Efficacy and safety of difluprednate for macular edema management: a systematic review and meta-analysis

Background Macular edema is a significant cause of impairment to visual functions due to the disruption of the blood-retinal barrier. Its current management includes intravitreal anti-VEGF agents, corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and laser photocoagulation. However, corticosteroids injected intravitreally increase the risks of elevated IOP and cataract and require invasive administration. Difluprednate is lipophilic and has corneal penetration superior to the traditional ophthalmic corticosteroids. Objective To evaluate the efficacy and safety of difluprednate on the management of macular edema. Methods Relevant research articles were identified in the Cochrane Library Central Register of Controlled Trials, PubMed, Scopus, Web of Science, Embase and Google Scholar. The retrieved publications were screened, and only research articles investigating the efficacy and safety of difluprednate on the management of macular edema were included. The risk of bias was assessed using the JBI for case report, NIH quality assessment tool for observational cohort studies and NIH quality assessment tool for case series. Data were systematically extracted and analyzed. Random-effects meta-analyses were conducted using pooled estimates and 95% CIs, and heterogeneity between studies was assessed using the I 2 statistic. Results Ten studies were included in the review. Difluprednate significantly improved visual outcomes, demonstrating improvements in visual acuity (SMD = 0.198, 95% CI: 0.142–0.254; p < 0.001) and BCVA at 90 days (SMD = −0.506, 95% CI: −0.731 to −0.282; p < 0.001). Anatomical outcomes also improved significantly, with reductions in central macular thickness (SMD = −1.020, 95% CI: −1.479 to −0.560; p < 0.001) and retinal thickness (SMD = −0.915, 95% CI: −1.299 to −0.531; p < 0.001). Complete intraretinal fluid resolution ranged from 44% to 69% by 90 days. The pooled adverse event rate was 26.8% (95% CI: 16.0–41.2), with intraocular pressure elevation (11–21%) and cataract development (4%) representing the most frequently reported steroid-related adverse events. Conclusion Topical difluprednate may reduce macular thickness and improve visual outcomes in selected macular edema phenotypes. In addition, treatment may be associated with steroid-related adverse events, particularly intraocular pressure elevation and cataract development .