Corneal epithelial deficiency induced by the use of beta-blocker eye drops

Two studies were conducted to check the effects of beta-blocker eye drops, 2% carteolol (Mikelan) and 0.5% timolol (Timoptol), on regeneration of corneal epithelium in rabbit eyes. For the short-term study, epithelial deficiency was artificially induced in the cornea of albino rabbits. One of the beta-blocker eye drops or 0.005% benzalkonium chloride was applied in the right eye and physiological saline solution was applied to the left eye four times a day, and wound healing rate was calculated. Two weeks later, images of the surface epithelium were analyzed by scanning electron microscopy and proliferative capacity was studied, using proliferating cell nuclear antigen as a marker. The long-term study was conducted similarly except that the eye drops were applied twice a day and epithelial deficiency was re-induced every two weeks. In the short-term study, epithelial wound healing rate was slowed in beta-blocker groups. Significant differences were detected between the Mikelan and Timoptol groups, and the benzalkonium and physiological saline groups. The beta-blocker groups had severe epithelial cell desquamation, as well as detachment. In the long-term study, the Mikelan group had significantly delayed wound healing at first induction, the benzalkonium group showed delay up to the third induction and the Timoptol group up to the fifth induction. These studies indicate that beta-blocker eye drops delay corneal epithelial wound healing and supported the concept that corneal epithelial deficiency occurs clinically after the long-term administration of beta-blocker eye drops.