Project Summary This SBIR Phase IIB project focuses on developing, characterizing, and validating the next-generation clinical visible-light optical coherence tomography (vis-OCT) as a clinical tool to improve the clinical management of glaucoma. The new vis-OCT (Aurora X3) by Opticent, Inc. will offer 1.3-µm axial resolution at an A-line rate of up to 250 kHz. The new Aurora X3 system embodies a newly-designed red laser scanning internal eye fixation and a fully integrated near-infrared scanning laser ophthalmology with a principally new balanced-detection vis- OCT, which approaches shot-noise limited imaging for the first time. The adoption of Aurora X3 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 retracting retinal ganglion cell (RGC) dendrites in the inner plexiform layer (IPL). Identifying 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 clinical standard. Measuring retinal sO2 and specific arteriole-venule couplets can determine the oxygen extraction in the regions served by those vessels, and our preliminary data indicate that regions showing damage in glaucomatous eyes have lower oxygen extraction than similar areas in healthy eyes. This 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. This project will conduct a multi-site clinical test using the latest Aurora X3 clinical vis-OCT at New York University, Stanford University, and University of Virginia to validate the proposed IPL and sO2 biomarkers in glaucoma.