Quantitative Analysis of Aging Retina

描述(由申请人提供)：对老年性黄斑病变(ARM)患者的临床治疗已经通过对视网膜近组织学细节的非侵入性成像而发生了革命性的变化。成像对于教育患者眼睛健康和跟踪疾病进展、监测治疗结果以及指定、设计和验证新仪器是必不可少的。我们建议进行翻译性研究，以指导临床使用光谱域光学相干断层扫描(SD-OCT)，它提供所有脉络膜视网膜层的横断面图，以及眼底反射和自体荧光(AF)成像，两者都提供视网膜色素上皮(RPE)的正面(面对面)图像。我们将在ARM的不同阶段开发独特的人类供眼资源，以产生视网膜图像解释的黄金标准。使用SD-OCT进行黄斑病变管理和研究所必需的识别点尚未得到系统验证。我们将获得切除的黄斑和视神经的SD-OCT图像，然后进行高分辨率、宽视野的组织切片。黄斑计划(由Lamina分析公司公布的黄斑病变)将使用老年正常、早期手臂、地理萎缩和新生血管手臂来：1.识别同眼SD-OCT图像和相应组织切片的特征，特别注意消除来自相邻层的组合信号的歧义，并识别玻璃体以外的手臂病理。2.测量黄斑和周边视网膜对照区域的视网膜各层、Bruchs膜(BRM)和脉络膜的厚度。3.建立手臂病理电子地图集，通过完整扫描每一张组织切片并将其放入在线数字病理档案，为下一代断层成像提供信息。RPE是手臂的中心发病机制，临床上已经使用反射和自体荧光(AF)信号在临床上显示了RPE的面部方向，后者来自RPE脂褐素。RPE普查项目将使用脉络膜视网膜整体显微镜、DIC和共焦显微镜，以及不同年龄和手臂状态的眼睛来：4.量化特定位置的RPE填充几何形状，以生成描述RPE地形图的连续数学函数；描述玻璃体和基底沉积物上的破裂。5.在明确的位置量化RPE房颤；使用共聚焦显微镜图像的三维重建，确定与玻璃体和基底沉积物相关的RPE中断的房颤。改进的黄斑解剖知识将有助于评估晚期ARM的风险和评估治疗。我们预计，这些数据将被临床成像领域的意见领袖、仪器工程师、眼科教育者和插图画家以及ARM新动物模型的开发者使用。我们获得的基本数据将对这一代和未来几代成像有用。 与公共卫生相关：由于视网膜很容易通过眼睛的光学装置看到，临床成像现在是对参与老年性黄斑病变(ARM)临床试验的患者进行分期和监测的重要组成部分。ARM是老年人视力丧失的主要原因。我们建议通过对手臂不同阶段的人类组织标本的视网膜和脉络膜进行定量分析，来改进对两种日益常见的视网膜成像方法(光学相干断层扫描和眼底自发荧光)的临床解释。

DESCRIPTION (provided by applicant): The clinical management of patients with age-related maculopathy (ARM) has been revolutionized by non-invasive imaging of the retina at near-histological detail. Imaging is essential for educating patients about eye health and following disease progression, monitoring treatment outcomes, and specifying, designing, and validating new instruments. We propose translational research directed toward informing the clinical use of spectral domain optical coherence tomography (SD-OCT), which provides cross-sectional views of all chorioretinal layers, and fundus reflectance and autofluorescence (AF) imaging, which both provide en face (face on) views of the retinal pigment epithelium (RPE). We will exploit a unique resource of human donor eyes at different stages of ARM to produce gold standards for retinal image interpretation. Points of identification essential for maculopathy management and research using SD-OCT have not been systematically validated. We will obtain SD-OCT images of excised macula and optic nerve followed by high-resolution, wide-field histological cross-sections. Project MACULA (Maculopathy Unveiled by Laminar Analysis) will use aged normal, early ARM, geographic atrophy, and neovascular ARM to: 1. Identify features in SD-OCT images and corresponding histological cross-sections of the same eyes, with special attention to disambiguating combined signals from adjacent layers and identifying ARM- pathology beyond drusen. 2. Measure the thickness of each retinal layer, Bruch's membrane (BrM), and choroid across the macula and in comparison regions of peripheral retina. 3. Establish an electronic atlas of ARM pathology to inform next-generation tomographic imaging by scanning each tissue slide in its entirety and placing it an online digital pathology archive. The RPE, central to ARM pathogenesis, has been visualized clinically in the en face direction using both reflectance and autofluorescence (AF) signals, the latter from RPE lipofuscin. Project RPE Census will use chorioretinal whole mounts, DIC and confocal microscopy, and eyes of different ages and ARM status to: 4. Quantify RPE packing geometry at well-specified locations to generate a continuous mathematical function describing RPE topography; describe disruptions over drusen and basal deposits. 5. Quantify RPE AF at well-specified locations; identify AF correlates of RPE disruptions associated with drusen and basal deposits, using 3-dimensional reconstruction of confocal microscopy images Improved knowledge about macular anatomy will help inform assessment of risk for advanced ARM and the assessment of treatments. We anticipate that data will be used by opinion leaders in clinical imaging, instrumentation engineers, ophthalmic educators and illustrators, and developers of new animal models of ARM. The fundamental data that we obtain will be useful for this and future generations of imaging. PUBLIC HEALTH RELEVANCE: Because the retina is so readily visible through the eye's optics, clinical imaging is now an essential component of staging and monitoring patients involved in clinical trials for treatments of age- related maculopathy (ARM), the large and debilitating cause of vision loss among the elderly. We propose to improve clinical interpretation of two increasingly common retinal imaging methods (optic coherence tomography and fundus autofluorescence) by quantitative analysis of retina and choroid from human tissue specimens at different stages of ARM.