DRUG DISTRIBUTION IN THE VITREOUS-HUMOR OF THE HUMAN EYE - THE EFFECTS OF INTRAVITREAL INJECTION POSITION AND VOLUME

Purpose. The purpose of this study was to determine how the position a nd volume of an intravitreal injection affect the distribution and eli mination of drug from the vitreous humor. Methods. A mathematical mode l that had been developed and used previously to study drug distributi on in the vitreous humor of the rabbit eye was modified to match the p hysiology of the human eye. Fluorescein and fluorescein glucuronide we re used as the model compounds for these studies. Four extreme injecti on locations were considered: a central injection, an injection displa ced towards the retina, an injection displaced towards the lens, and a n injection displaced towards the hyaloid membrane. Injections contain ing an equal mass of drug dissolved in volumes of either 15 mu L or 10 0 mu L were compared. Results. The location of an intravitreal injecti on was found to have a substantial effect on elimination and distribut ion in the vitreous. Peak concentrations at different vitreous locatio ns varied by over three orders of magnitude, depending on the injectio n location. The mean concentration of drug remaining in the vitreous 2 4 hours after the intravitreal injection varied by up to a factor of 3 .8, depending on the injection location. Changing the volume of the in jection from 15 mu L to 100 mu L dampened the effects of the initial i njection location; however, mean concentrations at 24 hours still vari ed by up to a factor of 2.5. Conclusions. Careful control of the condi tions of an intravitreal injection could reduce treatment variability, improve bioavailability, and reduce the possibility of retinal toxici ty.