Anti-VEGF combined with ocular corticosteroids therapy versus anti-VEGF monotherapy for diabetic macular edema focusing on drugs injection times and confounding factors of pseudophakic eyes: A systematic review and meta-analysis

Purpose: To assess the effectiveness and safety of combining intravitreal endothelial growth factor inhibitor (antiVEGF) and ocular corticosteroids for diabetic macular edema (DME). Methods: Articles concentrating on the efficacy and safety of combining anti-VEGF and ocular corticosteroids therapy for DME versus anti-VEGF monotherapy was screened systematically. Meta-analysis was conducted on the basis of a protocol registered in the PROSPERO (CRD42023408338) and performed on the extracted continuous variables and dichotomous variables. The outcome was expressed as weighted mean difference (MD) and risk ratio (RR). Results: Add up to 21 studies including 1468 eyes were enrolled in this study. The MD for best-corrected visual acuity (BCVA) improvement at 1/3/6/12-month between the combination therapy group and monotherapy group were 2.56 (95% CI [0.43, 4.70]), 2.46 (95% CI [-0.40, 5.32]), - 1.76 (95% CI [-3.18, -0.34]), - 1.94 (95% CI [-3.87, 0.00]), respectively. The MD for central retinal thickness (CMT) reduction at 1/3/6/12-month between two groups were - 66.27 (95% CI [-101.08, -31.47]), - 33.62 (95% CI [-57.55, -9.70]), - 4.54 (95% CI [-16.84, 7.76]), - 26.67 (95% CI [-41.52, - 11.82]), respectively. Additionally, the combination group had higher relative risk of high intraocular pressure and cataract progression events. Conclusions: Anti-VEGF combined with ocular corticosteroids had a significant advantage over anti-VEGF monotherapy within 3 months of DME treatment, which reached the maximum with increasing anti-VEGF injection times to 3. However, with the prolongation of the treatment cycle, the effect of combined therapy after 6 months was no better than monotherapy, and the side effects of combined therapy were more severe.