Objective: To assess the effectiveness, safety, and treatment burden in eyes with persistent diabetic macular edema (DME) for up to 1 year after administration of 0.19 mg fluocinolone acetonide (FAc) implant (Iluvien®).Methods: This retrospective study at one private practice in the US included 40 eyes from 33 patients treated with an FAc implant. Eyes had previously been treated with VEGF antagonists, dexamethasone, or focal laser. The primary outcome was change in central foveal thickness from baseline. Data were also collected on demographics, visual acuity, intraocular pressure (IOP), use of IOP-lowering drugs for elevated IOP, lens clarity, and treatment burden before and after the implant.Results: Average duration of diabetes and DME at baseline was 19 and 5 years, respectively, and average glycated hemoglobin was 7.21%. Severity of diabetic retinopathy before the implant had a slight bimodal distribution: moderate nonproliferative diabetic retinopathy (35%) and proliferative diabetic retinopathy (40%). Improvements in central foveal thickness from baseline were evident at 3 months (mean change –74.2 µm, P<0.001) and sustained through 12 months (–55.3 µm; P=0.005) for most eyes. Mean visual acuity remained stable (66.2 letters at baseline versus 67.2 letters at 12 months, roughly equivalent to 20/50 vision; P=0.855). On average, eyes required one anti-VEGF injection every 1.9 months before and one every 6.6 months after the implant, while 60% of eyes did not require additional anti-VEGF injections. Small but significant increases in IOP at months 3, 6, and 9 were not sustained to month 12, and mean IOP was normal throughout follow-up.Conclusion: In patients with DME previously treated with a steroid, and treated according to licensed indications in the US, an FAc implant not only reduces the burden of disease in the real-world setting, but also the burden of injections and office visits for patients.