Treatment of choroidal subretinal neovascularization with immune agents

免疫制剂治疗脉络膜视网膜下新生血管

• 批准号: 8149176
• 负责人: Robert Nussenblatt
• 金额: $ 20.92万
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8149176
• 关键词: Age related macular degeneration; Anti-Inflammatory Agents; Anti-inflammatory; Arterial Fatty Streak; Atherosclerosis; Clinical; Data; Disease; Drusen; Elderly; Epidemic; Eye diseases; Immune; Immune System Part; Immune system; Immunosuppressive Agents; Incidence; Inflammatory Response; Injection of therapeutic agent; Injury; Lipids; Lipoproteins; Odds Ratio; Ophthalmology; Patients; Pharmaceutical Preparations; Phase; Play; Randomized; Recurrence; Retina; Risk; Risk Factors; Role; Safety; Secondary to; Structure of retinal pigment epithelium; Therapeutic immunosuppression; Thick; United States; Visual Acuity; geographic atrophy; macrophage; neovascularization

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.

随着人口老龄化，年龄相关性黄斑变性 （AMD）将在美国达到流行病的程度。治疗方法 目前，抗血管生成治疗已得到了广泛关注，结果好坏参半。 最近的研究表明，免疫系统发挥着重要作用 AMD 发病机制中的作用。玻璃疣的成分之一 AMD 最早的临床发现已被广泛研究。 补体、脂质、脂蛋白 B 和 E 常见于眼部 玻璃疣就像动脉粥样硬化斑块中的玻璃疣一样。哈格曼等人提出 玻璃疣是局部炎症反应的产物 视网膜色素上皮损伤后发生。最近的报道有 进一步支持了免疫系统发挥作用的概念（但尚未 AMD 中已完全定义）。年龄相关眼病研究（AREDS） 评估与高龄相关的发生率的危险因素 黄斑变性，发现使用抗炎药物 显着降低（优势比 0.22，C.I. 0.08-0.59）的风险 发展出AMD的地理萎缩形式。实验模型和 迄今为止，患者材料表明巨噬细胞和 补充。我们假设导致的潜在机制 脉络膜新生血管（CNV）与以下情况相似： 动脉粥样硬化。如果是这种情况，则应进行 CNV 治疗 适合针对特定部位的新免疫调节剂 免疫系统。 我们的目的是研究效果 湿型疾病临床过程中的免疫抑制治疗。我们 比较抗 VEGF 疗法加三种全身免疫抑制疗法之一 与单独抗 VEGF 治疗相比，治疗与以下疾病相关的复发性脉络膜新生血管 年龄相关性黄斑变性。这是一项试点、I/II 期、前瞻性、随机、非掩蔽、单中心试验。因与年龄相关性黄斑变性相关的复发性脉络膜新生血管形成继发视网膜下渗出的患者被纳入研究 学习。患者被随机分配至 1 或 3 个全身免疫抑制剂组 （达克珠单抗、雷帕霉素或英夫利昔单抗）6 个月加上眼内抗 VEGF 治疗，如果 与仅接受抗 VEGF 治疗（如果有指示）的组进行比较。 结果：每组抗VEGF注射次数、视力、视网膜厚度、 并对所有组的安全措施进行了评估。 13 名患者被随机分组​​； 比较研究之前和研究期间的抗 VEGF 注射， 5 次注射，达珠单抗从每月 0.73 次注射到 0.42 次，达珠单抗从每月 0.67 次注射到 0.34 次 观察到西罗莫司，而英夫利昔单抗或英夫利昔单抗均未观察到明显下降。 观察。所有组的视力均得到维持。 结论：这些初步数据表明一些免疫抑制剂 全身给予可以改变湿型疾病的临床病程并提供支持 年龄相关性黄斑的免疫介导的更明确的临床试验 表明有退化。 这些数据已在 2009 年美国眼科学会会议上公布，并将很快出现在 Retina 中。