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: 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
• 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

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 -球蛋白血液疾病，可引起溶血和血管阻塞