PROJECT SUMMARY This is a resubmission application for a Bioengineering Research Partnership (BRP) which brings together a highly collaborative and experienced team of engineers and ophthalmic surgeons to advance the state of the art in image-guided surgical interventions. We seek to overcome limitations to the surgeon’s current stereo microscopic view of ocular structures by continuing to integrate optical coherence tomography (OCT) technology, which is already well accepted in ophthalmic practice, into the operating room. In modern ophthalmic microsurgery, the limited depth perception and capacity for data within oculars, the physically demanding constraints the microscope places on the surgeon, and the inability to distinguish delicate, microscopic tissue structures of subtle contrast limits achievement of surgical endpoints and patient outcomes. Over the past seven years, our team has developed the leading intra-operative OCT program in ophthalmic surgery in the US. Under initial R21 support, our first-generation microscope-integrated OCT (MIOCT) design enabled live cross-sectional imaging during surgery, and is the approach which has been adopted by multiple vendors in current commercial offerings. Our current BRP funded work introduced the first live “4D” (volumetric imaging through time) MIOCT technology which images microsurgery with micrometer-scale resolution at several fully rendered volumes per second, interactively viewable by the surgeon from an arbitrary perspective through a novel stereoscopic heads-up display. We have demonstrated and documented the performance of these systems in over 250 live human eye surgeries at the Duke Eye Center, with innovations and results documented in over 95 publications and presentations resulting from the prior BRP funding period by Partners and other team members. The overall goals of the proposed renewal project are to instigate dramatic technical advances to continue surgeon-driven improvement of live 4D MIOCT surgery, and to enhance the utility of OCT image-guided microsurgery by improving related aspects of the surgical milieu. To do this, we will significantly increase the speed and ease of use of intra-operative MIOCT by developing next-generation OCT engine technology coupled with a novel wide-field automated eye-tracking MIOCT scanner. We will empower surgeons to take full advantage of this new information by developing novel integrated data visualizations including operating room high-definition 3DTV and augmented/virtual reality head-mounted displays. Each of these improvements are motivated by specific current needs in both macular and anterior segment surgery, and will be developed through our well-established translational methodology of incorporating iterative feedback between multidisciplinary team members. We believe this developments will not only improve outcomes in current surgeries, but will also enable novel ophthalmic and other microsurgeries not possible due to current li...