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

基本信息

批准号：
10440805
负责人：
Yuen Ping Toco Chui
金额：
$ 83.74万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
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/10440805
关键词：
Affect Age American Angiography Area Biological Biological Assay Biological Markers Biological Response Modifier Therapy Black American Black race Blood capillaries Blood flow Caring Cessation of life Chronic Disease Clinical Clinical Data Clinical Pathology Data Data Collection Data Element Data Sources Databases Development Disease 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 Interruption Laboratories Leukocytes Light 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 Veno-Occlusive Disease Visit 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 rho sex success time interval tool treatment response

项目摘要

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.

镰状细胞病 (SCD) 是一种高发病率的 β-珠蛋白血液疾病，可导致溶血和血管损伤闭塞，导致疼痛、器官损伤和过早死亡。进步的一个关键障碍是目前疾病监测生物标志物与临床结果的相关性较弱，因为它们不直接测量引起临床病理的机制。眼睛的透明介质提供了机会直接可视化视网膜微血管系统，作为其他微血管状态的间接表示器官系统并量化血流的短暂中断（SCD 病理学的主要原因）。我们的研究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在几分钟到几小时内进行比较，可以产生可靠的视网膜灌注指标比任何现有的临床生物标志物都能更好地预测 SCD 的严重程度和死亡率。使用光学相干断层扫描血管造影（OCTA）和自适应光学扫描光检眼镜（AOSLO）假设视网膜成像的创新可用于创建新的生物标志物来指导疾病监测并提高对疾病机制的了解。在我们的前期工作中，我们开发了几个高度可靠的视网膜灌注指标，确定了 SCD 中小血管闭塞的 4 种机制，并显示一种新颖的灌注指标，即会话间间歇流量指数 (IFI)，优于所有当前的灌注指标生物标志物作为疾病严重程度的衡量标准和死亡率的预测指标。我们建议进行前瞻性使用连续视网膜成像和临床数据收集的队列研究 1) 开发可靠的视网膜指标灌注（由变异系数和个体指数确定），2) 验证灌注指标作为疾病严重程度、治疗反应和死亡风险的客观指标，3) 比较 5种主要SCD表型中导致微血管闭塞的机制。以保证最大限度普遍性和与其他数据源协调的潜力，将使用以下方式收集临床数据由 NHLBI 镰状细胞实施联盟临床数据注册中心开发的工具。为了完成为了实现这些重要目标，拟议的项目汇集了眼科、视网膜成像、高罕见疾病、利益相关者参与和 SCD 的效率研究设计和分析。