Novel ultrahigh speed swept source OCT angiography methods in diabetic retinopathy

糖尿病视网膜病变(DR)是导致工作年龄人群失明的主要原因。血糖控制保持不变 预防或减缓疾病进展的最佳策略。然而，及早发现视力威胁 视网膜改变和及时治疗对于在更晚期保留视功能是必要的。 糖尿病视网膜病变的临床治疗还需要客观的工具来评估视网膜结构和微血管。 异常，以及评估治疗反应的方法。这个多学科项目的目标是 开发新的光学相干断层扫描(OCT)成像方法和生物标志物，可以识别和 描述糖尿病视网膜病变的视网膜微血管和血流改变，可用于早期疾病 检测、预测进展、监测治疗反应和提高临床试验效率。我们会 开发下一代OCT血管成像(OCTA)技术和分析框架(目标1)。这个硬件- 软件创新将开发超高速扫源OCT(SS-OCT)，以实现更高的动态 视网膜血流的范围OCTA表征，更高清晰度的体积数据以可视化血管系统 毛细血管水平，并实现宽视野结构和血管成像。这些进展将开发出一种 视网膜微血管毛细血管水平血流速度的定量替代标记物。有能力 在毛细血管水平评估血流速度代表着OCTA成像的范式转变，使检测 发生在疾病早期的微妙的血管血流改变，这与疾病的发病机制有关 糖尿病黄斑水肿(DME)、毛细血管无灌注和新生血管。新的运动校正软件 技术可以校正三维眼球运动的OCT/OCTA体积数据和人工智能 /深度学习技术可以为OCTA生成可靠的层分割，以促进纵向跟踪 在多个患者就诊期间的变化。使用超高速SS-OCT和OCTA血流生物标志物，我们将 在一组糖尿病患者和年龄匹配的健康对照组中进行横断面研究(目标2)。这个 研究将评估OCTA驱动的Vista血流标志物的重复性，调查OCTA血流生物标志物 与DR严重程度相关，如果与DME、毛细血管无灌注或 新生血管。最后，我们将对DR Eyes进行纵向监测，以调查细微血流的作用 疾病进展的变化和预测治疗反应(目标3)。假设是OCTA的血液 血流生物标志物可以识别血流异常的区域，这些区域血栓形成的风险增加， 渗漏，因此DME，以及缺血的区域，新生血管的风险增加。 同样，我们还将调查OCTA血流生物标志物是否可以用来预测抗血管内皮生长因子的反应 (血管内皮生长因子)治疗，包括DME消退、新生血管消退和/或治疗 耐用性。如果成功，这项计划有可能改善临床DR管理并帮助DR患者 以达到更好的视力效果。

Diabetic retinopathy (DR) is a leading cause of blindness in working age populations. Glycemic control remains the best strategy for preventing or slowing disease progression. However, early detection of vision threatening retinal changes and prompt treatment is necessary for preserving visual function in more advanced stages. Clinical management of DR also requires objective tools for assessing retinal structure and microvascular abnormalities, as well as methods to evaluate treatment response. The goal of this multidisciplinary program is to develop novel optical coherence tomography (OCT) imaging methods and biomarkers that can identify and characterize retinal microvasculature and blood flow alterations in DR, which can be used for early disease detection, predicting progression, monitoring treatment response, and improving clinical trial efficiency. We will develop next generation OCT angiography (OCTA) technology and analysis frameworks (Aim 1). This hardware- software innovation will develop ultrahigh speed swept-source OCT (SS-OCT) to enable increased dynamic range OCTA characterization of retinal blood flow, higher definition volumetric data to visualize vasculature at the capillary level, and enable wide field structural and vascular imaging. These advances will develop a quantitative surrogate marker for capillary level blood flow speeds in retinal microvasculature. The ability to assess blood flow speeds at the capillary level represents a paradigm shift in OCTA imaging, enabling detection of subtle vascular flow alterations that occur at earlier disease stages, which are related to pathogenesis of diabetic macular edema (DME), capillary non-perfusion and neovascularization. New software motion correction technology can correct volumetric OCT/OCTA data for eye motion in three dimensions and artificial intelligence / deep learning techniques can generate reliable layer segmentations for OCTA, to facilitate tracking longitudinal changes across multiple patient visits. Using ultrahigh speed SS-OCT and OCTA blood flow biomarkers, we will perform a cross-sectional study in a cohort of diabetic patients and age-matched healthy controls (Aim 2). The study will evaluate repeatability of OCTA-driven VISTA flow markers, investigate if OCTA blood flow biomarkers are correlated with DR severity, and if they are associated with DME, capillary non-perfusion or neovascularization. Finally, we will monitor DR eyes longitudinally to investigate the role of subtle blood flow alterations in disease progression and predicting treatment response (Aim 3). The hypothesis is that OCTA blood flow biomarkers can identify regions with abnormal blood flow, which are at increased risk of thrombosis and leakage, and hence DME, as well as regions that are ischemic, and at increased risk of neovascularization. Similarly, we will also investigate if OCTA blood flow biomarkers can be used to predict response to anti-VEGF (vascular endothelial growth factor) therapy, including DME resolution, neovascular regression, and/or treatment durability. If successful, this program has the potential to improve clinical DR management and help DR patients to achieve better vision outcomes.