Does Pharmaceutical Compounding of Vascular Endothelial Growth Factor Inhibitors for Intravitreal Use Alter the Risk of Post-injection Endophthalmitis?

ABSTRACT

Purpose

To investigate the safety of pharmaceutically compounded syringes for intravitreal administration of anti-vascular endothelial growth factor (anti-VEGF) drugs.

Methods

Single center, retrospective chart review. From 2015 to 2019, Oslo University Hospital, Norway gradually implemented pharmaceutical compounding and splitting of bevacizumab, ranibizumab, and aflibercept vials into multiple prefilled syringes for intravitreal use. Medical records of all post-injection endophthalmitis (PIE) cases in this 5-year period were reviewed. The incidences of PIE associated with compounded and clinician-withdrawn syringes were compared.

Results

In 5 years, the total number of anti-VEGF injections was 112,926; 68,150 procedures (60%) utilized compounded syringes, and 44,776 procedures (40%) utilized clinician-withdrawn syringes. A total of 11 PIE cases were identified (incidence 0.10 per 1000; 95% CI 0.05–0.17). Five PIE cases were associated with compounded syringes (incidence 0.07 per 1000; 95% CI 0.03–0.17); 3 of these were culture positive. Six PIE cases were associated with clinician-withdrawn syringes (incidence 0.13 per 1000; 95% CI 0.06–0.29); 2 of these were culture positive. The relative risk of PIE following procedures utilizing compounded versus clinician-withdrawn syringes was 0.55 (95% CI 0.17–1.79; p = 0.32).

Conclusion

Use of compounded anti-VEGF drugs in a large clinical setting was not associated with an altered risk of PIE. The finding adds to the evidence that splitting of vials into prefilled syringes for intravitreal injections is safe, provided that an appropriate pharmaceutical compounding procedure is strictly followed.

KEYWORDS:

• Post-injection endophthalmitis
• pharmaceutical compounding
• anti-VEGF
• intravitreal injections

Acknowledgments

The authors would like to thank Leif Arthur Steffensen for providing the hospital episode data.

Disclosure statement

MSS is an investigator in an Alcon-sponsored clinical trial. ØKJ has received lecture fees from Allergan, Alcon, Bayer, and Novartis and is member of a Bayer, Allergan, and Roche advisory board. MCM has received lecture fees from Bayer and is member of a Bayer, Novartis, and Allergan advisory board.