Multiscale mathematical modeling of ocular blood flow and oxygenation and their relevance to glaucoma

Abstract

Glaucoma is a multifactorial ocular disease progressively leading to irreversible blindness. There is clear evidence of correlations between alterations in ocular hemodynamics and glaucoma; however, the mechanisms giving rise to these correlations are still elusive. The objective of this thesis is to develop mathematical models and methods to help elucidate these mechanisms. First, we develop a mathematical model that describes the deformation of ocular structures and ocular blood flow using a reduced-order fluid-structure interaction model. This model is used to investigate the relevance of mechanical and vascular factors in glaucoma. As a first step in expanding this model to higher dimensions, we propose a novel energy-based technique for coupling partial and ordinary differential equations in blood flow, using operator splitting. Next, we combine clinical data and model predictions to propose possible explanations for the increase in venous oxygen saturation in advanced glaucoma patients. We develop a computer-aided manipulation process of color Doppler images to extract novel waveform parameters to distinguish between healthy and glaucomatous individuals. The results obtained in this work suggest that: 1) the increase in resistance of the retinal microcirculation contributes to the influence of intraocular pressure on retinal hemodynamics; 2) the influence of cerebrospinal fluid pressure on retinal hemodynamics is mediated by associated changes in blood pressure; 3) the increase in venous oxygen saturation levels observed among advanced glaucoma patients depends on the value of the patients’ intraocular pressure; 4) the normalized distance between the ascending and descending limb of the ophthalmic artery velocity profile is significantly higher in glaucoma patients than in healthy individuals.