OCTA Precursors of Vision-Threatening Complications of Diabetic Retinopathy

项目总结 糖尿病视网膜病变(DR)是导致视力丧失的主要原因。这种视力损失很大程度上是可以通过及时预防的 诊断和治疗。目前识别危险眼睛的方法依赖于对关键字的定性评估 临床检查或眼底照片上的特征。虽然这种方法对风险进行了分层，但它确实是这样做的 不确切地说，需要转诊许多患者，以确定少数需要治疗的人。我们提出了一个 另一种方法，关注威胁视力的并发症的直接前兆，使用高级 光学相干断层血管成像(OCTA)。这种方法有可能更准确地识别 与摄影筛查相比，高危患者出现这些并发症，减轻了系统负担。 我们的初步数据已经确定了威胁视力的DR并发症的OCTA先兆：增殖性 糖尿病视网膜病变(PDR)和中心性糖尿病黄斑水肿(CI-DME)。使用这些生物标记物 在实际的临床环境中，OCTA必须具有大视野和高分辨率，同时还必须提供高成像 投降。此外，这些生物标记物必须是临床医生可以接触到的，需要自动化和可靠 识别和分割。目前可用的系统不能满足这些要求。我们建议 进行根本性的技术改进，以解决目前的限制并验证我们的假设 PDR和CI-DME的OCTA前驱指标可以准确地识别有风险的眼睛： 在具体目标1中，我们将开发一种高速(1 MHz)、大视场(120？)和高分辨率(10微米横向 分辨率)系统能够从一次扫描中获得可靠、高产量的OCTA，而不需要剪辑或 偏心注视。此视野可与目前可用的超宽视野荧光素血管造影术相媲美。 基于GPU的实时处理将减少运动伪影，提高扫描采集的可靠性。 在具体目标2中，我们将开发识别这些前兆的深度学习算法。其前身是 新生血管(PNV)是视网膜前高反射性物质，血流信号高于内限值 用常规成像看不见的膜。活动性微动脉瘤(AMA)的特征是 管腔内有流动信号的高反射壁。我们将使用深度学习技术来准确地 对这些特征进行细分和量化，并以直观和可解释的格式实时呈现生物标记物。 在具体目标3中，我们将评估晚期OCTA衍生生物标记物的临床意义。(1)在2- 一年的前瞻性研究，我们将跟踪100名中到重度非增殖性糖尿病视网膜病变患者的基线 开发PDR或CI-DME。(2)在横断面研究中，我们将比较检测的敏感性 应用先进的OCTA和超宽视野治疗重度NPDR和PDR的新生血管病变50眼 荧光素血管造影术与眼底照相。(3)在一项探索性研究中，我们将跟踪50名患者 接受晚期OCTA治疗PDR或CI-DME 6个月，看看晚期OCTA 生物标志物可以提供临床上有意义的信息来监测或预测治疗反应。

PROJECT SUMMARY Diabetic retinopathy (DR) is a leading cause of vision loss. This vision loss is largely preventable through timely diagnosis and treatment. The current method for identifying eyes at risk relies on qualitative evaluation of key features on clinical examinations or fundus photographs. While this approach stratifies risk, it does so imprecisely, requiring referral of many patients in order to identify the few who need treatment. We propose an alternative approach that focuses on the direct precursors of vision-threatening complications using advanced optical coherence tomography angiography (OCTA). This approach has the potential to more precisely identify patients at high risk for these complications than photographic screening, reducing the burden on the system. Our preliminary data has identified OCTA precursors of the vision-threatening DR complications: proliferative diabetic retinopathy (PDR) and center-involved diabetic macular edema (CI-DME). To use these biomarkers in real clinical settings, OCTA must have a wide field of view with high resolution while also providing a high imaging yield. In addition, these biomarkers must be accessible to clinicians, requiring automated and reliable identification and segmentation. The currently available systems fall short of these requirements. We propose making fundamental technological improvements to address the present limitations and to test our hypothesis that the OCTA precursors of PDR and CI-DME can precisely identify eyes at risk: In Specific Aim 1, we will develop a high-speed (1-MHz), wide-field (120?), and high-resolution (10-µmtransverse resolution) system capable of reliable, high-yield OCTA from a single scan that does not require montaging or eccentric fixation. This field of view is comparable to currently available ultra-widefield fluorescein angiography. GPU-based real-time processing will reduce motion artifacts and improve scan acquisition reliability. In Specific Aim 2, we will develop deep-learning algorithms that identify these precursors. The precursors of neovascularization (pNV) are epiretinal hyperreflective material with flow signal above the internal limiting membrane that are invisible with conventional imaging. Active microaneurysms (aMA) are characterized by hyperreflective walls with flow signal within the lumen. We will use deep-learning techniques to accurately segment and quantify these features and present the biomarkers in intuitive and interpretable format in real time. In Specific Aim 3, we will evaluate the clinical significance of advanced-OCTA derived biomarkers. (1) In a 2- year prospective study, we will follow 100 patients with moderate to severe nonproliferative DR at baseline for development of PDR or CI-DME. (2) In a cross-sectional study, we will compare the sensitivity for detecting neovascular lesions in 50 eyes with severe NPDR and PDR using the advanced OCTA vs. ultra-widefield fluorescein angiography vs. fundus photographs. (3) In an exploratory study, we will follow 50 patients undergoing treatments for PDR or CI-DME with advanced OCTA for 6 months to see if the advanced-OCTA biomarkers can provide clinically meaningful information to monitor or predict treatment response.