Intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs is the main treatment for diabetic macular edema (DME), however, 30% of patients still respond poorly to its treatment. At present, imaging markers that can indicate the prognosis of anti-VEGF drug treatment include ischemic index, deep retinal capillary plexus foveal avascular zone area, number of microaneurysms, blood flow density, disorder of the inner retinal layer, outer membrane and/or the degree of damage to the ellipsoid zone, strong reflex foci, intraretinal cysts, subretinal fluid. Biomarkers include high-sensitivity C-reactive protein, neutrophil to lymphocyte ratio, anti-fumarase antibody, intraocular aqueous humor cell adhesion molecule-1, interleukin (IL)-6, IL-8, etc. Understanding these clinical markers that may predict and evaluate the prognosis of anti-VEGF drug therapy can be beneficial to adjust the treatment plan, and more effectively monitor, treat, and manage DME patients.