Anti-Vascular Endothelial Growth Factor Combined with Ocular Steroid Therapy for Persistent Diabetic Macular Edema: A Systematic Review and Meta-Analysis.

: Our purpose was to appraise the efficacy and safety of intravitreous vascular endothelial growth factor inhibitor (anti-VEGF) therapy combined with steroids for persistent diabetic macular edema. : A systematic review was conducted of the research evaluating the combination therapy of anti-VEGF and steroids for persistent diabetic macular edema compared to anti-VEGF alone. A meta-analysis was performed using a protocol registered in PROSPERO (CRD42023476333). Continuous and binary variables were extracted. Results were expressed as the mean difference (MD) and risk ratio (RR). : A total of 9 trials with 537 eyes were included. The MDs of improvement in best-corrected visual acuity (BCVA) at 1/2/3/6/9/12 months between the combined and monotherapy groups were 1.33 (95% CI [-1.31,3.96]), 3.03 (95% CI [0.01, 6.06]), -0.37 (95% CI [-4.74, 4.00]), -1.37 (95% CI [-4.65, 1.91]), 1.05 (95% CI [-3.68, 5.77]), and 1.70 (95% CI [-3.52, 6.93]). The MDs concerned with a central retinal thickness (CMT) decline in at 1/2/3/6/9/12 months between the two groups were -47.33, 95% CI [-94.35, -0.32]), -89.19 (95% CI [-114.38, -64.00]), -58.84 (95% CI [-96.93, -20.74]), -57.23 (95% CI [-102.62, -11.84]), -40.59 (95% CI [-80.59, -0.58]), and -38.89 (95% CI [-77.38, -0.40]), respectively. Furthermore, the combined group obtained higher relative risks of experiencing events with high intraocular pressure and progressed cataracts. : Anti-VEGF combined with ocular steroids showed a significant advantage in improving the retinal anatomical structure compared to anti-VEGF monotherapy for persistent diabetic macular edema. However, as the treatment period extended, the combination treatment was no more effective than monotherapy after 2 months, with more severe side effects.