Treatment of choroidal subretinal neovascularization with immune agents

随着我们人口的老龄化，老年性黄斑变性 (AMD)在美国将达到流行的程度。治疗方法 数据集中在抗血管生成治疗上，结果喜忧参半。 最近的研究表明，免疫系统在 在AMD发病机制中的作用。干酪的成分，干酪是 AMD最早的临床表现，已被广泛研究。 补体、类脂、脂蛋白B和E常见于眼部 因为他们在动脉粥样硬化斑块中。哈格曼等人提出了 玻璃体是局部炎症反应的产物 会发生在视网膜色素上皮损伤后。最近的报道说 进一步支持免疫系统发挥作用的概念(但仍 待完全定义)。年龄相关性眼病研究(AREDS) 高龄相关疾病发生的危险因素评价 黄斑变性发现使用消炎药 显著降低(优势比0.22，C.I.0.08-0.59) 发展为AMD的地理萎缩形式。实验模型和 到目前为止，患者材料表明巨噬细胞和 互补性。我们假设导致这种现象的潜在机制 脉络膜新生血管(CNV)类似于 动脉硬化。如果是这种情况，那么CNV治疗应该是 对针对特定部位的新免疫调节剂具有顺应性 免疫系统。 治疗后使用抗血管生成药物不会导致持续性 年龄相关性黄斑脉络膜新生血管的缓解 退行性变，参与者将接受三种治疗之一 免疫调节剂或将与其联合观察 持续的抗血管生成治疗。因此，参与者将继续 他们在随机分组后接受的抗血管生成治疗。我们 假设这种联合疗法将抑制肿瘤的进展 脉络膜新生血管与年龄相关性黄斑病变 变性(AMD)。这是一种开放标签，II期，随机，单一 20名研究参与者随机接受一项研究的中心临床试验 三种免疫调节剂或将联合观察 他们的抗血管生成疗法。患者随机接受以下两种治疗 雷帕霉素、Daclizumab、Remicade或与任何 主治医师认为有必要进行抗血管生成治疗。病人 将在治疗6个月后进行评估。我们发现，在随机抽取13名患者后，我们发现，在接受这些药物治疗的患者中，使用三种治疗药物中的两种，与单独使用抗血管内皮生长因子治疗相比，抗血管内皮生长因子注射减少了一半。这些数据将在2009年美国眼科学会会议上公布。第二项研究将在下一财年开始。

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 are randomized to receive either 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. We have found that after 13 patients randomized we found that two of the three therapeutic agents used decreased anti-VEGF injections by half in the patients receiving these medications as compared to anti-VEGF therapy alone. These data will be presented at the 2009 American Academy of Ophthalmology meeting. A second study will begin this coming fiscal year.