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Ralph Pinheiro, Claudia Panfil, R Michael Dutescu, Norbert Schrage; The impact of glaucoma medication on the corneal irritability and effect on corneal healing in case of abrasions. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4687.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the impact of anti-glaucoma drugs on the corneal healing process.
The four eye drops Xalatan® (latanoprost 50 µg/mL, Pfizer), Monoprost® (latanoprost 50 µg/mL, Théa Pharma), Taflotan sine® (tafluprost 15 μg/mL, Santen) and Travatan® (travoprost 40 μg/mL, Alcon) were tested regarding their corneal irritability and effect on corneal healing. As positive control, 0.02% benzalconium chloride (BAC) solution was employed, HyloComod® (1 mg/mL sodium hyaluronate, URSAPHARM) as negative control. Eye drops and BAC were tested on three corneae, HyloComod on a single cornea. Formulas were tested over 3 days and administered 6 times daily on rabbit corneas cultured on an artificial anterior chamber with a constant flow of an aqueous humor supplement (Ex Vivo Eye Irritation Test (EVEIT) system). Initially, four small corneal abrasions (2.5-7 mm2) were applied. All defects were monitored during drug application by fluorescein stains and photographs. At day 3, the corneal permeability condition was quantified photometrically in the anterior chamber fluid after incubation with apically applied fluorescein-sodium (5 mg/ml, 100 µl). Glucose/lactate concentrations were monitored for corneal metabolic activity evaluation.
After administration of Xalatan®, the corneal erosion size increased from 14.65 mm2 to 66.57 mm2, comparable to BAC (14.80 / 87.26 mm2). Travatan® and Taflotan sine® did not interfere with the corneal healing process. Monoprost® delayed corneal healing. For Xalatan® and BAC, histology shows severe alteration of the superficial cornea with distinct edema. An increase in anterior chamber lactate concentration and an enhanced fluorescein sodium corneal permeability indicates corneal toxicity for Xalatan®, BAC and Monoprost®.
The corneal toxicity of Xalatan® is most probably caused by BAC which is the preservative in this formulation. Compared to Travatan®, Taflotan sine® and Hylocomod®, Monoprost® delays the corneal healing process which is not well understood. The Monoprost effects could be caused by one of its additives, macrogolglycerolhydroxystearate 40. This excipient is a known skin irritant, and its concentration is relatively elevated in Monoprost, 50 mg/ml; i.e. in a w/w ratio of 1000/1 vs. latanoprost.
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