Assessment of Retinal Capillary Density, Morphology and Function in Retinal Vascular Disease Using Novel OCT Angiography Based Metrics

使用基于 OCT 血管造影的新型指标评估视网膜血管疾病中的视网膜毛细血管密度、形态和功能

• 批准号: 10004661
• 负责人: Amir H Kashani
• 金额: $ 14.12万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10004661
• 关键词: African American; Age; Angiography; Animals; Background Diabetic Retinopathy; Biological Markers; Blindness; Blood Vessels; Blood capillaries; Blood flow; Caliber; Childhood; Clinical; Clinical Research; Clinical Trials; Clinical Trials Design; Confounding Factors (Epidemiology); Cost of Illness; Cross-Sectional Studies; Custom; Data; Detection; Development; Devices; Diabetes Mellitus; Diabetic Retinopathy; Diagnosis; Diagnosis Clinical Trials; Diagnostic; Disease; Disease Management; Dot Immunoblotting; Early Diagnosis; Engineering; Evaluation; Eye; Eye diseases; FDA approved; Fluorescein Angiography; Functional disorder; Funding; Gender; Goals; Heme; Human; Hyperoxia; Hypertension; Image; Impairment; Institutes; Institutional Review Boards; Intervention; Intervention Trial; Ischemia; Latino; Lead; Light; Los Angeles; Measurable; Measurement; Measures; Methods; Microscopic; Morphology; Non-Insulin-Dependent Diabetes Mellitus; Optical Coherence Tomography; Outcome; Pathologic; Patient Care; Perfusion; Physicians; Physiological; Population Study; Preparation; Procedures; Protocols documentation; Publishing; Race; Research; Research Design; Research Personnel; Resolution; Retina; Retinal Diseases; Scientist; Severities; Source; Staging; Stimulus; Structure; Technology; Testing; Time; Tissues; United States National Institutes of Health; Vascular Diseases; arteriole; base; burden of illness; clinical examination; clinical practice; cohort; cost; cotton wool spots; density; diabetic; human subject; improved; in vivo; innovation; medical schools; minimal risk; neovascularization; novel; novel marker; potential biomarker; response

Abstract Diabetes mellitus (DM) and hypertension (HTN) are two prototypical vascular diseases associated with microscopic pathological changes in retinal capillary structure. These changes ultimately lead to capillary dysfunction, capillary closure, ischemia and vision loss. Current clinical methods and diagnostics for staging these diseases are neither effective in detecting the earliest capillary changes nor in detecting incremental capillary changes (improvement or worsening) in later stages of the disease. For example, clinical detection of capillary loss is generally not possible by clinical examination alone. Fluorescein angiography (FA) is an invasive test that has been traditionally used to assess retinal perfusion but human studies show that the resolution and technical limitations of FA is only effective in detecting capillary loss after ~50% or more of capillaries are already non-perfused. In addition, FA is not clinically indicated unless there are already clinical signs of late stage disease and neovascularization. Therefore, reliably detecting and characterizing subclinical retinal capillary changes in DM and HTN represents an important opportunity to decrease disease burden and cost by enabling early diagnosis, clinical trials and interventions before irreversible tissue damage. Optical coherence tomography angiography (OCTA) is a safe, non-invasive and FDA approved method that provides a unique opportunity to achieve these goals. Our group of physicians, scientists and engineers have been pioneers in the development and application of OCTA technology. In this proposal, we seek to shift the current research and clinical practice paradigms in assessment of retinal vascular disease by utilizing cutting-edge commercially available OCTA technology and novel image acquisition methods to identify and measure subclinical changes in capillary structure and function. Our preliminary data shows that subclinical capillary loss occurs in all stages of DR. In this proposal we will (1) further characterize capillary changes in well controlled, non-interventional clinical trial of human subjects across race, age, gender and other possible confounding variables by taking advantage of well-characterized subjects from NIH-funded population based studies. (2) Assess the feasibility and reliability of novel OCTA measures of retinal capillary function. (3) To further characterize the magnitude and physiological relevance of these capillary changes we will use a custom built functional swept-source OCTA (FOCTA) to assess real time and in vivo retinal vascular responses during a focal physiologic light stimulus. The successful outcome of this proposal will develop and implement novel SD- and SS-OCTA based technology in human subjects to identify novel biomarkers of capillary loss or closure in DM and HTN. Application of these biomarkers will improve the diagnosis and management of disease by allowing direct evaluation of capillary changes and ischemia in a clinical setting. Our proposal uses spectral domain (SD) and swept-source (SS)-OCTA devices that are FDA approved so our results will be directly transferable to patient care.

摘要 糖尿病（DM）和高血压（HTN）是两种典型的血管疾病， 视网膜毛细血管结构的显微病理改变。这些变化最终导致毛细血管 功能障碍、毛细血管闭合、局部缺血和视力丧失。目前的临床分期方法和诊断 这些疾病既不能有效地检测最早的毛细血管变化， 毛细血管变化（改善或恶化）在疾病的后期阶段。例如，临床检测 毛细血管损失通常不可能仅通过临床检查来实现。血管造影（FA）是一种 传统上用于评估视网膜灌注的侵入性测试，但人体研究表明， FA的分辨率和技术局限性仅在检测约50%或更多的 毛细血管已经是非灌注的。此外，FA没有临床指征，除非已经有临床 晚期疾病和新血管形成的迹象。因此，可靠地检测和表征亚临床 糖尿病和高血压性视网膜病变患者的视网膜毛细血管改变是减少疾病负担的重要机会， 通过在不可逆的组织损伤之前进行早期诊断、临床试验和干预来降低成本。光学 相干断层扫描血管造影术（OCTA）是一种安全、非侵入性和FDA批准的方法， 实现这些目标的独特机会。我们的医生、科学家和工程师团队 OCTA技术开发和应用的先驱。在这个提议中，我们试图改变目前的 研究和临床实践范例在视网膜血管疾病的评估，利用先进的 市售的OCTA技术和新的图像采集方法，以识别和测量 毛细血管结构和功能的亚临床变化。我们的初步数据显示，亚临床毛细血管 损失发生在DR的所有阶段。在本提案中，我们将（1）进一步表征井中的毛细变化 人类受试者的对照、非干预性临床试验，包括种族、年龄、性别和其他可能的 通过利用NIH资助人群中特征良好的受试者来混淆变量 问题研究(2)评估新的OCTA测量视网膜毛细血管功能的可行性和可靠性。(3)到 为了进一步表征这些毛细血管变化的幅度和生理相关性，我们将使用定制的 建立了功能扫描源OCTA（FOCTA），以评估真实的时间和体内视网膜血管反应， 局部生理光刺激。该提案的成功结果将开发和实施新的 在人类受试者中基于SD和SS-OCTA的技术，用于鉴定毛细血管损失或闭合的新型生物标志物 在DM和HTN。这些生物标志物的应用将通过以下方式改善疾病的诊断和管理： 允许在临床环境中直接评价毛细血管变化和局部缺血。我们的建议使用光谱 域（SD）和扫频源（SS）-FDA批准的OCTA设备，因此我们的结果将直接 转移到病人护理上