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Jackson Abou Chehade, Saba Alniemi, Benjamin Nicholson, Raymond Iezzi; Dose Accuracy and Variation of Anti-VEGF Drug Injections . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1495.
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Currently, little is known about the dose accuracy and variation of intraocular anti-VEGF injections. This study aims to characterize the dosing accuracy and variability of 4 anti-VEGF drugs and deionized (DI) water among three injectors.
In this laboratory study, each injector was asked to follow their standard clinical protocol to deliver an intended volume of 0.05 ml into a rubber sealed vial. Each performed 26 injections per agent (bevacizumab 25mg/ml, ranibizumab 6mg/ml and 10mg/ml, aflibercept 40mg/ml and DI water) using 1 ml syringes. The syringes were weighed pre- and post-injection to an accuracy of 100 micrograms. Injection volume was calculated to an accuracy of 0.1 microliters using the specific gravity of the drug formulations, and the measured syringe weight difference. One filter needle per agent was used.
For all injectors, we observed a significant dose variation from the intended dose of 0.05 ml (p <0.001). Underdosing was noted for 2 injectors who attempted to titrate their syringe content to 0.05 ml (mean ±SD in ml for the first and second injector respectively; 0.037 ± 0.005 and 0.041 ± 0.008 for bevacizumab, 0.041 ± 0.008 and 0.043 ± 0.008 for ranibizumab 10 mg/ml, 0.039 ± 0.009 and 0.043 ± 0.009 for ranibizumab 6 mg/ml, 0.033 ± 0.006 and 0.039 ± 0.01 for aflibercept, 0.038 ± 0.009 and 0.043 ± 0.007 for DI water). To avoid underdosing, a third injector’s standard clinical protocol consisted of loading the syringe content to 0.06mL. This resulted in overdosing for all agents (mean ±SD in mL; 0.069 ± 0.006 for bevacizumab, 0.073 ± 0.006 for ranibizumab 10 mg/ml, 0.071 ± 0.008 for ranibizumab 6 mg/ml, 0.064 ± 0.008 for aflibercept and 0.068 ± 0.006 DI water). The range of dose variation we measured could result in significant differences in expected dose duration (9.9 days for bevacizumab, 5.3 and 6.7 days respectively for ranibizumab 10 and 6 mg/mL and 8.8 days for aflibercept), (p<0.001). Furthermore, for 2 of the injectors, ANOVA showed a significantly lower mean volume delivered for aflibercept relative to all other agents (p<0.05).
We observed both intra- and inter-injector variation of dose delivered among all agents. This significantly changed the calculated dose duration for each drug. This could, in turn affect patient therapeutic response and management. Drug-specific factors may be associated with the lower aflibercept volumes delivered.
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