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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：
10461105
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 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10461105
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.

项目总结