Comparison of Diquafosol and Rebamipide Ophthalmic Solutions in Patients with Refractory Sjögren’s Syndrome-Dry Eye

Purpose: To analyze the additive effect of the use of diquafosol or rebamipide ophthalmic solution in combination with standard treatment for patients with refractory Sjögren’s syndrome with dry eye (SSDE).Methods: The study included 52 SSDE patients treated with 0.05% cyclosporine eye drops and hyaluronic acid from December 2023 to March 2024. The patients were divided into a diquafosol group (n = 25) and a rebamipide group (n = 27). Tear breakup time (BUT), tear meniscus height (TMH), the Schirmer test, corneal and conjunctival staining scores, the conjunctival hyperemia index, the Standardized Patient Evaluation of Eye Dryness (SPEED) score, and tear levels of MMP-9 were evaluated. In subgroup analyses, we compared BUT, TMH, and corneal and conjunctival staining scores (CSS) among patients with a pretreatment MMP-9 expression level of 3 or higher.Results: Both groups showed significant improvement in BUT, TMH, the Schirmer test, corneal staining score, conjunctival hyperemia index, and SPEED scores after 3 months of treatment (p < 0.05). The CSS and MMP-9 grade significantly decreased only in the rebamipide group, being lower than those of the diquafosol group after treatment. In subgroup analyses, the rebamipide group exhibited improvement in all clinical parameters while the diquafosol group only improved in corneal staining scores.Conclusions: Rebamipide may be a good choice for treating SSDE patients when there is severe inflammation of the ocular surface and impairment of conjunctival epithelial cells.