Chronic cystoid macular oedema (CME) can develop secondary to various pathologies such as diabetic maculopathy, retinal vein occlusion and uveitis. It can cause significant visual impairment and macular damage. The therapeutic effect of corticosteroids in CME is through one or more of their properties, i.e. suppression of inflammation, vascular permeability reduction, stabilisation of endothelial tight junctions, and inhibition of synthesis of VEGF and cytokines. The purpose of this study was to examine the effect of dexamethasone drug delivery system (DEX-DDS) in patients with severely recalcitrant CME of average 20 months duration that had a poor or short-term response to other treatment modalities, i.e. intravitreal ranibizumab, intravitreal bevacizumab, intravitreal triamcinolone, periocular triamcinolone injections and / or focal / grid laser. A second goal was to compare treatment results between different CME etiologic groups (branch retinal vein occlusion [BRVO], central retinal vein occlusion [CRVO], uveitis and diabetic macular oedema [DME]). Thirty-seven eyes of 33 patients were included in the study. Eyes were categorised into three groups: diabetic macular oedema (DME, n=14), vein occlusion (n=15) and uveitis (n=7). The mean follow-up was 22±6.9 weeks. Mean age was 61.5±13.1 years (range 26-87). The average duration of CME prior to DEX-DDS injection was 20.3±16 months (range 4-68, median 15.5). Best corrected visual acuity (BCVA) improved from 0.62±0.38 to 0.35±0.29 logMAR (p<0.0001). An improvement in BCVA greater than one ETDRS line was seen in 73% of the eyes (27 of 37). Prior to DEX-DDS injection, 10 of 37 eyes (27%) presented with a BCVA of 20/40 or better. Following DEX-DDS injections, 25 of 37 eyes (68%) achieved a BCVA of 20/40 or better. At the last follow-up visit 11 of 37 eyes (30%) maintained a BCVA of 20/40 or better. A subgroup analysis of the DME, vein occlusion and uveitis groups showed no statistical difference in baseline, best-achieved and last follow-up BCVA between the groups. Central macular thickness (CMT) decreased by 184±246µm from baseline (p<0.0001). In eyes where CME resolved and recurred, the average CME-free period was 11 weeks. The patients had a total of 53 DEX-DDS injections. Thirty-seven eyes received one injection, 12 eyes received two injections, two eyes received three injections and two eyes received four injections. Mean follow-up time after a second DEX-DDS injection was 25.12 weeks. Twenty-three of 37 eyes (62%) demonstrated complete resolution of CME, achieved 6.7±4.4 weeks (median 6.1) after the injection. Nineteen eyes (51%) had CME recurrence 17.3±3.6 (range 12–25) weeks after the injection. Those 19 eyes with CME resolution and a later recurrence had a mean CME-free period of 10.7±5 weeks (range 4–21, median 10.1). The remaining 14 eyes (38%) did not reach a complete resolution of CME, but 13 of those 14 eyes did have a decrease in CME manifested in an average CMT decrease of 181µm or 33% from baseline. The uveitis group showed faster CME resolution (two weeks) and a longer CME-free period (20 weeks). Eighty-six percent of the retreated eyes were in the vein occlusion group, which also showed an overall less favourable response. This study is limited by a small cohort and its retrospective nature.