Pinheiro Ralph, Panfil Claudia, Schrage Norbert, Dutescu R Michael
*Aachen Centre of Technology Transfer in Ophthalmology (ACTO e.V.), An-Institute¸medizinischen Fakultät RWTH Aachen †Department of Ophthalmology, RWTH Aachen University, Aachen, Germany.
J Glaucoma. 2016 Jan;25(1):122-7. doi: 10.1097/IJG.0000000000000279.
To evaluate the impact of antiglaucoma drugs on the corneal healing process and corneal toxicity.
Four eye drops to treat glaucoma--Xalatan (latanoprost 50 μg/mL; Pfizer), Monoprost (latanoprost 50 μg/mL; Théa Pharma), Taflotan Sine (tafluprost 15 μg/mL; Santen Pharmaceutical Co.), Travatan (travoprost 40 μg/mL; Alcon), and 0.02% benzalkonium chloride (BAC) solution and HyloComod (1 mg/mL sodium hyaluronate; Ursapharm) as positive and negative control were tested regarding corneal irritability and effect on corneal healing. Formulas were tested over 3 days and administered 6 times daily on rabbit corneas cultured on an artificial anterior chamber (the Ex Vivo Eye Irritation Test system). Initially, 4 corneal abrasions (2.5 to 5.7 mm2) were applied. All defects were monitored during drug application by fluorescein stains and photographs. Glucose/lactate concentrations were monitored for corneal metabolic activity evaluation.
For Xalatan and BAC, the corneal erosion size increased from 14.65 to 66.57 mm2 and 14.80 to 87.26 mm2. Travatan and Taflotan Sine did not interfere with corneal healing. Monoprost delayed corneal healing. For Xalatan and BAC, histology showed severe alteration of the superficial cornea. An increase in anterior chamber lactate concentration indicates corneal toxicity for Xalatan, BAC, and Monoprost.
Corneal toxicity of Xalatan is most probably caused by BAC. Monoprost delays corneal healing, which is not well understood. The Monoprost effects could be caused by its additive, macrogolglycerolhydroxystearate 40. This excipient is a known skin irritant, and its concentration is relatively elevated in Monoprost, 50 mg/mL, compared with its active ingredient, latanoprost (0.05 mg/mL).
评估抗青光眼药物对角膜愈合过程及角膜毒性的影响。
用于治疗青光眼的四种滴眼液——适利达（拉坦前列素50μg/mL；辉瑞公司）、蒙诺前列腺素（拉坦前列素50μg/mL；泰亚制药公司）、苏为坦（他氟前列素15μg/mL；参天制药株式会社）、 travatan（曲伏前列素40μg/mL；爱尔康公司），以及0.02%苯扎氯铵（BAC）溶液和海露（透明质酸钠1mg/mL；乌尔萨制药公司）作为阳性和阴性对照，针对角膜刺激性及对角膜愈合的影响进行测试。将配方药物在3天内进行测试，并每天6次施用于在人工前房（体外眼刺激试验系统）中培养的兔角膜上。最初，施加4处角膜擦伤（面积为2.5至5.7mm²）。在给药期间，通过荧光素染色和拍照对所有缺损进行监测。监测葡萄糖/乳酸浓度以评估角膜代谢活性。
对于适利达和BAC，角膜糜烂面积从14.65mm²增加至66.57mm²以及从14.80mm²增加至87.26mm²。travatan和苏为坦未干扰角膜愈合。蒙诺前列腺素延迟了角膜愈合。对于适利达和BAC，组织学显示浅表角膜有严重改变。前房乳酸浓度升高表明适利达、BAC和蒙诺前列腺素具有角膜毒性。
适利达的角膜毒性很可能由BAC引起。蒙诺前列腺素延迟角膜愈合，其原因尚不清楚。蒙诺前列腺素的作用可能由其辅料聚乙二醇氢化蓖麻油40引起。这种辅料是一种已知的皮肤刺激物，与它的活性成分拉坦前列素（0.05mg/mL）相比，其在蒙诺前列腺素中的浓度相对较高，为50mg/mL。
