Silicone oil microdroplets in repackaged bevacizumab syringes: Identification, quantification, and strategies for reducing clincal impact

Abstract

Purpose : Bevacizumab (BEV) is an anti-VEGF agent that is used for off-label treatment of retinal diseases. Most BEV intravitreal injections given in the US are repackaged by a third party compounding pharmacy. The low dead space present in insulin-style syringes minimizes drug overfill and thus reduces cost. Silicone oil (SO) microdroplets have been identified in the vitreous of patients following injection with such syringes. These patients may report persistent floaters that are visually significant and, in severe cases, require vitrectomy. The incidence of symptomatic patients has escalated, prompting statements from professional organizations including AAO, ASRS, and OMIC. The purpose of this study is to develop a method for identification and quantification of SO droplets in repackaged BEV syringes and investigate possible strategies for reducing their clinical impact.

Methods : BEV pre-filled 31g syringes (BD, Franklin Lakes, NJ) were purchased from Avella Pharmacy (Phoenix, AZ). The syringes were taken from a lot number used in patient care. All syringe manipulations were performed by a retina specialist. Four groups were studied: 1) PBS control (n=12), 2) First half injection (0.025 mL, n=12), 3) Second half injection (0.025 mL, n=12), and 4) Complete evacuation (0.05 mL plus air to clear the hub and needle, n=12). The contents of each group were labeled with hydrophobic BODIPY® 493/503 on a hemacytometer and imaged with EVOS FL auto cell imaging system (Invitrogen, Carlsbad, CA). SO droplets of four 1mm² areas were counted in a masked fashion.

Results : SO was adherent to the syringe wall and not suspended in solution (Figure 1A). BODIPY staining allowed differentiation of SO bubbles from air. Stained SO bubbles were of variable size (Figure 1B and 1C). The first half of expelled BEV volume contained 0.1 bubbles/mm², vs 8.6 bubbles/mm² in the second half (p=0.01), and 17.3 bubbles/mm² in the complete evaucation group.

Conclusions : SO is present on the wall of insulin-style syringes pre-filled with BEV. SO bubbles expelled during injection can be labeled and counted. There is significantly more SO expressed during the latter portions of the injection process, presumably due to squeegee effect of the plunger along the walls of the syringe. Small volume overfill with incomplete evacuation may be a mechanism to reduce the clinical impact of this phenomenon.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.