Diagnosis And Treatment Of Ocular Inflammatory Disease (

该项目的目标是开发改进的方法，用于诊断和治疗所有年龄的人类患者的眼部炎症性疾病，包括葡萄膜炎、巩膜炎、眼表炎症性疾病和眼内恶性肿瘤。在过去的一年里，临床研究继续关注于检查新的治疗药物的有效性，这些药物的安全性比目前可用的标准免疫抑制药物更温和。今年，我们开始使用英夫利昔单抗（Remicade），这是一种嵌合人/鼠单克隆抗体，可中和tnf - α的生物活性，用于治疗白塞氏病、巩膜炎和后段葡萄膜炎（包括视网膜血管炎）。虽然英夫利昔单抗似乎是治疗眼部炎症性疾病的有效替代疗法，但潜在的眼部并发症可能限制了该药物的使用。daclizumab （HAT, Zenapax）是一种人源化单克隆抗il -2受体抗体，目前正在对非感染性中间和后葡萄膜炎患者进行临床研究，并在其他地方进行了讨论。其他正在进行的临床研究包括评估英夫利昔单抗治疗活动性硬化炎和Daclizumab治疗儿童JIA的疗效。我们将很快开始一项研究，以评估Raptiva在非感染性葡萄膜炎中的作用。除了使用皮质类固醇进行全身治疗外，眼部炎症性疾病还可使用皮质类固醇进行局部或眼内或眼周注射治疗。在过去的一年里，我们证实了之前的研究表明，结膜下类固醇可以有效地局部治疗无眼压升高或青光眼病史的非坏死性巩膜炎。我们还证明，选择性T淋巴细胞和B淋巴细胞抑制剂霉酚酸酯可作为活动性硬膜炎患者有效的类固醇保留剂。我们继续分析原发性眼内淋巴瘤（PIOL）和葡萄膜炎患者的玻璃体细胞因子水平，并继续使用IL-10与IL-6比值大于1.0的疾病诊断临界值。我们已经使用免疫病理学技术来证明视网膜变性患者的推定原因。此外，我们也是多中心葡萄膜炎类固醇治疗研究的一个地点，该研究将评估类固醇眼内植入物在标准治疗中的使用（这将单独报道）。我们将很快开始介绍结节病的自然史。病程将被记录下来，并与NHLBI肺组一起进行。

The goal of this project is to develop improved methods for the diagnosis and treatment of ocular inflammatory diseases in human patients of all ages including uveitis, scleritis, inflammatory diseases of the ocular surface, and intraocular malignancies. Over the past year clinical studies have continued to focus on examining the effectiveness of new therapeutic agents with a milder safety profile than that offered by currently available standard immunosuppressive medications. This year we have initiated our experience with infliximab (Remicade), a chimeric human/murine monoclonal antibody that neutralizes the biologic activity of TNF-alpha for the treatment of Behcet's disease, scleritis, and posterior segment uveitis including retinal vasculitis. Although infliximab seems to be an effective alternate therapy for the treatment of ocular inflammatory disease the potential for ocular complications may limit the usage of the agent. Clinical studies with daclizumab (HAT, Zenapax), a humanized monoclonal anti-IL-2 receptor antibody, are ongoing in patients with non-infectious intermediate and posterior uveitis and are discussed elsewhere. Other clinical studies in development include evaluating the therapeutic efficacy of infliximab for the treatment of active scleritis and Daclizumab for the treatment of JIA in children. We will be starting shortly a study to evaluate the role of Raptiva in non-infectious uveitis. In addition to systemic therapy with corticosteroids, ocular inflammatory disease can be treated with corticosteroids given topically or by injection in or around the eye. In the past year we have verified previous work showing that subconjunctival steroids can be effective local therapy for the treatment of non-necrotizing scleritis in patients without a history of increased intraocular pressure or glaucoma. We also demonstrated that mycophenolate mofetil, a selective inhibitor of T and B lymphocytes can be used as an effective steroid sparing agent in patients with active scleritis. We continue to analyze vitreal cytokine levels from primary intraocular lymphoma (PIOL) and uveitic patients and continue to use the cutoff point in disease diagnosis with an IL-10 to IL-6 ratio greater than 1.0 for PIOL. We have used immunopathologic techniques to demonstrate the putative cause of retinal degeneration in patients. As well, we are are a site for the MUST (multicenter uveitis steroid treatment study which will evaluate the use of the steroid intraocular implant to standard therapy (this will be reported separately). We will shortly start a natural history of sarcoidosis. The disease course will be documented and is being done in conjunction with the pulmonary group of NHLBI.