ObjectiveTo evaluate the therapeutic efficacy of vitrectomy with internal limiting membrane (ILM) peeling and subretinal injection of balance salt solution (BSS) for refractory diabetic macular edema (DME).MethodsA retrospective case series study. From November 2017 to August 2018, 24 eyes of 19 patients affected with DME resistant to anti-VEGF therapy [central macualar thickness (CMT) more than 275 μm despite undergoing anti-VEGF therapy at least 3 times] in Ophtalmology Department of Central Theater Command General Hospital of Chinese People's Liberation Army were enrolled in this study. All the patients underwent 25G pars plana vitrectomy with ILM peeling and subretinal injection of BSS. The BCVA was measured using the international standard visual acuity chart, and the results were converted to the logMAR visual acuity. The CMT and the macular volume (MV) were assessed with swept-source optical coherence tomography at baseline and each month postoperatively. The differences in BCVA, CMT and MV before and after surgery were analyzed.ResultsThe mean BCVA was 0.74±0.29 at baseline, which increased significantly to 0.62±0.28, 0.56±0.25, 0.47±0.26, 0.46±0.23 at 2 weeks, 1 month, 3 months and 6 months after treatment respectively (F=4.828, P=0.001). At 6 months, BCVA improved by more than 0.3 logMAR units in 16 eyes (66.7%). The mean CMT was 554.58±102.86 μm at baseline, which reduced to 338.17±58.09 μm, 299.42±52.66 μm, 275.75±41.24 μm and 270.96±38.33 μm at 2 weeks, 1 month, 3 months and 6 months after treatment respectively (F=84.867, P＜0.001). The mean MV was 13.01±0.88 mm3 at baseline, which decreased to 11.50±0.73 mm3, 11.00±0.74 mm3, 10.68±0.61 mm3 and 10.52±0.56 mm3 at 2 weeks, 1 month, 3 months and 6 months after treatment respectively (F=47.364, P＜0.001). Macular edema recurred in 5 eyes (20.8%) 6 months after surgery. No severe systemic or ocular side effect was reported during the follow-up.Conclusions25G vitrectomy with ILM peeling and subretinal injection of BSS for refractory DME can improve the visual acuity, facilitate a rapid resolution of macular edema.