African Descent and Glaucoma Evaluation (ADAGES) IV: Alterations of the lamina cribrosa in progression

项目摘要 总体目标：本研究的重点是青光眼患者筛板的形态变化。 发病和进展，以及这些变化如何影响视觉功能，重点是种族差异。这 该项目利用现有谚语中对青光眼患者子集的纵向监测 其中3.7年(平均)增强深度成像光学相干断层扫描(EDIOCT)和 可使用视野标准视野检查(VF)。谚语研究的总体目标是确定 什么眼睛，全身和遗传因素导致青光眼患病率，严重程度， 与欧洲人相比，非洲人后裔(AD)的疾病进展率 下降(ED)。具体目的是：1)确定筛板的进行性变化 在青光眼谚语中纵向观察，患者将与更大的室颤进展相关 8年(至少)EDOCT和VF随访成像，如果这种关联在不同种族之间不同。2)至 确定视神经头(ONH)的基线形态特征与 筛板和ONH的进行性重塑。3)确定机械设备是否 在体内和纵向测量的ONH的顺应性与椎板的重塑有关 筛骨和进行性神经组织(结构)和室颤损害(功能)。设计：参试者148人 患有青光眼的AD和144名ED患者，平均有3.7年的ONH EDIOCT成像和室颤 来自谚语队列的纵向数据。人口统计变量，眼科检查，包括 立体照片，标准视野的视觉功能，眼内和全身压力，以及其他 风险因素将被纵向记录下来。筛板和筛板的形态和顺应性 将通过EDIOCT和VF成像对60名新入院的ED和60名AD青光眼患者的ONH进行量化 超过5年或更长时间的随访。影响：青光眼发生和进展的可能性是普通人的4到5倍 阿尔茨海默病患者较ED患者视力严重受损。我们的小组已经确定了几个 筛板和乳头状巩膜周围形态和力学行为的种族差异 这表明这些差异将对负重产生有意义的影响或可能是原因 结缔组织重塑在自然衰老和青光眼的发生和发展中均可见。这个 这项研究的种族特定和广泛的纵向数据将提供对 ONH承重组织重塑与结构重构的病理生理关系 视网膜神经组织的损伤和由此导致的进行性视力损害。这项研究，通过 包括一项创新的生物力学顺应性测试协议，将为开发 青光眼发生非低眼压所必需的相关生物标记物 青光眼治疗的目标是改变ONH的机械应变驱动的病理生理学。

Project Abstract Overall Objective: This proposal is focused on morphological changes in the lamina cribrosa with glaucoma onset and progression, and how those changes impact visual function, with a focus on racial disparities. This project leverages on the longitudinal monitoring of a subset of glaucoma patients in the existing ADAGES cohort of which 3.7 years(average) of enhanced depth imaging optical coherence tomography (EDIOCT) and visual field standard perimetry (VF) is available. The overall objective of the ADAGES studies is to identify what ocular, systemic and genetic factors account for the differences in the glaucoma prevalence, severity, and rates of disease progression in individuals of African Descent (AD) compared to those of European Descent (ED). The specific aims are: 1) To determine if the progressive changes in lamina cribrosa observed longitudinally in glaucomatous ADAGES patients will be associated with greater VF progression in a 8(at least) year of EDOCT and VF follow-up imaging, and if this association differs across race. 2) To determine what baseline morphologic characteristics of the optic nerve head (ONH) are associated with progression-dependent remodeling of the lamina cribrosa and ONH. 3) To determine if mechanical compliance of the ONH as measured in-vivo and longitudinally is associated with remodeling of the lamina cribrosa and progressive neural tissue (structure) and VF damage (function). Design: Participants are 148 AD and 144 ED individuals with glaucoma who have 3.7 years(average) of ONH EDIOCT imaging and VF longitudinal data from the ADAGES cohort. Demographic variables, ophthalmological examination including stereo-photographs, visual function with standard perimetry, intraocular and systemic pressures, and other risk factors will be documented longitudinally. The morphology and compliance of the lamina cribrosa and ONH will be quantified on 60 newly enrolled ED and 60 AD glaucoma patients by EDIOCT and VF imaging over a follow-up of 5 or more years. Impact: Glaucoma is 4 to 5 times more likely to occur and progress to severe visual impairment in persons of AD compared to persons of ED. Our group has identified several racial differences in the morphology and mechanical behavior of the lamina cribrosa and peripapillary sclera that suggest these differences will meaningfully impact or possibly be causative of the load bearing connective tissue remodeling seen in both natural aging and in the onset and progression of glaucoma. The race-specific and extensive longitudinal data of this study will provide a detailed insight of the pathophysiologic relationship between remodeling of the ONH load bearing tissues with the rate of structural damage of the retinal neural tissue and the resulting progressive visual impairment. This study, through the inclusion of an innovative biomechanical compliance testing protocol, will inform the development of mechanistically relevant biomarkers for glaucoma necessary for the development of non-IOP lowering glaucoma therapies targeted at altering mechanical strain-driven pathophysiology of the ONH.!