Associations and Prognostic Significance of Fluctuations in Diabetic Retinopathy Severity in Eyes Treated for Diabetic Macular Edema

Introduction: The aim of our study was to investigate factors associated with diabetic retinopathy (DR) severity fluctuations in patients undergoing intravitreal injections for diabetic macular edema and to explore risk factors for proliferative DR (PDR). Methods: We graded ultra-widefield fundus photography imaging at each visit using the Early Treatment Diabetic Retinopathy Study severity scale (DRSS). We calculated the deviation from the mode (DM) of DRSS values as a proxy of DR severity fluctuations, and we analyzed its clinical associations with linear models. We computed risk factors for PDR with Cox hazard models. We included the DRSS area-under-the-curve (AUC) of DRSS scores as a covariate in all analyses. Results: We included 111 eyes with median follow-up of 44 months. Higher DRSS-AUC values (=+0.03 DRSS DM for unitary DRSS/month increase, p=0.01) and a higher number of anti-VEGF injections (=+0.07 DRSS DM for injection, p=0.045) were associated with wider DR severity fluctuations. Higher DRSS-AUC values (HR=1.45 for unitary DRSS/month increase, p=0.001) and wider DR severity fluctuations (HR=22.35 4th quartile vs. 1st-3rd quartile of DRSS DM, p=0.01) were risk factors for PDR. Discussion/Conclusion: Patients with larger DR variability in response to intravitreal injections may be at higher risk of DR progression. We advocate attentive follow-up in these patients to recognize PDR early.