Dry eye disease (DED) treatment has come a long way since simple lubrication; newer options—at least internationally—now include mucin and water secretagogues. Among these agents is rebamipide, which can increase mucin secretion from the keratoconjunctival epithelium, increase the conjunctival goblet cell density and decrease ocular surface epithelial damage scores.1-5 Studies have confirmed the safety and efficacy of rebamipide, leading to the approval of 2% rebamipide as a mucin secretagogue in the treatment of DED in Japan in September 2011.6,7

To clarify the pharmacological effects of 2% rebamipide eye drops, researchers investigated keratoconjunctival alterations at the cellular level. They found that these drops were associated with improvements in ocular surface differentiation due to changes in mucosal functions at the cellular level, which they note may explain improvements in DED.8

The study included 15 patients with DED who received treatment with 2% rebamipide eye drops QID for 12 weeks. The team analyzed symptom score, tear film break-up time, fluorescein and lissamine green staining score, lid wiper epitheliopathy score, corneal sensitivity, squamous metaplasia grade and goblet cell density. They also evaluated nucleocytoplasmic ratios and corneal epithelial cells.8

The study authors saw a significant improvement in average symptom scores, tear film break-up times, staining scores, lid wiper scores and squamous metaplasia grades after treatment. They add that there were similar significant improvements in the average corneal epithelial cell densities and nucleocytoplasmic ratios upon cessation of treatment.8 

1. Urashima H, Takeji Y, Okamoto T, et al. Rebamipide increases mucin-like substance contents and periodic acid Schiff reagent-positive cells density in normal rabbits. J Ocul Pharmacol Ther. 2012;28(3):264-70.

2. Urashima H, Okamoto T, Takeji Y, et al. Rebamipide increases the amount of mucin-like substances on the conjunctiva and cornea in the N-acetylcysteine-treated in vivo model. Cornea. 2004;23(6):613-9.

3. Itoh S, Itoh K, Shinohara H. Regulation of human corneal epithelial mucins by rebamipide. Curr Eye Res. 2014;39(2):133-41.

4. Ohguchi T, Kojima T, Ibrahim OM, et al. The effects of 2% rebamipide ophthalmic solution on the tear functions and ocular surface of the superoxide dismutase-1 (sod1) knockout mice. Invest Ophthalmol Vis Sci. 2013;54:7793-802.

5. Takeji Y, Urashima H, Aoki A, et al. Rebamipide increases the mucin-like glycoprotein production in corneal epithelial cells. J Ocul Pharmacol Ther. 2012;28(3):259-63.

6. Kinoshita S, Awamura S, Nakamichi N, et al. A multicenter, open-label, 52-week study of 2% rebamipide (OPC-12759) ophthalmic suspension in patients with dry eye. Am J Ophthalmol. 2014;157:576-83.

7. Dogru M, Nakamura M, Shimazaki J, et al. Changing trends in the treatment of dry-eye disease. Expert Opin Investig Drugs. 2013;22(12):1581-601.

8. Simsek C, Dogru M, Shinzawa M, et al. The efficacy of 2% topical rebamipide on conjunctival squamous metaplasia and goblet cell density in dry eye disease. J Ocul Pharmacol Ther. June 28, 2019. [Epub ahead of print].