Comparison of Convective Transport of Drug between Intravitreal Injection and Controlled Release Implant

It is important to know the drug distribution following administration of drug in order to properly treat with adequate dosage and thus, avoid damage to tissues due to excessive high concentrations. A computer model was developed to determine drug distribution by convective-diffusive transport processes in a rabbit eye. When compared with pure diffusion within vitreous, the ratio of the amount of a model compound, fluorescein, reaching the retina to that cleared by aqueous outflow increased by 93% and 84% for intravitreal injection and implant, respectively, with maximum vitreous outflow (glaucomatous eye). The result shows that the combined "convective" effect due to the vitreous outflow and "wash out" effect by aqueous outflow has significant impact on drug distribution for both intravitreal injection and implant. These two effects should be considered in the design of drug delivery strategies. INTRODUCTION Aqueous humor (AH) is actively secreted by the ciliary process and drains through two major pathways; trabecular outflow, and uveoscleral outflow. Most of the AH (70-90%) leaves via the trabecular outflow while the remaining (10-30%) of it exits through uveosclera outflow (Forrester et a1. 2002). However, there is a strong evidence that a fraction of fluid from the ciliary process flows through the vitreous in healthy eye (Araie et a1. 1991), called vitreous outflow (Fig. 1). Obstruction of aqueous outflow increases intraocular pressure (lOP), which results in the pathogenesis of glaucoma. The vitreous outflow will increase in case of glaucoma because of the increase of the aqueous outflow resistance. To overcome the blood-retinal barrier, either intravitreal injections or controlled release implants are currently being used to treat retinal and vitreal disease. This study compares 1rug distribution between intravitreal injection and implant with different vitreous outflow i.e. healthy and glaucomatous