Development of Robust Corneal Biomechanical Biomarkers for Glaucoma Using Brillouin Microscopy

Project Summary: While elevated intraocular pressure (IOP) is the only modifiable risk factor for glaucoma, up to one third of patients have glaucoma at normal IOPs and patients with ocular hypertension may have high IOP for years without any detectable glaucoma damage. This is in part because, in biomechanical terms, the IOP describes the applied force or stress applied to the ocular tissues but not the effect of the applied force, the deformation or strain. Differences in intrinsic biomechanical properties of collagenous ocular tissues may explain the difference in response to the stress of IOP. While prior work has shown some differences in the corneal biomechanical properties between glaucoma subjects and controls, the widespread adoption of corneal biomechanics as glaucoma biomarkers has been hampered by the limitations of current technologies. Specifically, the currently used modalities rely on mechanical perturbations of the cornea which give variable results that are confounded by IOP. The rationale underlying this proposal is that Brillouin microscopy, a highly precise, IOP-independent, and more direct method for determining corneal biomechanics, will improve our understanding of glaucoma biomechanics and that its use will result in robust biomarkers for the disease. In Specific Aim 1, we will compare the Brillouin corneal modulus in a cross-sectional study of primary open angle glaucoma (POAG) patients and age-matched controls. We hypothesize that the Brillouin corneal modulus will be significantly lower in eyes with POAG, indicating a cornea that is less stiff. In Specific Aim 2 we will conduct a longitudinal study to assess the effect of short-term use of topical prostaglandin analogs (PGA) on the corneal modulus in POAG patients and controls. We expect that PGA use will result in a reduced corneal modulus (i.e. a decrease in corneal stiffness), which has important implications in terms of assessing the IOP targets and treatment success after use of PGAs. We plan to use the results of this study as preliminary data for a larger, longer-term, and more comprehensive study to establish corneal biomechanics as robust biomarkers for the disease.