Systemic and ocular diseases affecting retinal vascular development, perfusion, and neovascularization are preventable causes of moderate to severe vision impairment in millions of people worldwide. While many adults can cooperate with and hold still for advanced retinal imaging, a significant number of patients including infants, young children, and older patients who, due to sickness, mobility, anesthesia, or a variety of other reasons, are unable to cooperate (I/Y/UC patients) cannot. These patients are often the youngest and/or sickest patients who are at the highest risk of vascular, neurovascular, or ischemic disease that can affect the eye. At present, these patients cannot access advanced imaging technologies that would provide valuable diagnostic information and would contribute to advancing our understanding of their diseases. Optical coherence tomography (OCT) is the gold standard for diagnosis of retinal diseases. OCT angiography (OCTA) is a functional extension of OCT that enables non-invasive, depth resolved imaging of retinal microvasculature without the need for exogenous contrast agents. Because of its dense sampling requirements, OCTA requires long scans and compliant patients who can hold their head and eyes steady. While large tabletop systems can simplify imaging with active tracking, I/Y/UC patients typically cannot position at a chinrest for the duration of the scan. We believe that the development of an ultra-high-speed commercial handheld OCTA device would provide physicians a valuable research and diagnostic tool for imaging of these underserved patients. Under previous NIH funding, Theia Imaging has developed the T1 system, a portable OCT device with a light-weight HH-OCT probe. Here, we propose to develop the T1-A, an ultra-high-speed upgrade to the T1 system that can bring state-of-the-art OCTA imaging to bedside. This will be achieved through the following Specific Aims. Aim 1: Development of an ultra-high-speed handheld OCTA system. We will develop an ultra- high-speed OCT device by upgrading components in the existing T1 OCT. Aim 2: Development of OCTA acquisition and processing software. We will develop OCTA capture and visualization software, including a novel high-speed aiming mode and capable of providing real-time feedback, even at these extremely high scan rates. Aim 3: Validation study. We will demonstrate system feasibility by conducting a validation study evaluating the performance of the T1-A system. The expected outcome of this proposal is the development of an ultra-high-speed, handheld OCTA imaging tool, ready for clinician-scientists and caregivers to use to gather vascular data that would otherwise be inaccessible. This tool will improve the care of these underserved populations. Upon successful completion of this project, we will submit a follow-on Phase II proposal to the system, construct additional prototype devices, and work with collaborators to perform a multi-center clinical study to obtai...