Prefilled syringes and post-intravitreal injection endophthalmitis: A network meta-analysis

Optimally, syringe-filling technique may reduce the risk of post-injection endophthalmitis (PIE), yet there is wide variation between ophthalmologists and jurisdictions regarding syringe-filling practices. This frequentist network meta-analysis (PROSPERO: CRD42024555196) of rare events sought to compare the odds of PIE between manufactured prefilled syringes (PFS), compounded syringes, and traditional vial preparation of syringes (VPS) for intravitreal anti-vascular endothelial growth factor therapy. Given outcome rarity, we included studies whose primary outcome was PIE incidence. From 20 observational studies (3746 PIE events; 41,611,960 injections), the odds of PIE were significantly lower with PFS (OR: 0.45, 95 % confidence interval [CI]: 0.40-0.49) and compounded syringes (OR: 0.69, 95 % CI: 0.64-0.74) compared to VPS. The odds of PIE were significantly lower with PFS compared to compounded syringes (OR: 0.65, 95 % CI: 0.58-0.72). The odds of culture-positive PIE were significantly lower with PFS than both VPS (OR: 0.15, 95 % CI: 0.06-0.41) and compounded syringes (OR: 0.15, 95 % CI: 0.05-0.44). No significant difference in culture-positive PIE was observed between VPS and compounded syringes (OR: 1.02, 95 % CI: 0.66-1.58). Low certainty evidence supports that PFS significantly reduce the rate of clinical and culture-positive PIE compared to VPS and compounded syringes. Future studies should further characterize the role of confounding.