Evaluating failure, re-intervention, and safety outcomes of bevacizumab as an adjunct to trabeculectomy: A systematic review and meta-analysis

Glaucoma filtration surgery remains a cornerstone of intraocular pressure (IOP) control; however, trabeculectomy function is limited by bleb failure and procedure-related complications. Anti-vascular endothelial growth factor (anti-VEGF) agents have been proposed as adjuncts to mitomycin-C (MMC) to modulate wound healing and improve surgical success. Bevacizumab is increasingly used off-label as an adjunct to glaucoma filtration surgery, yet uncertainty remains regarding its impact on surgical failure, re-intervention, and sight-threatening complications compared with standard antifibrotic regimens. Robust safety data are needed to guide clinical adoption. This systematic review and meta-analysis was prospectively registered on PROSPERO (CRD42025636056). Medline, EMBASE and Web of Science were searched to July 2025 for randomised controlled trials (RCTs) comparing trabeculectomy with and without anti-VEGF agents in adults with non-neovascular glaucoma. Primary outcomes were surgical failure and postoperative complications, including hypotony, choroidal detachment/effusion, bleb leak, encapsulated blebs, bleb needling, reoperation and a composite re-intervention endpoint. Risk of bias was assessed with RoB 2.0, and certainty of evidence was graded using GRADE. Random-effect meta-analyses generated pooled odds ratios (ORs) with 95% confidence intervals (CIs) as the primary analytic approach. Nineteen RCTs (1,049 participants; 1,055 eyes) were included. Compared with trabeculectomy with MMC alone, augmentation with MMC plus bevacizumab was associated with lower odds of surgical failure. Using bevacizumab without MMC was associated with a higher risk of encapsulated bleb compared with MMC-augmented surgery, this was also observed with a 2.5mg dose of bevacizumab. This might indicate the lack of MMC’s protective role rather than a direct harmful effect of the drug bevacizumab. Sub-group analyses also demonstrated higher odds of bleb needling with the subconjunctival route. No significant differences were observed in hypotony, choroidal detachment/effusion, bleb leak, hyphaema, shallow anterior chamber, reoperation, or visual acuity changes at 6 and 12 months. No systemic thromboembolic or cardiovascular events were reported across the included trials. Augmenting trabeculectomy with MMC and bevacizumab may be associated with lower odds of surgical failure; there is no clear evidence that its use increases the risk of any major ocular complications. Bevacizumab without MMC was associated with higher odds of encapsulated blebs than MMC-augmented trabeculectomy. Further adequately powered safety-focused trials with standardised outcome definitions are needed.