Predictive markers for diabetic retinopathy via quantitative imaging of retinal capillary functions

通过视网膜毛细血管功能的定量成像预测糖尿病视网膜病变的标志物

基本信息

批准号：
10250563
负责人：
Ji Yi
金额：
$ 46.93万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-30 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10250563
关键词：
3-Dimensional Academy Address Adult Affect American Angiography Attention Background Diabetic Retinopathy Benchmarking Blindness Blood Blood Vessels Blood capillaries Blood flow Blood-Retinal Barrier Boston Caring Chronic Clinic Clinical Clinical Research Collaborations Detection Development Devices Diabetic Retinopathy Diffuse Disease Disease Progression Dyes Extravasation Eye Eye diseases Fluorescein Fluorescein Angiography Fluorescence Functional disorder Goals Gold Hemoglobin Hemorrhage Human Hyperglycemia Hypoxia Image Imaging Device Imaging Techniques Individual Injections Lasers Lead Measurement Measures Medical center Monitor Multi-modal optical imaging Multimodal Imaging Natural History Ophthalmology Ophthalmoscopy Optical Coherence Tomography Oxygen Pathogenicity Pathology Patients Pattern Perfusion Prevention Preventive treatment Process Prognostic Marker Public Health Resistance Resolution Retina Retinal Diseases Retinal Hemorrhage Risk Scanning Severities Speed Statistical Data Interpretation System Techniques Testing Three-Dimensional Imaging Time Treatment Factor Treatment outcome United States Vascular Endothelial Growth Factors Visible Radiation Vision aging population base clinical examination diabetic diabetic patient diagnosis standard eye center fluorescence imaging follow-up imaging biomarker imaging capabilities imaging modality in vivo insight macular edema multimodality neovascularization novel novel imaging technique optical imaging predicting response predictive marker prevent prognostic value proliferative diabetic retinopathy quantitative imaging recruit response retinal imaging standard of care success targeted imaging treatment response treatment strategy

项目摘要

PROJECT SUMMARY Diabetic retinopathy (DR) remains the leading cause of blindness, affecting over 4 million Americans. The prediction of DR progression and treatment outcome holds the key in the care for DR and the prevention of vision-threating conditions. However, clinicians are now faced with the challenge of limited established predictors for the development of DR and treatment response. Our hypothesis is that capillary dysfunction, as the central crux of the DR pathology, is a sensitive predictor of DR progression and treatment outcome. In diabetic eyes, hyperglycemia leads to capillary dysfunction which leads to a breakdown of the blood retinal barrier (BRB) resulting in capillary leakage. This capillary dysfunction further leads to capillary loss and non- perfusion, which causes ischemic hypoxia. The combined effects of capillary leakage and hypoxia results in neovascularization and retinal hemorrhage, signifying the onset of proliferative DR. In this pathogenic process, capillary leakage, oxygenation, and capillary blood flow are three key aspects of capillary function, and therefore have become our targets of imaging and quantification. We have developed visible light optical coherence tomography (OCTA) to non-invasively quantify blood oxygenation at the capillary level. We have also shown that measuring the dynamics of near infrared OCTA allows quantification of the flow dynamics of capillary flow. The quantification of both oxygenation and flow dynamics provides measurement of capillary perfusions. In addition, we have developed a novel multimodal 3D imaging technique, oblique scanning laser ophthalmology (oSLO), which unprecedentedly enables wide-field 3D fluorescence imaging in the retina. Since the administration of fluorescein dye is a component of the standard of care and fluorescein angiography (FA) is the gold standard for diagnosing DR, the 3D imaging capability of oSLO can uniquely provide sensitive detection of dye leakage. Taken altogether, we will explore three specific aims. 1) To develop a multimodal oSLO/OCT system to quantify capillary blood oxygenation, flow dynamics, and leakage, with large field of view, high resolution and high speed. 2) To conduct a pilot clinical study to assess the correlation of DR severity to retinal capillary function in humans. 3) To explore the prognostic value of imaging markers for capillary functions that can predict anti-VEGF treatment response. IMPACT ON PUBLIC HEALTH: 1) The success of this project will lead to a groundbreaking new imaging device that is currently not available. 2) The validity of the imaging method could also lead to further clinical studies on predictive imaging markers on DR progression and treatment response. 3) The multiple measurements of capillary functions will provide further insight into the pathophysiology and new treatment strategies for this debilitating eye disease.

项目概要糖尿病视网膜病变 (DR) 仍然是导致失明的主要原因，影响着超过 400 万美国人。这预测 DR 进展和治疗结果是 DR 护理和预防的关键威胁视力的情况。然而，临床医生现在面临着有限的挑战。 DR 发展和治疗反应的预测因子。我们的假设是毛细血管功能障碍 DR 病理学的核心关键是 DR 进展和治疗结果的敏感预测因子。在糖尿病眼，高血糖会导致毛细血管功能障碍，从而导致血视网膜破裂屏障（BRB）导致毛细管渗漏。这种毛细血管功能障碍进一步导致毛细血管损失和非灌注，导致缺血性缺氧。毛细血管渗漏和缺氧的综合作用导致新生血管形成和视网膜出血，标志着增殖性 DR 的开始。在这个致病过程中，毛细血管渗漏、氧合和毛细血管血流是毛细血管功能的三个关键方面，因此成为我们成像和量化的目标。我们开发了可见光光学相干断层扫描（OCTA）可无创地量化毛细血管水平的血氧。我们有还表明，测量近红外 OCTA 的动态可以量化流动动态毛细管流动。氧合和流动动力学的量化提供了毛细管的测量灌注。此外，我们还开发了一种新颖的多模态 3D 成像技术，倾斜扫描激光眼科 (oSLO)，前所未有地实现了视网膜的宽视场 3D 荧光成像。自从荧光素染料的使用是护理和荧光素血管造影 (FA) 标准的一部分是诊断 DR 的黄金标准，oSLO 的 3D 成像能力可以独特地提供敏感的检测染料泄漏。总的来说，我们将探讨三个具体目标。 1）发展多式联运 oSLO/OCT 系统可量化毛细血管血氧、血流动力学和渗漏，具有大视野，高分辨率和高速度。 2) 进行一项试点临床研究，以评估 DR 严重程度与人类视网膜毛细血管功能。 3）探讨毛细血管成像标志物的预后价值可以预测抗 VEGF 治疗反应的功能。对公众健康的影响： 1) 的成功该项目将带来一种目前尚不可用的突破性的新型成像设备。 2) 有效性该成像方法还可以促进对 DR 进展的预测成像标记物的进一步临床研究和治疗反应。 3）毛细管功能的多次测量将提供对毛细管功能的进一步了解。这种使人衰弱的眼病的病理生理学和新的治疗策略。