OCTA and Glaucoma Progression in the Non-Human Primate

非人类灵长类动物的 OCTA 和青光眼进展

• 批准号: 10649710
• 负责人: Nimesh Bhikhu Patel
• 金额: $ 55.5万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10649710
• 关键词: 3-Dimensional; Age; Anatomy; Angiography; Animals; Autopsy; Basement membrane; Blindness; Blood Vessels; Blood capillaries; Blood flow; Cannulations; Cell Density; Clinical; Data; Data Set; Disease; Disease Progression; Endothelial Cells; Euthanasia; Experimental Models; Exposure to; Eye; Eye diseases; Face; Glaucoma; Health; Histologic; Human; Image; Immunohistochemistry; Individual; Individual Differences; Left; Measures; Metabolic; Methods; Modeling; Monitor; Nature; Optic Disk; Optical Coherence Tomography; Papillary; Pathologic; Pathology; Patients; Perfusion; Pericytes; Perimetry; Physiologic Intraocular Pressure; Population; Prevalence; Process; Property; Radial; Regulation; Retina; Retinal Ganglion Cells; Risk; Risk Factors; Scanning; Scanning Electron Microscopy; Structure; Technology; Testing; Thick; Thinness; Time; Tissues; Transmission Electron Microscopy; Vascular blood supply; Vision; adaptive optics scanning laser ophthalmoscopy; anterior chamber; comparative; density; disorder risk; experimental analysis; experimental study; high risk; human subject; in vivo; innovation; macula; neural; nonhuman primate; optic nerve disorder; perfusion imaging; pressure; reconstruction; regional difference; response; retinal damage; retinal nerve fiber layer; vascular factor

DESCRIPTION Glaucoma is a group of diseases that results in a pathological loss of retinal ganglion cells (RGC) and irreversible vision loss. Increased intraocular pressure (IOP) is a major risk factor for glaucoma, but some individuals with elevated pressures never develop disease, and others with low pressures progress to blindness. Similarly, in the non-human primate experimental glaucoma model, animals with similar IOP profiles are shown to have significant differences in the extent and rate of retinal nerve fiber layer (RNFL) thickness loss. Both clinical and experimental models suggest that in addition to IOP, other factors need to be considered for glaucoma progression. We hypothesize the variability in disease progression can be explained by vascular factors. The retina is one of the most metabolic tissues in the body, and it is unknown if eyes with relatively lower vascular volume, or eyes that show greater change in perfusion with changes in IOP are at greater risk of pathology. Furthermore, although eyes with optic neuropathy have reduced vascular density, it remains unknown if there are changes in retinal vasculature that precede RGC loss. Optical coherence tomography angiography (OCTA) is a non-invasive method for three-dimensional vascular perfusion imaging. However, analysis of OCTA imaged vasculature is based on slab projections, where the three-dimensional nature of tissue is lost. In addition, OCTA vascular perfusion is often considered a static measure, but vascular flow velocity has temporal properties. For this project, we have optimized OCTA scans to quantify vascular volume and vascular volume density, and using sequential and registered scans, OCTA temporal variability. In the non-human primate experimental glaucoma model, we will determine; 1. if the rate of disease progression is related to baseline global and regional measures of vascular volume / volume density and regional OCTA temporal variability, 2. if there is loss of vascular volume prior to inner retinal thickness, 3. if the rate of structural and functional changes are is related to the extent to which vascular perfusion changes with IOP challenge, and 4. using post-mortem tissue, define vascular anatomy (pericyte coverage, endothelial cell density, capillary basement membrane thickness/integrity) in healthy and disease eyes and association with in vivo OCTA measures. Successful completion of these aims will establish if vascular measures as quantified using OCTA can be used to determine risk of pathology, and rate of glaucoma progression.

描述 青光眼是一组导致视网膜神经节细胞（RGC）病理性丧失且不可逆转的疾病 视力丧失。眼内压 (IOP) 升高是青光眼的主要危险因素，但某些患有青光眼的人 压力高的人永远不会患病，而压力低的人会导致失明。同样，在 非人类灵长类动物实验性青光眼模型，具有相似眼压特征的动物被证明具有 视网膜神经纤维层（RNFL）厚度损失的程度和速率存在显着差异。无论是临床还是 实验模型表明，除了眼压外，青光眼还需要考虑其他因素 进展。我们假设疾病进展的变异性可以通过血管因素来解释。这 视网膜是体内代谢最频繁的组织之一，尚不清楚血管相对较低的眼睛是否会受到影响。 体积或随眼压变化而显示灌注变化较大的眼睛发生病理学的风险更大。 此外，尽管患有视神经病变的眼睛血管密度降低，但仍不清楚是否存在这种情况。 是 RGC 损失之前视网膜脉管系统的变化。光学相干断层扫描血管造影（OCTA） 是一种三维血管灌注成像的非侵入性方法。然而，OCTA 成像分析 脉管系统基于平板投影，组织的三维特性丢失了。此外，奥克塔 血管灌注通常被认为是静态测量，但血管流速具有时间特性。为了 在这个项目中，我们优化了 OCTA 扫描来量化血管体积和血管体积密度，并使用 顺序扫描和配准扫描、OCTA 时间变异性。在非人类灵长类实验性青光眼中 模型，我们将确定； 1. 疾病进展率是否与全球和区域基线指标相关 血管体积/体积密度和局部 OCTA 时间变异性，2. 是否存在血管体积损失 3. 在内层视网膜厚度之前，如果结构和功能变化的速率与视网膜厚度的程度有关 血管灌注随 IOP 挑战而变化，以及 4. 使用死后组织，定义血管解剖结构 （周细胞覆盖度、内皮细胞密度、毛细血管基底膜厚度/完整性） 疾病眼睛及其与体内 OCTA 测量的关联。成功完成这些目标将确定： 使用 OCTA 量化的血管测量可用于确定病理风险和青光眼发生率 进展。