Glaucomatous damage to retinal nerve fiber bundles

7.项目摘要 被称为“青光眼”的进行性视神经病变组是不可逆性青光眼的主要原因。 这是世界范围内的失明，也是美国失明的主要原因之一。三大挑战 目前治疗青光眼的主要因素是：大约一半的青光眼视野丧失患者没有 被诊断，视神经边缘面积或视网膜神经纤维层（RNFL）厚度的测量不能 区分健康和功能失调的神经节细胞的轴突，并且很难区分 快速进展的青光眼患者与相对稳定的青光眼患者。本研究项目 提出通过确定单个视网膜神经纤维的特性是否 束（RNFB）可以提供对具有昏迷性视野损伤的眼睛的快速客观检测， 确定哪些属性最好地区分稳定与进行性损害，并采用 心理物理学工具，可以区分健康和功能失调的轴突。拟议研究 将使用先进的自适应光学（AO）视网膜成像系统，以执行高分辨率分析的 特征良好的青光眼患者和年龄相似的对照组中个体RNFB的特性。这 有可能显著提高检测RNFB早期变化的能力， 高级损伤。具体目标1将评估单个RNFB的宽度、厚度和反射率， 以及束间距，在青光眼患者受损的RNFL区域内和附近，以及在未受损的RNFL区域， RNFL在年龄相似的控制。这将决定哪些RNFB属性最适合用于检测早期损坏 并且最适合区分中度损伤和晚期损伤。具体目标2将评估分布 在单个RNFB内的高反射子结构;这些子结构的密度降低， 这可能是RNFL受损的原因，并且可能是临床器械所见的RNFL反射率降低的原因。具体目标3 将开发一种高通量光学相干断层扫描（OCT）系统，用于对RNFB及其 三维的子结构。具体目标4将检验关于神经节细胞功能障碍、死亡或 轴突病，相关的功能缺陷，在相应的RNFB属性的改变。这些目标将 深入了解临床器械和新使用工具的生物学反射缺陷 在临床试验阶段

7. Project Summary Abstract The group of progressive optic neuropathies referred to as “glaucoma” is the leading cause of irreversible blindness worldwide and one of the primary causes of blindness in the United States. Three challenges in managing glaucoma today are: that approximately half of people with glaucomatous visual field loss have not been diagnosed, that measures of optic nerve rim area or retinal nerve fiber layer (RNFL) thickness cannot distinguish between axons of healthy and dysfunctional ganglion cells, and that it is difficult to distinguish patients with rapidly progressing glaucoma from those with relatively stable glaucoma. This research project proposes to address these challenges by determining whether properties of individual retinal nerve fiber bundles (RNFBs) can provide rapid objective detection of eyes with glaucomatous visual field damage, determining which properties best discriminate stable versus progressing damage, and employing psychophysical tools that can differentiate between healthy and dysfunctional axons. The proposed research will use advanced adaptive optics (AO) retinal imaging systems to perform high-resolution analysis of the properties of individual RNFBs in well-characterized patients with glaucoma and age-similar controls. This has the potential to dramatically improve ability to detect early changes in RNFBs, and better differentiate moderate from advanced damage. Specific Aim 1 will assess width, thickness and reflectance of individual RNFBs, as well as bundle spacing, in and near regions of damaged RNFL in patients with glaucoma, and in undamaged RNFL in age-similar controls. This will determine which RNFB properties are best for detecting early damage and which are best for differentiating moderate from advanced damage. Specific Aim 2 will assess distributions of highly-reflective substructures within individual RNFBs; the density of these substructures is reduced in damaged RNFBs and may account for decreased RNFL reflectance seen with clinical devices. Specific Aim 3 will develop a high-throughput optical coherence tomography (OCT) system for imaging RNFBs and their substructures in 3 dimensions. Specific Aim 4 will test hypotheses about ganglion cell dysfunction, death or axonopathy, relating functional defects to alterations in properties of corresponding RNFBs. These aims will provide insight into the biology underlying reflectance defects seen with clinical devices, and new tools for use in clinical trials.