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

镰状细胞病(SCD)是一种发病率较高的β-珠蛋白血液疾病，可导致溶血和血管生成。 闭塞，导致疼痛、器官损伤和过早死亡。取得进展的一个关键障碍是目前 疾病监测生物标记物与临床结果的相关性很弱，因为它们不直接测量 导致临床病理的机制。眼睛的透明介质提供了一个机会 直接可视化视网膜微血管系统，作为其他患者微血管状态的间接表示 并量化血液流动的一过性中断(SCD病理的一个主要原因)。我们的 研究小组发现，量化视网膜血流异常的新方法，如可变地形图 对灌注区进行几分钟到几小时的比较，可以得出可靠的视网膜灌注量 比目前任何可用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。使用光纤 相干断层血管成像(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能被用来创造新的生物标记物来指导疾病 监测和改进对疾病的机械性理解。在我们的前期工作中，我们开发了几个 高度可靠的视网膜血流灌注测量，确定了SCD中小血管阻塞的4种机制，并显示 一种新的血流灌注指标，间歇血流指数(IFI)，表现优于所有的电流 生物标志物作为衡量疾病严重程度和死亡率的预测因子。我们建议进行一次预期的 使用连续视网膜成像和临床数据收集的队列研究：1)开发可靠的视网膜测量方法 灌注(由变异系数和个体指数确定)，2)验证灌注度量 作为疾病严重性、治疗反应和死亡风险的客观指标，以及3)比较 在5种主要的SCD表型中，导致微血管闭塞的机制。为了确保最大限度地 概括性和与其他数据来源协调的可能性，临床数据将使用以下方式收集 从NHLBI镰状细胞实施联盟临床数据注册中心开发的工具。要完成 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.