Intraocular pressure and injection forces during intravitreal injection into enucleated porcine eyes

Injection of biological molecules into the intravitreous humor is of increasing interest for the treatment of posterior segment eye diseases such as age-related degenerative macular degeneration. The injection volume is limited by an increase in intraocular pressure (IOP) and 50-100 mu L are typically used for most intravitreally (IVT) applied commercial products. Direct measurement of IOP is difficult and has not been studied dependent on solution properties and injection rates. We used an instrumental set-up to study IOP ex vivo using healthy enucleated porcine eyes. IOP was determined as a function of injection volume for viscosities between 1 and 100 mPas, injection rates of 0.1, 1, and 1.5 mL/min, and needle length and diameter (27/30G and 0.5/0.75 '') using Dextran solutions. IOP increased exponentially for injection volumes larger than 100 mu L. We did not observe differences in IOP dependent on viscosity, injection rate, and needle diameter. However, variability increased significantly for injection volumes larger than 100 mu L and, unexpectedly, declined with higher viscosities. We demonstrate that the exponential increase in IOP is not reflected by injection force measurements for typical configurations that are used for IVT application. The present findings may guide injection volumes for intravitreal injection and inform injection force considerations during technical drug product development.

Automated summary

This study investigated the effect of injection volume on intraocular pressure using healthy enucleated porcine eyes, revealing an exponential increase in IOP for injection volumes larger than 100 µL. Interestingly, there were no significant differences in IOP based on viscosity, injection rate, and needle diameter, but variability increased significantly for injection volumes larger than 100 µL. Additionally, the exponential increase in IOP was not reflected by injection force measurements for typical configurations used for intravitreal injection, providing important insights for injection volume guidance and injection force considerations in drug product development.