Multicenter uveitis trial using a steroid implant and inflammatory mediators

葡萄膜炎是指以眼内炎症为特征的几种眼部疾病，其在美国总体上是视力丧失和失明的主要原因。中间葡萄膜炎、后葡萄膜炎和全葡萄膜炎通常是葡萄膜炎的更严重形式，具有最高的视力丧失风险，通常需要长期全身治疗。醋酸氟轻松眼内植入物是一种手术植入的皮质类固醇储库，设计持续约2.5年，以提供长期控制葡萄膜炎。 多中心葡萄膜炎类固醇治疗（MUST）试验（NEI是参与中心）的主要目的是比较标准化全身治疗与醋酸氟轻松植入治疗非感染性中间葡萄膜炎、后葡萄膜炎或全葡萄膜炎严重病例的疗效。根据标准化指南，活动性葡萄膜炎患者以1：1的分配比例随机接受醋酸氟轻松植入剂治疗或标准化全身治疗，包括口服皮质类固醇和补充免疫抑制药物（如有指征）。该研究的设计结果变量是视力;其他结果包括视觉功能的其他方面，控制葡萄膜炎的成功，视网膜形态学结果，生活质量，成本效益，以及葡萄膜炎和治疗的潜在眼部和全身并发症的发生。截至2008年11月24日，已达到250人的初始入组目标，并允许在入组过程中积极参与的参与者签署知情同意书并接受初始评估。这将参加人数上限提高到255人。本研究将持续至共同研究结束，即2007年1月1日之前入组的患者从入组开始起5年。 此外，我们已经建立了一个协议，以评估玻璃体的患者谁接受类固醇植入在这里和其他参与中心。在手术中取出的少量玻璃体通常被丢弃。我们将使用显微技术来观察多种细胞因子，也将评估玻璃体蛋白质组的小样本。2008年，本研究对NIH获得的所有玻璃体标本开放（以及来自华盛顿合作的视网膜研究中心-视网膜组的对照标本，根据OHRS许可和NIH与RGW之间的MTA协议，在那里收集样本，但尚未转移到NEI），迄今为止从MUST参与研究中心收集了大量玻璃体样本和外周血样本。到目前为止，已经使用多重测定法分析了初始样品，初步结果显示玻璃体中存在炎性细胞因子。蛋白质组学分析将是明年的主要目标之一。 Nida Sen博士已成为方案的PI

Uveitis refers to several ocular disorders characterized by intraocular inflammation, which in the aggregate are a major cause of visual loss and blindness in the United States. Intermediate uveitis, posterior uveitis, and panuveitis are generally the more severe forms of uveitis, with the highest risk of vision loss, often requiring long-term systemic treatment. The fluocinolone acetonide intraocular implant is a surgically implanted reservoir of corticosteroid designed to last approximately 2.5 years in order to provide long-term control of uveitis. The primary objective of the Multicenter Uveitis Steroid Treatment (MUST) Trial, with the NEI being a participating center is to compare the efficacy of standardized systemic therapy versus fluocinolone acetonide implant therapy for the treatment of severe cases of non-infectious intermediate uveitis, posterior uveitis or panuveitis. Patients with active uveitis have been randomized, with a 1:1 allocation ratio, to treatment with either the fluocinolone acetonide implant or standardized systemic therapy consisting of oral corticosteroids and supplementary immunosuppressive drugs when indicated, according to standardized guidelines. The design outcome variable for the study is visual acuity; other outcomes include other aspects of visual function, success in controlling uveitis, retinal morphologic outcomes, quality of life, cost-effectiveness, and occurrence of potential ocular and systemic complications of uveitis and of therapy. As of November 24, 2008 initial enrollment goal of 250 had been met, and allowed for participants active in the enrollment process who had signed a consent form and had undergone initial evaluations to enroll. This raised the enrollment ceiling to 255 participants. The study will continue until a common study closeout which will be five years from the start of enrollment for patients enrolled prior to January 1, 2007. In addition, we have established a protocol to evaluate the vitreous of patients who undergo the steroid implant here and at other participating centers. The small amount of vitreous that is removed during surgery is usually discarded. We will use microtechnology to look at multiple cytokines and as well will evaluate the small sample for the vitreous proteome as well. In 2008 this study has been opened to all vitreous specimens obtained here at the NIH (as well as control specimens from collaborating outsidfe center-Retina group of Washington under an OHRS clearance and an MTA agreement between NIH and RGW where samples are collected but not yet transferred to NEI), with a large number of vitreous samples and peripheral blood samples collected to date from MUST participating sites. Initial samples have so far been analyzed using multiplex assay and preliminary results have shown the presence of inflammatory cytokines in the vitreous. Proteomic analysis will be one of the major goals this coming year. Dr.Nida Sen has become the PI on the protocol