒疗法，包括 蛋白水解酶抑制剂和核苷类似物，已导致降低 人类免疫缺陷病毒(HIV)载量和CD4+计数增加。 我们一直在研究免疫修复的效果 联合抗HIV治疗巨细胞病毒视网膜炎。这最后一年我们 报告4例艾滋病患者和CD4+细胞计数增加 高效联合抗逆转录病毒化疗诱导世卫组织 尽管没有特异性的抗CMV抗体，但CMV视网膜炎一直处于非活动性状态 药物。NEI目前正在进行一项临床试验，以确定 抗肿瘤药物是否导致CD4+细胞计数升高 HIV对12名患者的CMV视网膜炎控制有效 将停止特定的抗CMV药物。主端点 这项研究的重点将是CMV视网膜炎的进展。次要的 终点将包括眼外CMV疾病的发生， 发病率、死亡率、病毒学和免疫学数据以及艾滋病毒负担。 参加这项研究的学生应在明年内完成。 NEI一直有兴趣确定哪些临床和 实验室参数预测巨细胞病毒视网膜炎的发展。我们 回顾了234名HIV血清阳性患者的医疗记录 1980至1993年间的NEI。93例(39.7%)患者 患上了巨细胞病毒性视网膜炎。CD_4~+细胞的敏感性和特异性 巨细胞病毒视网膜炎的细胞计数小于或等于50个/微升 分别为96.9%和48.7%。尽管任何眼球的存在 症状是常见的，眼部主诉是CMV的特异性 视网膜炎仅占29.1%。对新飞蚊的抱怨似乎是 是CMV视网膜炎的一个相当特异的预测指标，具有优势比 (95%可信区间1.86，8.61，p=0.0004)。我们的分析 显示如果常规眼科筛查在什么时候开始 患者出现新的飞蚊，或CD4+细胞计数为50个/微升 或更少时，很少有CMV视网膜炎被漏诊。爱滋病个案 在欠发达国家，CMV视网膜炎正在增加 无法获得CD4+细胞计数。对患者进行教育以改善患者的健康状况 识别新的眼部症状，如飞蚊，可能导致 巨细胞病毒视网膜炎的早期诊断和治疗。 最后，一些用于治疗艾滋病的药物有眼部副作用 效果。我们首先报道了抗逆转录病毒药物二磷酸核苷 导致视网膜毒性。我们一直在使用眼电图仪 (EOG)，测量来自视网膜的电信号，以 监测二磷酸核苷对视网膜的潜在毒性作用 感染艾滋病毒的儿童。在过去的一年里我们发现 Ddanosine治疗与两者的显著降低有关 EOG的暗谷和亮峰成分。我们发现 EOG的标准报告没有发现这些异常，这表明 需要对电子记录进行详细分析以 准确描述视网膜功能减退可以 与Ddanosine治疗有关。

The goal of this project is to develop improved methods for diagnosing and treating the ocular complications of the acquired immunodeficiency syndrome (AIDS). This project encompasses clinical trials evaluating new diagnostic and therapeutic approaches for patients with AIDS related eye disorders as well as natural history studies of patients with Cytomegalovirus (CMV) retinitis. Cytomegalovirus (CMV) retinitis is the most common intraocular infection in patients with AIDS and tends to occur after CD4+ cell counts decrease to less than 50 cells/mul. Although anti-CMV therapy with ganciclovir, foscarnet sodium, or cidofovir initially leads to inactivation of the retinitis, the disease progresses in almost all patients despite continued therapy because of inadequate control of the replicating virus. Recent studies have shown that treatment with highly active combination antiretroviral therapy, consisting of protease inhibitors and nucleoside analogs, has lead to decreased human immunodeficiency virus (HIV) loads and increased CD4+ counts. We have been investigating the effect of immune restoration following combination anti-HIV therapy on CMV retinitis. This last year we reported 4 patients with AIDS and increases in CD4+ cell counts induced by highly active combination antiretroviral chemotherapy who had persistently inactive CMV retinitis despite no specific anti-CMV medications. The NEI is now conducting a clinical trial to determine whether elevated CD4+ cell counts resulting from medications against HIV are effective in controlling CMV retinitis in 12 patients who will discontinue specific anti-CMV medications. The primary endpoint of the study will be progression of CMV retinitis. Secondary endpoints will include the occurrence of extraocular CMV disease, morbidity, mortality, virologic and immunologic data, and HIV burden. Enrollment into this study should be completed within the next year. The NEI has been interested in determining which clinical and laboratory parameters predict the development of CMV retinitis. We reviewed the medical records of 234 HIV seropositive patients seen at the NEI between 1980 and 1993. Ninety-three (39.7%) of the patients developed CMV retinitis. The sensitivity and specificity of a CD4+ cell count less than or equal to 50 cells/mul for CMV retinitis was 96.9% and 48.7%, respectively. Although the presence of any ocular symptoms was common, the specificity of ocular complaints for CMV retinitis was only 29.1%. The complaint of new floaters appeared to be a fairly specific predictor for CMV retinitis, with an odds ratio of 3.93 (95% confidence interval 1.86, 8.61, p=0.0004). Our analysis showed that if routine ophthalmologic screening is started when patients develop new floaters, or a CD4+ cell count of 50 cells/mul or less, few cases of CMV retinitis would be missed. Cases of AIDS and CMV retinitis are increasing in less developed countries where CD4+ cell counts are not available. Patient education to improve the recognition of new ocular symptoms like floaters could lead to earlier diagnosis and treatment of CMV retinitis. Finally, a number of medications used to treat AIDS have ocular side effects. We first reported that the antiretroviral agent didanosine caused retinal toxicity. We have been using the electro-oculogram (EOG), which measures the electrical signal from the retina, to monitor the potentially toxic effect of didanosine on the retina in HIV-infected children. Over the past year we discovered that didanosine therapy was associated with a significant decrease in both dark trough and light peak components of the EOG. We found that standard reports of the EOG missed these abnormalities, suggesting that a detailed analysis of the electrical recording is needed to accurately describe the diminished retinal function that can be associated with didanosine therapy.