Early versus Late Switch to an Intravitreal Dexamethasone Implant after Failed Anti-VEGF Therapy for Diabetic Macular...

Monthly anti-vascular endothelial growth factors (VEGFs) are the primary line of management of diabetic macular edema (DME). However, a large number of patients do not respond to anti-VEGF and require dexamethasone implants (DEXIs) as a second line of therapy. There remains a clinical conundrum on the optimal timing of the switch to DEXI. We systematically reviewed the literature to assess outcomes after an early versus late switch to DEXI after failed anti-VEGF therapy in DME.

Relevant studies were identified by searching PubMed, CENTRAL, Scopus, Web of Science, and Embase till 25th December 2024. We assessed changes in central retinal thickness (CRT), best-corrected visual acuity (BCVA), and risk of ocular hypertension between early versus late switch groups.

Six studies were included. Pooled analysis of all six studies showed that there was a tendency of improved CRT (MD: 19.01; 95% CI: -27.29, 65.31; I2 = 85%) and BCVA (MD: 0.05; 95% CI: -0.04, 0.14; I2 = 72%) with early switch as compared to late switch group but without statistical significance. Removing one outlier study showed statistically significant improvement in CRT (MD: 36.84; 95% CI: 7.54, 66.14; I2 = 48%) and BCVA with early switch (MD: 0.09; 95% CI: 0.08, 0.11; I2 = 0%). Subgroup analysis based on the definition of late switch indicated better outcomes with an early switch when the late switch was defined as after >6 anti-VEGF injections. No difference was noted in the risk of ocular hypertension between the two groups (OR: 0.81; 95% CI: 0.38, 1.73; I2 = 30%).

An early switch to DEXI may tend toward better outcomes as compared to a late switch in treatment-resistant DME patients. High heterogeneity of the meta-analysis and outlier studies are important limitations of present evidence, which can only be resolved with high-quality randomized controlled trials.