Drug distribution in the vitreous humor of the human eye: The effects of aphakia and changes in retinal permeability and vitreous diffusivity

The majority of eyes that receive drug therapy exhibit some form of pathophysiological degradation. Two common pathophysiological states are retinal inflammation, which results in breakdown of the blood-retinal barrier, and aphakia. The purpose of this study was to examine the effects of aphakia and changes in retinal permeability and vitreous diffusivity on drug distribution in the vitreous humor of the human eye. The study was performed using a finite element model that accurately accounts for the vitreous geometry and boundary conditions. Intravitreal injection is the most common method for treating posterior segment disorders; therefore, this administration method was simulated using the models. Elimination from aphakic and phakic eyes was compared for four extreme injection locations and for two retinal permeabilities. When the retinal permeability was fixed at 5.0 x 10(-5) cm/s, increasing the drug diffusivity through the vitreous from 5.4 x 10(-7) to 2.4 x 10(-5) cm(2)/s decreased the half-life of drug from 64 hours to 2.7 hours. When the drug diffusivity was fixed at 5.6 x 10(-6) cm(2)/s, increasing the retinal permeability of the drug from 1.0 x 10(-7) to 1.0 x 10(-4) cm/s decreased the half-life of drug from 44 hours to 7 hours. Therefore, drug diffusivity and retinal permeability are key factors that influence elimination from the vitreous, and must be considered, particularly if the blood retinal barrier has been compromised. Faster drug elimination was observed in aphakic eyes than in phakic eyes, especially for drugs with a low retinal permeability and injected close to the lens capsule. Injection position is also important if the drug is injected in close proximity to a primary elimination barrier.