Glaucomatous damage to retinal nerve fiber bundles

青光眼对视网膜神经纤维束的损害

• 批准号: 9365407
• 负责人: WILLIAM H. SWANSON
• 金额: $ 39.38万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9365407
• 关键词: 3-Dimensional; Address; Age; Animals; Apoptosis; Area; Axon; Axonal Transport; Biological; Biology; Birefringence; Blindness; Burn injury; Cell Density; Cessation of life; Clinical; Clinical Management; Clinical Trials; Computer software; Cross-Sectional Studies; Custom; Data; Defect; Detection; Devices; Diagnosis; Eye; Eye diseases; Functional disorder; Glaucoma; Human; Image; Indiana; Individual; Lasers; Lateral; Location; Longitudinal Studies; Measurement; Measures; Methods; Mitochondria; Nerve Fibers; Ophthalmoscopy; Optic Disk; Optic Nerve; Optical Coherence Tomography; Optics; Patients; Phase; Photoreceptors; Principal Investigator; Program Effectiveness; Property; Psychophysics; Quantitative Evaluations; Reproducibility; Research; Research Project Grants; Resolution; Retina; Retinal; Sampling; Scanning; Structure; System; Testing; Thick; Three-dimensional analysis; Tissues; Treatment Effectiveness; United States; Universities; Visual; Visual Fields; Visual impairment; Width; adaptive optics; adaptive optics scanning laser ophthalmoscopy; age effect; axonopathy; clinical Diagnosis; clinical imaging; density; ganglion cell; high resolution imaging; imaging modality; imaging system; improved; insight; instrument; optic nerve disorder; physical property; retinal damage; retinal nerve fiber layer; tool

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.

7.项目摘要摘要 被称为青光眼的进行性视神经疾病是不可逆转的主要原因。 全世界范围内的失明，也是美国失明的主要原因之一。三大挑战 当今青光眼的治疗方法是：大约一半的青光眼视野丧失患者没有 被诊断为视神经边缘面积或视网膜神经纤维层(RNFL)厚度测量不能 区分健康和功能障碍的神经节细胞的轴突，以及很难区分 快速发展的青光眼患者与相对稳定的青光眼患者不同。这项研究项目 建议通过确定单个视网膜神经纤维的特性是否 束(RNFBs)可以提供青光眼视野损害的快速客观检测， 确定哪些属性最能区分稳定性和进行性损害，并采用 可以区分健康轴突和功能失调轴突的心理物理工具。拟议的研究 将使用先进的自适应光学(AO)视网膜成像系统对 特征明确的青光眼患者和年龄相似的对照组中个体RNFBs的特性。这有 极大地提高检测RNFBs早期变化的能力，并更好地区分中度 免受高级伤害。具体目标1将评估单个RNFBs的宽度、厚度和反射率，如 青光眼患者和非青光眼患者RNFL受损区域内和附近的束间距 RNFL在年龄相似的对照组中。这将确定哪些RNFB属性最适合检测早期损坏 哪些是区分中度损伤和重度损伤的最佳方法。特定目标2将评估分配 在单个RNFBs内的高反射子结构；这些子结构的密度在 RNFBs受损，可能是临床设备RNFL反射率下降的原因。具体目标3 将开发一种高通量光学相干层析成像(OCT)系统，用于成像RNFBs和他们的 三维子结构。特定目标4将测试关于神经节细胞功能障碍、死亡或 轴突病，将功能缺陷与相应的RNFBs的特性改变联系起来。这些目标将 深入了解临床设备所见的反射缺陷的生物学基础，以及新的使用工具 在临床试验中。