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。 我们调查了它的影响。 临床病程中采用免疫抑制疗法治疗湿性本病。我们 抗血管内皮生长因子疗法与三种全身免疫抑制疗法之一的比较 与单用抗血管内皮生长因子治疗复发性脉络膜新生血管相关的对照 老年性黄斑变性。这是一项试点、I/II期、前瞻性、随机、无掩蔽的单中心试验。年龄相关性黄斑变性复发性脉络膜新生血管继发视网膜下渗出的患者包括在 学习。患者随机服用1到3种全身用药。 (达利珠单抗、雷帕霉素或英夫利昔单抗)6个月加眼内抗血管内皮生长因子治疗 提示，与仅接受抗血管内皮生长因子治疗的组相比，如果有提示，只接受抗血管内皮生长因子治疗。 结果：每组注射抗血管内皮生长因子的次数、视力、视网膜厚度、 并对所有组的安全措施进行评估。13名患者被随机分为两组； 比较研究前和研究期间注射抗血管内皮生长因子的情况， 5次注射，从每月0.73次注射到0.42次达利珠单抗，从0.67次到0.34次 西罗莫司被发现，而英夫利昔单抗或英夫利昔单抗均未见明显下降 观察。所有组均保持视力。 结论：这些初步的但基本的数据证明表明，系统地给予某些免疫抑制剂可以改变湿性疾病的临床病程和支持。 关于老年性黄斑免疫调节的更明确的临床试验 有退化的迹象。 正在讨论和准备更新的免疫治疗方法

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 investigated 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 but proof of priniciple 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. Newer approaches to immune therapy are being discussed and prepared