Macular Edema Treatment Trials Associated with MUST (META-MUST)

描述(申请人提供)：黄斑水肿是葡萄膜炎患者视力丧失的最常见原因。这项建议的目标是解决葡萄膜炎黄斑水肿治疗中的两个关键问题：1)葡萄膜炎黄斑水肿的最佳初始治疗；2)持续性黄斑水肿(即初始治疗后仍未消退的黄斑水肿)的最佳治疗。局部注射皮质类固醇是治疗的主要方法。 治疗葡萄膜炎黄斑水肿。然而，有不同的路线和配方，从来没有在试验中进行比较，并且缺乏明确的试验导致在临床实践中有相当大的变异性。对于持续性黄斑水肿，通常需要重复注射皮质类固醇。然而，对玻璃体内注射甲氨蝶呤和玻璃体内雷尼比珠单抗(Lucentis)的初步研究表明了疗效，可能比皮质类固醇注射更少的眼部副作用，尽管在雷尼比珠单抗的情况下可能会更频繁地注射。还没有对这些方法进行对比试验。现有的必须研究集团的基础设施将被用来进行两项治疗葡萄膜炎黄斑水肿的比较有效性临床试验。这些试验的具体目的是：1)比较曲安奈德、玻璃体内曲安奈德和地塞米松玻璃体内植入(Ozurdex)治疗葡萄膜黄斑水肿的相对有效性；以及2)比较雷尼比单抗(Lucentis)和氨甲蝶呤玻璃体内注射与玻璃体内地塞米松植入(Ozurdex)治疗玻璃体内注射曲安奈德后持续存在的葡萄膜黄斑水肿的相对疗效。阅读中心设计并改进了在整个必须研究期间评估葡萄膜炎黄斑水肿的分级程序，并开发了创新的分析软件，该软件将允许整合来自所有研究地点的数据，尽管测量仪器不同。形态学结果对于资格确定、治疗决策和关键终点非常重要，有助于确定正在研究的各种治疗方式的相对有效性和安全性。 相关性：葡萄膜炎与高视力丧失有关，通常由结构性并发症引起，其中葡萄膜黄斑水肿是最常见的并发症之一。此外，黄斑水肿是葡萄膜炎患者视力丧失的最常见原因。两项拟议的疗效比较试验将为指导临床医生治疗葡萄膜炎黄斑水肿提供证据基础。

DESCRIPTION (provided by applicant): Macular edema is the most common cause of visual loss among patients with uveitis. The goal of this proposal is to address two critical issues in th treatment of uveltic macular edema: 1) the optimal initial treatment for uveitic macular edema; and 2) the optimal treatment of persistent macular edema (i.e. macular edema that has not resolved after initial treatment). Regional corticosteroid injections are the mainstay of treatment for uveitic macular edema. However, there are different routes and formulations, which never have been compared in a trial, and the lack of definitive trials has led to considerable variabilit in clinical practice. For persistent macular edema, repeat injections of corticosteroids typically are administered. However, pilot studies of intravitreal methotrexate and of intravitreal ranibizumab (Lucentis) have suggested efficacy, possibly with fewer ocular side effects than corticosteroid injections, although in the case of ranibizumab possibly with more frequent injections. No comparative trials have been performed of these approaches. The existing MUST Research Group infrastructure will be leveraged to perform two comparative effectiveness clinical trials on the treatment of uveitic macular edema. The specific aims of the trials are: 1) o compare the relative effectiveness of periocular triamcinolone acetonide, intravitreal triamcinolone acetonide (Triescence), and the intravitreal dexamethasone implant (Ozurdex) for the treatment of uveitic macular edema; and 2) to compare the relative effectiveness of intravitreal ranibizumab (Lucentis) and intravitreal methotrexate to the intravitreal dexamethasone implant (Ozurdex) for the treatment of uveitic macular edema that persists after intravitreal triamcinolone injections. The Reading Center has devised and refined grading programs for evaluation of uveitic macular edema throughout the MUST studies and has developed innovative analysis software that will allow integration of data from all study sites despite variation in measurement instruments. Morphologic findings are important for eligibility determination, treatment decisions, and critical endpoints that assist in determining relative efficacy and safety of the various treatment modalities being studied. RELEVANCE: Uveitis is associated with high rates of visual loss, typically caused by structural complications, of which uveitic macular edema is among the most common. Furthermore, macular edema is the most frequent cause of visual loss among patients with uveitis. The two proposed comparative effectiveness trials will provide an evidence base to guide clinicians in the management of uveitic macular edema.