SCD REVIVE - Retina to Evaluate Vaso occlusion In the Vasculature of the Eye

SCD REVIVE - 视网膜评估眼睛血管系统中的血管闭塞

• 批准号: 10602464
• 负责人: Yuen Ping Toco Chui
• 金额: $ 81.49万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-10 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10602464
• 关键词: Affect; Age; American; Angiography; Area; Biological; Biological Assay; Biological Markers; Black American; Black race; Blood Vessels; Blood capillaries; Blood flow; Caring; Categories; Cessation of life; Chronic Disease; Classification; Clinical; Clinical Data; Clinical Pathology; Data; Data Collection; Data Element; Data Sources; Databases; Development; Disease; Disparity; Dose; Ensure; Environmental sludge; Erythrocytes; Evaluation; Event; Exhibits; Eye; FDA approved; Frequencies; Funding; Goals; Hematological Disease; Hemolysis; Hour; Image; Image Analysis; Imaging technology; Individual; Individuality; Inequity; Interruption; Laboratories; Leukocytes; Light; Maps; Measurement; Measures; Mediating; Monitor; Morbidity - disease rate; National Heart, Lung, and Blood Institute; Normal Cell; Normal Range; Ophthalmology; Ophthalmoscopy; Optical Coherence Tomography; Organ; Outcome; Pain; Pathology; Patient Outcomes Assessments; Performance; Perfusion; Phenotype; Prospective cohort; Prospective, cohort study; Race; Rare Diseases; Reference Values; Research; Research Design; Retina; Retinal Diseases; Scanning; Severity of illness; Sickle Cell; Sickle Cell Anemia; Standardization; Stigmatization; Uncertainty; United States National Institutes of Health; Variant; Visit; Visualization; Work; adaptive optics; beta Globin; biomarker signature; body system; cell injury; clinical biomarkers; clinical heterogeneity; clinical phenotype; cohort; cost; data registry; density; disease phenotype; follow-up; health care availability; improved; improved outcome; in vivo; indexing; innovation; mortality; mortality risk; non-invasive imaging; novel; novel strategies; novel therapeutics; perfusion imaging; premature; quantitative imaging; retinal damage; retinal imaging; retinal ischemia; rho; sex; success; time interval; tool; treatment response

Sickle Cell Disease (SCD) is a high-morbidity, beta-globin blood disorder that causes hemolysis and vaso- occlusion, leading to pain, organ damage and premature death. A key barrier to progress is that current disease-monitoring biomarkers correlate weakly with clinical outcomes because they do not directly measure the mechanisms that cause clinical pathology. The transparent media of the eye presents the opportunity to directly visualize the retinal microvasculature, as an indirect representation of the microvascular status of other organ systems and to quantify transient interruptions in blood flow (a major cause of SCD pathology). Our group found that new approaches to quantifying retinal perfusion abnormalities, such as mapping variably perfused areas and comparing them over minutes to hours, can produce reliable metrics of retinal perfusion that predict SCD severity and mortality better than any currently available clinical biomarker. Using Optical coherence tomography angiography (OCTA) and adaptive optics scanning light ophthalmoscopy (AOSLO) we hypothesize that innovations in retinal imaging may be leveraged to create new biomarkers to guide disease monitoring and improve mechanistic understanding of disease. In our preliminary work, we developed several highly-reliable retinal perfusion metrics, identified 4 mechanisms of small-vessel occlusion in SCD, and showed that one novel perfusion metric, between-session intermittent flow index (IFI), outperformed all current biomarkers as a measure of disease severity and predictor of mortality. We propose to conduct a prospective cohort study using serial retinal imaging and clinical data collection to 1) develop reliable metrics of retinal perfusion (as determined by coefficients of variation and indexes of individuality), 2) validate perfusion metrics as objective indicators of disease severity, treatment response and mortality risk, and 3) compare the mechanisms that cause microvascular occlusion among the 5 major SCD phenotypes. To ensure maximum generalizability and potential for harmonization with other data sources, clinical data will be collected using tools developed from the NHLBI Sickle Cell Implementation Consortium Clinical Data Registry. To accomplish these important goals, the proposed project brings together expertise in ophthalmology, retinal imaging, high- efficiency study design and analyses for rare diseases, stakeholder engagement and SCD.

镰状细胞疾病（SCD）是一种高多个，β-珠蛋白血液疾病，会导致溶血和血管 阻塞，导致疼痛，器官损伤和过早死亡。进步的关键障碍是当前 疾病监测生物标志物与临床结果微弱相关，因为它们没有直接测量 引起临床病理的机制。眼睛的透明媒体为 直接可视化视网膜微脉管系统，作为其他其他微血管状态的间接表示 器官系统并量化血流中的短暂性中断（SCD病理的主要原因）。我们的 小组发现，量化视网膜灌注异常的新方法，例如可变映射 灌注区域并将它们比较数分钟到几小时，可以产生可靠的视网膜灌注指标 这比当前可用的临床生物标志物更好地预测SCD的严重性和死亡率。使用光学 相干断层扫描血管造影（八八块）和自适应光学扫描光眼镜检查（AOSLO）我们 假设可以利用视网膜成像中的创新来创建新的生物标志物来指导疾病 监测和改善对疾病的机械理解。在我们的初步工作中，我们开发了几个 高度可靠的视网膜灌注指标，鉴定 那个新颖的灌注度量指标，会议间间歇性流量指数（IFI）的表现优于所有当前 生物标志物作为疾病严重程度和死亡率预测指标的量度。我们建议进行潜在的 使用串行视网膜成像和临床数据收集的队列研究1）开发视网膜的可靠指标 灌注（由变异和个性索引的系数确定），2）验证灌注指标 作为疾病严重程度，治疗反应和死亡率风险的客观指标，3）比较 在5种主要的SCD表型中引起微血管阻塞的机制。确保最大程度 可推广性和与其他数据源协调的潜力，将使用临床数据收集 由NHLBI镰状细胞实施联盟临床数据注册中心开发的工具。完成 这些重要的目标是，拟议的项目汇集了眼科，视网膜成像，高级的专业知识 效率研究设计和分析稀有疾病，利益相关者参与和SCD。