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

工程摘要 总体目的：本研究的重点是青光眼筛板的形态学变化 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ADAGES中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）的队列， 视野标准视野检查（VF）可用。ADAGES研究的总体目标是确定 什么样的眼部、全身和遗传因素导致青光眼患病率、严重程度 非洲裔（AD）个体的疾病进展率与欧洲人相比， 下降（艾德）。具体目的是：1）确定筛板是否进行性改变 在ADAGES昏迷患者中纵向观察到， EDOCT和VF随访成像8年（至少），以及这种关联是否在种族间存在差异。2)到 确定视神经乳头（ONH）的基线形态学特征与 筛板和ONH的进展依赖性重塑。3)以确定是否机械 在体内和纵向测量的ONH的顺应性与椎板的重塑相关 筛和进行性神经组织（结构）和VF损伤（功能）。设计：参与者148人 AD和144例艾德青光眼患者，接受ONH EDIOCT成像和VF的平均时间为3.7年 ADAGES队列的纵向数据。人口统计学变量、眼科检查，包括 立体照片、标准视野检查的视觉功能、眼内压和体循环压以及其他 风险因素将纵向记录。筛板的形态和顺应性， 将通过EDIOCT和VF成像对60例新入组的艾德和60例AD青光眼患者的ONH进行定量 在5年或更长时间的随访中。影响：青光眼的发生和进展的可能性是正常人的4至5倍。 与ED患者相比，AD患者存在严重的视力障碍。我们的研究小组已经确定了几个 筛板和视乳头周围巩膜的形态和力学行为的种族差异 这表明这些差异将有意义地影响或可能导致承载 结缔组织重塑见于自然衰老和青光眼的发作和进展。的 这项研究的种族特异性和广泛的纵向数据将提供一个详细的见解， ONH承重组织的重塑与结构性坏死率之间的病理生理关系 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 包括一个创新的生物力学符合性测试协议，将告知发展， 非IOP降低发展所必需的青光眼机械相关生物标志物 青光眼治疗旨在改变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.!