Latanoprost-Eluting Contact Lenses in Glaucomatous Monkeys

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• 作者：Joseph B. Ciolino ; MD¹ ; ² ; ³ ; ^{Joseph_Ciolino@meei.harvard.edu" class="auth_mail" title="E-mail the corresponding author} ; Amy E. Ross ; MSc¹ ; ² ; ³ ; Rehka Tulsan ; MSc¹ ; ² ; ³ ; Amy C. Watts ; OD¹ ; Rong-Fang Wang ; MD⁴ ; David Zurakowski ; PhD³ ; Janet B. Serle ; MD⁴ ; Daniel S. Kohane ; MD ; PhD³ ; ^{daniel.kohane@childrens.harvard.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：CLHI ; high-dose contact lens ; CLLO ; low-dose contact lens ; IOP ; intraocular pressure ; OCT ; optical coherence tomography ; PBS ; phosphate-buffered saline ; PLGA ; poly(lactic-co-glycolic) acid
• 刊名：Ophthalmology
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：123
• 期：10
• 页码：2085-2092
• 全文大小：487 K

文摘

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 (CL_LO) and high-dose contact lenses (CL_HI) 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 CL_LO, CL_HI, or daily latanoprost ophthalmic solution in the same monkeys. Each monkey consecutively received 1 week of continuous-wear CL_LO, 3 weeks without treatment, 5 days of latanoprost drops, 3 weeks without treatment, and 1 week of continuous-wear CL_HI. 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 CL_LO 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 CL_HI 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 CL_LO and CL_HI, the IOP was statistically significantly reduced compared with the untreated baseline at most time points measured. The CL_HI 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.