ABSTRACT: Keratoconus and surgical correction of myopia are separate but interrelated issues of major significance for which a clear unmet need is the measurement of local corneal biomechanical properties. Indeed, the lack of effective biomechanical measurements forces clinicians to rely on morphologic surrogates, e.g. curvature and thickness, which are insufficient to identify keratoconus before vision is compromised, screen at-risk surgical candidates, or predict treatment outcomes after laser vision correction (LVC) or corneal cross-linking (CXL). To address this need, in the initial funding period of our research program we developed a highly sensitive clinical instrument based on Motion-Tracking (MT) Brillouin microscopy; measured Brillouin corneal maps in over 200 eyes; provided the first demonstration of superior performance of biomechanical vs morphologic imaging in identifying early-stage and subclinical keratoconus; and, characterized biomechanical alterations after LVC and CXL. Our goal for this proposal is to realize the clinical potential of MT-Brillouin microscopy: on the clinical side, in Aim 1, we are going to address the most relevant clinical task that continues to elude clinicians, i.e. predict keratoconus progression risk; in Aim 2, we are going to improve the predictive power of Finite Element Modeling (FEM) to a point where it becomes a clinically useful tool by combining it with Brillouin mechanical measurement of the cornea; on the technology side, in Aim 3, we will develop and validate rapid/automatic MT-Brillouin microscopy to enable a mechanical imaging session within 2 minutes and thus facilitate integration in the existing clinical workflow. This research is significant because accurate and nonperturbative elasticity-based metrics will drive a paradigm shift in how keratoconus is identified and managed as well as in how LVC and CXL treatments are ultimately individualized using patient-specific localized corneal biomechanical information to improve procedure safety and efficacy.