Rates of endophthalmitis in prefilled versus nonprefilled syringes for intravitreal injections
March 2026
Intravitreal injections (IVIs) are the most common therapeutic procedure in ophthalmology, with over a million administered annually in the United States. While generally safe, they carry a small risk of endophthalmitis – a serious eye infection that can cause devastating vision loss. In recent years, prefilled syringes (PFSs) have emerged as a potential alternative to the traditional glass vial preparation (GVP) method, offering both convenience and a possible safety advantage. This systematic review and meta-analysis was conducted to formally compare endophthalmitis rates between PFSs – including both manufacturer-prefilled (MPFS) and pharmacy-compounded (PCS) varieties – and GVPs.
The researchers searched PubMed, Embase, and Scopus for relevant studies, ultimately including 11 retrospective cohort studies published between 2018 and 2023. These studies spanned multiple countries including the United States, Japan, France, Norway, India, and Israel, and collectively covered over 7.3 million intravitreal injections. Medications studied included bevacizumab, ranibizumab, and aflibercept. Risk ratio meta-analyses were performed to compare overall endophthalmitis rates as well as culture-positive cases across the different syringe preparation types.
The analysis found a pooled endophthalmitis rate of 1 in 5,461 injections for PFSs compared to 1 in 3,200 for GVPs – a statistically significant difference. Both MPFSs and PCSs were associated with roughly 47–48% lower risk of endophthalmitis compared to GVPs. Additionally, culture-positive endophthalmitis – generally associated with more aggressive infections and worse visual outcomes – was significantly less common with MPFSs than with GVPs. Notably, streptococcal infections, which tend to cause particularly severe vision loss, appeared exclusively in the GVP group, suggesting PFSs may reduce contamination from oral-flora droplets.
The authors conclude that PFSs appear to offer a meaningful safety benefit over GVPs by reducing the number of medication handling steps and maintaining a closed sterile system until the moment of injection. This benefit was consistent across diverse clinical settings and injection protocols. However, the authors caution that all included studies were retrospective, which limits the strength of evidence. They call for prospective studies before formal clinical guidelines can recommend PFSs over GVPs, and they urge regulatory agencies and manufacturers to prioritize PFS development earlier in the drug approval process given the accumulating safety evidence.
