High-resolution imaging of the normal and diseased retina

正常和患病视网膜的高分辨率成像

• 批准号: 8161839
• 负责人: Jason Porter
• 金额: $ 36.8万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8161839
• 关键词: Age; Anterior; Area; Autopsy; Axon; Blindness; Blood Vessels; Caliber; Cell Death; Cessation of life; Clinical; Contralateral; Data; Development; Diagnosis; Diagnostic Imaging; Disease; Disease Progression; Early Diagnosis; Electroretinography; Etiology; Experimental Models; Eye; Fundus photography; Future; Glaucoma; Goals; Height; Human; Image; Imaging Techniques; Knowledge; Lasers; Lateral; Lead; Life; Light; Macaca; Macaca mulatta; Measurement; Measures; Mechanics; Methods; Mission; Monkeys; Morphology; National Institute of Biomedical Imaging and Bioengineering; Nerve Degeneration; Nerve Fibers; Neural Canal; Neurons; Ophthalmoscopes; Optic Disk; Optic Nerve; Optical Coherence Tomography; Optics; Pathology; Patients; Pattern; Perimetry; Primary Open Angle Glaucoma; Procedures; Property; Relative (related person); Research; Resolution; Retina; Retinal Diseases; Retinal Ganglion Cells; Risk Factors; Role; Scanning; Severity of illness; Shapes; Site; Staging; Surface; Techniques; Testing; Thick; Time; Tissue Model; Vision; Visual Fields; Work; adaptive optics; age related; base; bioimaging; clinically significant; density; imaging modality; improved; in vivo; innovation; insight; instrument; nonhuman primate; normal aging; novel; optical imaging; pressure; prevent; research study; response; retinal nerve fiber layer; retinal neuron; tool

DESCRIPTION (provided by applicant): Glaucoma is the second leading cause of blindness worldwide and results in the degeneration of retinal ganglion cell axons and retinal ganglion cell (RGC) death. Strong evidence supports the idea that RGC axons are initially damaged due to structural alterations in the lamina cribrosa within the optic nerve head (ONH). However, the vast majority of supporting studies are based on data from excised eyes. A lack of high- resolution in vivo imaging data of the normal and glaucomatous lamina cribrosa has prevented thorough understanding of the impact of changes in laminar geometry on disease progression in the living eye. This proposed work will test the hypothesis that structural alterations in laminar pores underlie subsequent axonal damage and vision loss in the normal aged eye and eyes with glaucoma. The hypothesis will be examined by pursuing three specific aims. The first aim will measure in vivo changes in laminar pore geometry over the time course of experimental glaucoma in macaque monkeys with a confocal adaptive optics scanning laser ophthalmoscope (AOSLO). These data will be combined with changes in visual function (standard automated perimetry and electroretinography) and retinal nerve fiber layer (RNFL) thickness (using optical coherence tomography) at corresponding time-points to test the hypothesis that laminar pore changes precede axonal and vision loss in experimental glaucoma. The second aim will determine age-related differences in laminar pore geometry in normal living human eyes using the AOSLO and test the hypothesis that laminar pore size increases with age and is associated with small increases in cupping (measured via fundus photography) and decreased RNFL thickness and visual function. The last aim applies the same methods to measure laminar pore geometry in patients with primary open-angle glaucoma. It will test the hypothesis that larger pore sizes and increased cupping occur in eyes with increasing disease severity and are correlated with decreases in RNFL thickness and visual function. This research plan is based on defining procedures and relationships with experimental glaucoma and extending them to human patients to test their clinical significance. It is aligned with the missions of the NEI and NIBIB in that it investigates a potential mechanism underlying a blinding retinal disease and seeks to improve the diagnosis and assessment of glaucoma in human patients via a new application of a biomedical imaging technique (i.e., AOSLO imaging). The approach is innovative because it uses confocal AOSLO imaging to increase the lateral resolution and contrast of laminar images relative to current clinical instruments, thereby allowing laminar pore geometry to be reliably measured in living normal and glaucomatous eyes. The proposed research is significant because it will lead to more sensitive in vivo imaging techniques to examine structural changes and better clarify the etiology of glaucoma. Ultimately, such knowledge will enhance our understanding of the lamina's role in the development and progression of this disease and may provide an earlier marker of structural damage (i.e., laminar pore alteration) in glaucoma. PUBLIC HEALTH RELEVANCE: This project will use a state-of-the-art high-resolution imaging method to explore the impact of changes in the lamina cribrosa on neuronal damage and vision loss in living eyes with glaucoma. The results of this study will provide a better understanding of the structural properties of the lamina cribrosa in normal and diseased eyes and of the mechanisms responsible for the death of retinal neurons in the glaucomatous and normal, aging retina. They may also result in more sensitive imaging diagnostics that could prevent vision loss via earlier detection of structural damage and better evaluate and track the efficacy of disease treatments.

描述（由申请人提供）：青光眼是全世界第二大失明原因，导致视网膜神经节细胞轴突退化和视网膜神经节细胞（RGC）死亡。强有力的证据支持这样的观点：RGC 轴突最初是由于视神经乳头 (ONH) 内筛板的结构改变而受损。然而，绝大多数支持性研究都是基于摘除眼睛的数据。由于缺乏正常和青光眼筛板的高分辨率体内成像数据，无法彻底了解层状几何形状的变化对活体眼睛疾病进展的影响。这项拟议的工作将检验以下假设：层状孔隙的结构改变是正常老年眼睛和患有青光眼的眼睛随后轴突损伤和视力丧失的基础。该假设将通过追求三个具体目标来检验。第一个目标是使用共焦自适应光学扫描激光检眼镜 (AOSLO) 测量猕猴实验性青光眼随时间推移的体内层状孔隙几何形状的变化。这些数据将与相应时间点的视觉功能（标准自动视野检查和视网膜电图）和视网膜神经纤维层（RNFL）厚度（使用光学相干断层扫描）的变化相结合，以检验层状孔变化先于轴突和视力丧失的假设在实验性青光眼中。第二个目标将使用 AOSLO 确定正常人眼中层状毛孔几何形状与年龄相关的差异，并检验层状毛孔尺寸随年龄增长而增大且与杯状小幅增加（通过眼底摄影测量）和 RNFL 厚度减少相关的假设和视觉功能。最后一个目标应用相同的方法来测量原发性开角型青光眼患者的层状孔隙几何形状。它将检验这样一个假设：随着疾病严重程度的增加，眼睛中孔径会变大，杯状现象也会增加，并且与 RNFL 厚度和视觉功能的下降相关。该研究计划的基础是定义实验性青光眼的程序和关系，并将其扩展到人类患者以测试其临床意义。它与 NEI 和 NIBIB 的使命相一致，即研究致盲性视网膜疾病的潜在机制，并寻求通过生物医学成像技术（即 AOSLO 成像）的新应用来改善人类患者青光眼的诊断和评估）。该方法具有创新性，因为它使用共焦 AOSLO 成像来提高层状图像相对于当前临床仪器的横向分辨率和对比度，从而能够在活体正常眼和青光眼眼中可靠地测量层状孔隙几何形状。这项研究意义重大，因为它将带来更灵敏的体内成像技术来检查结构变化并更好地阐明青光眼的病因。最终，这些知识将增强我们对椎板在这种疾病的发生和进展中的作用的理解，并可能提供青光眼结构损伤（即层孔改变）的早期标志。 公共健康相关性：该项目将使用最先进的高分辨率成像方法来探索筛板变化对患有青光眼的活眼神经元损伤和视力丧失的影响。这项研究的结果将有助于更好地了解正常和患病眼睛中筛板的结构特性，以及青光眼和正常、老化视网膜中视网膜神经元死亡的机制。它们还可能带来更灵敏的成像诊断，通过更早检测结构损伤来防止视力丧失，并更好地评估和跟踪疾病治疗的功效。