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 complications of diabetic retinopathy before and after pharmaco-therapy. We hypothesize that functional imaging will be able to explain the response to pharmaco-therapy, as well as correlate with diabetic microvascular disease stages. In addition, we will explore the potential renal effects of antiVEGF on this population of patients using rigorous monitoring of renal function. The experiments proposed herein will capitalize on the interdisciplinary expertise of the PI's at Northwestern University. Dr. Fawzi is an NIH-funded clinician-scientist retinal specialist with special expertise in retinal imaging and retinal vasculr diseases. Dr. Zhang is an NIH-funded biomedical engineer, member of the ANSI laser safety committee whose expertise is in functional optical imaging and novel retinal imaging tools. 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 these researchers to validate their proof-of-principle animal data. The research collaboration includes co-I Dr. Jampol, a world-class ophthalmologist clinician-scientist. Nephrologist, Co-I (Dr. Quaggin) is a world-class clinician-scientist and expert on the glomerular function of VEGF and its signaling partners. In addition to fulfilling an important and clinically relevant need, succes of this proposal will provide quantitative tools to study retinal blood flow, oxygen delivery and extraction, in addition to vessel area, allowing researchers to study functional relationships between retinal vessel geometry and systemic micro- and macro-vascular diseases. 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.

Public Health Relevance

This proposal aims to validate a novel non-invasive imaging device capable of monitoring the health of the eye and response to therapy of diabetic complications in the eye. Success of this proposal will lead to non-invasive imaging approaches that can detect the health of the retina as well as identify patients at high risk of diabetic complications in the eye and elsewhere.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Type 1 Diabetes Targeted Research Award (DP3)
Project #
1DP3DK108248-01
Application #
9038125
Study Section
Special Emphasis Panel (ZDK1-GRB-9 (O1))
Program Officer
Jones, Teresa L Z
Project Start
2015-09-30
Project End
2019-08-31
Budget Start
2015-09-30
Budget End
2019-08-31
Support Year
1
Fiscal Year
2015
Total Cost
$1,931,117
Indirect Cost
$681,203
Name
Northwestern University at Chicago
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Nesper, Peter L; Soetikno, Brian T; Treister, Alison D et al. (2018) Volume-Rendered Projection-Resolved OCT Angiography: 3D Lesion Complexity Is Associated With Therapy Response in Wet Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci 59:1944-1952
Onishi, Alex C; Ashraf, Mohammed; Soetikno, Brian T et al. (2018) MULTILEVEL ISCHEMIA IN DISORGANIZATION OF THE RETINAL INNER LAYERS ON PROJECTION-RESOLVED OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY. Retina :
Treister, Alison D; Nesper, Peter L; Fayed, Alaa E et al. (2018) Prevalence of Subclinical CNV and Choriocapillaris Nonperfusion in Fellow Eyes of Unilateral Exudative AMD on OCT Angiography. Transl Vis Sci Technol 7:19
Chu, Sally; Nesper, Peter L; Soetikno, Brian T et al. (2018) Projection-Resolved OCT Angiography of Microvascular Changes in Paracentral Acute Middle Maculopathy and Acute Macular Neuroretinopathy. Invest Ophthalmol Vis Sci 59:2913-2922
Liu, Qi; Chen, Siyu; Soetikno, Brian et al. (2018) Monitoring Acute Stroke in Mouse Model Using Laser Speckle Imaging-Guided Visible-Light Optical Coherence Tomography. IEEE Trans Biomed Eng 65:2136-2142
Nesper, Peter L; Fawzi, Amani A (2018) Human Parafoveal Capillary Vascular Anatomy and Connectivity Revealed by Optical Coherence Tomography Angiography. Invest Ophthalmol Vis Sci 59:3858-3867
Ashraf, Mohammed; Nesper, Peter L; Jampol, Lee M et al. (2018) Statistical Model of Optical Coherence Tomography Angiography Parameters That Correlate With Severity of Diabetic Retinopathy. Invest Ophthalmol Vis Sci 59:4292-4298
Onishi, Alex C; Nesper, Peter L; Roberts, Philipp K et al. (2018) Importance of Considering the Middle Capillary Plexus on OCT Angiography in Diabetic Retinopathy. Invest Ophthalmol Vis Sci 59:2167-2176
Roberts, Philipp K; Nesper, Peter L; Goldstein, Debra A et al. (2018) RETINAL CAPILLARY DENSITY IN PATIENTS WITH BIRDSHOT CHORIORETINOPATHY. Retina 38:387-394
Nesper, Peter L; Lutty, Gerard A; Fawzi, Amani A (2018) RESIDUAL CHOROIDAL VESSELS IN ATROPHY CAN MASQUERADE AS CHOROIDAL NEOVASCULARIZATION ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY: Introducing a Clinical and Software Approach. Retina 38:1289-1300

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