Modeling the Effects of Disease, Drug Properties, and Material on Drug Transport From Intraocular Lenses.

PURPOSE

Surgically implanted intraocular lenses (IOLs) may be used as drug-delivery devices, but their effectiveness is not well defined. Computational fluid dynamics models were developed to investigate the capability of IOLs to release drugs at therapeutic concentrations.

METHODS

Models were generated using COMSOL Multiphysics. Primary open-angle glaucoma (POAG) and wet age-related macular degeneration (AMD) were simulated by reducing aqueous vein and choroidal blood flow, respectively. Release of dexamethasone, ganciclovir, or dextran was studied using common IOL materials, polydimethylsiloxane (PDMS) and poly(2-hydroxyethyl methacrylate) (PHEMA).

RESULTS

Drug clearance proceeds mainly through choroidal blood flow. When fully constricted, maximum concentration at the choroid (Cmax) values increased by 32.4% to 39,800%. Compared to dexamethasone, Cmax in different tissues decreased by 6.07% to 96.0% for ganciclovir and dextran, and clearance rates decreased by 16% to 69% for ganciclovir and by 92% to 100% for dextran. Using PDMS as the IOL reduced clearance rates by 91.3% to 94.6% compared to PHEMA.

CONCLUSIONS

In diseased eyes, drugs accumulate mainly in posterior tissue; thus, choroidal drug toxicity must be assessed prior to IOL implantation in POAG and AMD patients. Moreover, drug properties modulated concentration profiles in all ocular segments. The hydrophobic small-molecule dexamethasone attained the highest concentrations and cleared the fastest, whereas hydrophilic macromolecular dextran attained the lowest concentrations and cleared the slowest. Furthermore, high concentrations were achieved quickly following release from PHEMA, whereas PDMS allowed for sustained release.

TRANSLATIONAL RELEVANCE

In silico results can guide scientists and clinicians regarding important physiological and chemical factors that modulate tissue drug concentrations from drug-eluting IOLs.