Latanoprost-Eluting Contact Lenses in Glaucomatous Monkeys

Abstract

Purpose: To assess the ability of latanoprost-eluting contact lenses to lower the intraocular pressure (IOP) of glaucomatous eyes of cynomolgus monkeys.

Design: Preclinical efficacy study of 3 treatment arms in a crossover design.

Participants: Female cynomolgus monkeys with glaucoma induced in 1 eye by repeated argon laser trabeculoplasty.

Methods: Latanoprost-eluting low-dose contact lenses (CLLO) and high-dose contact lenses (CLHI) were produced by encapsulating a thin latanoprost-polymer film within the periphery of a methafilcon hydrogel, which was lathed into a contact lens. We assessed the IOP-lowering effect of CLLO, CLHI, or daily latanoprost ophthalmic solution in the same monkeys. Each monkey consecutively received 1 week of continuous-wear CLLO, 3 weeks without treatment, 5 days of latanoprost drops, 3 weeks without treatment, and 1 week of continuous-wear CLHI. On 2 consecutive days before initiation of each study arm, the IOP was measured hourly over 7 consecutive hours to establish the baseline IOP. Two-tailed Student t tests and repeated-measures analysis of variance were used for statistical analysis.

Main outcome measures: Intraocular pressure.

Results: Latanoprost ophthalmic solution resulted in IOP reduction of 5.4±1.0 mmHg on day 3 and peak IOP reduction of 6.6±1.3 mmHg on day 5. The CLLO reduced IOP by 6.3±1.0, 6.7±0.3, and 6.7±0.3 mmHg on days 3, 5, and 8, respectively. The CLHI lowered IOP by 10.5±1.4, 11.1±4.0, and 10.0±2.5 mmHg on days 3, 5, and 8, respectively. For the CLLO and CLHI, the IOP was statistically significantly reduced compared with the untreated baseline at most time points measured. The CLHI demonstrated greater IOP reduction than latanoprost ophthalmic solution on day 3 (P = 0.001) and day 5 (P = 0.015), and at several time points on day 8 (P < 0.05).

Conclusions: Sustained delivery of latanoprost by contact lenses is at least as effective as delivery with daily latanoprost ophthalmic solution. More research is needed to determine the optimal continuous-release dose that would be well tolerated and maximally effective. Contact lens drug delivery may become an option for the treatment of glaucoma and a platform for ocular drug delivery.

Figure 1.

The latanoprost-eluting contact lens. (A) Representative ocular coherence tomography image of the cross-section of the contact lens. The arrow points to the inner edge of the drug-polymer film within the hydrogel. (B) Photograph of latanoprost-eluting contact lens on the right monkey eye. The clear central aperture is surrounded by a translucent ring of drug-polymer film. The arrow points to the inner margin of the drug polymer film.

Figure 2.

IOP change from baseline over 7 hours on the last day of treatment in glaucomatous monkey eyes. Latanoprost drop data represent the change in IOP before and following the 5^th consecutive morning dose of 0.005% latanoprost solution. The contact lens data represents the change in IOP after removing the lenses following 7 days of continuous wear. P-values were calculated using Student t-tests comparing high dose contact lenses and latanoprost drops at the same time point. Data are means ± standard deviation. n = 4 for the latanoprost drop and the low dose contact lens and n = 3 for the high dose contact lenses. IOP = intraocular pressure.