Bleb needling with subconjunctival injection of antimetabolites had become a widely accepted approach for trabeculectomy failure. However, IOP reduction effects, success rates, and complications occurrence for this procedure showed great inconsistency among the different studies.

This is an in vitro study conducted to observe the safety and antiscarring effects of combined application of bevacizumab (BVZ) and 5-fluorouracil (5-Fu) or BVZ and mitomycin C (MMC) during glaucoma filtration surgery (GFS). The cytotoxicity of drug combinations in human Tenon's fibroblasts (HTFs) and human umbilical vein endothelial cells (HUVECs) was evaluated. Their effects on the levels of vascular endothelial growth factor (VEGF) in HUVECs, cell proliferation and migration in HTFs, and the expression of collagen type I alpha 1 (Col1A1) gene in HTFs were evaluated. In addition, the effects of combined drugs on VEGF(R) mRNA in HTFs were detected to explore the possible underlying drug mechanisms. The results showed that BVZ combined with 5-Fu demonstrated more significant antiscarring effects than BVZ or 5-Fu alone. However, the inhibitory effects of BVZ combined with MMC were similar to those of MMC alone. The cytotoxicity of the drug combinations was significantly greater than that of single drug, suggesting that combined application of BVZ and antimetabolites after GFS was safer when applied at different sites (such as subconjunctival injection at bilateral sides of the filtering bleb) or at varied time points.

The present study aimed at observing the effect of a single subconjunctival injection of bevacizumab (BVZ) combined with 5-fluorouracil (5-Fu) or mitomycin C (MMC) on the antiscarring effect of glaucoma filtration surgery (GFS). The inhibitory effect of combined BVZ and 5-Fu in retinal pigment epithelial cells on vascular endothelial growth factor (VEGF) levels was demonstrated through in vitro experiments. Combined BVZ and 5-Fu and combined BVZ and MMC inhibited cell cycle, induced apoptosis, and inhibited human umbilical vein endothelial cell migration. Also, the cytotoxicity of combined BVZ and 5-Fu was lower. In animal experiments, the observation of filtering bleb survival, hematoxylin and eosin and Masson staining of filtering bleb scars, and mRNA expression levels of fibrosis markers in filtering blebs showed that combined BVZ and 5-Fu had a better antiscarring effect compared with single drugs; however, the antiscarring effect of combined BVZ and MMC was not significantly different from MMC. Therefore, the findings of this study provided more reference for the clinical use of adjuncts to inhibit scarring after GFS and helped understand the regulatory effect of combined anti-VEGF antibody BVZ and antimetabolites on wound healing more comprehensively.