Functional Optical Coherence Tomography-derived Biomarkers for Diabetic Retinopathy

 描述(申请人提供)：糖尿病视网膜病变(DR)，与长期糖尿病有关，在美国是导致失明的主要原因。结构光学相干断层扫描(OCT)已经成为评估糖尿病黄斑水肿的标准方法；然而，需要有创性静脉注射染料的荧光素血管成像(FA)仍然需要评估毛细血管丢失和确认新生血管。最近，我们使用高速OCT系统进行了无创功能测量，如血管造影术、视网膜总血流量和视网膜动脉搏动性。该项目的目标是改进这些OCT衍生的功能生物标志物，并确定它们在DR早期检测和治疗中的作用。1.发展毛细血管脱落和视网膜新生血管(RNV)的OCT定量血管成像。利用一种新的分裂谱幅度-去相关算法，实现了三维OCT血管成像(3s内6x6 mm扫描)。算法将得到改进，OCT血管成像将使用物理流动模型进行校准。将开发自动化软件来量化以下血管造影生物标志物：无灌注区、RNV面积和血流指数，以及黄斑旁和黄斑周围血流指数。2.改进多普勒OCT测量视网膜总血流量(TRBF)和视网膜动脉搏动性的方法。3秒的三维多普勒OCT扫描将被用来测量TRBF，使用EN面部求和算法。将使用4秒圆柱形多普勒OCT扫描来测量视网膜动脉的搏动性。将为这些新的生物标志物开发自动测量算法。3.改进黄斑水肿的结构OCT测量方法。通过注册几个体积扫描，我们已经展示了视网膜增厚和液体空间(囊)的详细的标测和量化。这些结构生物标志物的全自动量化将被开发出来。4.在临床研究中评价OCT衍生的功能和结构生物标记物。在50例重度非增殖性(NPDR)和增殖性(PDR)患者(A组)和30例年龄匹配的非糖尿病对照组(C组)中，将测定OCT血管造影检测毛细血管脱落和RNV的特异性和敏感性。OCT衍生生物标记物用于早期检测视网膜异常的有效性将在80名患有或不伴有轻中度NPDR的受试者中进行评估(B组)。评估疾病变化的生物标志物的能力将在12个月的间隔内与A组和B组一起进行评估。与标准眼底照相相比，拟议的OCT衍生功能生物标志物将对早期血管变化更敏感，并可能为糖尿病临床试验提供更可靠的终点。与FA不同，功能性OCT是非侵入性的，可用于DR的常规临床筛查和监测。

 DESCRIPTION (provided by applicant): Diabetic retinopathy (DR), associated with long-term diabetes mellitus, is a leading cause of blindness in the US. Structural optical coherence tomography (OCT) has become the standard method for evaluating diabetic macular edema; however, fluorescein angiography (FA), which requires an invasive intravenous dye injection, is still needed to assess capillary dropout and confirm neovascularization. Recently, we have used a high- speed OCT system to make non-invasive functional measurements such as angiography, total retinal blood flow, and retinal arterial pulsatility. The goal of the proposed project is to improve these functional OCT-derived biomarkers and determine their roles in the early detection and management of DR. 1. Develop quantitative OCT angiography of capillary dropout and retinal neovascularization (RNV). Three dimensional (3D) OCT angiography has been made practical (6x6 mm scan in 3 seconds) by a novel split-spectrum amplitude-decorrelation algorithm. The algorithm will be improved and OCT angiograms will be calibrated by physical flow phantoms. Automated software will be developed to quantify the following angiographic biomarkers: non-perfusion area, RNV area and flow index, and parafoveal and perifoveal flow indexes. 2. Improve Doppler OCT measurement of total retinal blood flow (TRBF) and retinal arterial pulsatility. A 3-second 3D Doppler OCT scan will be used to measure TRBF using an en face summation algorithm. A 4-second cylindrical Doppler OCT scan will be used to measure retinal arterial pulsatility. Automated measurement algorithms will be developed for these novel biomarkers. 3. Improve structural OCT measurement of macular edema. By registering several volumetric scans, we have demonstrated detailed mapping and quantification of retinal thickening and fluid spaces (cysts). Fully automated quantification of these structural biomarkers will be developed. 4. Evaluate functional and structural OCT-derived biomarkers in clinical studies. The specificity and sensitivity of OCT angiography for detection of capillary dropout and RNV will be determined in 50 severe non-proliferative (NPDR) and proliferative (PDR) subjects (Group A) and 30 age-matched non-diabetic controls (Group C). The utility of OCT-derived biomarkers for early detecting retinal abnormalities will be evaluated in 80 subjects with or without mild to moderate NPDR (Group B). The capability of biomarkers for assessing the disease change will be evaluated with Groups A and B over a 12-month interval. The proposed functional OCT-derived biomarkers will be more sensitive to early vascular change compared to standard fundus photography and are likely to provide more reliable endpoints for diabetic clinical trials. Unlike FA, functional OCT is non-invasive and coul be used in routine clinical screening and monitoring of DR.