Integration of clinical measures and theoretical modeling to quantify sectorial specific changes in ocular structure, function, and hemodynamics

项目摘要 原发性开角型青光眼是全球第二大致盲原因， 以视网膜神经节细胞进行性死亡和不可逆转的视力丧失为特征。上一首 实验研究已经确定了视网膜结构和视网膜之间的关系。 功能，而其他研究表明血管健康和青光眼之间存在相关性。 然而，关于组织内结合的结构和血液动力学因素的统一理论 导致青光眼视力受损的基因缺失。这一创新技术的开发和使用 结合临床、数学和统计建模的方法将阐明具体的 组织结构、血流量与视野损失的关系。重要的是，青光眼 结构和功能的变化发生在组织的某些部分，我们的研究是 旨在展示内部结构、功能和血液流动的顺序和重要性 视网膜和视神经的特定区域(ONH)。 这项拟议的工作将使用最先进的成像技术来测量结构 元素(例如，包括杯盘比和视网膜神经纤维层在内的ONH参数 厚度)、血流动力学要素(例如，毛细血管流量、静脉饱和度、血管密度)，以及 健康和青光眼患者的功能要素(如视野指数)。建议数 这项工作还将产生一个数学模型，首次预测氧气的运输和 视网膜微血管系统的真实异质描述中的血流调节， 产生了可以用来识别视网膜大部分区域的氧合作用的空间预测 有功能受损的风险。最后，统计和数学的独特结合 将实施建模方法来创建描述以下各项依赖关系的函数 视网膜功能对视网膜特定区域的结构和血流动力学因素的影响 啊哈。这项提议的结果有可能改进诊断和治疗。 战略和改善全球数百万青光眼患者的生活。 这项研究提出的具体和新颖的行业分析是基于大量的 临床和研究数据的收集是使用非常重要和非常强大的 数学工具。由于血液动力学和结构性因素的单独作用不能 在临床环境中单独调整或确定，这是理论和临床相结合的 该方法将在青光眼治疗方面取得突破，同时也将推动 具有数学建模和计算技术的知识。

Project Summary Primary open angle glaucoma is the second-leading cause of blindness worldwide and is characterized by progressive retinal ganglion cell death and irreversible vision loss. Previous experimental studies have established aspects of the relationship between retinal structure and function, while others have demonstrated correlations between vascular health and glaucoma. However, a unified theory of the structural and hemodynamic factors that combine within tissue to cause visual impairment in glaucoma is missing. The development and use of this innovative combined clinical, mathematical, and statistical modeling approach will elucidate the specific relationships of tissue structure, blood flow and visual field loss. Importantly, glaucomatous changes to structure and function occur in certain segments of the tissue, and our study is designed to demonstrate order and importance of structure, function, and blood flow within specific regions of the retina and optic nerve (ONH). The proposed work will use state-of-the-art imaging techniques to measure structural elements (e.g., ONH parameters including cup-to-disc ratio, and retinal nerve fiber layer thickness), hemodynamic elements (e.g., capillary flow, venous saturation, vessel density), and functional elements (e.g., visual field indices) in healthy and glaucomatous patients. The proposed work will also produce a mathematical model that, for the first time, predicts oxygen transport and blood flow regulation in a realistic heterogeneous description of the retinal microvasculature, yielding spatial predictions of oxygenation that can be used to identify regions of the retina most at risk of functional damage. Finally, a unique combination of statistical and mathematical modeling approaches will be implemented to create functions that describe the dependence of retinal function on structural and hemodynamic factors within specific regions of the retina and ONH. The outcomes of this proposal have the potential for improving diagnostic and treatment strategies and improving the lives of millions of glaucomatous patients worldwide. The specific and novel sectorial analysis proposed in this study is based on a vast collection of clinical and research data that is conducted using non-trivial and highly powerful mathematical tools. Since the individual roles of hemodynamic and structural factors cannot be individually modulated or identified in a clinical setting, this integrated theoretical and clinical approach will lead to breakthroughs in glaucoma management while also advancing the knowledge of mathematical modeling and computational techniques.