Numerical Simulations of Ethacrynic Acid Transport from Precorneal Region to Trabecular Meshwork

Abstract

Topical application of drugs for treatment of intraocular diseases is often limited by inadequate transport and induced toxicity in corneal tissues. To improve the drug delivery, a mathematical model was developed to numerically simulate the transport process of ethacrynic acid (ECA), a potential drug for glaucoma treatment, in the anterior segment of a typical human eye. The model considered diffusion of ECA in all tissues and the aqueous humor (AH) as well as convection of ECA in the AH. The simulation results showed that ECA concentration in the eye depended on the rate of AH production, the half-life of ECA in the precorneal tear film, and the transport parameters in the model. In addition, the main pathway for ECA clearance from the eye was the trabecular meshwork (TM) and the rate of clearance was approximately proportional to the AH production rate. The model predicted that the most effective approach to improving topical drug delivery was to prolong its half-life in the precorneal tear film. These simulation results and model prediction, which could be verified experimentally, might be useful for improving delivery of ECA and other therapeutic agents to the TM as well as other tissues in the anterior segment of the eye.

Numerical investigation of topical drug transport in the anterior human eye

“…where Q ah = 2.4 lL min À1 is the rate of AH production [35], A cb = 34.04 mm 2 is the CB inner surface area (calculated in the study), S is a dimensionless coordinate that varies from 0 to 1 on the inlet surface, andñ cb is the outward normal vector at the CB. At the outlet TM, the viscous stresses are assumed to be zero, i.e.,…”

“…1(a)) and a 3D eye model ( Fig. 1(b)) are developed based on the anterior segment geometry data in [35] and posterior segment geometry data in [20], including the cornea, sclera, anterior chamber, posterior chamber, lens, vitreous, iris, TM and ciliary body (CB). Geometric dimensions of the eye models are listed in Table 1.…”

“…Wyatt et al [33,34] proposed 'a schematic and simplified' parabolic profile for the convective AH flow in the study anterior segment kinetics with focally applied mydriatics, and the convective AH flow was believed to play a substantial role in pharmacokinetics of the anterior segment. Recently, Lin and Yuan [35] numerically studied the transport of ethacrynic acid (ECA), an ophthalmic drug for the treatment of primary open-angle glaucoma (POAG), from the precorneal region to trabecular meshwork, but their model only incorporated secretion-drainage flow of the AH, and neglected AH natural convection. Since AH velocities generated by natural convection are at least the same order of magnitude as those caused by AH secretion-drainage and increase rapidly with increasing temperature difference across the eye [12], it is necessary to explore how temperature difference, hence AH natural convection, affects transport of topically applied drugs in the anterior eye.…”

An Efficient Graphics Processing Unit Scheme for Complex Geometry Simulations Using the Lattice Boltzmann Method

“…Length of the anterior chamber 12.8 mm Abouali [19] Depth of the anterior chamber 3.0 mm Ferreira [15] Radius of the cornea 8.3 mm Heys [20] Thickness of the iris 0.4 mm Heys [21] Angle of the iris 6.45°Lin [22] Diameter of the pupil 3.0 mm Abouali [19] Radius of the lens 10.0 mm Heussner [23] Surface area of the TM 18.0 mm 2 Heys [21] Height of the posterior chamber 0.5 mm Heys [21] Distance between iris and lens 0.15 mm Between Heys [21] and Crowder [24] III. IMPLEMENTATION…”

Numerical modeling of therapeutic lens drug delivery in the anterior human eye for the treatment of primary open-angle glaucoma

“…Extensive numerical studies related to heat transfer, aqueous humor (AH) flow and drug transport in all the domains of an eye when applied topically are reported in the literature. [7][8][9][10][11][12][13][14][15] However, very few mathematical models have been developed for drug delivery from the therapeutic lens. To this end, Ferreira et al 16 developed a two-dimensional (2D) model to study drug transport from a therapeutic lens.…”