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Advisory Committee Chair

J Crawford Downs

Advisory Committee Members

Jeffrey W Kiel

Paul Gamlin

Lindsay A Rhodes

Lawrence C Sincich

Document Type

Dissertation

Date of Award

2020

Degree Name by School

Doctor of Philosophy (PhD) School of Optometry

Abstract

Glaucoma is the second leading cause of blindness and third leading cause of visual impairment worldwide; 180 million people suffer from a glaucomatous visual disability. Glaucoma is an ocular neurodegenerative disease with several risk factors. The major identified risk factors of glaucoma are intraocular pressure (IOP), age, race, central cornea thickness, family history, and low diastolic blood pressure. The lowering of IOP is the only modifiable risk factor for the disease. However, we know little about the true character of IOP. Periodic IOP measurements are obtained every few months or at the discretion of the clinician during office hours and are of limited utility given the known IOP variability during any 24-hour period. IOP has long been thought to play a dominant role in glaucoma, but recent work suggests that cerebrospinal fluid pressure (CSFP) is also involved. IOP and CSFP are the critical component of the translaminar pressure (TLP=IOP-CSFP) surrounding the optic nerve head. We used a wireless telemetry system in nonhuman primates (NHPs) to continuously measure IOP, ocular perfusion pressure (OPP), intracranial pressure (ICP, a surrogate measure of CSFP, TLP and translaminar pressure gradient (TLPG=TLP/lamina cribrosa thickness) to determine which aspects of IOP, OPP or their fluctuations contribute to glaucoma development and progression. Due to the potential for CSFP to also be a factor of glaucoma progression we also characterized ICP dynamics in normal awake and active NHPs and anesthetized NHPs in multiple body positions using continuous telemetry. The data herein show the need for an expanse of our understanding of disease mechanisms underlying glaucoma based on these related fluctuations. Based on the data from healthy eyes, IOP, OPP, TLP and TLPG fluctuations may contribute to glaucoma and characterization of these fluctuations in comparison to mean IOP, OPP, TLP and TLPG alone could lead to a better understanding of disease risk and progression. As well as form the basis for new clinical diagnostics and treatments for glaucoma, as the data show that ICP, TLP and TLPG and their rank order of risk factors will vary among patients and a comprehensive assessment is necessary.

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