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世界范围内致盲的第二大原因， 其特征在于进行性视网膜神经节细胞死亡和不可逆的视力丧失。先前 实验研究已经建立了视网膜结构和视网膜细胞之间关系的方面， 功能，而其他人已经证明了血管健康和青光眼之间的相关性。 然而，组织内联合收割机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原因开发和使用这种创新的 结合临床，数学和统计建模方法将阐明具体的 组织结构、血流和视野丧失的关系。重要的是，昏迷 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、功能和血流的顺序和重要性 视网膜和视神经（ONH）的特定区域。 拟议的工作将使用最先进的成像技术来测量结构 元件（例如，ONH参数包括杯盘比和视网膜神经纤维层 厚度），血液动力学要素（例如，毛细血管流量、静脉饱和度、血管密度），以及 功能元件（例如，视野指数）。拟议 这项工作还将产生一个数学模型，第一次预测氧气的运输， 血流调节在视网膜微血管系统的现实异质描述中， 产生氧合的空间预测，其可用于识别视网膜的区域， 有功能损伤的危险。最后，一个独特的统计和数学的结合， 建模方法将被实现，以创建描述 视网膜功能对视网膜特定区域内的结构和血液动力学因素的影响， 哦。该提案的结果有可能改善诊断和治疗 战略和改善全世界数百万昏迷患者的生活。 本研究提出的具体和新颖的部门分析是基于一个巨大的 收集临床和研究数据，使用非平凡和非常强大的 数学工具由于血流动力学和结构因素的单独作用不能被 在临床环境中单独调制或识别，这种集成的理论和临床 这种方法将导致青光眼管理的突破，同时也促进了 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.