Abstract
Abstract: :
Purpose: In previous work (ARVO 2001; J Oc Pharm Ther, in press) anterior segment drug transport was modeled using a computation based on a sequence of stages, each stage occurring either by diffusion or by bulk flow in the anterior chamber convectional flow. In the present work, a finite element approach is used to model combined convection plus diffusion. In addition, secretory flow is incorporated into the model. Methods: A vertical slice through the center of the anterior chamber is modeled. The pattern of convectional fluid flow is based on the theoretical work of Canning et al. The model includes secretory aqueous flow—inflow through the pupil and outflow through the drainage apparatus. Drugs may be "applied" at a local location on the corneal surface. The drug then diffuses across the cornea, where it enters the aqueous flow and travels by means of simultaneous diffusion and bulk flow. Targets at various locations in the iris are considered, and a final diffusion path in the iris is included. Results: Several situations have been modeled: (i) An anterior chamber is filled with a uniform concentration of a substance, and pupillary inflow of aqueous (free of the substance), is allowed to occur. The model simulates Holm's (1968) observations with dark pupillary inflow into an anterior chamber loaded with fluorescein. (ii) A drug is applied focally at the limbus, to produce "sector" pupil dilation. Drug distribution in the anterior chamber and at the iris is predicted. Estimates of drug latencies for mydriatics are in reasonable accord with experimental observations. The earlier computational approach did not predict the experimental observation that a drug applied at the inferior limbus does not easily reach superior iris; the present model provides a plausible explanation. Conclusion: Inclusion of secretory flow in the pattern of anterior chamber fluid flow appears to help reconcile modeling with experiment. Although the speed of secretory flow is small compared to the speed of convectional flow, it can exert substantial effects near the iris surface.
Keywords: 534 pupil • 514 pharmacology • 324 aqueous