Aim To investigate late changes in peripheral ischemia in patients affected by diabetic macular edema (DME) and treated with repeated dexamethasone (DEX) intravitreal implants over a 1-year period. Methods In this retrospective cohort study, patients older than 18 years of age and with type 2 non-proliferative treatment-naïve diabetic retinopathy (DR) and DME at baseline were included. All patients were treated with two intravitreal DEX implants within 1 year of follow-up. A minimum of two annual ultra-widefield fluorescein angiography (UWF FA) were required to ensure that all cases had a baseline UWF FA (< 2 weeks before first treatment with dexamethasone) and a UWF FA performed at 12 months of follow-up. On baseline and 1-year UWFA images, peripheral retinal ischemia was quantified using the ischemic index (ISI). Results Six eyes of five patients (two males, three females) met the inclusion criteria and were enrolled in this study. Best-corrected visual acuity was 0.34 ± 0.22 LogMAR at baseline and improved to 0.21 ± 0.14 logMAR at the 1-year follow-up visit ( P  = 0.050). Mean ± SD central macular thickness was 467.6 ± 63.0 μm at baseline and 272.0 ± 14.7 μm at the 1-year follow-up visit ( P  = 0.043). Mean ± SD ISI was 26.7 ± 14.1% at baseline and reduced to 12.2 ± 5.0% at the 1-year follow-up visit ( P  = 0.012). Conclusions Improvement in retinal perfusion is still maintained 1 year after starting treatment with DEX implants. This improvement in retinal perfusion might be related to DEX implant-related positive effects on leukostasis.