PROJECT SUMMARY Glaucoma is a chronic, progressive, incurable disease that affects over 2 million individuals in the United States alone and over 60 million worldwide. Sensitive detection of early glaucoma damage is not only essential for vision preservation, but also can facilitate new neuroprotective therapy developments. In this proposal, we focus on two novel imaging markers enabled by visible light optical coherence tomography (VIS-OCT), namely the reflectance spectral marker from retinal nerve fiber layer (RNFL) and macular oxygen consumption. We showed in our recent cross-sectional clinical study that peripapillary RNFL reflectance spectral marker and arteriovenous oxygen saturation difference in the macular region better separated early stage of glaucoma suspect/pre- perimetric glaucoma eyes from normal ones than circumpapillary RNFL and macular ganglion cell complex (GCC) thickness. These promising results lead to three specific goals in the project. First, we will develop a second- generation dual channel VIS-OCT device to improve the resolution, total imaging range, and image quality to achieve near shot-noise limit performance. Second, we propose to characterize the macular oxygen consumption by combining blood oxygen saturation and flow and correlated with glaucoma severity. Macular region contains >30% of total RGCs in retina and is involved in early events in glaucoma. The macular visual damage impacts the quality of life the most since it is at the center of our vision. For the first time, we will provide quantitative assessment of macular oxygen consumption in a spectrum of glaucoma severity and shed light in the pathological role of vascular function in the early-stage glaucoma. Finally, we propose a prospective study to correlate VIS-OCT imaging markers, including RNFL reflectance spectral markers and macular oxygen markers, with the glaucoma worsening. We will evaluate whether VIS-OCT markers can detect the early damages proceeding to vision functional loss at a later point. IMPACT ON PUBLIC HEALTH: The successful completion of this program will rigorously evaluate the clinical performances of new VIS-OCT markers for early glaucoma detection, which is highly impactful in clinical care and blindness prevention.