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

非洲人后裔和青光眼评估 (ADAGES) IV：进展中筛板的改变

• 批准号: 9903321
• 负责人: Massimo Antonio Fazio
• 金额: $ 63.43万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9903321
• 关键词: Acute; Affect; African; Age; Aging; Anterior; Biological Markers; Biomechanical compliance; Biomechanics; Brain; Characteristics; Chronic; Clinical; Cohort Studies; Connective Tissue; Data; Development; Disease Progression; Enrollment; European; Evaluation; Evaluation Studies; Event; Eye; Functional disorder; Genetic; Glaucoma; Human; Image; Individual; Injury; Knowledge; Lead; Link; Measures; Mechanics; Monitor; Morphology; Neural Retina; Ophthalmology; Optic Disk; Optic Nerve; Optical Coherence Tomography; Participant; Patient Care Management; Patients; Perimetry; Persons; Prevalence; Process; Property; Protocols documentation; Race; Research; Research Personnel; Risk Factors; Science; Sclera; Severities; Stress; Structure; Surface; Testing; Thinness; Time; Tissue Donors; Tissues; Validation; Variant; Vision; Visual Fields; Visual impairment; Weight-Bearing state; aged; base; clinical care; cohort; design; disorder risk; follow-up; in vivo; innovation; insight; mechanical behavior; migration; novel; novel therapeutic intervention; optical imaging; pressure; progression marker; prospective; racial difference; racial disparity; relating to nervous system; resilience; response; retinal axon; retinal damage; retinal nerve fiber layer; spectrograph; targeted treatment; tool; visual information

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.!

项目摘要 总体目标：该提案的重点是青光眼筛板的形态变化 发病和进展，以及这些变化如何影响视觉功能，重点关注种族差异。这 项目利用现有 ADAGES 中对青光眼患者子集的纵向监测 其中 3.7 年（平均）的增强深度成像光学相干断层扫描 (EDIOCT) 和 提供视野标准视野检查 (VF)。 ADAGES 研究的总体目标是确定 哪些眼部、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）。具体目标是： 1) 确定筛板是否发生渐进性变化 在青光眼 ADAGES 患者中纵向观察到的结果将与以下患者更大的 VF 进展相关： 8（至少）年的 EDOCT 和 VF 随访成像，以及这种关联是否因种族而异。 2) 至 确定视神经乳头 (ONH) 的基线形态特征与哪些相关 筛板和 ONH 的进展依赖性重塑。 3）判断是否机械 体内和纵向测量的 ONH 顺应性与椎板重塑相关 筛子和进行性神经组织（结构）和室颤损伤（功能）。设计：参加者148人 AD 和 144 名患有青光眼的 ED 患者接受过 3.7 年（平均）的 ONH EDIOCT 成像和 VF 来自 ADAGES 队列的纵向数据。人口统计变量、眼科检查包括 立体照片、标准视野检查的视觉功能、眼内压和全身压以及其他 风险因素将被纵向记录。筛板的形态和​​顺应性 将通过 EDIOCT 和 VF 成像对 60 名新入组的 ED 和 60 名 AD 青光眼患者进行 ONH 量化 5年或更长时间的随访。影响：青光眼发生并进展为的可能性增加 4 至 5 倍 与 ED 患者相比，AD 患者有严重的视力障碍。我们小组已经确定了几个 筛板和视乳头周围巩膜的形态和机械行为的种族差异 这表明这些差异将显着影响或可能导致承载 在自然衰老和青光眼的发病和进展中都观察到结缔组织重塑。这 这项研究的特定种族和广泛的纵向数据将提供详细的见解 ONH承重组织重塑与结构破坏率之间的病理生理关系 视网膜神经组织损伤以及由此导致的进行性视力障碍。本研究通过 纳入创新的生物力学合规性测试协议，将为开发提供信息 青光眼机械相关的生物标志物对于非眼压降低的发展是必需的 青光眼疗法旨在改变机械应变驱动的 ONH 病理生理学！

项目成果

Association of foveal avascular zone change and glaucoma progression.

中心凹无血管区变化与青光眼进展的关联。

• DOI: 10.1136/bjo-2023-323970
• 发表时间: 2023-12-22
• 期刊: The British journal of ophthalmology
• 作者: Takashi Nishida;S. Moghimi;Evan Walker;Gopikasree Gunasegaran;Jo;Alireza Kamalipour;Golnoush Mahmoudinezhad;L. Zangwill;Robert N. Weinreb
• 通讯作者: Robert N. Weinreb

Imaging the deep optic nerve: developing mechanistic biomarkers for glaucoma.

深部视神经成像：开发青光眼的机械生物标志物。

• 发表时间: 2018-03
• 影响因子: 4
• 作者: Girkin; Christopher A
• 通讯作者: Christopher A