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

Abstract

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.

Figure 1.

Eye geometry with labeled subdomains. (A) Entire geometry (top view). (B) Details of the contents of the blue box in image A. Dimensions used to build geometry and subdomain material properties were obtained from the literature (values are listed in Supplementary Materials, Sections B and C).

Figure 2.

Boundary conditions for each physical interface. (A) The HT interface was used to generate the temperature profile. (B) The DL interface was used to generate the vitreous flow profile. (C) The DL and LFB interfaces were used to generate the choroidal blood flow profile. (D) The DL and LFA interfaces were used to generate the aqueous flow profile. (E) The DL and LFC interfaces were used to generate the aqueous vein blood flow profile.

Figure 3.

Boundary conditions for the TDS interface. (A) Entire geometry. (B) Details of the top blue box in image A. (C) Details of the bottom blue box in image A.

Figure 4.

(A) Temperature profile, (B) aqueous flow profile, and (C) vitreous flow profile. In (A), the legend represents temperature (°C). In (B) and (C), the legend represents flow velocity (m/s). In (A), point 1 is the central cornea (34.5°C), point 2 is the corneal limbus (35.5°C), and the gray boundary is the sclera outer surface (36.5°C). In (B), the aqueous/vitreous (green) boundary attains the maximum subdomain temperature of 36.1°C, and the aqueous/cornea (red) boundary attains the minimum subdomain temperature of 34.6°C; the gray and black boundaries are the aqueous humor points of entry and exit, respectively.

Figure 5.

Average drug concentration in the aqueous, cornea, and vitreous (A) and in the retina, sclera, and choroid (B) over a 50-hour period. Maximum concentration (C_max) is represented by the peak on each curve. C_max was greater in anterior tissue (aqueous, cornea) than posterior tissue (vitreous, retina, choroid, and sclera). In the anterior segment, C_max decreased from 6.04 × 10⁻³ mol/m³ to 5.63 × 10⁻³ mol/m³ with increasing distance from the IOL. In the posterior segment, C_max decreased from 1.41 × 10⁻³ mol/m³ to 3.35 × 10⁻⁶ mol/m³ with increasing distance from the IOL (exception of trend in choroid and sclera).

Figure 6.

Average dexamethasone concentration in the aqueous (A) and vitreous (B) over a 50-hour period following release from a PDMS IOL and a PHEMA IOL. Maximum concentration (C_max) is represented by the peak on each curve. In the aqueous, C_max values were 5.62 × 10⁻⁴ mol/m³ and 6.04 × 10⁻³ mol/m³ at 2.3 h and 1.4 h following release from a PDMS IOL and a PHEMA IOL, respectively. In the vitreous, C_max values were 1.15 × 10⁻⁴ mol/m³ and 1.41 × 10⁻³ mol/m³ at 5.9 h and 4.2 h following release from a PDMS IOL and a PHEMA IOL, respectively.