PROJECT SUMMARY The fundamental physical properties of the outer tunic of the eye 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. These biomechanical tissue characteristics not only influence our clinical interpretation of diagnostic tests, e.g., intraocular pressure measurement, but have been implicated as important factors in the development of glaucoma. In our previous studies, we have developed a new method to perform quantitative measurements of corneal elasticity in vivo in healthy and diseased eyes. Here, we will develop a next-generation method for the assessment of corneal viscoelasticity in 3D with high resolution, no contact, and in real-time that could potentially be used for routine clinical diagnosis and treatment. This method will take advantage of the interference of multiple mechanical waves and ultra-sensitive detection and analysis of the interfering waves in 3D throughout the cornea. Ultra-fast optical coherence tomography imaging and a new method for correcting for the loss in temporal and spatial coherence will enable 3D mechanical imaging within milliseconds, which is not possible with any existing methods. Our previous work has made fundamental advances in understanding corneal biomechanics through a novel approach with potentially impactful applications in other disciplines (e.g., cataract surgery, LASIK, corneal cross-linking (CXL), and tissue transplants with personalized treatments). The proposed studies will accelerate the transition of this technology into clinics, influence our selection and application of corneal surgical treatments, and help us understand the structural consequences of corneal disease and wound healing.