Robotic and handheld OCT imaging for diagnosis and treatment of diabetic retinopathy - PROJECT SUMMARY This proposal seeks to advance the state of the art in ophthalmic imaging to improve diagnosis and treatment of diabetic retinopathy (DR). DR is a leading cause of blindness in adults, and prevention of irreversible vision loss requires prompt identification and treatment. Prior work has shown that neurodegenerative findings in the retina, such as a decrease in thickness of the outer nuclear layer (ONL), occur alongside and may predate microvascular changes. Measurements of ONL thickness may therefore provide non-invasive metrics to monitor the progression of DR. Injectable agents like anti-VEGF therapy have revolutionized DR treatment, but they often require repeat and invasive procedures for patients. There has been great interest in novel in-office treatments that can be delivered into the suprachoroidal space; however clinicians performing these injections are limited to 2D surface visualization that offers no depth information. Optical coherence tomography (OCT) is a low-coherence interferometry technique that allows for high- resolution, volumetric imaging of the anterior and posterior eye. While OCT is currently the only clinical technology that can visualize individual layers of the retina in vivo, conventional OCT systems are not able to distinguish Henle’s Fiber Layer (HFL) from the ONL. Previous research has shown that HFL and the ONL can be correctly visualized in a single cross-sectional scan by offsetting the pupil entry position of the sample beam. Our research group has pioneered the invention of robotically-aligned OCT (RAOCT) that is capable of imaging freestanding individuals and has precise, automatic control of beam position at the pupil plane. We therefore propose to develop this technology for fully automated volumetric imaging of the complete HFL and the ONL, in order to investigate these measurements as potential clinical biomarkers to monitor DR progression. OCT similarly provides excellent in vivo visualization of distinct features in the anterior segment. We also propose to develop a custom anterior segment handheld OCT probe that can be used for in vivo, real- time visualization and quantification of suprachoroidal injections with novel therapeutics agents for DR. The expected outcome of the proposed research is a series of technologies that will provide automated measurement of a novel retinal biomarker as well as real-time 3D image guidance for a novel, less invasive clinical procedure. Our adapted RAOCT system will be capable of volumetric imaging and measurement of the corrected ONL when accounting for HFL, without the need for operator guidance or input; in addition, our custom handheld anterior segment OCT system will be able to provide real-time, 3D feedback to clinicians for guidance and evaluation of suprachoroidal injections. We believe our proposed developments have the potential to advance the state of the art in image guidance for diagnostics and therapeutics in DR.