Project Summary There are several ophthalmological diseases and ailments that perturb the normal water content or hydration levels of the corneal layer. Among these, Fuchs’ dystrophy, keratoconus, and elevated intraocular pressure (IOP) - a common cause of glaucoma, to name a few examples, can have a drastic impact on the patients’ vision. The work outlined in this proposal will develop terahertz spectroscopy instruments that enable spatially and spectrally resolved measurements across the entire corneal surface to map hydration gradients of the tissue in various disease models. Specifically, our hypothesis is that terahertz time-domain spectroscopy (Thz-TDS) can simultaneously measure axially and spatially varying hydration gradients due to elevated IOP or surgical disruption of the endothelial layer of the cornea using spectral multi-layer reflections from various corneal layers. We will test this hypothesis through the following specific aims: (1) We will determine the accuracy of a THz-TDS corneal scanner in hydration measurement of corneal phantoms and ex vivo models. (2) We will determine the sensitivity and specificity of THz-TDS imaging in mapping corneal hydration gradients using two in vivo experimental models. Results from these studies will determine the potential of THz-TDS technique as a new non-contact corneal imaging modality to accurately measure and map corneal hydration gradients. Moreover, the developed in vivo scanning instrument, and the methodology potentially can be used for diagnosis or as a research tool in studying disease that perturb corneal hydration such as Fuchs’ dystrophy or in evaluation of viability of corneal transplant surgeries.