Abstract: Objective To investigate the prognostic value of circulatory metabolic characteristics as predictors of treatment response to ranibizumab in patients with diabetic macular edema(DME). Methods This study was an observational clinical trial involving 46 patients diagnosed with DME involving the central fovea ［baseline central retinal thickness(CRT)≥320 μm］. All participants received intravitreal injections of ranibizumab for 3 months. CRT and best-corrected visual acuity(BCVA)were assessed at baseline and 3 months post-treatment. Baseline blood levels of metabolic markers related to glucose metabolism, cysteine metabolism, and creatine metabolism were measured. Univariate analyses were first performed to screen candidate variables, and then multivariate logistic regression analyses(adjusted for confounding factors such as age and sex)were conducted to investigate the associations between baseline metabolic markers and anatomical(CRT)and functional(BCVA)treatment responses. Results After 3 months of treatment, CRT significantly decreased from(568.20±103.30)μm to(453.6±103.30 )μm(P=0.000 4), and BCVA improved from 0.90±0.56 to 0.69±0.54(P<0.000 1). Analysis of systemic factors and clinical outcomes revealed significant negative correlations between glucose metabolism-related indicators(pyruvate, P=0.020 0; lactate, P=0.010 3; glucose, P=0.005 1; glycated hemoglobin, P=0.005 3)and CRT improvement. Additionally, creatinine levels related to creatine metabolism(P=0.031 8)were significantly negatively correlated with CRT improvement. Further analysis of systemic factors and visual prognosis showed significant negative correlations between lactate(P=0.030 0), glucose(P=0.028 3), glycated hemoglobin(P=0.013 9), and cysteine metabolism-related cystatin(P=0.019 7)with BCVA improvement. Multivariate logistic regression analysis further confirmed that glucose metabolism markers ［glucose odds ratio(OR)=1.66, HbA1c OR=1.71, lactate OR=2.19］ and creatinine(OR=1.02)independently predicted CRT improvement(all P<0.05), cystatin C(OR=8.55)combined with glucose metabolism indicators(glucose OR=1.42, HbA1c OR=1.64, lactate OR=1.91)independently predicted improvements in BCVA(all P<0.05). Conclusion Circulating metabolic characteristics in DME patients, particularly indicators related to glucose metabolism, creatine metabolism, and cysteine metabolism, can effectively predict the response to ranibizumab treatment, providing potential biomarkers for clinical practice.

Key words: Diabetic macular edema, Diabetic retinopathy, Ranibizumab, Metabolic characteristics, Clinical efficacy, Biomarkers