This Exploratory/Developmental Research Grant proposal seeks to advance the state of the art of pediatric diagnostic retinal imaging with a novel, auto-aligning hand-held optical coherence tomography (OCT) and OCT angiography (OCTA) probe capable of routine and repeatable high-quality retinal structure and angiographic imaging in infants and children. Current screening methods for pediatric retinal diseases (such as retinopathy of prematurity (ROP)) have been shown to be stressful for these young infants and may have lifelong neurological impact. Thus, there is a vital unmet need to develop low-stress and effective pediatric retinal diagnostics. OCT is a low coherence interferometric technique that has found widespread adoption in ophthalmology and has revolutionized the clinical care of many adult vitreoretinal diseases. Several research and commercial hand-held probes for OCT and OCTA have previously been developed by our group and others. These portable OCT systems have extended our fundamental knowledge of human retinal development and succeeded in visualizing important retinal biomarkers of ROP. However, even with the most skilled operators, to acquire consistent OCT and OCTA data capture for longitudinal follow up in uncooperative patients at the point of care (such as infants and children) remains notoriously difficult. Therefore, both the efficiency and the quality of OCT and OCTA data capture is hampered by the inability to achieve optimal alignment between the imaging device and the pediatric eye. Our research group has pioneered the invention of robotically-aligned OCT (RAOCT) systems capable of active tracking to compensate for subject motion. Our RAOCT systems utilizes the robot for gross alignment to the vicinity of the eye, while an optically based, fast-steering subsystem maintains precise pupil alignment. In this R21 project, we propose to combine our expertise in hand-held OCT/A probe development with the optical fast-steering components of the RAOCT system (relying on the human operator only to maintain gross alignment) to develop a novel hand-held OCT/A probe capable of stable and repeatable pediatric eye imaging. The expected outcomes of this proposal are a set of novel technologies capable of routine and repeatable high-quality retinal structure and angiographic imaging of infants and children. We expect that our proposed hand-held auto-aligning OCT/A system will provide quantifiably reproducible imaging in adult participants, and pilot imaging in pediatric subjects.