Association of hemoglobin-to-red cell distribution width ratio with diabetic retinopathy risk and severity.

Background: Diabetic retinopathy (DR) is a leading cause of blindness in diabetic patients, driven by inflammation, oxidative stress, and hypoxia. The hemoglobin-to-red cell distribution width ratio (HRR) is a novel inflammatory marker reflecting these pathological mechanisms. This study aimed to investigated the association of HRR with DR risk and severity. Methods: Data from the 2005-2008 National Health and Nutrition Examination Survey were analyzed using weighted logistic regression, subgroup analysis, restricted cubic splines, mediation analysis, and other methods. Results: Among 1,260 diabetic patients, HRR was inversely associated with DR development (OR = 0.85, P = 0.008), remaining significant post-propensity score matching. A non-linear relationship was identified, with an inflection point at HRR = 10.81 (P for non-linearity < 0.001), above which the protective effect strengthened with increasing HRR. Mediation analyses revealed diastolic blood pressure (15.9% mediation) and HbA1c (60.5% competitive mediation) as partial mediators of the HRR-DR association. HRR was also inversely associated with DR severity, particularly proliferative DR (vs. mild non-proliferative DR: OR = 0.67, P = 0.030; vs. severe non-proliferative DR: OR = 0.04, P = 0.002). Conclusions: HRR is negatively correlated with DR onset and progression, highlighting its potential as a cost-effective biomarker for DR risk stratification.