Treatment of choroidal subretinal neovascularization with immune agents

随着人口老龄化，老年性黄斑变性 (AMD)将在美国蔓延疗法来 迄今为止，抗血管生成疗法的研究成果参差不齐。 最近的研究表明，免疫系统起着重要的作用， 在AMD发病机制中的作用。玻璃疣的组成， AMD的最早临床发现已经被广泛研究。 补体、脂质和脂蛋白B和E通常在眼 玻璃疣，因为它们是在动脉粥样硬化斑块。Hageman等人提出， 玻璃疣是局部炎症反应的产物， 视网膜色素上皮损伤后会发生。最近的报告 进一步支持了免疫系统发挥作用的概念（但 在AMD中完全定义）。年龄相关眼病研究（AREDS） 评估高龄相关疾病发生的危险因素 发现使用抗炎药物 显著降低（比值比0.22，C.I. 0.08-0.59）的风险 发展成AMD的地图状萎缩形式。实验模型和 迄今为止，患者材料表明巨噬细胞的作用， 补体我们假设导致 脉络膜新生血管（CNV）与在 动脉粥样硬化如果是这种情况，那么CNV治疗应该是 适用于针对特定部分的新的免疫调节剂 免疫系统. 抗血管生成剂治疗后未导致持续性 年龄相关性黄斑病变所致脉络膜新生血管的缓解 退化，参与者将接受三种治疗之一 免疫调节剂或将与它们一起观察 继续抗血管生成治疗。因此，与会者将继续与 随机分组后接受的抗血管生成治疗。我们 假设这种联合治疗将抑制 脉络膜新生血管（CNV）与年龄相关性黄斑病变 这是一项开放标签、II期、随机、单次给药的研究。 20名研究参与者随机接受一项中心临床试验， 三种免疫调节剂或将与 他们的抗血管生成疗法患者将随机接受其他 雷帕霉素、达克珠单抗、remicade，或与任何 治疗医生认为必要的抗血管生成治疗。患者 将在治疗6个月后进行评估。虽然征聘工作尚未完成， 虽然人数不多，但趋势可能在不久的将来变得明显。

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 conjunction 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. While recruitment has not yet been completed and numbers are small, trends may become evident in the near future.