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

基本信息

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
项目类别：
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

项目摘要

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.

概括我们将重点关注以前很大程度上未充分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”。我们假设有治疗效果在早期萎缩性 AMD 中，很大一部分患者可能免于进行性视功能丧失而且在这个时间窗口进行冒险干预似乎比早期 AMD 阶段更合理。反对在这种背景下，对这种潜在的自然疾病进展的全面了解治疗裕度至关重要。我们将实施创新的多模态高分辨率视网膜成像，全面的功能测试，以及与视觉相关的生活质量（VRQoL）评估相结合前瞻性纵向研究中的标准化和探索性分析策略。这将使我们能够表征和量化微观结构变化以及相关的功能和 VRQoL 缺陷具有前所未有的准确度来检测患有早期萎缩性病变的眼睛。了解最严重的风险因素疾病进展加速将有助于识别视功能丧失风险最高的患者。此外，我们对疾病阶段特定危险因素的假设可以指导治疗靶点的选择早期萎缩性 AMD 特别容易受到影响。针对特定表型和疾病定制治疗方法阶段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。