Project Summary This collaborative technology focused project seeks to develop, characterize, and validate visible-light optical coherence tomography (vis-OCT) as a functional tool to transform the clinical management of glaucoma. We will address two unmet needs in clinical glaucoma diagnosis and detection of progression: (1) the ability to measure retinal sublayer structure and (2) to accurately assess local retinal hemoglobin oxygen saturation (sO2). The earliest structural changes in glaucoma are thought to be a retraction of retinal ganglion cell (RGC) dendrites in the inner plexiform layer (IPL). Specifically, this would occur in the outer IPL, where RGC “off” cells synapse. Identification of loss of synapses, either by decreased scattering or by the change in IPL sublayers’ thicknesses, could serve as an earlier and more sensitive biomarker for glaucoma than any other. Measuring retinal sO2 and specific arteriole-venule couplets can determine the oxygen extraction in the regions served by those vessels. Our preliminary data indicate that regions showing damage in glaucomatous eyes have lower oxygen extraction than similar areas in healthy eyes. Our observation suggests that such oxygen extraction abnormalities can be measured well beyond the “floor effect” threshold noted with conventional OCT, allowing assessment of disease beyond the time point that conventional structural OCT becomes insensitive. To achieve our long-term goal, we will focus on new vis-OCT optical system design, imaging protocols, and data processing methodologies to identify both metabolic and ultra-fine anatomical alternations in early glaucoma, both of which are beyond the capabilities of existing imaging technologies.