Mathematical Modeling of Ocular Mechanics, Circulation and Oxygenation and their Relation to Glaucoma

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Glaucoma is a disease in which the optic nerve is damaged, leading to progressive, irreversible loss of vision. Glaucoma is the second leading cause of blindness worldwide and yet its pathogenesis and treatment are not fully understood. Glaucoma is primarily associated with elevated intraocular pressure and is treated with interventions that lower this pressure. Paradoxically, it has been observed that many people develop glaucoma despite relatively low intraocular pressure and that many people never develop glaucoma despite elevated intraocular pressure. A link between impaired ocular circulation and glaucoma has been identified and helps to explain this paradox. It is unclear, however, if alterations in blood flow are a cause or effect of the retinal cell death associated with glaucoma. Therefore, the objective of this study is to use a mathematical model of ocular blood flow regulation and tissue perfusion and oxygenation to determine whether hemodynamic alterations are primary or secondary to glaucomatous damage. Specifically, the effects of impaired vascular regulation mechanisms and elevated intraocular pressure on blood flow will be compared using model simulations. These effects will be related to model predictions of tissue oxygenation in order to understand whether impaired ocular circulation causes cell death or if cell death is the cause of impaired circulation.The results of this study will aid the interpretation of clinical measurements of eye structure and blood flow and provide insight for new treatment strategies for glaucoma. The non-standard techniques required to obtain model solutions are active areas of research in mathematics, and thus this project will provide significant contributions to both medical and mathematical fields. Moreover, conducting studies in the eye is of particular importance because it is the only environment in the human body where blood flow and systemic vascular features can be observed and measured easily and non-invasively down to a very small level (capillary vessels). These measurements identify risk indicators not only of glaucoma but also of many systemic diseases currently diminishing the quality of human life, including diabetes, hypertension and atherosclerosis. By combining theoretical interpretations and descriptions of underlying principles of human physiology with experimental and clinical measurements, this study has a unique potential to impact the knowledge and treatment of multiple diseases.