Abstract
Purpose :
Build a 3D model of the eye to simulate the diffusion of Vancomycin (VAN) delivered via subconjunctival injection and predict VAN profile and concentration buildup in the vitreous.
Methods :
COMSOL Multiphysics was used to simulate VAN diffusion through the vitreous, where a “Time Dependent” and “Transport of Diluted Species” study was constructed.
The model was created by establishing three 2D work planes for each tissue layer in the eye. In each work plane, a curve with a diameter and thickness of the tissue layer was created and revolved around the central axis. In addition, the bottom of the sclera layer was made flat to represent a site where VAN diffusion begins. After the three layers were constructed, a solid sphere with the diameter of the vitreous was created to represent the vitreous humor. COMSOL's “Form Union” method was employed to create a single geometry object composed of many different domains.
Material properties and transport properties were applied to each layer. The initial concentration for the compartments were assume zero. The initial concentration of the flatted bottom of the eye was assumed to be 1 mg/ml in the subconjunctival space. After all parameters were set, the element size in Mesh was set to “Normal” to discretize the geometry. The simulation was executed over 1440 minutes (24 hours) and data were collected at 144 minute increments.
Results :
Final results from the simulation were displayed as a diffusion profile over a period of time (24 hours). The concentration of the eye was illustrated as both Streamline (with slices) and Surface (Figure 1).
The simulation suggests the steady build-up of VAN in the center of the vitreous over time where 12% of the initial VAN concentration is present in the vitreous after 24 hours and diffuses at a rate of ~0.005mg/ml per hour. Based on these findings, a therapeutic concentration (0.007 mg/ml) of VAN in the vitreous is achieved after 2 hours following injection. This preliminary model suggests potential to predict minimum drug loading requirements for sustained release drug delivery systems meant to be placed in the subconjunctival space.
Conclusions :
This model predicts drug build-up in the vitreous following a subconjunctival injection and can be expanded to predict sustained release drug delivery system drug loading requirements.
This is a 2021 ARVO Annual Meeting abstract.