Elad Moisseiev, MD: Accuracy and Precision in Intravitreal Injections

Elad Moisseiev, MD

Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are the most commonly performed ophthalmological procedure.

Administration involves injecting include bevacizumab, ranibizumab, or aflibercept, all of which require injecting a volume of 50 µL of the medicine into the vitreous cavity. Despite the fact that this the procedure is carried out frequently, there currently is no specially designed syringe for the injection and there have been few studies focusing on how accurate the current options are.

In a presentation at the American Academy of Ophthalmology Annual Meeting 2018 in Chicago, Illinois, Elad Moisseiev, MD, presented a poster titled “Accuracy and Precision of Intravitreal Injections of Anti-VEGF Agents in Real Life.” Dr. Moisseiev sat down with MD Magazine® to discuss the findings of the investigation that focused on real-world data to explore the accuracy and precision of different drawing techniques and syringe designs (see video).

“We were thinking about the accuracy and precision of these injections and that it might not be as good as we think it is, and possibly we're not really sure how much volume goes into the eye when we're injecting a drug into it," Dr. Moisseiev said. “So, we initiated a study to evaluate the accuracy and precision of these injections.”

The investigators observed 669 intravitreal injections during the study period. Each injection was sorted into 1 of 3 categories based on the syringe used and which drug was administered.

In group A, bevacizumab was injected using pre-filled standard 1 mL syringes that were compounded and delivered from an external GMP level pharmacy. In group B, ranibizumab was injected using a pre-filled small-volume syringe with a low-dead-space plunger that was specifically manufactured by Genentech. And in group C, aflibercept was injected using a tuberculin 1mL syringe, which was not pre-filled, the physician would draw the medicine from a sterile vial prior to injection.

The investigators measured the weight of the syringe and needle before and after the administration of the injection, using an analytical balance with a resolution of 0.1mg. The difference was the weight of the delivered amount of drug, which was converted to volumes by accounting for the different densities of the drugs, which was termed volume output.

Accuracy was defined as “the proximity of the volume output to the intended volume of 50 µL as determined using one-sample t-tests and the mean absolute percentage error.” And precision was defined as “the uniformity of repeated measures as represented graphically using a scatter plot and measured by the coefficient of variation.”

When compared to the target volume, the volume outputs of all groups were significantly greater than 50mL; group A was 54.53+4.69, group B was 56.06+5.36 and group C was 61.72+8.37 (p <0.0001).

“The most important finding of our study is that almost all of the injections regardless of drug syringe used and drawing technique are inaccurate,” Dr. Moisseiev explained, “Getting exactly 50 microliters is very, very hard and the variability is pretty big.”

The mean absolute percentage error values of groups A & B were not statistically significantly different (group A 12.25+5.92, group B 13.60+8.75; p=0.13), however, group C was significantly greater than the other groups with a mean average percent error of 24.69+14.84.

The differences may be attributed to the different drawing technique or to the higher protein content of aflibercept. Additionally, it is possible that the step in the preparation along with the different composition of the drug resulted in more air bubbles in the syringe and more difficulty in preparing the dose to be injected, thus leading to the reduced accuracy in group C, according to the authors.

The authors conclude that use of a pre-filled syringe may also be advantageous in improving the accuracy in administration and that a low dead space plunger design may be associated with improved precision. But the field could also benefit from a specially designed syringe for intravitreal injections.

“There is a need to design a special syringe for individual injections that are extremely common and are done in the millions worldwide per year,” Dr. Moisseiev stressed, “A syringe will improve accuracy and precision that may be of clinical benefit and also provide maybe additional safety because injecting to higher volume can cause an intraocular pressure (IOP) spike.”

Disclosures: none