Department of Ophthalmology and Visual Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Department of Ophthalmology, EL-Minia University Hospital, EL-Minia, Egypt.
Cutan Ocul Toxicol. 2020 Jun;39(2):158-164. doi: 10.1080/15569527.2020.1752228. Epub 2020 Apr 16.
Latanoprost ophthalmic solution is highly effective as a therapeutic agent for glaucoma and is applied worldwide. However, harmful effects on the corneal surface have been reported regarding the commercially available latanoprost ophthalmic solution. Corneal surface toxicity may be caused by the added preservative of the ophthalmic solution. In order to ascertain whether latanoprost itself can damage the cornea or if this is solely due to the added preservatives, this study attempted to determine the corneal changes that occur at different time periods following usage of preservative-free versus preserved latanoprost eye drops. Preservative-free latanoprost eye drops (Monoprost) or preserved latanoprost eye drops (Xalatan) containing 0.02% benzalkonium chloride (BAC) were instilled in the corneas of rabbits. For each of the two different eye drop solutions, the rabbits used in this experiment were divided into three exposure groups: 1 minute, 24 hour, and 1 week groups. Corneal transepithelial electrical resistance (TER) and scanning electron microscopy (SEM) were examined immediately (1 minute) after instillation, at 24 hours after instillation, and at 24 hours after 1 week of daily instillations of latanoprost. Hank's balanced salt solution was used in the control group. The mean corneal TER of the control group was 933.8 ± 279.0 Ω cm. In preservative-free latanoprost instilled corneas, there was no significant decrease in the TER or morphological changes at any of the time points, with the relative TER values of 117 ± 38%, 100 ± 34%, and 93 ± 21% for 1 minute, 1 day, and 1 week time points, respectively. In preserved latanoprost instilled corneas, SEM showed that only the immediate group exhibited superficial cell damage and a significant decrease in the corneal TER compared to the controls and other time points and to the immediate preservative-free latanoprost corneas. In the preserved latanoprost groups, the relative TER values were 18 ± 5%, 110 ± 28%, and 92 ± 10%, for the three respective observation time points. Preservative-free latanoprost can be safely instilled to the corneal epithelium. Latanoprost with 0.02% BAC has an immediate deleterious impact on the corneal epithelium; however, it disappears within 24 hours after instillation.
拉坦前列素滴眼液作为治疗青光眼的有效药物,已在全球范围内应用。然而,市售的拉坦前列素滴眼液对角膜表面有不良影响。角膜表面毒性可能是由于滴眼液中添加的防腐剂引起的。为了确定拉坦前列素本身是否会损害角膜,或者这是否仅仅是由于添加的防腐剂引起的,本研究试图确定使用无防腐剂和含防腐剂的拉坦前列素滴眼液后不同时间点角膜发生的变化。将无防腐剂的拉坦前列素滴眼液(Monoprost)或含 0.02%苯扎氯铵(BAC)的防腐剂拉坦前列素滴眼液(Xalatan)滴入兔角膜。对于两种不同的滴眼液溶液,本实验中使用的兔子分为三组暴露组:1 分钟组、24 小时组和 1 周组。在滴入后立即(1 分钟)、滴入后 24 小时和滴入后 1 周每天滴注拉坦前列素后 24 小时,检查角膜上皮间电阻(TER)和扫描电子显微镜(SEM)。对照组使用 Hank's 平衡盐溶液。对照组角膜 TER 的平均值为 933.8±279.0 Ω cm。在无防腐剂的拉坦前列素滴注的角膜中,在任何时间点均未见 TER 显著降低或形态变化,相对 TER 值分别为 117±38%、100±34%和 93±21%,分别为 1 分钟、1 天和 1 周。在含防腐剂的拉坦前列素滴注的角膜中,SEM 显示仅即刻组与对照组和其他时间点以及即刻无防腐剂的拉坦前列素角膜相比,表现出浅层细胞损伤和角膜 TER 显著降低。在含防腐剂的拉坦前列素组中,三个观察时间点的相对 TER 值分别为 18±5%、110±28%和 92±10%。无防腐剂的拉坦前列素可以安全地滴注到角膜上皮。含 0.02% BAC 的拉坦前列素对角膜上皮有即刻的有害影响;然而,它在滴注后 24 小时内消失。