322-OR: Delaying Progression of Diabetic Retinopathy Worsens the Risk for Age-Related Macular Degeneration
Authors: FICKWEILER WARD , CHOKSHI TANVI , O'DOHERTY EMER , VISHVA TEJA JANGOLLA SURYA , ZIEMNIAK NOLAN A. , WU I-HSIEN , MARTIN JACOBA CRIS , GULKAS SAMET , TALASPAYEVA ASSEL , CAVALLERANO JERRY D. , AIELLO LLOYD P. , SUN JENNIFER K. , KING GEORGE L. 
Published: June 2024

Given the increasing prevalence of diabetes in the elderly, understanding factors that influence age-related macular degeneration (AMD) and diabetic retinopathy (DR) is crucial to target intervention for both. Previously, we found an inverse relationship between DR and AMD in the Joslin 50-Year Medalist Study composed of individuals who have had insulin-dependent diabetes for over 50 years. This study evaluated the relationship between AMD and DR in an age-matched cohort of people with type 1 diabetes from the Beetham Eye Institute (BEI) at Joslin Diabetes Center (N=1413) with the Medalist Study. The presence of AMD and DR severity were assessed from fundus photography. Advanced glycation endproducts (AGEs), specifically carboxymethyl-lysine, carboxyethyl-lysine, and methylglyoxal-derived hydroimidazolone 1, were quantified using high-performance liquid chromatography mass spectrometry and inflammatory cytokines by ELISA. We found an inverse association between DR severity and the presence of AMD in the BEI cohort (P&lt;0.0001), consistent with previous findings in Medalists. The presence of AMD was associated with less frequent diabetic macular edema (7.6% vs 16.7%, P=0.01). In Medalists, there was no correlation of plasma inflammatory cytokines including interleukin-6 with DR, AMD, or their vitreous concentrations, whereas serum AGE levels were positively associated with DR severity, but inversely with AMD (P&lt;0.05). Higher triglyceride/high-density lipoprotein ratio and lower systemic insulin sensitivity were associated with DR severity, but inversely with AMD (P&lt;0.05). These findings suggest that metabolic control of hyperglycemia and lipidemia can delay DR, but may worsen the progression of AMD. The inverse risk of AMD and DR suggests accelerated aging is not likely a major cause of DR. Studies are needed urgently to evaluate the distinct effects of glucose and lipid metabolism on their contribution to inverse risks for DR and AMD.

Disclosure
W. Fickweiler: None. T. Chokshi: None. E. O'Doherty: None. S. Jangolla: None. N.A. Ziemniak: None. I. Wu: None. C. Jacoba: None. S. Gulkas: None. A. Talaspayeva: None. J.D. Cavallerano: None. L.P. Aiello: Advisory Panel; Novo Nordisk. Stock/Shareholder; Kalvista. Other Relationship; Optos. Consultant; Ceramedix. J.K. Sun: Research Support; Optovue, Boehringer-Ingelheim, Novo Nordisk, Roche Pharmaceuticals. Other Relationship; Roche Pharmaceuticals. Research Support; Physical Sciences, Inc, Boston Micromachines. G.L. King: None.

Funding
American Diabetes Association (7-21-PDF-022), National Eye Institute (R01EYE26080-01), the National Institute of Diabetes and Digestive and Kidney Diseases and National Institutes of Health (DP3- DK-094333-01); JDRF (17-2013-310); the Dianne Nunnally Hoppes Fund; the Beatson Pledge Fund