Do Adjunctive Anti-scarring Agents Including Mitomycin-C Improve Glaucoma Tube Shunt Surgery: Systematic Review and Meta-analysis

Adjunctive anti-scarring agents (ASAs), including mitomycin C (MMC), 5-Fluorouracil (5FU), corticosteroids and vascular endothelial growth factor antagonists (anti-VEGF), aim to improve glaucoma tube shunt (GTS) surgery by attenuating peri-endplate fibrosis. While used in trabeculectomy, ASAs are less established in GTS surgery, leading to varied practices. This systematic review and meta-analysis evaluated their efficacy and safety. Prospectively registered in PROSPERO (CRD 4,202,236,526), MEDLINE, EMBASE, and CENTRAL were searched for randomised controlled trials (RCTs) and comparative cohort studies (CCSs) comparing ASA and non-ASA use in GTS surgery. Outcomes included changes in intra-ocular pressure (IOP), anti-glaucoma medications, re-operation, and complication rates between baseline and post-operative months 3, 6, and 12. 28 studies (n = 1621 eyes) were included: 12 RCTs (n = 624 eyes) and 16 CCSs (n = 997 eyes). ASAs included MMC (n = 11/28), corticosteroids (n = 7/28), Anti-VEGF (n = 6/28), and 5FU (n = 2/28). Two studies used dual agents. ASA did not affect post-operative IOP [pooled difference (PD) 1.99 mmHg, 1.06 mmHg, 1.15 mmHg at month 3 (p = 0.059), 6 (p = 0.30), and 12 (p = 0.23), respectively]. ASA and MMC use resulted in fewer anti-glaucoma eyedrops required at month 3, 6, and 12 (PD = 0.56, 0.42, 0.49; p < 0.001, = 0.031, 0.013); (PD = 0.76, 0.73, 0.73; p < 0.001, = 0.001, < 0.013), respectively. Both increased hypotony development risk (OR = 2.06, p = 0.001; OR = 2.27, p = 0.001). All other complication rates were similar (all p > 0.05). The re‑operative rate was lower with MMC (OR = 0.42, p = 0.007). ASAs, particularly MMC, reduced glaucoma medication burden at 12 months, but increased the risk of post-operative hypotony.