Safety profile of intravitreal Dexamethasone implant to manage diabetic macular edema: A systematic review of real-world studies.

Introduction: With increasing experience using intravitreal dexamethasone implant (DEX-i), it has become a first-line therapy in patients with diabetic macular edema (DME), due mainly to its good efficacy profile. However, this treatment is not devoid of adverse events, which are predominantly transient and should be considered when administering it. Methods: This systematic review without meta-analysis adhered to the guidelines delineated in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Systematic electronic searches were conducted in the PubMed, Medline, Embase, and Google Scholar databases to identify real-world evidence (RWE) studies assessing the safety profile of DEX-i in patients with DME, covering the period from January 1, 2014, to March 1, 2024. Results: This review included Seventy-six RWE that evaluated the safety of DEX-i. Regarding intraocular pressure (IOP)-related adverse events (AEs), these AEs were very heterogeneous and have included different definitions. The incidence of IOP-related AEs varied significantly from study to study, from 2% to almost 60%. In general, the peak IOP increase was typically observed 60 days post-DEX-i injection, followed by a decrease in the subsequent months. In most patients, these IOP-related AEs were successfully and efficiently managed with topical IOP-lowering medication, although some patients required additional treatments (i.e., laser or surgery). Regarding cataract development rates, the results were conflicting, with some studies showing rates ≥40%, %, while others reported rates of 0% or less than 5%. Additionally, current evidence showed the beneficial effects of DEX-i in eyes with DME that underwent cataract surgery. Other serious ocular AEs related to DEX-i were rare, indeed, the reported-incidence-rate of endophthalmitis ranged between 0.07%-0.3%. Conclusions: Overall, the main DEX-i-related AEs were elevation of IOP and cataract. Episodes of ocular hypertension were usually transient and successfully controlled with topical treatment. Additionally, repeated treatment with DEX-i in the same eye was not associated with IOP-related AEs, but it was with cataract-related AEs.