AIM: To evaluate the efficacy, timing of retreatment and safety of dexamethasone (DEX) implant on macular edema (ME) secondary to diabetic retinopathy (DME) and retinal vein occlusion (RVO-ME) patients who were refractory to anti-vascular endothelial growth factor (VEGF) treatment. METHODS: This retrospective study included 37 eyes received at least one DEX implant treatment for DME or RVO-ME between January 1, 2019, and January 1, 2023. These refractory DME and RVO-ME cases received at least 5 anti-VEGF injections and failure to gain more than 5 letters or a significant reduction in central retinal thickness (CRT). The best corrected visual acuity (BCVA) and CRT were measured at baseline, and at 1, 3, 4 and 6mo post-DEX implant injection. Adverse events such as elevated intraocular pressure (IOP) and cataract were recorded. RESULTS: For RVO cases (n=22), there was a significant increase in BCVA from 0.27±0.19 to 0.35±0.20 at 6mo post-DEX injection (P<0.05) and CRT decreased from 472.1±90.6 to 240.5±39.0 µm at 6mo (P<0.0001). DME cases (n=15) experienced an improvement in BCVA from 0.26±0.15 to 0.43±0.20 at 6mo post-DEX implant injection (P=0.0098), with CRT reducing from 445.7±55.7 to 271.7±34.1 µm at 6mo (P<0.0001). Elevated IOP occurred in 45.9% of patients but was well-controlled with topical medications. No cases of cataract or other adverse events were reported. CONCLUSION: DEX implants effectively improve BCVA and reduce CRT in refractory DME and RVO-ME. Further research with larger cohorts and longer follow-up periods is needed to confirm these findings and assess long-term outcomes.