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. 我们的目的是研究 免疫抑制治疗在临床过程中的湿形式的疾病。我们 比较了抗VEGF治疗加三种全身免疫抑制治疗之一 与单独抗VEGF治疗复发性脉络膜新生血管相关 老年性黄斑变性这是一项初探性、I/II期、前瞻性、随机化、非盲态、强制入组试验。与年龄相关性黄斑变性相关的复发性脉络膜新生血管继发视网膜下渗出的患者包括在 study.患者随机分配至1或3个全身免疫抑制剂组 （达克珠单抗、雷帕霉素或英夫利西单抗）治疗6个月，如果 与仅接受抗VEGF治疗（如有指征）的组相比。 结果：每组抗VEGF注射次数、视力、视网膜厚度、 并对各组进行安全性评价。13例患者随机分组; 比较研究前和研究期间的抗VEGF注射， 5次注射，达克珠单抗从每月0.73次注射至0.42次， 西罗莫司，而英夫利西单抗或 观察.所有组均保持视力。 结论：这些初步数据表明，一些免疫抑制剂， 全身给药可以改变疾病的湿性形式的临床过程， 年龄相关性黄斑病变免疫调节的更明确的临床试验 退化的迹象。 这些数据在2009年美国眼科学会会议上发表，不久将发表在《视网膜》杂志上。

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. We aimed to investigate the effect of immunosuppressive therapy in the clinical course of the wet form of the disease. We compared anti-VEGF therapy plus one of three systemic immunosuppressive therapies versus anti-VEGF therapy alone for recurrent choroidal neovascularization associated with age-related macular degeneration. This was a pilot, Phase I/II, prospective, randomized, unmasked, singlecenter trial. Patients with subretinal exudation secondary to recurrent choroidal neovascularization associated with age-related macular degeneration were included in the study. Patients were randomized to 1 or 3 systemic arms immunosuppressive agents (daclizumab, rapamycin, or infliximab) for 6 months plus intraocular anti-VEGF therapy if indicated, compared with a group who received only anti-VEGF therapy if indicated. Results: The number of anti-VEGF injections per group, visual acuity, retinal thickness, and safety measures were assessed in all groups. Thirteen patients were randomized; comparing anti-VEGF injections before and during the study, a decrease in the number of 5 injections from 0.73 injections per month to 0.42 for daclizumab and from 0.67 to 0.34 for sirolimus was seen, while no apparent decrease was seen for either infliximab or observation. Visual acuities were maintained in all groups. Conclusion: These preliminary data suggest that some immunosuppressive agents given systemically can alter the clinical course of the wet form of the disease and support the notion that more definitive clinical trials of immune mediation of age-related macular degeneration are indicated. These data were presented at the 2009 American Academy of Ophthalmology meeting and will appear shortly in Retina.