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AIM: To investigate the influence of laser photocoagulation and vascular endothelial growth factor(VEGF)antagonists used alone or as combination therapy on clinical efficacy and safety of patients with diabetic macular edema(DME). METHODS: Totally 150 patients(156 eyes)with DME were chosen in the period from October 2014 to October 2016 in our hospital and randomly divided into both group including Group A(50 patients 52 eyes)with laser photocoagulation used alone, Group B(50 patients 51 eyes)with VEGF antagonists used alone and Group C(50 patients 53 eyes)with combination therapy; and the best corrected visual acuity, macular fovea thickness and retinal neovascularization leakage area before and after treatment and the complications incidence of both groups were compared. RESULTS: The best corrected visual acuity of Group B and Group C in 3, 6 and 12mo after treatment were significant better than that of Group A(PPPPP>0.05). CONCLUSION: Laser photocoagulation combined with VEGF antagonists in the treatment of patients with DME can efficiently improve visual acuity, reduce macular foveal thickness, control retinal neovascularization leakage and not increase adverse reactions.