CLINICAL INVESTIGATION Diquafosol sodium ophthalmic solution for the treatment of dry eye: clinical evaluation and biochemical analysis of tear composition Chika Shigeyasu 1,2,3 • Masakazu Yamada 1 • Yoko Akune 3 • Kazuo Tsubota 2 Received: 9 March 2015 / Accepted: 25 June 2015 Ó Japanese Ophthalmological Society 2015 Abstract Purpose To evaluate the clinical efficacy of 3 % diqua- fosol sodium ophthalmic solution for dry eye, and to ana- lyze the concentration of tear proteins and mucin-like substances after the treatment. Methods Fifty eyes of 25 patients with dry eye syndrome were prospectively enrolled. The patients were treated with diquafosol solution at a dose of 1 drop in each eye 6 times daily for 4 weeks. The parameters of clinical efficacy were tear osmolarity, tear breakup time (BUT), fluorescein staining scores for the cornea and conjunctiva, Schirmer test values, and subjective symptoms evaluated using the ocular surface disease index (OSDI). Tears collected with Schirmer test strips were analyzed by high-performance liquid chromatography, and the concentrations of the total protein and the 4 major tear proteins, namely, secretory IgA, lactoferrin, lipocalin-1, lysozyme, and N-acetyl-neu- raminic acid (Neu5Ac), were measured. Neu5Ac is a major sialic acid, a marker of secretory mucins. Results The BUT, keratoconjunctival staining scores, and Schirmer test values were improved with statistical sig- nificance after the treatment with diquafosol solution, while changes in the other parameters, including tear osmolarity, corneal staining scores, and OSDI scores were not signif- icant. The Neu5Ac concentration was significantly increased, which was not accompanied by changes in tear proteins. Conclusions Topical application of diquafosol signifi- cantly improved the clinical parameters of the BUT, ker- atoconjunctival staining scores, and Schirmer test values and was accompanied by increased sialic acid content in the tears of patients with dry eye. Keywords Diquafosol ophthalmic solution Á Dry eye syndrome Á Mucins Á Tears Á Sialic acid Introduction Recent investigations of dry eye have elucidated the cel- lular and molecular mechanisms of tear dysfunction and have led to the development of new therapies other than supplementation by ocular lubricants, with disease-related factors as the target [1]. One of these new therapies tar- geted to the biochemical mechanism is a P2Y 2 purinergic receptor agonist, diquafosol sodium. Diquafosol is more stable than other receptor agonists such as adenosine triphosphate and uridine 5 0 -triphosphate [2]. P2Y 2 recep- tors are present at various sites on the ocular surface, including goblet cells, the corneal epithelium, the meibo- mian glands, and ductal cells [3]. Binding of diquafosol to P2Y 2 receptors increases intracellular calcium concentra- tions and activates chloride ion transport, which drives fluid transport across the epithelial layer [4]. Studies have reported increased tear volume after the instillation of diquafosol in animal models [4, 5]. Increases in intracel- lular calcium concentrations induced by diquafosol also stimulate conjunctival goblet cell degranulation and the & Chika Shigeyasu shigeyasu@eye-center.org 1 Department of Ophthalmology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan 2 Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan 3 Division for Vision Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo 152-8982, Japan 123 Jpn J Ophthalmol DOI 10.1007/s10384-015-0408-y