To our knowledge, this is the first study that aims to integrate both systemic and OCT-based biomarkers in a multivariate analysis that aims to predict early response after anti-VEGF therapy in DME.A multivariate model, including SII, initial CMT, and the presence of IRC, proved to be an excellent predictor for early anatomical response (area under ROC curve of 0.911), indicating the role of chronic low-grade systemic inflammation in the pathology of diabetic microvascular complications, including diabetic retinopathy with DME. The gene discussed is VEGFA; the disease is diabetic retinopathy.