Ciolino Joseph B, Ross Amy E, Tulsan Rehka, Watts Amy C, Wang Rong-Fang, Zurakowski David, Serle Janet B, Kohane Daniel S
Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts; Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Departments of Anesthesia and Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts; Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Departments of Anesthesia and Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
Ophthalmology. 2016 Oct;123(10):2085-92. doi: 10.1016/j.ophtha.2016.06.038. Epub 2016 Aug 29.
To assess the ability of latanoprost-eluting contact lenses to lower the intraocular pressure (IOP) of glaucomatous eyes of cynomolgus monkeys.
Preclinical efficacy study of 3 treatment arms in a crossover design.
Female cynomolgus monkeys with glaucoma induced in 1 eye by repeated argon laser trabeculoplasty.
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.
Intraocular pressure.
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).
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.
评估拉坦前列素缓释隐形眼镜降低食蟹猴青光眼患眼眼压(IOP)的能力。
采用交叉设计的3个治疗组的临床前疗效研究。
通过重复氩激光小梁成形术使1只眼睛诱发青光眼的雌性食蟹猴。
拉坦前列素低剂量缓释隐形眼镜(CLLO)和高剂量缓释隐形眼镜(CLHI)是通过将一层薄的拉坦前列素 - 聚合物膜包裹在甲基纤维素水凝胶周边制成,然后将其加工成隐形眼镜。我们评估了CLLO、CLHI或每日拉坦前列素滴眼液对同一只猴子的降眼压效果。每只猴子依次连续佩戴CLLO 1周,不治疗3周,滴注拉坦前列素滴眼液5天,不治疗3周,连续佩戴CLHI 1周。在每个研究组开始前连续2天,连续7小时每小时测量一次眼压以确定基线眼压。采用双尾学生t检验和重复测量方差分析进行统计分析。
眼压。
拉坦前列素滴眼液在第3天使眼压降低5.4±1.0 mmHg,在第5天眼压降低峰值为6.6±1.3 mmHg。CLLO在第3天、第5天和第8天分别使眼压降低6.3±1.0 mmHg、6.7±0.3 mmHg和6.7±0.3 mmHg。CLHI在第3天、第5天和第8天分别使眼压降低10.5±1.4 mmHg、11.1±4.0 mmHg和10.0±2.5 mmHg。对于CLLO和CLHI,在大多数测量时间点,与未治疗的基线相比,眼压有统计学显著降低。CLHI在第3天(P = 0.001)和第5天(P = 0.015)以及第8天的几个时间点(P < 0.05)显示出比拉坦前列素滴眼液更大的眼压降低幅度。
隐形眼镜持续释放拉坦前列素至少与每日使用拉坦前列素滴眼液一样有效。需要更多研究来确定耐受性良好且效果最佳的最佳持续释放剂量。隐形眼镜药物递送可能成为治疗青光眼的一种选择以及眼部药物递送的一个平台。