Association of Glycemic Control with Inverse Risk of Age-Related Macular Degeneration and Diabetic Retinopathy Severity in Type 1 Diabetes

Introduction and Objective: To determine association of metabolic control with the presence of age-related macular degeneration (AMD) and diabetic retinopathy (DR) severity in patients with type 1 diabetes (T1D). Methods: Retinal images were examined for the presence of AMD (AREDS classification) and DR severity (ETDRS scale) in individuals with T1D from the Beetham Eye Institute (BEI, N=1413) and in an age-comparable group with T1D duration for over 50yrs (Joslin Medalists Study, N=1019) at Joslin Diabetes Center. Proteomic profiling of retinal tissue from a subset of Medalists (N=20) was performed using LS-MS/MS. Results: In both the BEI and Medalist cohorts, the presence of AMD was associated with less severe DR (BEI: no to mild non-proliferative DR (NPDR) 14.5% vs 3.0% for proliferative DR (PDR, P<0.0001); Medalists: (no to mild NPDR 23.4% vs 7.9% PDR, P<0.0001). Neovascular AMD was absent in Medalists. Continuous glucose monitoring (CGM) data from a subset of Medalists (N=75) revealed that increased time below range was positively associated with presence of AMD and inversely related to PDR (P<0.05), whereas poor glycemic control markers, such as advanced glycation products and time above range correlated with presence of PDR (P<0.05). In bivariate analyses, proteomic findings of the retina indicated that pathways enhancing glycolysis and mitochondrial metabolism correlated with less DR severity, but more severe AMD. Conclusion: These findings suggest that improving glycemic control in people with type 1 diabetes may alter the presence of AMD by changing glycolytic pathways and glucose/lipid metabolism in the retina. Further investigations are needed to validate the inverse relationship of AMD and DR severity in diabetes and the contributing role of glycemic control to the progression of AMD in people with diabetes. Disclosure: W. Fickweiler: None. S. Jangolla: None. T. Chokshi: None. E. O'Doherty: None. J. Gauthier: None. E.R. Viebranz: None. I. Wu: None. M. Yu: None. H. Shah: None. C. Jacoba: None. J.D. Cavallerano: None. L.P. Aiello: Consultant; Boehringer-Ingelheim, Ceramedix, Inc. Advisory Panel; Novo Nordisk. Stock/Shareholder; KalVista. J.K. Sun: Research Support; Optovue, Boehringer-Ingelheim. Other Relationship; Boehringer-Ingelheim. Research Support; Novo Nordisk, Roche Pharmaceuticals. Other Relationship; Roche Pharmaceuticals. Research Support; Physical Sciences, Inc, Boston Micromachines, Adaptive Sensory Technologies. G.L. King: None. Funding: NIH T32 DK007260-48, NEI (R01EYE26080-01), NIDDK (P30 DK036836, DP3- DK-094333-01); the Dianne Nunnally Hoppes Fund; the Beatson Pledge Fund