Skip to main content
Top
Published in: Japanese Journal of Ophthalmology 6/2015

01-11-2015 | Clinical Investigation

Diquafosol sodium ophthalmic solution for the treatment of dry eye: clinical evaluation and biochemical analysis of tear composition

Authors: Chika Shigeyasu, Masakazu Yamada, Yoko Akune, Kazuo Tsubota

Published in: Japanese Journal of Ophthalmology | Issue 6/2015

Login to get access

Abstract

Purpose

To evaluate the clinical efficacy of 3 % diquafosol sodium ophthalmic solution for dry eye, and to analyze 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-neuraminic 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 significance after the treatment with diquafosol solution, while changes in the other parameters, including tear osmolarity, corneal staining scores, and OSDI scores were not significant. The Neu5Ac concentration was significantly increased, which was not accompanied by changes in tear proteins.

Conclusions

Topical application of diquafosol significantly improved the clinical parameters of the BUT, keratoconjunctival staining scores, and Schirmer test values and was accompanied by increased sialic acid content in the tears of patients with dry eye.
Literature
1.
go back to reference Pflugfelder SC, Geerling G, Kinoshita S, Lemo MA, McCulley J, Nelson D, et al. Management and therapy of dry eye disease: report of the Management and Therapy Subcommittee of the International Dry Eye Workshop (2007). Ocul Surf. 2007;5:163–78.CrossRef Pflugfelder SC, Geerling G, Kinoshita S, Lemo MA, McCulley J, Nelson D, et al. Management and therapy of dry eye disease: report of the Management and Therapy Subcommittee of the International Dry Eye Workshop (2007). Ocul Surf. 2007;5:163–78.CrossRef
2.
go back to reference Nichols KK, Yerxa B, Kellerman DJ. Diquafosol tetrasodium: a novel dry eye therapy. Expert Opin Investig Drugs. 2004;13:47–54.CrossRefPubMed Nichols KK, Yerxa B, Kellerman DJ. Diquafosol tetrasodium: a novel dry eye therapy. Expert Opin Investig Drugs. 2004;13:47–54.CrossRefPubMed
3.
go back to reference Cowlen MS, Zhang VZ, Warnock L, Moyer CF, Peterson WM, Yerxa BR. Localization of ocular P2Y2 receptor gene expression by in situ hybridization. Exp Eye Res. 2003;77:77–84.CrossRefPubMed Cowlen MS, Zhang VZ, Warnock L, Moyer CF, Peterson WM, Yerxa BR. Localization of ocular P2Y2 receptor gene expression by in situ hybridization. Exp Eye Res. 2003;77:77–84.CrossRefPubMed
4.
go back to reference Murakami T, Fujihara T, Horibe Y, Nakamura M. Diquafosol elicits increases in net Cl-transport through P2Y2 receptor stimulation in rabbit conjunctiva. Ophthalmic Res. 2004;36:89–93.CrossRefPubMed Murakami T, Fujihara T, Horibe Y, Nakamura M. Diquafosol elicits increases in net Cl-transport through P2Y2 receptor stimulation in rabbit conjunctiva. Ophthalmic Res. 2004;36:89–93.CrossRefPubMed
5.
go back to reference Takaoka-Shichijyou Y, Murakami T, Nakamura M. Stimulatory effect of diquafosol tetrasodium on tear fluid secretion in normal rabbits [in Japanese]. Atarashii Ganka. 2011;28:1029–33. Takaoka-Shichijyou Y, Murakami T, Nakamura M. Stimulatory effect of diquafosol tetrasodium on tear fluid secretion in normal rabbits [in Japanese]. Atarashii Ganka. 2011;28:1029–33.
6.
go back to reference Jumblatt JE, Jumblatt MM. Regulation of ocular mucin secretion by P2Y2 nucleotide receptors in rabbit and human conjunctiva. Exp Eye Res. 1998;67:341–6.CrossRefPubMed Jumblatt JE, Jumblatt MM. Regulation of ocular mucin secretion by P2Y2 nucleotide receptors in rabbit and human conjunctiva. Exp Eye Res. 1998;67:341–6.CrossRefPubMed
7.
go back to reference Fujihara T, Murakami T, Nagano T, Nakamura M, Nakata K. INS365 suppresses loss of corneal epithelial integrity by secretion of mucin-like glycoprotein in a rabbit short-term dry eye model. J Ocul Pharmacol Ther. 2002;18:363–70.CrossRefPubMed Fujihara T, Murakami T, Nagano T, Nakamura M, Nakata K. INS365 suppresses loss of corneal epithelial integrity by secretion of mucin-like glycoprotein in a rabbit short-term dry eye model. J Ocul Pharmacol Ther. 2002;18:363–70.CrossRefPubMed
8.
go back to reference Nakamura M, Imanaka T, Sakamoto A. Diquafosol ophthalmic solution for dry eye treatment. Adv Ther. 2012;29:579–89.CrossRefPubMed Nakamura M, Imanaka T, Sakamoto A. Diquafosol ophthalmic solution for dry eye treatment. Adv Ther. 2012;29:579–89.CrossRefPubMed
9.
go back to reference Takamura E, Tsubota K, Watanabe H, Ohashi Y. A randomised, double-masked comparison study of diquafosol versus sodium hyaluronate ophthalmic solutions in dry eye patients. Br J Ophthalmol. 2012;96:1310–5.PubMedCentralCrossRefPubMed Takamura E, Tsubota K, Watanabe H, Ohashi Y. A randomised, double-masked comparison study of diquafosol versus sodium hyaluronate ophthalmic solutions in dry eye patients. Br J Ophthalmol. 2012;96:1310–5.PubMedCentralCrossRefPubMed
10.
go back to reference Matsumoto Y, Ohashi Y, Watanabe H, Tsubota K. Efficacy and safety of diquafosol ophthalmic solution in patients with dry eye syndrome: a Japanese phase 2 clinical trial. Ophthalmology. 2012;119:1954–60.CrossRefPubMed Matsumoto Y, Ohashi Y, Watanabe H, Tsubota K. Efficacy and safety of diquafosol ophthalmic solution in patients with dry eye syndrome: a Japanese phase 2 clinical trial. Ophthalmology. 2012;119:1954–60.CrossRefPubMed
11.
go back to reference Tauber J, Davitt WF, Bokosky JE, Nichols KK, Yerxa BR, Schaberg AE, et al. Double-masked, placebo-controlled safety and efficacy trial of diquafosol tetrasodium (INS365) ophthalmic solution for the treatment of dry eye. Cornea. 2004;23:784–92.CrossRefPubMed Tauber J, Davitt WF, Bokosky JE, Nichols KK, Yerxa BR, Schaberg AE, et al. Double-masked, placebo-controlled safety and efficacy trial of diquafosol tetrasodium (INS365) ophthalmic solution for the treatment of dry eye. Cornea. 2004;23:784–92.CrossRefPubMed
12.
go back to reference Koh S, Maeda N, Ikeda C, Oie Y, Soma T, Tsujikawa M, et al. Effect of diquafosol ophthalmic solution on the optical quality of the eyes in patients with aqueous-deficient dry eye. Acta Ophthalmol. 2014;92:e671–5.CrossRefPubMed Koh S, Maeda N, Ikeda C, Oie Y, Soma T, Tsujikawa M, et al. Effect of diquafosol ophthalmic solution on the optical quality of the eyes in patients with aqueous-deficient dry eye. Acta Ophthalmol. 2014;92:e671–5.CrossRefPubMed
13.
go back to reference Arita R, Suehiro J, Haraguchi T, Maeda S, Maeda K, Tokoro H, et al. Topical diquafosol for patients with obstructive meibomian gland dysfunction. Br J Ophthalmol. 2013;97:725–9.PubMedCentralCrossRefPubMed Arita R, Suehiro J, Haraguchi T, Maeda S, Maeda K, Tokoro H, et al. Topical diquafosol for patients with obstructive meibomian gland dysfunction. Br J Ophthalmol. 2013;97:725–9.PubMedCentralCrossRefPubMed
14.
go back to reference Yokoi N, Kato H, Kinoshita S. Facilitation of tear fluid secretion by 3% diquafosol ophthalmic solution in normal human eyes. Am J Ophthalmol. 2014;157:85–92.CrossRefPubMed Yokoi N, Kato H, Kinoshita S. Facilitation of tear fluid secretion by 3% diquafosol ophthalmic solution in normal human eyes. Am J Ophthalmol. 2014;157:85–92.CrossRefPubMed
16.
go back to reference Hwang HS, Sung YM, Lee WS, Kim EC. Additive effect of preservative-free sodium hyaluronate 0.1% in treatment of dry eye syndrome with diquafosol 3% eye drops. Cornea. 2014;33:935–41.CrossRefPubMed Hwang HS, Sung YM, Lee WS, Kim EC. Additive effect of preservative-free sodium hyaluronate 0.1% in treatment of dry eye syndrome with diquafosol 3% eye drops. Cornea. 2014;33:935–41.CrossRefPubMed
17.
go back to reference Shimazaki J, Tsubota K, Kinoshita S, Ohashi Y, Shimomura Y, Tagawa Y, et al. Definition and diagnosis of dry eye 2006 [in Japanese]. Atarashii Ganka. 2007;24:181–4. Shimazaki J, Tsubota K, Kinoshita S, Ohashi Y, Shimomura Y, Tagawa Y, et al. Definition and diagnosis of dry eye 2006 [in Japanese]. Atarashii Ganka. 2007;24:181–4.
18.
go back to reference Lemp MA, Baudouin C, Baum J, Dogru M, Foulks GN, Kinoshita S, et al. The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye Workshop (2007). Ocul Surf. 2007;5:75–92.CrossRef Lemp MA, Baudouin C, Baum J, Dogru M, Foulks GN, Kinoshita S, et al. The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye Workshop (2007). Ocul Surf. 2007;5:75–92.CrossRef
19.
go back to reference Shimmura S, Ono M, Shinozaki K, Toda I, Takamura E, Mashima Y, et al. Sodium hyaluronate eyedrops in the treatment of dry eyes. Br J Ophthalmol. 1995;79:1007–11.PubMedCentralCrossRefPubMed Shimmura S, Ono M, Shinozaki K, Toda I, Takamura E, Mashima Y, et al. Sodium hyaluronate eyedrops in the treatment of dry eyes. Br J Ophthalmol. 1995;79:1007–11.PubMedCentralCrossRefPubMed
20.
go back to reference Koh S, Watanabe H, Hosohata J, Hori Y, Hibino S, Nishida K, et al. Diagnosing dry eye using a blue-free barrier filter. Am J Ophthalmol. 2003;136:513–9.CrossRefPubMed Koh S, Watanabe H, Hosohata J, Hori Y, Hibino S, Nishida K, et al. Diagnosing dry eye using a blue-free barrier filter. Am J Ophthalmol. 2003;136:513–9.CrossRefPubMed
21.
22.
go back to reference Schiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL. Reliability and validity of the ocular surface disease index. Arch Ophthalmol. 2000;118:615–21.CrossRefPubMed Schiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL. Reliability and validity of the ocular surface disease index. Arch Ophthalmol. 2000;118:615–21.CrossRefPubMed
23.
go back to reference Yamada M, Mochizuki H, Kawai M, Tsubota K, Bryce TJ. Decreased tear lipocalin concentration in patients with meibomian gland dysfunction. Br J Ophthalmol. 2005;89:803–5.PubMedCentralCrossRefPubMed Yamada M, Mochizuki H, Kawai M, Tsubota K, Bryce TJ. Decreased tear lipocalin concentration in patients with meibomian gland dysfunction. Br J Ophthalmol. 2005;89:803–5.PubMedCentralCrossRefPubMed
24.
go back to reference Shigeyasu C, Hirano S, Akune Y, Mochizuki H, Yamada M. Evaluation of the frequency of ophthalmic solution application: washout effects of topical saline application on tear components. Curr Eye Res. 2013;38:722–8.CrossRefPubMed Shigeyasu C, Hirano S, Akune Y, Mochizuki H, Yamada M. Evaluation of the frequency of ophthalmic solution application: washout effects of topical saline application on tear components. Curr Eye Res. 2013;38:722–8.CrossRefPubMed
25.
go back to reference Yasueda S, Yamakawa K, Nakanishi Y, Kinoshita M, Kakehi K. Decreased mucin concentrations in tear fluids of contact lens wearers. J Pharm Biomed Anal. 2005;39:187–95.CrossRefPubMed Yasueda S, Yamakawa K, Nakanishi Y, Kinoshita M, Kakehi K. Decreased mucin concentrations in tear fluids of contact lens wearers. J Pharm Biomed Anal. 2005;39:187–95.CrossRefPubMed
26.
go back to reference Nakamura Y, Yokoi N, Tokushige H, Kinoshita S. Sialic acid in human tear fluid decreases in dry eye. Jpn J Ophthalmol. 2004;48:519–23.CrossRefPubMed Nakamura Y, Yokoi N, Tokushige H, Kinoshita S. Sialic acid in human tear fluid decreases in dry eye. Jpn J Ophthalmol. 2004;48:519–23.CrossRefPubMed
27.
go back to reference Kinoshita S, Kiorpes TC, Friend J, Thoft RA. Goblet cell density in ocular surface disease: a better indicator than tear mucin. Arch Ophthalmol. 1983;101:1284–7.CrossRefPubMed Kinoshita S, Kiorpes TC, Friend J, Thoft RA. Goblet cell density in ocular surface disease: a better indicator than tear mucin. Arch Ophthalmol. 1983;101:1284–7.CrossRefPubMed
28.
go back to reference Ralph RA. Conjunctival goblet cell density in normal subjects and in dry eye syndromes. Invest Ophthalmol. 1975;14:299–302.PubMed Ralph RA. Conjunctival goblet cell density in normal subjects and in dry eye syndromes. Invest Ophthalmol. 1975;14:299–302.PubMed
29.
go back to reference Corrales RM, de Paiva CS, Li DQ, Farley WJ, Henriksson JT, Bergmanson JP, et al. Entrapment of conjunctival goblet cells by desiccation-induced cornification. Invest Ophthalmol Vis Sci. 2011;52:3492–9.PubMedCentralCrossRefPubMed Corrales RM, de Paiva CS, Li DQ, Farley WJ, Henriksson JT, Bergmanson JP, et al. Entrapment of conjunctival goblet cells by desiccation-induced cornification. Invest Ophthalmol Vis Sci. 2011;52:3492–9.PubMedCentralCrossRefPubMed
30.
go back to reference Argueso P, Balaram M, Spurr-Michaud S, Keutmann HT, Dana MR, Gipson IK. Decreased levels of the goblet cell mucin MUC5AC in tears of patients with Sjogren syndrome. Invest Ophthalmol Vis Sci. 2002;43:1004–11.PubMed Argueso P, Balaram M, Spurr-Michaud S, Keutmann HT, Dana MR, Gipson IK. Decreased levels of the goblet cell mucin MUC5AC in tears of patients with Sjogren syndrome. Invest Ophthalmol Vis Sci. 2002;43:1004–11.PubMed
31.
go back to reference Danjo Y, Watanabe H, Tisdale AS, George M, Tsumura T, Abelson MB, et al. Alteration of mucin in human conjunctival epithelia in dry eye. Invest Ophthalmol Vis Sci. 1998;39:2602–9.PubMed Danjo Y, Watanabe H, Tisdale AS, George M, Tsumura T, Abelson MB, et al. Alteration of mucin in human conjunctival epithelia in dry eye. Invest Ophthalmol Vis Sci. 1998;39:2602–9.PubMed
32.
go back to reference Gipson IK, Hori Y, Argueso P. Character of ocular surface mucins and their alteration in dry eye disease. Ocul Surf. 2004;2:131–48.CrossRefPubMed Gipson IK, Hori Y, Argueso P. Character of ocular surface mucins and their alteration in dry eye disease. Ocul Surf. 2004;2:131–48.CrossRefPubMed
Metadata
Title
Diquafosol sodium ophthalmic solution for the treatment of dry eye: clinical evaluation and biochemical analysis of tear composition
Authors
Chika Shigeyasu
Masakazu Yamada
Yoko Akune
Kazuo Tsubota
Publication date
01-11-2015
Publisher
Springer Japan
Published in
Japanese Journal of Ophthalmology / Issue 6/2015
Print ISSN: 0021-5155
Electronic ISSN: 1613-2246
DOI
https://doi.org/10.1007/s10384-015-0408-y

Other articles of this Issue 6/2015

Japanese Journal of Ophthalmology 6/2015 Go to the issue

Scientific Reviewers

Scientific Reviewers