The aim of this study is to assess the effect of repeated injections of dexamethasone implants in patients with persistent diabetic macular edema (DME) despite prior therapies. 2 intravitreal injections of dexamethasone. Group 1 (34 eyes) received a dexamethasone monotherapy, whereas group 2 (13 eyes) received a combination therapy with intravitreal antivascular endothelial growth factor as needed. The duration of dexamethasone effect until retreatment and the change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were defined as outcome measures. m before reinjection (groups1 and 2, respectively). The maximal CRT before each implantation remained stable over time. In eyes with chronic DME that respond incompletely to prior therapy or require frequent reinjections, dexamethasone shows promising long-term anatomic and functional improvement. The absence of a treatment effect reduction over time argues against a relevant rebound phenomenon.