Transient Vision Loss Associated with Prefilled Aflibercept Syringes: A Case Series and Analysis of Injection Force

Abstract

Objective: To describe cases of significant vision loss following intravitreal aflibercept using pre-filled syringes (PFS) and to study the relationship between syringe design, injection speed, and injection force.

Design: Retrospective case series and experimental study.

Subjects: 12 patients who received intravitreal aflibercept PFS.

Methods: All retina specialists (N=13) at Oregon Health & Science University and the Veterans Affairs Portland Medical Center were queried in December 2020 to report episodes of significant vision loss following aflibercept PFS use. Chart review was completed for all affected patients for demographics and pertinent ocular history. Using a commercially available force measuring system, injection force was measured for aflibercept PFS, ranibizumab PFS, and a tuberculin syringe at various injection speeds.

Main outcome measures: Number of significant vision loss episodes following aflibercept PFS use; average injection force (Newton, N) at various injection speeds across different syringes.

Results: Ten specialists (76.9%) reported a perceived increase in post-injection vision loss with aflibercept PFS. Three specialists had no cases of vision loss. 16 events of light perception or worse vision immediately following aflibercept PFS use were reported. Chart review was available for 12 of these events. The indication for aflibercept was exudative age-related macular degeneration (N=8), diabetic macular edema (N=3), and central serous chorioretinopathy (N=1). The median age of affected patients was 71 years (range 49-94). Two patients were being treated for glaucoma (N=1) or ocular hypertension (N=1); one patient was a glaucoma suspect. Anterior chamber paracentesis was performed in four patients to normalize intraocular pressure (IOP) promptly. Laboratory experiments demonstrated that higher injection speeds were associated with higher injection forces for all syringe types. Injection forces were consistently greater with aflibercept PFS than with the ranibizumab PFS or tuberculin syringes (p < 0.0001).

Conclusions: Retina specialists within our institutions have noted numerous cases of severe transient vision loss with aflibercept PFS use. Some affected patients have reported increased injection-related anxiety. The average injection force may be greater with the aflibercept PFS when compared to other intravitreal anti-VEGF options. Additional clinical studies are needed to better understand how syringe design and fluid dynamics may contribute to post-injection vision loss.

Figure 1

A, Photograph showing the syringe force measuring system with attached telecentric lens system. B, Telecentric photograph showing an aflibercept prefilled syringe and the proper fill level for the plunger tip location.

Figure 2

Photograph showing hydrophilic water gels.

Figure 3

A–C, Graphs showing average injection force generated with (A) aflibercept prefilled syringes, (B) ranibizumab prefilled syringes, and (C) 1-ml tuberculin syringes at varying injection speeds (0.67 mm/second, 1.33 mm/second, 2.66 mm/second, and 3.90 mm/second). The associated error bars represent standard deviation. D–F, Graphs showing the area under the receiver operating characteristic curve measured at each injection speed compared for all syringe types. The horizontal dotted lines represent the 25th to 75th percentiles, whereas the dashed line represents median values. ∗∗P < 0.01 and ∗∗∗∗P < 0.0001 compared with 0.67 mm/second; #P < 0.05, ##P < 0.01, and ###P < 0.001 compared with 1.33 mm/second. N = Newton.

Figure 4

A–D, Graphs showing comparison of average injection force generated with aflibercept prefilled syringes, ranibizumab prefilled syringes, and 1-ml tuberculin syringes at injection speeds of (A) 0.67 mm/second, (B) 1.33 mm/second, (C) 2.66 mm/second, and (D) 3.90 mm/sec. The associated error bars represent 1 standard deviation above and below the mean. E–H, Graphs showing the area under the receiver operating characteristic curve measured at each injection speed compared for all syringe types. The horizontal dotted lines represent the 25th to 75th percentiles, whereas the dashed line represents median values. ∗P < 0.5 and ∗∗∗∗P < 0.0001 compared with aflibercept prefilled syringes. #P < 0.05 compared with ranibizumab prefilled syringes.