Skip to main content
SpringerLink
Log in

Diquafosol Ophthalmic Solution 3 %: A Review of Its Use in Dry Eye

  • Adis Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Diquafosol ophthalmic solution 3 % (Diquas®) is a P2Y2 receptor agonist that promotes tear fluid and mucin secretion and is currently approved in Japan and South Korea for the treatment of dry eye. In randomized, double-blind, multicentre trials in patients with dry eye, significantly greater improvements in fluorescein and rose bengal staining scores were seen with diquafosol ophthalmic solution 3 % than with placebo, and diquafosol ophthalmic solution 3 % was noninferior to sodium hyaluronate ophthalmic solution 0.1 % in terms of the improvement in the fluorescein staining score and more effective than sodium hyaluronate ophthalmic solution 0.1 % in terms of the improvement in the rose bengal staining score. The efficacy of diquafosol ophthalmic solution 3 % in the treatment of dry eye was maintained in the longer term, with improvements also seen in subjective dry eye symptoms, and was also shown in a real-world setting. Diquafosol ophthalmic solution 3 % also demonstrated efficacy in various specific dry eye disorders, including aqueous-deficient dry eye, short tear film break-up time dry eye, obstructive meibomian gland dysfunction, dry eye following laser in situ keratomileusis surgery and dry eye following cataract surgery, as well as in contact lens wearers and visual display terminal users. Diquafosol ophthalmic solution 3 % was generally well tolerated in patients with dry eye, with eye irritation the most commonly reported adverse event. In conclusion, diquafosol ophthalmic solution 3 % is a useful option for the treatment of dry eye.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye workshop (2007). Ocul Surf. 2007;5(2):93–107

  2. Foulks GN. Pharmacological management of dry eye in the elderly patient. Drugs Aging. 2008;25(2):105–18.

    Article  CAS  PubMed  Google Scholar 

  3. 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(2):75–92

  4. Skalicky SE, Petsoglou C, Gurbaxani A, et al. New agents for treating dry eye syndrome. Curr Allergy Asthma Rep. 2013;13(3):322–8.

    Article  CAS  PubMed  Google Scholar 

  5. Lau OCF, Samarawickrama C, Skalicky SE. P2Y2 receptor agonists for the treatment of dry eye disease: a review. Clin Ophthalmol. 2014;8:327–34.

    PubMed Central  PubMed  Google Scholar 

  6. 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(2):163–78

  7. Santen. Diquas® (diquafosol soium) ophthalmic solution 3 %: Japanese prescribing information. 2014

  8. Pendergast W, Yerxa BR, Douglass JG 3rd, et al. Synthesis and P2Y receptor activity of a series of uridine dinucleoside 5′-polyphosphates. Bioorg Med Chem Lett. 2001;11(2):157–60.

    Article  CAS  PubMed  Google Scholar 

  9. Fujihara T, Murakami T, Nagano T, et al. 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(4):363–70.

    Article  CAS  PubMed  Google Scholar 

  10. Li Y, Kuang K, Yerxa B, et al. Rabbit conjunctival epithelium transports fluid, and P2Y22 receptor agonists stimulate Cl− and fluid secretion. Am J Physiol Cell Physiol. 2001;281:C595–602.

    CAS  PubMed  Google Scholar 

  11. Murakami T, Fujihara T, Horibe Y, et al. Diquafosol elicits increases in net Cl− transport through P2Y2 receptor stimulation in rabbit conjunctiva. Ophthalmic Res. 2004;36(2):89–93.

    Article  CAS  PubMed  Google Scholar 

  12. Cowlen MS, Zhang VZ, Warnock L, et al. Localization of ocular P2Y2 receptor gene expression by in situ hybridization. Exp Eye Res. 2003;77(1):77–84.

    Article  CAS  PubMed  Google Scholar 

  13. Jumblatt JE, Jumblatt MM. Regulation of ocular mucin secretion by P2Y2 nucleotide receptors in rabbit and human conjunctiva. Exp Eye Res. 1998;67(3):341–6.

    Article  CAS  PubMed  Google Scholar 

  14. Fujihara T, Murakami T, Fujita H, et al. Improvement of corneal barrier function by the P2Y2 agonist INS365 in a rat dry eye model. Invest Ophthalmol Vis Sci. 2001;42(1):96–100.

    CAS  PubMed  Google Scholar 

  15. Takaoka-Shichijo Y, Shinomiya K, Katsuta O, et al. Stimulatory action of diquafosol tetrasodium on mucin-like glucoprotein secretion in rabbit conjunctival tissues [in Japanese]. Atarashii Ganka. 2011;28(4):543–8.

    CAS  Google Scholar 

  16. Takaoka-Shichijo Y, Murakami T, Nakamura M. Stimulatory effect of diquafosol tetrasodium on tear fluid secretion in normal rabbits [in Japanese]. Atarashii Ganka. 2011;28(7):1029–33.

    CAS  Google Scholar 

  17. Nakamura M, Imanaka T, Sakamoto A. Diquafosol ophthalmic solution for dry eye treatment. Adv Ther. 2012;29(7):579–89.

    Article  CAS  PubMed  Google Scholar 

  18. Kojima T, Dogru M, Ibrahim OM, et al. The effects of 3 % diquafosol sodium application on the tear functions and ocular surface of the Cu, Zn-superoxide dismutase-1 (Sod1)-knockout mice. Mol Vis. 2014;20:929–38.

    PubMed Central  PubMed  Google Scholar 

  19. Hori Y, Maeno T. Effects of diquafosol ophthalmic solutions and rebamipide ophthalmic suspension on tear fluid volume in normal rabbits [in Japanese]. Atarashii Ganka. 2013;30(7):1007–10.

    CAS  Google Scholar 

  20. Sakamoto A, Takaoka-Shichijo Y, Yamashita N, et al. Combined effect of diquafosol tetrasodium and purified sodium hyaluronate ophthalmic solutions on tear fluid volume in normal rabbits [in Japanese]. Atarashii Ganka. 2012;29(8):1141–5.

    CAS  Google Scholar 

  21. Takaoka-Shichijo Y, Sakamoto A, Nakamura M. Effect of diquafosol tetrasodium on MUC5AC secretion by rabbit conjunctival tissues [in Japanese]. Atarashii Ganka. 2011;28(2):261–5.

    CAS  Google Scholar 

  22. Takaoka-Shichijo Y, Nakamura M. Stimulatory effect of diquafosol tetrasodium on the expression of membrane-binging mucin genes in cultured human corneal epithelial cells [in Japanese]. Atarashii Ganka. 2011;28(3):425–9.

    CAS  Google Scholar 

  23. Dota A, Nakamura M. Combined effect of diquafosol tetrasodium and sodium hyaluronate ophthalmic solutions in rat dry eye model [in Japanese]. Atarashii Ganka. 2011;28(10):1477–81.

    CAS  Google Scholar 

  24. Hori Y, Shiba T, Maeno T. Comparison of efficacy between diquafosol ophthalmic solutions and rebamipide ophthalmic suspensions in treatment of rat dry eye model [in Japanese]. Atarashii Ganka. 2014;31(1):105–9.

    CAS  Google Scholar 

  25. 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(1):85–92.

    Article  CAS  PubMed  Google Scholar 

  26. Koh S, Maeda N, Ikeda C, et al. Effect of instillation of eyedrops for dry eye on optical quality. Invest Ophthalmol Vis Sci. 2013;54(7):4927–33.

    Article  PubMed  Google Scholar 

  27. Shigeyasu C, Hirano S, Akune Y, et al. Diquafosol tetrasodium increases the concentration of mucin-like substances in tears of healthy human subjects. Curr Eye Res. 2014. doi:10.3109/02713683.2014.967871

    PubMed  Google Scholar 

  28. Matsumoto Y, Ohashi Y, Watanabe H, et al. Efficacy and safety of diquafosol ophthalmic solution in patients with dry eye syndrome: a Japanese phase 2 clinical trial. Ophthalmology. 2012;119(10):1954–60.

    Article  PubMed  Google Scholar 

  29. Takamura E, Tsubota K, Watanabe H, et al. A randomised, double-masked comparison study of diquafosol versus sodium hyaluronate ophthalmic solutions in dry eye patients. Br J Ophthalmol. 2012;96(10):1310–5.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Yamaguchi M, Tsubota K, Watanabe H, et al. The safety and efficacy of long-term treatment with 3 % diquafosol ophthalmic solution for dry eye [in Japanese]. Atarashii Ganka. 2012;29(4):527–35.

    Google Scholar 

  31. Koh S, Ikeda C, Takai Y, et al. Long-term results of treatment with diquafosol ophthalmic solution for aqueous-deficient dry eye. Jpn J Ophthalmol. 2013;57(5):440–6.

    Article  CAS  PubMed  Google Scholar 

  32. Yamaguchi M, Nishijima T, Shimazaki J, et al. Clinical usefulness of diquafosol for real-world dry eye patients: a prospective, open-label, non-interventional, observational study. Adv Ther. 2014;31(11):1169–81.

    Article  CAS  PubMed  Google Scholar 

  33. Kamiya K, Nakanishi M, Ishii R, et al. Clinical evaluation of the additive effect of diquafosol tetrasodium on sodium hyaluronate monotherapy in patients with dry eye syndrome: a prospective, randomized, multicenter study. Eye. 2012;26(10):1363–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Hwang HS, Sung Y-M, Lee WS, et al. Additive effect of preservative-free sodium hyaluronate 0.1 % in treatment of dry eye syndrome with diquafosol 3 % eye drops. Cornea. 2014;33(9):935–41.

    Article  PubMed  Google Scholar 

  35. Koh S, Maeda N, Ikeda C, et al. Effect of diquafosol ophthalmic solution on the optical quality of the eyes in patients with aqueous-deficient dry eye. Acta Ophthalmol (Copenh). 2014;92(8):e671–5.

    Article  CAS  Google Scholar 

  36. Shimazaki-Den S, Iseda H, Dogru M, et al. Effects of diquafosol sodium eye drops on tear film stability in short BUT type of dry eye. Cornea. 2013;32(8):1120–5.

    Article  PubMed  Google Scholar 

  37. Kaido M, Uchino M, Kojima T, et al. Effects of diquafosol tetrasodium administration on visual function in short break-up time dry eye. J Ocul Pharmacol Ther. 2013;29(6):595–603.

    Article  CAS  PubMed  Google Scholar 

  38. Jung HH, Kang YS, Sung MS, et al. Clinical efficacy of topical 3 % diquafosol tetrasodium in short tear film break-up time dry eye [in Korean]. J Korean Ophthalmol Soc. 2015;56(3):339–44.

    Article  Google Scholar 

  39. Kobashi H, Kamiya K, Igarashi A, et al. Intraocular scattering after instillation of diquafosol ophthalmic solution. Optom Vis Sci. 2014; doi:10.1097/OPX.0000000000000490.

    PubMed  Google Scholar 

  40. Arita R, Suehiro J, Haraguchi T, et al. Topical diquafosol for patients with obstructive meibomian gland dysfunction. Br J Ophthalmol. 2013;97(6):725–9.

    Article  PubMed Central  PubMed  Google Scholar 

  41. Toda I, Ide T, Fukumoto T, et al. Combination therapy with diquafosol tetrasodium and sodium hyaluronate in patients with dry eye after laser in situ keratomileusis. Am J Ophthalmol. 2014;157(3):616–22.

    Article  CAS  PubMed  Google Scholar 

  42. Masuda A, Mori Y, Nejima R. Efficacy of long-term treatment with diquafosol sodium for dry eye due to laser in situ keratomileusis [in Japanese]. Atarashii Ganka. 2013;30(2):249–53.

    Google Scholar 

  43. Mori Y, Nejima R, Masuda A, et al. Effect of diquafosol tetrasodium eye drop for persistent dry eye after laser in situ keratomileusis. Cornea. 2014;33(7):659–62.

    Article  PubMed  Google Scholar 

  44. Takeshita T. Effect of diquafosol sodium ophthalmic solution for dry eye after cataract surgery [in Japanese]. Rinsho Ganka. 2013;67(3):327–30.

    Google Scholar 

  45. Watanabe K. Efficacy and safety of combined 3 % diquafosol sodium and 0.3 % purified sodium hyaluronate for treatment of dry eye in wearers of frequent-replacement of one-day disposable soft contact lenses [in Japanese]. Nihon Contact Lens Gakkaishi. 2014;56:121–5.

    Google Scholar 

  46. Uchino Y, Tsubota K. Effect of switching treatment from existing therapy to 3 % diquafosol sodium eyedrops for dry eye in VDT users [in Japanese]. Atarashii Gankka. 2013;30(6):871–4.

    Google Scholar 

  47. Gong L, Sun X, Ma Z, et al. A randomised, parallel-group comparison study of diquafosol ophthalmic solution in patients with dry eye in China and Singapore. Br J Ophthalmol. 2015; doi:10.1136/bjophthalmol-2014-306084.

    Google Scholar 

  48. Takashima Y, Goya K, Matsuo M. Effect of switching from hyaluronate to diquafosol ophthalmic solution for mild dry eye [in Japanese]. Rinsho Ganka. 2013;67(6):929–33.

    Google Scholar 

  49. Tauber J, Davitt WF, Bokosky JE, 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(8):784–92.

    Article  CAS  PubMed  Google Scholar 

Download references

Disclosure

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit. Gillian Keating is a salaried employee of Adis/Springer.

Author information

Authors and Affiliations

  1. Springer, Private Bag 65901, Mairangi Bay 0754, Auckland, New Zealand

    Gillian M. Keating

Authors
  1. Gillian M. Keating
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gillian M. Keating.

Additional information

The manuscript was reviewed by: Y. Hori, Department of Ophthalmology, Toho University Omori Medical Center, Tokyo, Japan; S. Koh, Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka, Japan; Y. Mori, Miyata Eye Hospital, Miyakonojo, Japan; M. Yamada, Department of Ophthalmology, Kyorin University School of Medicine, Tokyo, Japan.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Keating, G.M. Diquafosol Ophthalmic Solution 3 %: A Review of Its Use in Dry Eye. Drugs 75, 911–922 (2015). https://doi.org/10.1007/s40265-015-0409-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-015-0409-7

Keywords

Search

Navigation