Progression of Early Atrophic Lesions in Age-related Macular degeneration

年龄相关性黄斑变性早期萎缩性病变的进展

• 批准号: 10635325
• 负责人: Monika Fleckenstein
• 金额: $ 38.5万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10635325
• 关键词: Acceleration; Address; Age related macular degeneration; Angiography; Area; Atrophic; Belief; Biological Markers; Blindness; Cells; Cessation of life; Clinical; Clinical Research; Clinical Trials Design; Color; Data; Data Set; Deposition; Development; Disease; Disease Progression; Evaluation; Eye; Fundus; Future; Image; Image Analysis; Individual; Intervention; Kinetics; Knowledge; Learning; Lesion; Location; Manuals; Measures; Modeling; Monitor; Nonexudative age-related macular degeneration; Optical Coherence Tomography; Outcome Measure; Patient Outcomes Assessments; Patients; Pattern; Perimetry; Phenotype; Predictive Factor; Predisposition; Probability; Prognosis; Prognostic Factor; Quality of life; Questionnaires; Reading; Resolution; Risk; Risk Factors; Risk-Benefit Assessment; Sample Size; Scotoma; Speed; Standardization; Testing; Therapeutic; Therapeutic Effect; Therapeutic Intervention; Time; Tissues; Training; Translations; United States Food and Drug Administration; Variant; Vision; Visual Acuity; Visual Fields; Visual impairment; analysis pipeline; automated segmentation; clinically relevant; deep learning; experience; fundus imaging; genetic variant; geographic atrophy; high risk; imaging Segmentation; innovation; instrument; longitudinal, prospective study; loss of function; luminance; multimodality; new therapeutic target; novel; patient prognosis; patient safety; personalized medicine; precision medicine; prevent; primary outcome; prognostic; prospective; retinal imaging; risk variant; therapeutic target; tool; transfer learning; trend; trial design; visual dysfunction

SUMMARY We will focus on a previously largely under-explored but highly relevant time window in progression of age-related macular degeneration (AMD), i.e., `early atrophic AMD'. We postulate that a therapeutic effect in early atrophic AMD would probably save a large proportion of patients from progressive visual function loss and that it seems more justifiable to risk interventions in this time window than in earlier AMD stages. Against this background, a comprehensive knowledge of the natural disease progression in this potential therapeutic margin is essential. We will implement innovative multimodal high-resolution retinal imaging, comprehensive functional testing, and assessment of vision-related quality of life (VRQoL) combined with standardized and exploratory analysis strategies in a prospective, longitudinal study. This will enable us to characterize and quantify the microstructural changes and associated functional and VRQoL deficits in eyes with early atrophic lesions with unprecedented accuracy. Knowledge of the strongest risk factors for accelerated disease progression will allow identification of patients at highest risk for visual function loss. Moreover, our hypothesis on disease-stage specific risk-factors may guide selection of therapeutic targets that are particularly susceptible in early atrophic AMD. Tailoring therapeutics to specific phenotypes and disease stages may be key to prevent irreversible vision loss and the associated reduced quality of life in patients with AMD.

总结 我们将重点关注以前在很大程度上未被探索但高度相关的时间窗口， 年龄相关性黄斑变性（AMD），即，早期萎缩性AMD我们假设治疗效果 在早期，萎缩性AMD可能会使大部分患者免于进行性视功能丧失 并且在这个时间窗内进行风险干预似乎比在早期AMD阶段更合理。对 这种背景下，在这种潜在的自然疾病进展的全面知识 治疗边缘是必不可少的。我们将实施创新的多模式高分辨率视网膜成像， 综合功能测试，以及视觉相关生活质量（VRQoL）评估， 标准化和探索性的分析策略，在前瞻性，纵向研究。这将使我们能够 表征和量化微结构变化以及相关的功能和VRQoL缺陷， 以前所未有的准确性检查早期萎缩性病变的眼睛。了解最强的风险因素， 加速的疾病进展将允许识别处于视觉功能丧失的最高风险的患者。 此外，我们关于疾病阶段特异性风险因素的假设可以指导治疗靶点的选择， 在早期萎缩性AMD中特别敏感。针对特定表型和疾病定制治疗方法 分期可能是预防不可逆视力丧失和相关生活质量下降的关键， AMD.