PROJECT SUMMARY Glaucoma is a leading cause of blindness in the US. The management of glaucoma is based on early detection, followed by careful evaluation and monitoring to identify those with rapid disease progression and high risk for vision loss. This allows for the rational use of medical, laser, and surgical treatments. Current methods of assessing glaucoma have significant limitations. Visual field (VF) testing has a low sensitivity for detecting early disease, and its reproducibility worsens in advanced stages, reducing its reliability for monitoring disease progression. Optical coherence tomography (OCT) precisely measure the peripapillary nerve fiber layer (NFL) thickness and is the most commonly used technology for objective glaucoma evaluation. However, NFL thickness has limited sensitivity in detecting early glaucoma, and reaches a floor value in moderate glaucoma, which prevents it from tracking glaucoma progress into later stages. The goal of the proposed research is to develop advanced OCT technology that will enhance detection of early glaucoma, improve the sensitivity of detecting significant disease progression, and increase the accuracy of measuring progression speed. The Specific Aims are: 1. Develop a directional high-resolution OCT and OCT angiography prototype to improve imaging of structure and perfusion. The prototype will have real-time control of beam direction to maintain perpendicular incidence on the NFL for accurate reflectance analysis, which has shown promise for very sensitive detection of early glaucoma. Sensorless adaptive-optics aberration correction will enable high transverse resolution to enhance the detection of nerve fiber bundle and capillary defects. Ultrahigh axial resolution will enable assessment of the pentalaminar structure of the inner plexiform layer. 2. Wide-field OCT and OCT angiography analyses and visual field simulation. Wide peripapillary and macular scans, using a next-generation commercial spectral-domain OCT system, will allow visualization of nerve fiber and perfusion defects from the disc margin to temporal raphe, thus improving early glaucoma detection. VF simulation will be performed to convert OCTA perfusion measurement to a VF-equivlaent dB- scale familiar to clinicians for monitoring progression. The simulation has higher reproducibility than actual VF, which improves detection of disease progression and measurement of progression speed. 3. Clinical studies in glaucoma diagnosis and monitoring. The clinical study will test whether the proposed new technologies can improve the detection of pre-perimetric glaucoma, detection of disease progression, and the accuracy of measuring the speed of progression. This research is likely to transform the clinical practice of glaucoma by developing novel objective functional and structural tests that can be practically implemented on the next generation of clinical OCT systems. This will save vision by achieving accurate diagnosis i...