PROJECT SUMMARY The mechanical properties of the cornea determine the structural characteristics of the ocular globe and may be altered in several devastating disease states, including axial elongation in myopia, pathological deformation in keratoconus, and iatrogenic keratoectasia following corneal refractive surgery. Accurate measurement of corneal biomechanics with high spatial resolution would not only influence our clinical interpretation of diagnostic tests, e.g., measuring intraocular pressure or assessing effects of drug therapies, but also predict the development of posterior eye diseases, such as glaucoma. Currently, there is no available reliable method to perform quantitative measurement of corneal elasticity in vivo and with high resolution. Here we propose a novel method for a “no- touch” assessment of corneal elastic properties. Such a technology, termed heart-beat optical coherence elastography (hbOCE), could revolutionize methods for routine corneal examination, bringing additional mechanical information and warrant rapid clinical adaptation. The project has four primary Specific Aims: Aim 1 is focused on the development of a hbOCE system capable of high-speed volumetric measurement of corneal deformation under small intrinsic IOP changes. Aim 2 will test the developed system in the eyes ex vivo. Aim 3 will test the system in eyes in vivo in rabbits. Aim 4 will perform in vivo human studies to refine measurement methods for broader clinical use. The proposed project will make fundamental advances in the understanding of corneal biomechanics through a novel approach with potentially impactful applications in other disciplines (e.g., corneal surgery, LASIK, corneal cross-linking, corneal transplants, personalized treatments). Most importantly, the proposed studies will accelerate the transition of ocular elastography into clinics, influence our selection and application of corneal surgical treatments, and will help us understand the structural consequences of corneal diseases and wound healing.