Epidemiology of Biomarkers of AMD Progression

项目摘要 目前还没有有效的治疗萎缩性老年性黄斑变性(AMD)的方法 因为在地理萎缩(GA)发展之后，我们可能在疾病过程中干预得太晚了。一个 更可取的策略是在疾病的早期阶段进行干预，但对 关于疾病生物标记物，以选择最合适的患者以及可能是 用于在临床实际的时间范围内进行干预试验。这在很大程度上是因为 缺乏一个足够细粒度的分期系统来描述AMD从早期到晚期的进展。最好的 目前可用的数据来自与年龄相关的眼病研究和海狸 DAM眼科研究，但这些研究主要基于具有AMD疾病特征的彩色眼底照片 使用胶片成像时代开发的历史协议进行评估。AMD疾病严重程度量表 根据这些研究建立的分期系统不够细粒度，无法利用现代、 光学相干层析成像(OCT)和OCT血管成像等普及的数字成像技术 (OCT-A)，它们很容易量化。在过去的十年里，广泛的研究已经 确定了AMD的一些结构OCT特征，如视网膜内高反射灶和视网膜下 红褐色沉积，这似乎增加了发展为晚期AMD(萎缩和/或)的风险 新生血管)。最近，脉络膜毛细血管(CC)血流缺陷被显示随着年龄的增长而增加 在AMD中。CC血流缺陷与AMD的发病和分期的关系仍有待进一步研究 已定义。此外，虽然已经确定了一些AMD的遗传风险因素，但 AMD的进展尚未阐明。这项研究应用程序建议解决这些关键问题 通过评估之前被招募为AMD一部分的老年AMD受试者的知识差距 NEI资助的阿米什眼科研究。亚米希人在环境方面代表了一个同质的群体 和社会暴露，这降低了变异性，使这一群体非常适合于疟疾流行病学研究 AMD进展。通过之前的研究，基线(和一些2年的随访)临床，多模式 成像(包括OCT)和遗传数据已经收集完毕。然而，长期(7年)数据， 这将是我们提议的研究的重点，对于实际确定哪些人将继续 进展到晚期AMD，这对于确定哪些基线要素与更高的 进展风险，并开发AMD的颗粒和定量分期系统。的发展。 这一新的AMD分期系统将提供干预点和结果评估，以实现 早期干预临床试验，为遗传学和病理生理学提供新的见解 AMD。

Project Abstract There are currently no effective treatments for atrophic age-related macular degeneration (AMD), in part because we may be intervening too late in the disease course after geographic atrophy (GA) has developed. A far preferable strategy would be to intervene at an earlier phase of the disease, but there is uncertainty with regards to disease biomarkers to select the most appropriate patients as well as endpoints which could be used to conduct an interventional trial in a clinically-practical time-frame. This is in large part because of the lack of a sufficiently granular staging system describing the progression from early to late stage AMD. The best currently available data comes from studies such as the Age-Related Eye Diseases Study and the Beaver Dam Eye Study, but these studies were largely based on color fundus photographs with AMD disease features assessed using historical protocols developed in the film-based imaging era. The AMD disease severity scales and staging systems built from these studies are insufficiently granular and fail to take advantage of modern, pervasive digital imaging technologies such as optical coherence tomography (OCT) and OCT angiography (OCT-A) which readily lend themselves to quantification. Extensive research over the past decade has identified a number of structural OCT features of AMD, such as intraretinal hyper-reflective foci and subretinal drusenoid deposits, which appear to increase the risk for developing late AMD (atrophy and/or neovascularization). More recently, choriocapillaris (CC) flow deficits have been shown to increase with age and in AMD. The relationship between CC flow deficits and the onset and stage of AMD still remains to be defined. In addition, although a number of genetic risk factors for AMD have been identified, the genetics of AMD progression are not yet elucidated. This research application proposes to address these critical knowledge gaps by evaluating elderly subjects with AMD who have previously been recruited as part of the NEI-funded Amish Eye Study. The Amish represent a homogenous population with regards to environmental and social exposures which reduces variability and makes this group ideally suited for epidemiologic studies of AMD progression. Through that previous study, baseline (and some 2-year follow up) clinical, multimodal imaging (including OCT), and genetic data have already been collected. However, long-term (7 year) data, which will be a focus of our proposed research, is critical to actually establish which individuals go on to progress to late AMD, which is vital in order to determine which baseline features are associated with a higher risk of progression, and to develop a granular and quantitative staging system for AMD. The development of this novel AMD staging system will provide points of intervention and outcome assessment to enable early intervention clinical trials and provide new insights into the genetics and pathophysiology of AMD.