The Efficacy of 2% Topical Rebamipide on Conjunctival Squamous Metaplasia and Goblet Cell Density in Dry Eye Disease

Purpose: To clarify the pharmacological effects of 2% rebamipide eye drops on mucosal membrane functions of the ocular surface epithelium, we investigated keratoconjunctival alterations at the cellular level in this study. Methods: Fifteen patients with definite dry eye disease were recruited from outpatient clinics of the Department of Ophthalmology, Ichikawa General Hospital. The patients received treatment with 2% rebamipide eye drops q.i.d for 12 weeks. Symptom score assessment, tear film breakup time, fluorescein and lissamine green ocular surface vital staining, grading of lid wiper epitheliopathy, Cochet–Bonnet corneal sensitivity, assessment of squamous metaplasia grades, and goblet cell density calculations from conjunctival impression cytology samples, as well as evaluation of nucleocytoplasmic ratios and corneal epithelial cells from in vivo confocal microscopy images before and 3 months after treatment were performed. Results: The mean symptom scores, tear film breakup time values, ocular surface fluorescein and lissamine green vital staining scores, and lid wiper scores showed a significant improvement after treatment (P < 0.01). The mean squamous metaplasia grade also showed a significant improvement (1.2 ± 0.1 → 0.3 ± 0.1) 3 months after treatment (P = 0.004). There were similar significant improvements in the mean corneal epithelial cell density (660.1 ± 62.6 → 1015.5 ± 43.5 cells/mm(2)) (P = 0.002) and nucleocytoplasmic ratios (0.1 ± 0.0 → 0.2 ± 0.0) (P = 0.0042) after treatment. Conclusions: Topical use of 2% rebamipide for 3 months was associated with improvements in ocular surface differentiation due to changes of mucosal functions at the cellular level. These alterations may explain objective and subjective improvements in dry eye disease.