Treatment of choroidal subretinal neovascularization wit

随着我们的人口变老，年龄相关性黄斑变性（AMD）将在美国达到流行病的比例。迄今为止的治疗集中在抗血管生成治疗上，结果好坏参半。最近的研究表明，免疫系统在AMD的发病机制中起着重要作用。玻璃疣是AMD最早的临床表现之一，其成分已被广泛研究。补体、脂质和脂蛋白B和E在眼玻璃疣中常见，就像它们在动脉粥样硬化斑块中一样。Hageman等人提出玻璃疣是视网膜色素上皮损伤后发生的局部炎症反应的产物。最近的报告进一步支持了免疫系统在AMD中发挥作用（但尚未完全定义）的概念。年龄相关性眼病研究（AREDS）评估了晚期年龄相关性黄斑变性发病率的风险因素，发现使用抗炎药物显著降低（比值比0.22，C.I. 0.08 - 0.59）发展成地图状萎缩形式的AMD的风险。迄今为止，实验模型和患者材料表明巨噬细胞和补体的作用。我们假设导致脉络膜新生血管（CNV）的潜在机制与动脉粥样硬化中的机制相似。如果是这样的话，那么CNV治疗应该服从于针对免疫系统特定部分的新免疫调节剂。 在使用抗血管生成药物治疗后，未导致年龄相关性黄斑变性所致脉络膜新生血管持续缓解，受试者将接受三种免疫调节剂之一治疗，或将与其持续抗血管生成治疗联合观察。因此，受试者将在随机化后继续接受抗血管生成治疗。我们假设这种联合治疗将抑制与年龄相关性黄斑变性（AMD）相关的脉络膜新生血管（CNV）的进展。这是一项开放标签、II期、随机、单中心临床试验，20名研究参与者随机接受三种免疫调节剂之一或将与其抗血管生成治疗联合观察。患者将随机接受其他雷帕霉素、达利珠单抗、remicade，或与治疗医生认为必要的任何抗血管生成治疗相结合的观察。患者将在治疗6个月后接受评估。

As our population gets older, age related macular degeneration (AMD) will reach epidemic proportions in the United States. Therapies to date have focused on the anti-angiogenic therapy with mixed results. Recent studies would suggest that the immune system plays a significant role in the pathogenesis of AMD. The composition of drusen, one of the earliest clinical findings in AMD, have been extensively investigated. Complement, lipids, and lipoproteins B and E are commonly found in ocular drusen as they are in atherosclerotic plaques. Hageman et al have proposed that drusen are the product of a localized inflammatory response which would occur after retinal pigment epithelium injury. Recent reports have supported further the notion of the immune system playing a role (but yet to be fully defined) in AMD. The age related eye disease study (AREDS) evaluated the risk factors for the incidence of advanced age related macular degeneration and found that using anti-inflammatory medication significantly reduced (Odds Ratio 0.22, C.I. 0.08-0.59) the risk of developing the geographic atrophy form of AMD. Experimental models and patient material have, to date, suggested a role for macrophages and complement. We hypothesize that the underlying mechanism that leads to choroidal neovascularization (CNV) is similar to those at play in atherosclerosis. If this is the case, then CNV treatment should be amenable to new immunomodulatory agents directed against specific parts of the immune system. After therapy with anti-angiogenic agents not leading to a persistent remission of choroidal neovascularization due to age related macular degeneration, participants will be treated with one of three immunomodulatory agents or will be observed in conjunction with their continued anti-angiogenic therapy. Thus the participant will continue with the anti-angiogenic therapy they are receiving after randomization. We hypothesize that this combination therapy will inhibit progression of choroidal neovascularization (CNV) associated with age related macular degeneration (AMD).This is an open-label, phase II, randomized, single center clinical trial of 20 study participants randomized to receive one of three immunomodulatory agents or will be observed in conjuntion with their anti-angiogenic therapy.Patients will be randomized to receive other rapamycin, daclizumab, remicade, or observation in conjunction with any anti-angiogenic therapy the treating physician deems necessary. Patients will be evaluated after 6 months of therapy.