Anti‐glaucoma drugs and their additives, testing the influence of excipients on the corneal healing process in the EX‐Vivo Eye Irritation Test (EVEIT) system

Abstract

AbstractPurpose This study examined the impact of anti‐glaucoma medications and their additives on the corneal healing process and corneal toxicity.Methods BAK‐free PG analogues (Lumigan UD, Monoprost, Taflotan Sine), soft preserved Travatan BAK free, as well as polyquaternium‐1 (0.001%) and Macrogolglycerolhydroxystearate 40 (5%) were tested regarding corneal irritability and effect on corneal healing against HYLO COMOD (1 mg/mL sodium hyaluronate) as positive and 0.02% benzalkonium chloride (BAK) as negative control. Formulas were applied over three days, six times daily on rabbit corneas cultured on an artificial anterior chamber the Ex Vivo Eye Irritation Test (EVEIT) system. Initially, four corneal abrasions (2.5–4.5 mm2) were induced. All defects were monitored by fluorescein stains and photographs.Results For BAK, the corneal erosion size increased from 14.16 mm² to 88.89 mm². A delay of corneal healing is evident for Monoprost (14.84 mm² to 9.45 mm²) and Macrogolglycerolhydroxystearate 40 (11.58 mm² to 1.56 mm²) in comparison to a complete healing for HYLO COMOD, Lumigan, Taflotan Sine, Travatan and polyquaternium‐1®. For both Monoprost and macrogolglycerolhydroxystearate 40, a bright opaque halo around the remaining erosion area could be noticed. Histology revealed severe alterations of the superficia stroma. Cornea tested without erosions show no corneal toxicity of macrogol 4000.Conclusion Macrogolglycerolhydroxystearate 40, an additive found in Monoprost® shows corneal toxicity solely in case of corneal erosions. This excipient is a known skin irritant. Therefore, the use of Monoprost® in patients with epithelial defects should be questioned. Commercial interest