Evaluation of photoreceptors health and function in diabetic retinopathy patients using a high-resolution retinal imaging device with controlled light stimulus

Project Summary/AbstractPhysical Sciences Inc (PSI), in collaboration with Joslin Diabetes Center (JDC), proposes to enable objective characterization of the photoreceptor response to light and thus quantification of differences between normal and diseased eyes by adding controlled light stimulus capabilities to an existing high-resolution retinal imaging platform and validating it on a group of volunteers at JDC. We aim to demonstrate the ability to induce and measure vessel diameter changes and to induce and measure reflectivity, transmission, and length changes in cone photoreceptors with the purpose of developing robust biomarkers for diabetic retinopathy (DR). Functional testing of retinal circuitry can provide an unbiased evaluation of one’s vision and enable early detection of retinal diseases and monitoring treatment results.PSI has been developing and offering multiple types of commercial high-resolution retinal imagers for more than fifteen years and is well known as one of the leaders in the field. Based on this experience, we propose to develop and implement light flicker stimulus capabilities in our multichannel adaptive optics retinal imaging (MAORI-X5) platform to objectively test retinal function. MAORI-X5 combines AO-assisted optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO) in one instrument and provides in vivo cellular-level resolution imaging of retinal microstuctures. There is no commercially available SLO or OCT system with light flicker capabilities. We propose to fill in this gap and enhance the capabilities of our retinal imaging platform by implementing two types of light flicker: local, cone-level illumination for testing the health and function of photoreceptors, and large area illumination for testing neurovascular coupling. Both types of measurements will reveal the effects of light stimulation with cellular-level resolution. Adding stimulus capabilities to MAORI-X5 enables investigations of neurovascular coupling and functional assessment of retinal photoreceptors on a commercially available platform. We will validate the ability of the technique to measure cellular level effects in Phase I as a proof-of-principle demonstration on a very limited cohort of ten volunteers in collaboration with our clinical partner, Dr. Jennifer Sun, at JDC. A more extensive study will be proposed to quantify these effects and demonstrate clinical usefulness in a subsequent Phase II.PSI prior experience developing advanced ophthalmic imaging systems gives us a competitive advantage in developing the proposed functionality. A successful completion of the Phase I and a subsequent Phase II development will provide clinicians with a high-performance retinal imaging platform for functional imaging. Early adaptors of this technology within the research community will grow our understanding of vision and its disruption by DR, and will enable the investigation of the effects of new drugs and therapies. PSI, the only company worldwide offering commercially AO-SLO-OCT instruments, proposes to develop the next generation of retinal imaging research instruments as a reliable tool to quantify clinically the effects of DR on vision.