latanoprost and Corneal-Injuries

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).

Topics: Administration, Topical; Animals; Antihypertensive Agents; Benzalkonium Compounds; Cornea; Corneal Injuries; Glaucoma; Intraocular Pressure; Latanoprost; Ophthalmic Solutions; Preservatives, Pharmaceutical; Prostaglandins F; Prostaglandins F, Synthetic; Rabbits; Travoprost; Wound Healing

Cationic emulsions (CEs), developed as vehicles for lipophilic drugs, have been shown to be safe and effective for the treatment of dry eye. The aim of this study was to investigate the effects of a preservative-free latanoprost 0.005% CE (latanoprost-CE) in in vitro and in vivo models of corneal wound healing.. An in vitro wound was made by scraping through a confluent layer of human corneal epithelial cells. Cytotoxicity, cell migration, and proliferation were analyzed after an exposure to phosphate-buffered saline, CE, latanoprost-CE, 0.02% benzalkonium chloride (0.02%BAK), and Xalatan (latanoprost). In vivo, the recovery and integrity of corneal wound healing were assessed in rat eyes instilled twice a day for 5 days with the above treatments after deepithelialization of the superior cornea.. In vitro wound distances decreased at 2 and 24 hours for human corneal epithelial cells exposed to CE, latanoprost-CE, and phosphate-buffered saline, whereas they progressively increased for 0.02%BAK-treated and latanoprost-treated cells. The greater wound closure was associated with a higher number of Ki67-positive cells. In CE- and latanoprost-CE-treated rats, reepithelialization of the cornea was enhanced, restoring normal appearance and function. In contrast, 0.02%BAK or latanoprost delayed corneal healing, induced inflammation, and decreased MUC5-AC expression.. Both models effectively evaluated the cytotoxicity and dynamic recovery of corneal wound healing, and their correlation supports the potential of the in vitro model as a reliable alternative to in vivo ocular toxicity tests. Both models demonstrated that in the face of corneal injury, CEs favored corneal healing, whereas BAK was deleterious.

Topics: Animals; Antihypertensive Agents; Benzalkonium Compounds; Cell Proliferation; Cells, Cultured; Conjunctiva; Cornea; Corneal Injuries; Disease Models, Animal; Drug Evaluation, Preclinical; Emulsions; Epithelium, Corneal; Eye Injuries; Humans; Ki-67 Antigen; Latanoprost; Male; Microscopy, Confocal; Mucin 5AC; Preservatives, Pharmaceutical; Prostaglandins F, Synthetic; Rats; Wound Healing