Quantitative Analysis of Aging Retina

描述（由申请人提供）：视网膜近组织学细节的非侵入性成像彻底改变了年龄相关性黄斑病变（ARM）患者的临床管理。成像对于教育患者眼部健康和跟踪疾病进展、监测治疗结果以及指定、设计和验证新仪器至关重要。我们建议进行转化研究，以指导临床使用光谱域光学相干断层扫描（SD-OCT），它提供所有脉络膜层的横切面视图，以及眼底反射和自身荧光（AF）成像，它们都提供视网膜色素上皮（RPE）的正面视图。我们将利用ARM不同阶段的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对黄斑病变管理和研究至关重要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、宽视场的组织学横截面。MACULA项目（Maculopathy revealed by Laminar Analysis）将使用老年正常、早期ARM、地理萎缩和新生血管性ARM来：识别同只眼睛的SD-OCT图像和相应的组织学横截面的特征，特别注意消除来自相邻层的组合信号的歧义，并识别除drusen以外的ARM病理。2. 测量视网膜各层、布鲁氏膜（Bruch’s membrane, BrM）和脉络膜在黄斑和周围视网膜比较区域的厚度。3. 建立ARM病理电子图谱，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身荧光（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整体显微镜、DIC和共聚焦显微镜，以及不同年龄和ARM状态的眼睛：量化指定位置的RPE填充几何形状，生成描述RPE地形的连续数学函数；描述岩石和基底沉积物的破坏。5. 在明确指定的地点量化RPE AF；利用共聚焦显微镜图像的三维重建，识别与肾衰竭和基底沉积相关的RPE破坏相关的AF，提高对黄斑解剖学的了解将有助于评估晚期ARM的风险和评估治疗方法。我们预计这些数据将被临床成像的意见领袖、仪器工程师、眼科教育者和插图画家以及ARM新动物模型的开发人员使用。我们获得的基本数据将对这一代和未来几代的成像有用。

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.