Epidemiology of Biomarkers of AMD Progression

项目摘要 目前对于萎缩性年龄相关性黄斑变性（AMD）没有有效的治疗方法，部分原因是 因为在地图状萎缩（GA）发展后，我们可能干预得太晚了。一 更可取的策略是在疾病的早期阶段进行干预，但 关于疾病生物标志物，以选择最合适的患者以及可能 用于在临床实用的时间范围内进行干预性试验。这主要是因为 缺乏描述从早期到晚期AMD进展的足够粒度的分期系统。最好的 目前可用的数据来自于一些研究，如与眼睛相关的眼病研究和海狸研究。 Dam Eye Study，但这些研究主要基于具有AMD疾病特征的彩色眼底照片 使用基于胶片的成像时代开发的历史协议进行评估。AMD疾病严重程度量表 从这些研究中建立的分期系统不够精细， 普及的数字成像技术，如光学相干断层扫描（OCT）和OCT血管造影 （OCT-A），其容易使其自身量化。过去十年的广泛研究 确定了AMD的许多结构OCT特征，例如视网膜内高反射灶和视网膜下高反射灶。 玻璃疣样沉积物，这似乎增加了发展晚期AMD的风险（萎缩和/或 新血管形成）。最近，脉络膜毛细血管（CC）流量赤字已被证明随着年龄的增长而增加 在AMD CC血流缺损与AMD的发病和分期的关系仍有待进一步研究 定义了此外，尽管已经确定了AMD的许多遗传风险因素，但AMD的遗传学特征仍然存在。 AMD进展尚未阐明。本研究旨在解决这些关键问题。 通过评估先前作为研究的一部分招募的老年AMD受试者， NEI资助的Amish眼科研究。阿米什人在环境方面是一个同质的群体 和社会暴露，减少了变异性，使这一群体非常适合流行病学研究， AMD进展。通过先前的研究，基线（和一些2年随访）临床，多模式 成像（包括OCT）和遗传数据已经收集。然而，长期（7年）数据， 这将是我们拟议研究的重点，对于实际确定哪些人会继续 进展到晚期AMD，这对于确定哪些基线特征与更高的AMD相关至关重要。 风险的进展，并制定一个粒度和定量分期系统的AMD。的发展 这种新的AMD分期系统将提供干预点和结果评估， 早期干预临床试验，并提供新的见解，遗传学和病理生理学的 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.