3D modeling of aflibercept transport in the vitreous humor

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Abstract

Aflibercept is an anti-vascular endothelial growth factor (anti-VEGF) drug used to treat several retinal diseases such as macular degeneration. It accomplishes this by binding and inhibiting VEGF, which is the growth factor that is responsible for abnormal blood vessel growth. Overexpression of VEGF can lead to interference with the macula, and subsequent vision loss. Aflibercept is prescribed to treat macular degeneration due to VEGF overexpression. It is administered via intravitreal injection. Analysis of the transport of aflibercept through the vitreous humor is critical to understanding whether or not patients are receiving appropriate amounts of drug at the macula boundary, where the abnormal growth of blood vessels is contributing to macular degeneration. This study will assess if the current market dose of aflibercept is successfully inhibiting VEGF for an appropriate time period.

The scope of analysis involved construction of a three-dimensional geometry of the vitreous humor in COMSOL, an implementation of physical properties and parameters of the vitreous humor and aflibercept, an illustration of key results, a sensitivity analysis on certain parameters, and a validation of the COMSOL implementation.

The analysis was conducted for a 3D diffusion problem, coupled with convection. Convection is due to pressure-driven flow, a result of the inherent pressure difference in the vitreous humor. Degradation or inactivation of aflibercept was also considered by modeling the second-order binding of aflibercept to VEGF. The distribution of aflibercept throughout the vitreous humor was successfully determined. Due to asymmetry in the injection site, or the placement of drug, it was found that the distribution of drug is asymmetric at early times, and becomes more uniform at later times. A similar result was found at the macula boundary, which is the target area of interest for this study. It was also shown that VEGF concentration is successfully inhibited upon the introduction of aflibercept. Based on the model, VEGF began to accumulate after initial suppression within 20 to 40 days of aflibercept injection. This coincides with the recommended interval between aflibercept injections, which is 28 days.

Improvements in future model implementation could provide a result that more accurately represents the transport of aflibercept in the eye. These improvements include implementing an initial injection velocity when aflibercept is introduced, and the use of a more realistic geometry, such as an MRI scan, to build the geometry in the COMSOL model.

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2017-05-11
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aflibercept, macular degeneration, VEGF, vitreous humor, COMSOL
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