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Purpose: To evaluate the efficacy of difluprednate 0.05% in reducing postsurgical inflammatory macular edema.

Methods: This retrospective cohort study included 28 patients (33 eyes) who were treated for postsurgical inflammatory cystoid macular edema (CME) between January 2017 and June 2025. The primary endpoint was the change in best-corrected visual acuity (BCVA). Secondary endpoints included changes in central retinal thickness (CRT), intraocular pressure (IOP), treatment duration, dosing frequency, as well as the proportion of eyes with complete CME resolution on optical coherence tomography (OCT).

Results: Eighteen patients (64%) were female and ten (36%) were male. Thirteen patients (46%) presented with recurrent CME. Complete resolution was achieved in 14 eyes, while 19 eyes showed residual fluid at the final follow-up. The mean dosing frequency of difluprednate was twice daily, with a mean treatment duration of 278 days. Intraocular pressure (IOP) increased by less than 5 mmHg in 14 eyes (42%), by 5–10 mmHg in 14 eyes (42%), and by more than 10 mmHg in one eye (3%). IOP-lowering medication was required in one eye (3%), and treatment discontinuation due to IOP elevation occurred in three eyes (9%). Mean best-corrected visual acuity (BCVA) improved from 0.40 ± 0.30 logMAR to 0.20 ± 0.30 logMAR (10 letters) (p = 0.035), and mean CRT decreased from 500 ± 121 µm to 382 ± 75 µm (p < 0.001).

Conclusion: Difluprednate 0.05% was effective and generally well tolerated for treating postsurgical CME. Despite the retrospective design, the findings support its use in routine clinical practice.