Effect of topical 3% diquafosol sodium on eyes with dry eye disease and meibomian gland dysfunction

Shiro Amano, Kenji Inoue, Shiro Amano, Kenji Inoue

Abstract

Purpose: To prospectively evaluate the effect of topical diquafosol sodium on eyes with dry eye disease (DED) and meibomian gland dysfunction (MGD).

Patients and methods: The subjects were consecutive patients diagnosed with both DED and MGD at Inouye Eye Hospital between March and September of 2016. The subjects were administered topical 3% diquafosol sodium ophthalmic solution six times a day for 3 months. At each study visit, subjects underwent slit-lamp examination and completed MGD symptoms and dry eye-related quality of life score (DEQS) questionnaires. Meibum quality (meibum score) and meibomian gland loss (meiboscore) were evaluated. Tear lipid layer thickness was measured in both eyes with an ocular surface interferometer immediately after clinic arrival and 20 minutes after instillation of one drop of topical diquafosol.

Results: Thirteen patients (3 men, 10 women) with a mean age of 69.5±8.3 years completed the 3-month study. The number of telangiectasia and plugged meibomian gland orifices significantly decreased from baseline after 1 month of diquafosol use. The meibum score and the meiboscore significantly decreased from baseline at 3 months. Also, the lipid layer thickness was greater after diquafosol administration than before administration at baseline and 1, 2, and 3 months by 12.2, 11.5, 9.5, and 17.0 nm, respectively, but this difference was only significant at 3 months (p=0.039). The DEQS ocular symptom (p=0.065) and MGD questionnaire (p=0.081) scores tended to be lower than baseline at 3 months.

Conclusion: Diquafosol sodium ophthalmic solution improves DED- and MGD-related signs in eyes with MGD.

Keywords: diquafosol; dry eye; meibomian gland dysfunction.

Conflict of interest statement

Disclosure Dr Amano reports a grant and personal fees from Santen Pharmaceutical. Dr Inoue reports personal fees from Santen Pharmaceutical. The authors report no other conflicts of interest in this work.

References

    1. Vallejo CG, Lobaton CD, Quintanilla M, Sillero A, Sillero MA. Dinucleosidasetetraphosphatase in rat liver and Artemia salina. Biochim Biophys Acta. 1976;438(1):304–309.
    1. Hosoya KI, Ueda H, Kim KJ, Lee VH. Nucleotide stimulation of Cl(−) secretion in the pigmented rabbit conjunctiva. J Pharmacol Exp Ther. 1999;291(1):53–59.
    1. Jumblatt JE, Jumblatt MM. Regulation of ocular mucin secretion by P2Y2 nucleotide receptors in rabbit and human conjunctiva. Exp Eye Res. 1998;67(3):341–346.
    1. 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(2):89–93.
    1. Nichols KK, Yerxa B, Kellerman DJ. Diquafosol tetrasodium: a novel dry eye therapy. Expert Opin Investig Drugs. 2004;13(1):47–54.
    1. Tauber J, Davitt WF, Bokosky JE, et al. Double-masked, placebo-controlled safety and efficacy trial of diquafosol (INS365) ophthalmic solution for the treatment of dry eye. Cornea. 2004;23(8):784–792.
    1. Matsumoto Y, Ohashi Y, Watanabe H, Tsubota K, et al. Diquafosol Ophthalmic Solution Phase 2 Study Group Diquafosol ophthalmic solution phase 2 study group. Efficacy and safety of diquafosol ophthalmic solution in patients with dry eye syndrome: a Japanese phase 2 clinical trial. Ophthalmology. 2012;119(10):1954–1960.
    1. 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(1):77–84.
    1. Tanioka H, Kuriki Y, Sakamoto A, Katsuta O, Kawazu K, Nakamura M. Expression of the P2Y2 receptor on the rat ocular surface during a 1-year rearing period. Jpn J Ophthalmol. 2014;58(6):515–521.
    1. Arita R, Suehiro J, Haraguchi T, et al. Topical diquafosol for patients with obstructive meibomian gland dysfunction. Br J Ophthalmol. 2013;97(6):725–729.
    1. Amano S, Inoue K. Clinic-based study on meibomian gland dysfunction in Japan. Invest Ophthalmol Vis Sci. 2017;58(2):1283–1287.
    1. Shimazaki J, Tsubota K, Kinoshita S, et al. Definition and diagnosis of dry eye 2006. Atarasii Ganka. 2007;24(2):181–184. Japanese.
    1. Finis D, Pischel N, Schrader S, Geerling G. Evaluation of lipid layer thickness measurement of the tear film as a diagnostic tool for Meibomian gland dysfunction. Cornea. 2013;32(12):1549–1553.
    1. Ji YW, Lee J, Lee H, Seo KY, Kim EK, Kim TI. Automated measurement of tear film dynamics and lipid layer thickness for assessment of non-Sjögren dry eye syndrome with meibomian gland dysfunction. Cornea. 2017;36(2):176–182.
    1. Sakane Y, Yamaguchi M, Yokoi N, et al. Development and validation of the dry eye-related quality-of-life score questionnaire. JAMA Ophthalmol. 2013;131(10):1331–1318.
    1. Arita R, Minoura I, Morishige N, et al. Development of definitive and reliable grading scales for meibomian gland dysfunction. Am J Ophthalmol. 2016;169:125–137.
    1. Yamaguchi M, Kutsuna M, Uno T, Zheng X, Kodama T, Ohashi Y. Marx line: fluorescein staining line on the inner lid as indicator of meibomian gland function. Am J Ophthalmol. 2006;141(4):669–675.
    1. Yokoi N, Uchino M, Uchino Y, et al. Importance of tear film instability in dry eye disease in office workers using visual display terminals: the Osaka study. Am J Ophthalmol. 2015;159(4):748–754.
    1. van Bijsterveld OP. Diagnostic tests in the Sicca syndrome. Arch Ophthalmol. 1969;82(1):10–14.
    1. Shimazaki J, Goto E, Ono M, Shimmura S, Tsubota K. Meibomian gland dysfunction in patients with Sjogren syndrome. Ophthalmology. 1998;105(8):1485–1488.
    1. Arita R, Itoh K, Inoue K, Amano S. Noncontact infrared meibography to document age-related changes of the meibomian glands in a normal population. Ophthalmology. 2008;115(5):911–915.
    1. Shirakawa R, Arita R, Amano S. Meibomian gland morphology in Japanese infants, children, and adults observed using a mobile pen-shaped infrared meibography device. Am J Ophthalmol. 2013;155(6):1099–1103.
    1. Fukuoka S, Arita R. Increase in tear film lipid layer thickness after instillation of 3% diquafosol ophthalmic solution in healthy human eyes. Ocul Surf. 2017 S1542–0124(16):30288–30289.
    1. Kam WR, Liu Y, Ding J, Sullivan DA. Do cyclosporine A, an IL-1 receptor antagonist, uridine triphosphate, rebamipide, and/or bimatoprost regulate human meibomian gland epithelial cells? Invest Ophthalmol Vis Sci. 2016;57(10):4287–4494.
    1. Wen Q, Li Y, Kuang K, Yerxa B, Fischbarg J. Effects of P2Y2 agonists on lipid secretion by cultured rabbit meibocytes. Invest Ophthalmol Vis Sci. 2002;43(13):3146.
    1. Yerxa BR, Sabater JR, Davis CW, et al. Pharmacology of INS37217 [P1-(uridine 5′)-P4-(2′-deoxycytidine 5′)tetraphosphate, tetrasodium salt], a next-generation P2Y2 receptor agonist for the treatment of cystic fibrosis. J Pharmacol Exp Ther. 2002;302(3):871–880.

Source: PubMed

3
订阅