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To evaluate the long-term efficacy of bevacizumab for the treatment of chronic diffuse diabetic macular edema after various previous treatments.A total of 126 patients (mean age: 66 years) with chronic diffuse diabetic macular edema were consecutively incorporated in this prospective, noncomparative case series. Inclusion was performed independently from the size of edema, retinal thickness, visual acuity (VA), age, metabolic control, type of diabetes, or type of previous treatments. The patients underwent a complete eye examination including best-corrected VA with ETDRS charts, slit lamp examination, intraocular pressure measurement, stereoscopic biomicroscopy of the macula, retinal thickness measurement using optical coherence tomography (OCT), fluorescein angiography, and fundus photography. All patients were treated with repeated intravitreal injections of bevacizumab (1.25 mg). Patients were observed in intervals of 4–12 weeks for a period of up to 6–12 months.All patients had received various previous treatments such as laser treatment (62% focal laser treatment, 38% panretinal laser treatment), vitrectomy (11%), or intravitreal injection of triamcinolone (41%). All patients completed 6 months and 59 patients (47%) completed 12 months of follow-up; within this period 48% had received at least three intravitreal injections of bevacizumab. Mean diameter of foveal avascular zone was 858 ± 341 μm. At baseline mean VA was 40.3 ETDRS letters (0.82 logMAR Snellen VA) and mean central retinal thickness on OCT was 463 μm. Throughout follow-up VA changes were not significant with a mean change of −1.6 ETDRS letters after 6 months, but significant with +5.1 ETDRS letters after 12 months. Mean central retinal thickness (OCT) decreased to 374 μm after 6 months (P < 0.001) and to 357 μm after 12 months (P < 0.001). Changes of retinal thickness and visual acuity did not correlate. No other factors investigated, such as age, central retinal thickness, or previous treatments, were predictive for a change of VA. Macular ischemia was not exacerbated as a result of the treatment.Even in cases with chronic diffuse ischemic diabetic macular edema, a long-term decrease of central retinal thickness can be observed following repeated intravitreal injections of bevacizumab. In these patients, mean decrease in retinal thickness is aligned with a gain in mean VA. Treatment with bevacizumab at an earlier stage of diabetic macular edema without ischemia may be associated with an even better functional outcome.