The Increase of Aqueous Tear Volume by Diquafosol Sodium in Dry-eye Patients With Sjögren's Syndrome

A Pilot Study

N Yokoi; H Kato; S Kinoshita


Eye. 2016;30(6):857-864. 

In This Article

Abstract and Introduction


Purpose To investigate the effect of 3% diquafosol sodium ophthalmic solution (DQS) on aqueous tear volume increase in dry-eye patients with Sjögren's syndrome (SS).

Methods In this pilot study, 17 dry-eye patients with SS (1 male and 16 females; mean age: 66.4 years) were enrolled and underwent topical instillation of two ophthalmic solutions, artificial tears (AT) in one eye and DQS in the fellow eye, in a masked manner. The central lower tear meniscus radius (TMR) curvature was measured before and at 15 min after instillation by video-meniscometry. Simultaneously, all patients self-evaluated their symptoms of wetness and stinging using a visual analog scale (VAS, in millimeters).

Results Topical instillation of DQS significantly increased the TMR at 15 min (mean: 0.21±0.08 (SD) mm) compared with at baseline (mean: 0.16±0.07 mm) (P<0.001, paired t-test), whereas AT had no effect at baseline (mean: 0.18±0.09 mm) or at 15 min (mean: 0.18±0.09 mm). The visual VAS score of wetness at 15-min post-instillation increased in both groups compared with at baseline. In the DQS-treated eyes, the post-instillation change in TMR from baseline was not correlated with the baseline value of the Schirmer test, corneal staining score, or conjunctival staining score.

Conclusions Topical instillation of DQS increased aqueous tear volume on the ocular surface of dry-eye patients with SS, with its action being independent of lacrimal gland function.


According to the Dry Eye WorkShop (DEWS) definition, dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear-film instability with potential damage to the ocular surface. It is accompanied by increased tear-film osmolarity and inflammation of the ocular surface.[1] In addition, the DEWS definition classifies dry eye as either aqueous tear-deficient dry eye or evaporative dry eye. Aqueous tear-deficient dry eye is the type of dry eye typically observed in Sjögren's syndrome (SS) cases. SS is an organ-specific autoimmune disease[2] and is considered to be associated with decreased tear-fluid secretion from the lacrimal gland and inflammation at the lacrimal gland and the ocular surface.[3–5]

Diquafosol sodium (DQS) ophthalmic solution, which has been approved in Japan for the treatment of dry eye, increases fluid secretion,[6–8] mucin secretion,[9,10] and membrane-binding mucin gene expression on the corneal surface.[11] Reportedly, DQS increases tear-film stability on the ocular surface, thereby improving the subjective symptoms and objective signs of dry eye.[12–15] In addition, DQS exhibits P2Y2 receptor agonist activity and accelerates fluid transport from the serosal to mucosal (tear) side via chloride channel activation following intracellular calcium ion concentration elevation in the conjunctival epithelium.[16,17] The findings of a previous study suggested that the stimulatory action of DQS on fluid secretion is independent of lacrimal gland function, because the Schirmer test results for a rat model of lacrimal gland removal showed aqueous fluid secretion.[6]

Reflective meniscometry is a method used to optically measure the tear meniscus radius (TMR).[18–21] In a previous study, we measured the changes in TMR over time in normal human eyes after instillation of DQS using meniscometry, and reported that there was a significant increase in the fluid volume up until 30 min after the instillation.[8] In this pilot study, we used meniscometry to evaluate the changes in aqueous tear volume after instillation of DQS in patients for whom a definitive diagnosis of SS with dry eye (determined by a Schirmer 1 test value of <10 mm) had been provided, and compared the results with those obtained after instillation of an artificial tear (AT) solution.