Computational modeling of drug transport in the posterior eye.

Abstract

Posterior segment eye diseases cause vision impairment and blindness in millions of people. A number of these diseases including age-related macular degeneration, glaucoma, and retinopathy can cause irreversible blindness and are currently treated with the help of drugs. Delivering drugs to the posterior eye is a challenge because of the presence of various physiological and anatomical barriers. Systemic delivery is infeasible due to the size of the eye. Topical delivery is also ineffective due to various barriers and elimination routes associated with the anterior eye. Intravitreal delivery, which is currently the preferred mode of drug delivery, provides a localized drug depot in the vitreous, but the method is invasive and frequent interventions can lead to endophthalmitis, retinal detachment, and hemorrhage. Recently, delivering drug via the transscleral route has gained attention as the sclera has been shown to be permeable to drug molecules and the method is invasive and provides a localized drug source as well. The objective of the dissertation was to provide better understanding of drug transport in the posterior eye with the help of a computational model. In particular, the following specific aims were pursued. 1. Quantification of the relative importance of the tissue related barriers and elimination factors in the posterior tissues like the sclera, choroid, and the retina and its pigment epithelium. 2. Investigation of the effect of saccade induced sloshing of the vitreous following vitreous liquefaction or vitrectomy, on drug distribution in the posterior eye Posterior segment eye diseases cause vision impairment and blindness in millions of people. A number of these diseases including age-related macular degeneration, glaucoma, and retinopathy can cause irreversible blindness and are currently treated with the help of drugs. Delivering drugs to the posterior eye is a challenge because of the presence of various physiological and anatomical barriers. Systemic delivery is infeasible due to the size of the eye. Topical delivery is also ineffective due to various barriers and elimination routes associated with the anterior eye. Intravitreal delivery, which is currently the preferred mode of drug delivery, provides a localized drug depot in the vitreous, but the method is invasive and frequent interventions can lead to endophthalmitis, retinal detachment, and hemorrhage. Recently, delivering drug via the transscleral route has gained attention as the sclera has been shown to be permeable to drug molecules and the method is invasive and provides a localized drug source as well. The objective of the dissertation was to provide better understanding of drug transport in the posterior eye with the help of a computational model. In particular, the following specific aims were pursued. 1. Quantification of the relative importance of the tissue related barriers and elimination factors in the posterior tissues like the sclera, choroid, and the retina and its pigment epithelium. 2. Investigation of the effect of saccade induced sloshing of the vitreous following vitreous liquefaction or vitrectomy, on drug distribution in the posterior eye animal data, which are mostly done on an intact vitreous, to old patients whose vitreous might be liquefied. The model developed could also drive design of delivery systems in order to increase the efficiency of the treatment.