This Shared Equipment Evaluation Program (ShEEP) application requests a state-of-the-art Upgrade of an existing Ultrahigh resolution Retinal Optical Coherence Tomography (OCT) instrument to a Multi-Modality instrument that will substantially enhance the technological potential of existing retinal degeneration studies and allow the development of collaborations which were difficult or impossible to achieve with the existing instrument. The existing instrument, while functional, is old technology and is only capable of en face imaging and b-scan cross sectional imaging, the data analysis is tedious and slow, and while initially highly competitive for our research group in 2011, it no longer incentivizes research to answer the type of research questions that are critical in the contemporary preclinical retinal studies. One of the challenges in retinal investigations is to make multiple measures in the same retinal volume elements. This can include, for example, OCT measures of segmented retinal layer thicknesses that assess the vitality of a particular cell type (e.g., photoreceptors) while simultaneously evaluating which area of the imaged retina was transduced by a viral vector, in order to determine whether the therapeutic cargo of the vector succeeded in rescuing retinal degeneration or, alternatively, promoted toxicity. The Upgrade will add six additional modalities to the standard ultrahigh resolution OCT. These include: 1) Fundus photography, 2) Fundus Autofluorescence, 3) Fundus Fluorescence for Arbitrary Fluors, 4) Fluorescein Angiography, 5) Angiographic-OCT, and 6) Adaptive Optics. All of the additional modalities will fully integrate into existing UHR OCT Platform and use some of the preexisting architecture in the Upgrade. Multiple projects will be greatly assisted by the Upgrade. The Sullivan Lab (idea champion) will directly benefit by having a multimodal OCT machine that addresses critical variables in preclinical gene therapy studies (VA and NIH supported), for example, where quantitation of outer retinal therapeutic rescue can be correlated with definitive measured areas of outer retinal cellular viral vector transduction. The Fliesler Lab will directly benefit with a multimodal OCT machine that can assess outer retinal degeneration as well as vascular injury as may occur in Ocular Blast Trauma. The Feng Lab will benefit with access to enhanced instrumentation that can elucidate the impact of mutations in specific genes causally associated with Parkinson’s Disease on the microanatomy and function of the rodent retina and collaboration with the Sullivan Lab to develop and test gene therapeutics for PD in the retina. The Russo Lab is interested in the eye as a site to investigate the establishment of systemic infection the focalizes within the eye that is due to hypervirulent Klebsiella pneumonia and to discern pathogenicity variables and take steps to novel therapeutic strategies. The Troen Lab is interested in aging and metabolism and the diseases of macular degeneration and diabetic retinopathy offer opportunities for collaboration with the Sullivan Lab to investigate mechanisms of disease and the development of novel therapeutics. In Summary, the Upgrade Multimodal Retinal Imaging System will be greatly useful in strengthening the technological approaches to preclinical gene therapy strategies, to strengthen understanding mechanisms of orphan inherited outer retinal degenerations and common AMD and Diabetic Retinopathy. It will also be greatly useful in building upon existing collaborations, and starting new ones that use the retina as a springboard into other Veteran-relevant disease states that are the focus of other outstanding VA Investigators. The Multimodal Retinal Imaging System Upgrade will also serve as a training tool for students and the next generation of investigators.

Potential Impact on Veterans Health. Age-related macular degeneration, retinal degenerations, Parkinson’s Disease, Diabetic Retinopathy, and Endophthalmitis all cause visual disability in adults and the elderly and cause profound changes in the visual health of many US Veterans. For example, four million people in the US have severe visual disability due to AMD, and this burden is expected to triple by 2020. Millions of American Veterans are added to these ranks each year. The Upgraded Multimodal OCT-based Retinal Imaging System requested in this ShEEP application will allow investigators at the VA Western NY to pursue ongoing and novel collaborative studies in the retina, which were heretofore impossible to conduct. The upgrade expands functional technology for imaging the retina to greatly enhance ongoing retinal degeneration studies and preclinical therapeutic studies on a Pre-IND track. The device upgrade also serves to enhance or create new collaborations that use the retina as a model system in Veteran Related disease states.