Preventative Effect of Topical Rebamipide Against Corneal Epithelium Disorders Caused by Diclofenac Sodium

Purpose: This study aimed to investigate the relationship between diclofenac sodium ophthalmic solution (DFNa) and corneal epithelial cell damage and to evaluate the preventive effect of rebamipide (RBM) on it. Methods: DFNa, DFNa/preservative-free (PF), or 0.5% chlorobutanol (CB) solution was instilled into the conjunctival sac of a normal rabbit eye, and corneal resistance measurement (using a corneal resistance device [CRD]) was performed 120 min after the end of instillation. Then, fluorescent staining (FL), corneal tissue staining (hematoxylin and eosin [H&E]), and immunostaining (zona occlusion-1) were performed (RBM-untreated group). However, RBM was instilled into the eyes of another group of normal rabbits, followed by each of the solutions; 120 min after the end of instillation, all evaluations were performed for this group (RBM treatment group). Results: Using the CRD method, in the RBM-untreated group, corneal resistance (CR; %) was found to be significantly reduced in DFNa (79.9 ± 19.4%), DFNa/PF (89.1 ± 17.3%), and 0.5% CB (83.8 ± 10.6%). In addition, DFNa and 0.5% CB solutions showed positive staining in the FL staining method. In the H&E staining method, some clear voids were observed in the outermost layer of the cornea using DFNa and 0.5% CB solutions. However, corneal epithelial damage was suppressed in the RBM treatment group. ZO-1 immunostaining in DFNa and 0.5% CB solutions revealed discontinuous localization of ZO-1 at the cell periphery. Conclusions: RBM eye drops were effective in preventing corneal epithelial damage caused by DFNa eye drops, and CB was considered to be the main causative agent of this damage.