Exploring Drug Distribution via the Suprachoroidal Space in a Human and Rabbit Eye Using Computational Modeling

Abstract

 

Purpose

 

Drug delivery to the posterior segment of the eye is challenging due to the presence of various physiological and anatomical barriers. Delivery to the suprachoroidal space (SCS), located between the choroid and sclera, can provide a targeted delivery of drug to the site of action (choroid and retina). A computational model was developed to understand the intraocular pharmacokinetics of SCS drug delivery in a rabbit and human eye.

 

Methods

 

An anatomically accurate 3D computational fluid dynamic model of the rabbit and human eye were developed to simulate a SCS microneedle injection of fluorescein. In the simulation, fluorescein circumferentially filled the entire choroidal space, mimicking the in vivo distribution. The compound fluorescein was chosen since the material properties of the ocular tissues are known and the availability of animal data (Patel, 2012).

 

Results

 

The assumptions made in the simulation were validated against the in vivo rabbit data. The drug distribution profiles in the ocular tissues between the rabbit and human were similar, but anatomical differences between the species resulted in concentration differences in the vitreous and choroid-retina interface (Figure 1). The difference between choroidal volumes between species (rabbit ~103 µl and human ~398 µl) suggest larger concentrations/volumes can be injected into the human eye, thus resulting in higher concentrations in the choroid-retina interface. Although the human eye has a larger SCS the diffusion of fluorescein into the vitreous was more diffuse in the rabbit (Figure 2) resulting in different vitreous concentration-time profiles.

 

Conclusions

 

Suprachoroidal drug delivery is an effective route of administration providing targeted delivery to the chorioretinal tissues. While animal models are necessary for studying ocular pharmacokinetics, computational modeling can be utilized as a translational tool to better understand and predict drug distribution in humans for various ocular delivery routes.

 

 

Simulation and experimental concentration of fluorescein along the visual axis following a SCS injection in the rabbit eye.

 

 

Contour plots of concentration on the symmetry plane (top) and choroid-retina interface (bottom) at t=120 min post dose for a human (left) and rabbit (right). At t=0 the concentration of the SCS injection is equivalent to 1.

 

Keywords: 763 vitreous • 473 computational modeling • 688 retina