Anti-VEGF Monotherapy vs Anti-VEGF and Steroid Combination Therapy for Diabetic Macular Edema: A Meta-analysis

<b>Purpose:</b> To compare the safety and efficacy of antivascular endothelial growth factor (anti-VEGF) monotherapy vs anti-VEGF and steroid combination therapy in treatment-naïve and treatment-resistant patients with diabetic macular edema (DME). <b>Methods:</b> A systematic literature search was conducted from January 2005 to December 2022. Sixteen randomized control trials (RCTs) published in English that reported the efficacy or safety of monotherapy and combination therapy in patients with DME were included. <b>Results:</b> The 16 RCTs included 1166 eyes. Monotherapy was associated with a significantly better best-corrected visual acuity (BCVA) at the final follow-up (weighted mean difference [WMD], -0.04 logMAR; 95% CI, -0.07 to -0.02; <i>P</i> = .002; <i>I</i> ² = 0%). No significant differences were observed in the change in BCVA between groups at the final observation. Monotherapy was associated with a significantly smaller change in retinal thickness at the final follow-up (WMD, 37.63 μm; 95% CI, 11.67-63.60; <i>P</i> = .005; <i>I</i> ² = 78%) and with a significantly lower risk for intraocular pressure-related adverse events (AEs) (risk ratio, 0.27; 95% CI, 0.15-0.46; <i>P</i> ≤ .001; <i>I</i> ² = 0%). The risk for cataract-related AEs was not significantly different between groups (<i>P</i> = .06). The results in treatment-naïve patients were similar. In treatment-resistant patients, the change in retinal thickness at the final follow-up was similar between groups (<i>P</i> = .14), but the risk for cataract-related AEs was significantly lower in the monotherapy group in 2 RCTs (risk ratio, 0.09; 95% CI, 0.01-0.66; <i>P</i> = .02; <i>I</i> ² = 0%). <b>Conclusions:</b> The changes in BCVA were similar despite combination therapy being associated with greater changes in retinal thickness. However, increased complications were seen with combination therapy. Most results in treatment-naïve patients and treatment-resistant patients were similar.