Skip to main content

Multicenter, Randomized, Controlled Study Comparing Tafluprost/Timolol Fixed Combination with Latanoprost/Timolol Fixed Combination in Primary Open-Angle Glaucoma and Ocular Hypertension

Advances in Therapy volume 35, pages 796–808 (2018)Cite this article

A Correction to this article was published on 08 January 2019

This article has been updated

Abstract

Introduction

This was the first exploratory randomized controlled study to compare the efficacy and safety of a preserved tafluprost/timolol fixed combination (TAF/TIM) with a preserved latanoprost/timolol fixed combination (LAT/TIM).

Methods

This prospective, randomized, open-label study was conducted in Japanese patients with primary open-angle glaucoma, including normal-tension glaucoma or ocular hypertension. Following a 4-week LAT/TIM run-in period, eligible patients entered a 12-week treatment period, during which they received either LAT/TIM or TAF/TIM. The efficacy endpoint was the change in intraocular pressure (IOP) from baseline to week 12 and the safety endpoints included the changes from baseline to week 12 in superficial punctate keratopathy (SPK) score, tear breakup time (TBUT), and hyperemia score, as well as adverse events (AEs). At week 6, ocular symptoms were evaluated using a questionnaire.

Results

In total, 131 patients provided informed consent. Of these, 115 completed the run-in period and were assigned to receive TAF/TIM (n = 60) or LAT/TIM (n = 55). At week 12, there were no significant differences between the TAF/TIM and LAT/TIM groups in the change from baseline in trough IOP and IOP at 4–6 h after instillation. There were no significant differences between the two groups in the change from baseline to week 12 in SPK score, TBUT, and hyperemia score. However, only in the TAF/TIM group, the total SPK score and the inferior cornea SPK score were significantly lower at week 12 compared with baseline. Eye irritation and eye pain were significantly decreased in the TAF/TIM group compared with the LAT/TIM group. Two treatment-related AEs were reported in the TAF/TIM group (3.3%) and none in the LAT/TIM group, while no serious AEs were reported in either group.

Conclusion

TAF/TIM is as effective as LAT/TIM in terms of IOP-reducing effect, with fewer ocular symptoms. TAF/TIM was associated with a significant improvement in SPK scores.

Trial Registration

UMIN Clinical Trials Registry Identifier, UMIN000023862.

Funding

Santen Pharmaceutical Co., Ltd., Osaka, Japan.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Change history

  • 08 January 2019

    In the original publication, the range to derive the P values is incorrectly represented in Table 2 and Table 3. The corrected tables are provided below.

References

  1. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90:262–7.

    Article  CAS  Google Scholar 

  2. Marquis RE, Whitson JT. Management of glaucoma: focus on pharmacological therapy. Drugs Aging. 2005;22:1–21.

    Article  CAS  Google Scholar 

  3. National Institute for Health and Care Excellence. Glaucoma: diagnosis and management, NICE guideline [NG81] 2017. https://www.nice.org.uk/guidance/ng81.

  4. Newman-Casey PA, Robin AL, Blachley T, et al. The most common barriers to glaucoma medication adherence: a cross-sectional survey. Ophthalmology. 2015;122:1308–16.

    Article  Google Scholar 

  5. Weinreb RN, Aung T, Medeiros FA. The pathophysiology and treatment of glaucoma: a review. JAMA. 2014;311:1901–11.

    Article  Google Scholar 

  6. Tsai JC, McClure CA, Ramos SE, Schlundt DG, Pichert JW. Compliance barriers in glaucoma: a systematic classification. J Glaucoma. 2003;12:393–8.

    Article  Google Scholar 

  7. Hollo G, Topouzis F, Fechtner RD. Fixed-combination intraocular pressure-lowering therapy for glaucoma and ocular hypertension: advantages in clinical practice. Exp Opin Pharmacother. 2014;15:1737–47.

    Article  CAS  Google Scholar 

  8. European Glaucoma Society. Terminology and guidelines for glaucoma, 4th edition—Chapter 3. Br J Ophthalmol. 2017;101:129–91.

    Google Scholar 

  9. Russ HH, Nogueira-Filho PA, Barros Jde N, et al. Ocular surface evaluation in patients treated with a fixed combination of prostaglandin analogues with 0.5% timolol maleate topical monotherapy: a randomized clinical trial. Clinics (Sao Paulo). 2013;68:1318–24.

    Article  Google Scholar 

  10. Shoji T, Sato H, Mizukawa A, et al. Hypotensive effect of latanoprost/timolol versus travoprost/timolol fixed combinations in NTG patients: a randomized, multicenter, crossover clinical trial. Invest Ophthalmol Vis Sci. 2013;54:6242–7.

    Article  CAS  Google Scholar 

  11. Topouzis F, Melamed S, Danesh-Meyer H, et al. A 1-year study to compare the efficacy and safety of once-daily travoprost 0.004%/timolol 0.5% to once-daily latanoprost 0.005%/timolol 0.5% in patients with open-angle glaucoma or ocular hypertension. Eur J Ophthalmol. 2007;17:183–90.

    Article  CAS  Google Scholar 

  12. Kanamoto T, Kiuchi Y, Tanito M, et al. Comparison of the toxicity profile of benzalkonium chloride-preserved tafluprost and SofZia-preserved travoprost applied to the ocular surface. J Ocul Pharmacol Ther. 2015;31:156–64.

    Article  CAS  Google Scholar 

  13. Shimmura S, Ono M, Shinozaki K, et al. Sodium hyaluronate eyedrops in the treatment of dry eyes. Br J Ophthalmol. 1995;79:1007–11.

    Article  CAS  Google Scholar 

  14. Li T, Lindsley K, Rouse B, et al. Comparative effectiveness of first-line medications for primary open-angle glaucoma. Ophthalmology. 2016;123:129–40.

    Article  Google Scholar 

  15. Aihara M. Clinical appraisal of tafluprost in the reduction of evaluated intraocular pressure (IOP) in open-angle glaucoma and ocular hypertension. Clin Ophthalmol. 2010;4:163–70.

    Article  Google Scholar 

  16. Hollo G, Vuorinen J, Tuominen J, Huttunen T, Ropo A, Pfeiffer N. Fixed-dose combination of tafluprost and timolol in the treatment of open-angle glaucoma and ocular hypertension: comparison with other fixed-combination products. Adv Ther. 2014;31:932–44.

    Article  CAS  Google Scholar 

  17. Lou H, Wang H, Zong Y, Cheng JW, Wei RL. Efficacy and tolerability of prostaglandin-timolol fixed combinations: an updated systematic review and meta-analysis. Curr Med Res. 2015;31:1139–47.

    Article  CAS  Google Scholar 

  18. Konstas AG, Voudouragkaki IC, Boboridis KG, et al. 24-hour efficacy of travoprost, timolol BAK-free versus latanoprost, timolol fixed combinations in patients insufficiently controlled with latanoprost. Adv Ther. 2014;31:592–603.

    Article  CAS  Google Scholar 

  19. Fuwa M, Ueda K, Akaishi T, et al. Advantages of efficacy and safety of fixed-dose tafluprost/timolol combination over fixed-dose latanoprost/timolol combination. PLoS One. 2016;11:e0158797.

    Article  Google Scholar 

  20. Baudouin C, Labbé A, Liang H, Pauly A, Bringnole-Baudouin F. Preservatives in eyedrops: the good, the bad and the ugly. Prog Retin Eye Res. 2010;29:312–34.

    Article  CAS  Google Scholar 

  21. Aihara M, Ikeda Y, Mizoue S, Arakaki Y, Kita N, Kobayashi S. Effect of switching to travoprost preserved with SofZia in glaucoma patients with chronic superficial punctate keratitis while receiving BAK-preserved latanoprost. J Glaucoma. 2016;25:e610–4.

    Article  Google Scholar 

  22. Aihara M, Oshima H, Araie M. Effects of SofZia-preserved travoprost and benzalkonium chloride-preserved latanoprost on the ocular surface—a multicentre randomized single-masked study. Acta Ophthalmol. 2013;91:e7–14.

    Article  CAS  Google Scholar 

  23. Suzuki K, Teranishi S, Sagara T, et al. Safety and efficacy of benzalkonium chloride-optimized tafluprost in Japanese glaucoma patients with existing superficial punctate keratitis. J Glaucoma. 2015;24:e145–50.

    Article  Google Scholar 

  24. Aihara M, Adachi M, Matsuo H, et al. Additive effects and safety of fixed combination therapy with 1% brinzolamide and 0.5% timolol versus 1% dorzolamide and 0.5% timolol in prostaglandin-treated glaucoma patients. Acta Ophthalmol. 2017;95:e720–6.

    Article  CAS  Google Scholar 

  25. Adriaens E, Remon JP. Mucosal irritation potential of personal lubricants relates to product osmolality as detected by the slug mucosal irritation assay. Sex Transm Dis. 2008;35:512–6.

    Article  CAS  Google Scholar 

  26. Tsai JC. A comprehensive perspective on patient adherence to topical glaucoma therapy. Ophthalmology. 2009;116:S30–6.

    Article  Google Scholar 

  27. Chen PP. Blindness in patients with treated open-angle glaucoma. Ophthalmology. 2003;110:726–33.

    Article  Google Scholar 

  28. Denis P, Lafuma A, Berdeaux G. Medical outcomes of glaucoma therapy from a nationwide representative survey. Clin Drug Investig. 2004;24:343–52.

    Article  Google Scholar 

  29. Forsman E, Kivela T, Vesti E. Lifetime visual disability in open-angle glaucoma and ocular hypertension. J Glaucoma. 2007;16:313–9.

    Article  Google Scholar 

Download references

Acknowledgements

We wish to express our gratitude to the participants of the study.

Funding

Sponsorship for this study and article processing charges were funded by Santen Pharmaceutical Co., Ltd., Osaka, Japan. All authors had full access to all of the data in these studies and take complete responsibility for the integrity of the data and accuracy of the data analysis.

Medical Writing

We would like to thank Sheridan Henness, Sarah Greig, and Georgii Filatov, inScience Communications, Springer Healthcare, who wrote the outline and the first draft of this manuscript. This medical writing assistance was funded by Santen Pharmaceutical Co., Ltd.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published.

Authorship Contributions

Please refer to Supplementary Table 1 for the full list of participants in the Tafluprost/Timolol Versus Latanoprost/Timolol (TTVLT) Study Group.

Disclosures

Katsuyoshi Suzuki has received research grants and consultant fees from Alcon Pharmaceuticals, Kowa Pharmaceutical Co., Ltd., Nitten Pharmaceutical Co., Ltd., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., and Senju Pharmaceutical Co., Ltd.; lecture fees from Alcon Pharmaceuticals, AMO Japan, Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., and Senju Pharmaceutical Co., Ltd.; writing fees from Alcon Pharmaceuticals, Pfizer Japan Inc., and Santen Pharmaceutical Co., Ltd.; and non-financial support from Alcon Pharmaceuticals, AMO Japan, Kowa Pharmaceutical Co., Ltd., Nitten Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., and Senju Pharmaceutical Co., Ltd. Yasuaki Kuwayama has received consultant fees from Alcon Pharmaceuticals, Kowa Company, Ltd., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., and Santen Pharmaceutical Co., Ltd.; and lecture fees from Alcon Japan, Alcon Pharmaceuticals, Glaukos Corporation, Kowa Company, Ltd., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., and Senju Pharmaceutical Co., Ltd. Masayo Hashimoto is an employee of Santen Pharmaceutical Co., Ltd. Naomi Otsuka is an employee of Santen Pharmaceutical Co., Ltd. Hiroko Hizaki is an employee of Santen Pharmaceutical Co., Ltd.

Compliance with Ethics Guidelines

The ethics review boards of Santen Pharmaceutical Co., Ltd. and at study sites reviewed and approved the study protocol. All procedures performed in studies involving human participants were in accordance with Ethical Guidelines for Medical and Health Research Involving Human Subjects (Ministry of Health, Labour and Welfare, Japan, 2014), the ethical standards of the institutional and/or national research committee, and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study prior to commencement of any study procedures (visit 1; week − 4 ± 2 weeks).

Data Availability

The data sets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

Author information

Authors and Affiliations

  1. Suzuki Eye Clinic, Yamaguchi, Japan

    Katsuyoshi Suzuki

  2. Santen Pharmaceutical Co., Ltd., Osaka, Japan

    Naomi Otsuka, Hiroko Hizaki & Masayo Hashimoto

  3. Fukushima Eye Clinic, Osaka, Japan

    Yasuaki Kuwayama

Authors
  1. Katsuyoshi Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Naomi Otsuka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hiroko Hizaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masayo Hashimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yasuaki Kuwayama
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

On behalf of the Tafluprost/Timolol Versus Latanoprost/Timolol (TTVLT) Study Group

Corresponding author

Correspondence to Katsuyoshi Suzuki.

Additional information

Enhanced digital features

To view enhanced digital features for this article go to https://doi.org/10.6084/m9.figshare.6275282.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 183 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Suzuki, K., Otsuka, N., Hizaki, H. et al. Multicenter, Randomized, Controlled Study Comparing Tafluprost/Timolol Fixed Combination with Latanoprost/Timolol Fixed Combination in Primary Open-Angle Glaucoma and Ocular Hypertension. Adv Ther 35, 796–808 (2018). https://doi.org/10.1007/s12325-018-0718-9

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12325-018-0718-9

Keywords

  • Beta-blocker
  • Efficacy
  • Intraocular pressure
  • Latanoprost
  • Ocular hypertension
  • Ophthalmology
  • Primary open-angle glaucoma
  • Prostaglandin
  • Safety
  • Tafluprost