Epidemiology of Biomarkers of AMD Progression

AMD 进展生物标志物的流行病学

• 批准号: 10489288
• 负责人: Jonathan L Haines
• 金额: $ 58.26万
• 依托单位: DOHENY EYE INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10489288
• 关键词: Address; Age; Age Years; Age related macular degeneration; Amish; Angiogenesis Inhibitors; Angiography; Atrophic; Background Diabetic Retinopathy; Biological Markers; Blindness; Calibration; Choroid; Choroidal Neovascularization; Classification; Clinic; Clinical; Clinical Research; Clinical Trials; Color; Data; Deposition; Development; Diabetic Retinopathy; Disease; Drusen; Early Intervention; Elderly; Epidemiology; Evolution; Eye; Eye diseases; Film; Functional disorder; Funding; Fundus; Genetic; Genetic Markers; Genetic Variation; Image; Imaging technology; Individual; Intervention; Intervention Trial; Knowledge; Methods; Modeling; Modernization; Multimodal Imaging; Nonexudative age-related macular degeneration; Optical Coherence Tomography; Outcome Assessment; Patients; Phase; Phenotype; Population; Population Study; Principal Component Analysis; Probability; Protocols documentation; Research; Research Personnel; Resources; Retina; Risk; Risk Factors; Series; Severities; Severity of illness; Staging; Staging System; System; Techniques; Testing; Therapeutic Trials; Time; Uncertainty; United States; Validation; Visit; age related; clinical practice; cohort; cost; deep learning; design; digital imaging; effective therapy; effectiveness evaluation; epidemiology study; follow-up; genetic risk factor; geographic atrophy; high risk; improved; insight; learning algorithm; macula; neovascularization; novel; population based; prevent; progression risk; recruit; risk variant; social; statistical learning; success; therapy development; three-dimensional visualization

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.

项目摘要 目前尚无针对萎缩性年龄相关性黄斑变性（AMD）的有效治疗方法，部分原因是 因为在地理萎缩 (GA) 发生后，我们可能对病程进行干预得太晚了。一个 更好的策略是在疾病的早期阶段进行干预，但存在不确定性 关于疾病生物标志物，以选择最合适的患者以及可能的终点 用于在临床实用的时间范围内进行介入试验。这在很大程度上是因为 缺乏足够精细的分期系统来描述从早期到晚期 AMD 的进展。最好的 目前可用的数据来自年龄相关眼病研究和海狸研究等研究 Dam Eye 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 使用基于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 根据这些研究构建的分期系统不够精细，无法利用现代、 普及的数字成像技术，例如光学相干断层扫描 (OCT) 和 OCT 血管造影 (OCT-A) 很容易量化。过去十年的广泛研究已经 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 类玻璃膜疣沉积物，这似乎会增加患晚期 AMD（萎缩和/或 新生血管形成）。最近，脉络膜毛细血管 (CC) 血流不足已被证明随着年龄的增长而增加 和AMD。 CC 流量不足与 AMD 的发病和阶段之间的关系仍有待研究 定义的。此外，虽然已经确定了 AMD 的许多遗传风险因素，但 AMD 的遗传因素 AMD 的进展尚未阐明。这项研究应用旨在解决这些关键问题 通过评估患有 AMD 的老年受试者来弥补知识差距，这些受试者之前曾被招募为该项目的一部分 NEI 资助的阿米什眼科研究。阿米什人在环境方面代表了一个同质群体 和社会暴露，减少了变异性，使该群体非常适合流行病学研究 AMD 进展。通过之前的研究，基线（以及一些 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， 这将是我们提出的研究的重点，对于实际确定哪些人继续进行至关重要 进展到晚期 AMD，这对于确定哪些基线特征与更高的 AMD 相关联至关重要 进展风险，并为 AMD 开发细粒度和定量的分期系统。的发展 这种新颖的 AMD 分期系统将提供干预点和结果评估，以实现 早期干预临床试验并为遗传学和病理生理学提供新的见解 AMD。

项目成果

Effect of OCT B-Scan Density on Sensitivity for Detection of Intraretinal Hyperreflective Foci in Eyes with Age-Related Macular Degeneration.

• DOI: 10.1080/02713683.2022.2081981
• 发表时间: 2022-09
• 期刊: Current eye research
• 影响因子: 2

Longitudinal evaluation of the distribution of intraretinal hyper-reflective foci in eyes with intermediate age-related macular degeneration.

中度年龄相关性黄斑变性眼视网膜内高反射灶分布的纵向评估。

• DOI: 10.21203/rs.3.rs-3273570/v1
• 发表时间: 2023
• 期刊: Research square
• 作者: Sadda,Srinivas;Verma,Aditya;Corradetti,Giulia;Nittala,Muneeswar;He,Ye;Nassisi,Marco;Velaga,SwethaBindu;Haines,Jonathan;Pericak-Vance,Margaret;Stambolian,Dwight
• 通讯作者: Stambolian,Dwight

Enhanced Detection of Reticular Pseudodrusen on Color Fundus Photos by Image Embossing.

• DOI: 10.1080/02713683.2022.2126860
• 发表时间: 2022-11
• 期刊: Current eye research
• 影响因子: 2

Drusen morphometrics on optical coherence tomography in eyes with age-related macular degeneration and normal aging.

• DOI: 10.1007/s00417-023-06088-z
• 发表时间: 2023-09
• 期刊: GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
• 影响因子: 2.7
• 作者: Oncel, Deniz;Corradetti, Giulia;Wakatsuki, Yu;Nittala, Muneeswar Gupta;Velaga, Swetha Bindu;Stambolian, Dwight;Pericak-Vance, Margaret A.;Haines, Jonathan L.;Sadda, SriniVas R.
• 通讯作者: Sadda, SriniVas R.

Risk Factors for Progression of Age-Related Macular Degeneration: Population-Based Amish Eye Study.

• DOI: 10.3390/jcm11175110
• 发表时间: 2022-08-30
• 期刊: Journal of clinical medicine
• 影响因子: 3.9