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Jackson Abou Chehade, Ebrahim Elborgy, Saba Alniemi, Benjamin Nicholson, Raymond Iezzi; Experimental model to characterize bubble formation in intravitreal injections.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3329.
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© ARVO (1962-2015); The Authors (2016-present)
In prior work, we observed significant inter-injector variation in anti-VEGF drug dosing using ranibizumab, bevacizumab and aflibercept. Under-dosing was associated with bubble formation in the syringe and was noted to be drug-specific. Bubble formation within the syringe was proportional to the protein concentration of each anti-VEGF drug. Agents with higher protein concentration were associated with greater intra-syringe bubble volumes. The purpose of this experiment was to develop a model of bubble formation using solutions of bovine serum albumin that match the protein content of each anti-VEGF drug previously tested.
Nine agents were examined (DI water, ranibizumab 6 and 10 mg/mL, bevacizumab 25 mg/mL, aflibercept 40 mg/mL and BSA solutions of 6, 10, 25 and 40 mg/mL). Tuberculin syringes were loaded with 0.2ml of test solution using a filter needle. Ten trials per agent were conducted, using a new syringe for each agent. After the filter needle was replaced with a 0.5 inch 32-gauge needle, the plunger was advanced until the first fluid drop appeared. For each test solution, the volume of fluid and bubbles in the syringe was photographically measured using a microscope and digital camera (Olympus SZX16 stereo microscope, Olympus DP25 camera, CellSens software). To measure the volume of agent within each syringe, the syringe/32-gauge needle combination was weighed before and after each injection using a digital microbalance (Ohaus AV 64C). The air bubble volume was calculated by subtracting the total volume measured in the photographs from the fluid volume computed by weight for every trial.
Bubble volumes measured within anti-VEGF drugs and BSA model solution are presented in table 1. These data are graphed with best-fit lines in figure 2. While solutions containing BSA uniformly produced slightly higher degrees of bubble formation, both anti-VEGF and BSA solutions were similarly fit to regression lines of R2 = 0.98 and 0.97 respectively.
Protein-containing solutions have long been known to form foams. This study demonstrates that this phenomenon occurs within anti-VEGF drug solutions within the small-volume syringes we use to administer these drugs. Further, we found that air bubble formation and stability were increased with increasing protein concentration and that this phenomenon can further be studied with a low-cost protein containing solution model.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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