Secondary Logo

Institutional members access full text with Ovid®

Share this article on:


What Is Actually in the Syringe?

Loewenstein, Itamar*; Goldstein, Michaella, MD*,†; Moisseiev, Joseph, MD†,‡; Moisseiev, Elad, MD*,†

doi: 10.1097/IAE.0000000000002170
Original Study: PDF Only

Purpose: To evaluate the accuracy and precision of anti–vascular endothelial growth factor volume delivery by intravitreal injections in the clinical setup.

Methods: Volume output was measured in 669 intravitreal injections administered to patients, calculated from the difference in syringe weight before and after expelling the drug. Three groups were included: prefilled bevacizumab 1.0 mL syringe (Group 1, n = 432), pre-filled ranibizumab in a small-volume syringe with low dead-space plunger design (Group 2, n = 125), and aflibercept drawn and injected using a 1.0-mL syringe (Group 3, n = 112). Accuracy was analyzed by mean absolute percentage error, and precision by coefficient of variation.

Results: Volume outputs in all 3 groups were significantly different from the target of 50 μL (P < 0.0001 for all), and mean absolute percentage error values were 12.25% ± 5.92% in Group 1, 13.60% ± 8.75% in Group 2, and 24.69% ± 14.84% in Group 3. No difference was found between groups 1 and 2, but both were significantly more accurate than Group 3 (P < 0.0001 for both).

Conclusion: The current practices used for intravitreal injections are highly variable, with overdelivery of the anti–vascular endothelial growth factor drugs measured in most cases, but underdelivery in 16.3% of injections. Use of a prefilled syringe was associated with improved accuracy, and low dead-space plunger design may improve precision.

This is the first study to investigate the accuracy and precision of anti–vascular endothelial growth factor agents delivered by intravitreal injection to patients. Results revealed a surprising degree of variability, including a potential for undertreatment. Prefilled syringes were the most accurate, and a low dead-space plunger design was found to improve precision.

*Department of Ophthalmology, Tel Aviv Medical Center, Tel Aviv, Israel;

Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; and

Department of Ophthalmology, Sheba Medical Center, Ramat Gan, Israel.

Reprint requests: Elad Moisseiev, MD, Department of Ophthalmology, Tel Aviv Medical Center, 6 Weizmann street, Tel Aviv, Israel 64239; e-mail:

None of the authors has any financial/conflicting interests to disclose.

M. Goldstein equal contribution as first author.

© 2019 by Ophthalmic Communications Society, Inc.