Functional Retinal Imaging to Monitor Pharmaco-Therapies in Diabetic Retinopathy

Diabetic retinopathy is a leading cause of blindness, while diabetic nephropathy is a leading cause of end-stage renal disease. Both of these conditions are manifestations of diabetic microvascular disease and, hence, would greatly benefit from a clinical tool that is able to predict patients at risk for disease progression and can monitor oxygen supply and demand in real time. We will test the hypothesis that imaging of the retinal metabolic rate of oxygen, using an innovative OCT approach, can provide a much-needed, non-invasive biomarker of diabetic microvascular disease. In this proposal, we will establish a normative database of retinal metabolic rate in healthy subjects, before proceeding to examining diabetic patients with various forms of complications of diabetic retinopathy before and after therapy. We hypothesize that our functional imaging tool will be able to explain the response to pharmaco-therapy, as well as correlate with diabetic microvascular disease progression in the eye as well as systemically. We further hypothesize that there is a metabolic signature for high-risk proliferative diabetic retinopathy that can be detected with this approach, and that in these patients functional retinal metabolic imaging will correlate tightly with therapeutic response. The experiments proposed herein will capitalize on the interdisciplinary expertise of the PI’s at Northwestern University. Dr. Fawzi is a clinician-scientist retinal specialist with special expertise in retinal imaging and retinal vascular diseases, and is NIH-funded to study novel retinal imaging modalities. Dr. Zhang is an NIH-funded biomedical engineer, with expertise in functional optical imaging and novel retinal imaging approaches. Dr. Zhang has an established laboratory at Northwestern, with strong collaborative ties to Dr. Fawzi, as they share an NIH-funded research program. The current proposal will allow further studies in diabetic patients, in order to validate the proof-of-principle animal data obtained by the PI’s in their existing collaboration. The research collaboration includes clinical co-investigator in department of Ophthalmology (Dr. Jampol) to ensure successful recruitment of patients undergoing therapy. In addition, our nephrologist Co-I (Dr. Quaggin) is a world-class clinician-scientist and expert on the important glomerular function of VEGF and its signaling partners. In addition to fulfilling an important and clinically relevant need, success of this proposal will provide tools to further investigate the biological principles that underlie correlations between retinal vessel geometry and systemic micro- and macro-vascular diseases as well as explain the functional correlates of regression of diabetic retinopathy in patients receiving antiVEGF therapies. Since our imaging approach will provide quantitative information regarding retinal blood flow, oxygen delivery and extraction, in addition to vessel area, the relationships will be better understood in the contest of their functional impact. We believe that our proposal will provide a paradigm shift in patient management, as well as greatly improve our understanding of the pathophysiology of diabetic retinopathy.