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 to 10(-7) to 2.4 x 10(-5) cm2/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) cm2/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 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.