Supplementary Material for: Early vs late switch to an intravitreal Dexamethasone implant after failed Anti-VEGF therapy for diabetic macular edema: A systematic review and meta-analysis

Introduction: Monthly anti-vascular endothelial growth factors (VEGF) 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 (DEXI) 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 vs late switch to DEXI after failed anti-VEGF therapy in DME.
Methods: 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 vs late switch groups.
Results: 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%).
Conclusions: An early switch to DEXI may tend towards 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.