Background:Subthreshold nondamaging retinal laser therapy (NRT) provides a greater safety profile than conventional laser methods, but more data is needed on the efficacy and safety of subthreshold NRT in diabetic macular edema.Purpose:To evaluate the efficacy and safety of NRT for the treatment of clinically significant macular edema (CSME) that is partially responsive or resistant to intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment.Methods:This was a retrospective case series study. Fifty eyes of 38 diabetic patients with CSME previously treated with at least 6-monthly intravitreal bevacizumab injections with/without intravitreal Ozurdex therapy were evaluated. The patients received 577-nm yellow wavelength laser therapy with PASCAL laser system (Topcon Medical Laser Systems, Santa Clara, CA, USA). Best-corrected visual acuity (BCVA) and central subfield thickness (CST) were evaluated before and 1, 3, 6, 12 and 24 months after laser treatment.Results:Baseline mean CST was 368.06 ± 86.9 µm. The mean CST values at the 1-, 3-, 6-, 12-, and 24-month visits were 336.93 ± 79.8, 352.40 ± 113.5, 336.36 ± 109.3, 325.10 ± 104 µm, and 310.08 ± 84.7 µm, respectively. The mean CST decreased significantly at the first (p = 0.002) and second year visits (p < 0.001) when compared with pretreatment values. Although visual acuity was improved at the first year compared with baseline, this difference was not statistically significant (p = 0.03). There was no significant difference in visual acuities between pretreatment and posttreatment visits. During 24-month follow-up, while 37 eyes were treated with [mean: 5.7 ± 3.4 (1–14)] intravitreal anti-VEGF injections, 3 eyes were administered single-dose intravitreal steroids. Additional intravitreal injections were not required in 10 (20%) eyes.Conclusion:NRT is effective by itself or in combination with anti-VEGF agents in diabetic macular edema that is partially responsive or resistant to previous intravitreal injections. T role in treating this disorder should be assessed in more detail with prospective controlled studies.