Quantitative Analysis of Aging Retina

描述（由申请人提供）：通过近组织学细节的视网膜非侵入性成像，对年龄相关性黄斑病变（ARM）患者的临床管理发生了革命性变化。成像对于教育患者有关眼睛健康和疾病进展，监测治疗结果以及指定，设计和验证新仪器至关重要。我们提出的翻译研究，旨在通知临床使用的光谱域光学相干断层扫描（SD-OCT），它提供了所有脉络膜视网膜层的横截面视图，眼底反射和自体荧光（AF）成像，这两个提供正面（面对）的意见，视网膜色素上皮（RPE）。我们将在ARM的不同阶段利用人类供体眼睛的独特资源来产生视网膜图像解释的金标准。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，然后是高分辨率、宽视野组织学横截面。MACLIN项目（通过Laminar分析揭示的黄斑病变）将使用老年正常、早期ARM、地图样萎缩和新生血管ARM：1。识别同一只眼睛的SD-OCT图像和相应组织学横截面中的特征，特别注意消除相邻层的组合信号的歧义，并识别除玻璃疣之外的ARM病理学。2.测量每个视网膜层、布鲁赫膜（BrM）和跨黄斑的脉络膜以及周边视网膜的比较区域的厚度。3.建立ARM病理学的电子图谱，通过完整扫描每个组织切片并将其放置在在线数字病理学档案中，为下一代断层成像提供信息。RPE是ARM发病机制的核心，已经在临床上使用反射和自体荧光（AF）信号在正面方向上可视化，后者来自RPE脂褐素。RPE普查项目将使用脉络膜视网膜全标本、DIC和共聚焦显微镜以及不同年龄和ARM状态的眼睛来：4。量化在明确指定位置的RPE填充几何形状，以生成描述RPE形貌的连续数学函数;描述玻璃疣和基底沉积物上的破坏。5.在明确指定的位置量化RPE AF;使用共聚焦显微镜图像的三维重建来识别与玻璃疣和基底沉积物相关的RPE破坏的AF相关性关于黄斑解剖学的改进的知识将有助于为晚期ARM的风险评估和治疗评估提供信息。我们预计，这些数据将被意见领袖在临床成像，仪器工程师，眼科教育工作者和illustratives，以及开发新的动物模型的ARM。我们获得的基本数据将是有用的，这一代和未来的成像。 公共卫生相关性：因为视网膜通过眼睛的光学器件是如此容易地可见，所以临床成像现在是对参与治疗年龄相关性黄斑病（ARM）的临床试验的患者进行分期和监测的重要组成部分，所述年龄相关性黄斑病是老年人中视力丧失的大的且使人衰弱的原因。我们建议，以提高临床解释的两个越来越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）的定量分析视网膜和脉络膜从人类组织标本在不同阶段的ARM。

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.