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

镰状细胞病（SCD）是一种高发病率的β-珠蛋白血液疾病，其引起溶血和血管紧张素转换酶抑制剂。 闭塞，导致疼痛、器官损伤和过早死亡。进展的一个关键障碍是， 疾病监测生物标志物与临床结果的相关性较弱，因为它们不能直接测量 导致临床病理学的机制眼睛的透明媒介提供了机会， 直接可视化视网膜微血管，作为其他微血管状态的间接表示。 器官系统和定量血流的短暂中断（SCD病理学的主要原因）。我们 研究小组发现，定量视网膜灌注异常的新方法，如绘制视网膜灌注图， 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 其预测SCD严重程度和死亡率优于任何目前可用的临床生物标志物。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），我们 假设视网膜成像的创新可以用来创建新的生物标志物来指导疾病 监测和提高对疾病的机制理解。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，确定了SCD小血管阻塞的4种机制，并显示 一个新的灌注指标，会话间间歇性血流指数（IFI），优于所有目前 生物标志物作为疾病严重程度的量度和死亡率的预测因子。我们建议进行一次前瞻性的 使用连续视网膜成像和临床数据收集的队列研究，以1）开发视网膜病变的可靠指标， 灌注（由变异系数和个体指数确定），2）验证灌注度量 作为疾病严重程度、治疗反应和死亡风险的客观指标，以及3）比较 在5种主要SCD表型中引起微血管闭塞的机制。以确保最大 具有普遍性和与其他数据源协调的潜力，将使用以下方法收集临床数据： NHLBI镰状细胞实施联盟临床数据登记处开发的工具。完成 这些重要的目标，拟议的项目汇集了眼科，视网膜成像，高， 罕见病、利益相关者参与和SCD的效率研究设计和分析。

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.