Clinical and Biochemical Factors Are Inversely Associated in Diabetic Retinopathy and Age-Related Macular Degeneration

Abstract

Purpose : To characterize factors that may accelerate diabetic retinopathy severity (DR) but delay the presence of age-related macular degeneration (AMD).

Methods : Fundus photographs were graded in individuals who have had type 1 diabetes for >=50 years (N=1019, Joslin 50-Year Medalist Study) for severity of DR and AMD using ETDRS and AREDS classification, and by chart review of an age-matched cohort with shorter duration type 1 diabetes at the Beetham Eye Institute (BEI) of Joslin Diabetes Center (N=1413). Advanced glycation endproducts (AGEs) including carboxymethyl-lysine, carboxyethyl-lysine, and methylglyoxal-derived hydroimidazolone 1, were determined by high-performance liquid chromatography mass spectrometry, and inflammatory cytokines and retinol binding protein 3 (RBP3) by ELISA assays.

Results : Milder DR was associated with AMD presence in Medalists (P<0.0001). Similarly, AMD was associated with milder DR in the BEI cohort (P<0.0001, AMD: 14.5%, 8.2%, 3.0% for no to mild, moderate to severe, and proliferative DR, respectively). Milder DR at baseline was associated with higher risk of AMD over time in a subset of Medalists (23%) (19.5%, 10.0%, 4.8%, for no to mild, moderate to severe, and proliferative DR, respectively). AMD was associated with less frequent history of diabetic macular edema (7.6% vs 16.7% without AMD, P=0.007). In multivariable models adjusting for factors associated with DR and AMD in unadjusted analyses, AMD remained inversely associated with DR severity (P<0.0001). Plasma inflammatory cytokines including interleukin-6 and tumor necrosis factor-a did not correlate with AMD, DR or their vitreous levels. Higher systemic insulin sensitivity and lower triglyceride/high-density lipoprotein ratio were associated with AMD, but inversely associated with DR (P<0.05). Serum AGE levels were positively associated with DR, but inversely with AMD (P<0.05), whereas vitreous RBP3 inversely correlated with DR but positively with AMD.

Conclusions : These findings confirm an inverse risk of DR and AMD and demonstrate that acceleration of aging is not the major cause of DR severity. Further, metabolic changes such as hyperglycemia and lipidemia associated with DR may impede the onset and progression of AMD. New studies are needed to clarify the differential effects of glucose and lipid metabolism on neuro-retinal cells that are causing the inverse risks of DR and AMD.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.