Skip to main content

Additive Intraocular Pressure Lowering Effects of the Rho Kinase Inhibitor, Ripasudil in Glaucoma Patients Not Able to Obtain Adequate Control After Other Maximal Tolerated Medical Therapy

Advances in Therapy volume 33, pages 1628–1634 (2016)Cite this article

Abstract

Introduction

The aim of this study is to investigate the additive intraocular pressure (IOP)-lowering effects and safety of the selective Rho kinase inhibitor, 0.4% ripasudil, in patients with glaucoma not adequately controlled by other maximal tolerated medical therapies.

Methods

We retrospectively reviewed 92 glaucoma patients who received ripasudil as an additive glaucoma treatment. In spite of receiving prior maximal tolerated medical therapies, all patients had uncontrolled glaucoma before receiving ripasudil. IOP was recorded at all follow-up dates.

Results

The study population consisted of 43 primary open-angle glaucoma (POAG), 28 normal-tension glaucoma (NTG), ten secondary glaucoma, seven exfoliation glaucoma, and four developmental glaucoma patients. After ripasudil administration, there was a significant decrease in the IOP. The mean pre-administration IOP and % IOP reduction at the last follow-up were 19.7 ± 4.9 mmHg and 6.5 ± 17.0% for POAG, 15.5 ± 2.0 mmHg and 2.3 ± 10.4% for NTG, 22.8 ± 8.3 mmHg and 19.1 ± 13.5% for secondary glaucoma, 22.5 ± 4.4 mmHg and 2.1 ± 14.5% for exfoliation glaucoma, and 20.2 ± 8.9 mmHg and 11.4 ± 23.1% for developmental glaucoma, respectively. Side effects led to ripasudil discontinuation in 13 patients, with five exhibiting an allergic reaction, six developing blepharitis, and two having a burning sensation.

Conclusions

Use of ripasudil as an adjunctive therapy resulted in lowering of the IOP. Ripasudil was well tolerated.

Funding

Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (26462689).

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. Weinreb RN, Khaw PT. Primary open-angle glaucoma. Lancet. 2004;363:1711–20.

    Article  PubMed  Google Scholar 

  2. Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120:701–13.

    Article  PubMed  Google Scholar 

  3. Honjo M, Tanihara H, Inatani M, et al. Effects of Rho-associated protein kinase inhibitor, Y-27632, on intraocular pressure outflow facility. Invest Ophthalmol Vis Sci. 2001;42:137–44.

    CAS  PubMed  Google Scholar 

  4. Tokushige H, Inatani M, Nemoto S, et al. Effects of topical administration of Y-39983, a selective rho-associated protein kinase inhibitor, on ocular tissues in rabbits and monkeys. Invest Ophthalmol Vis Sci. 2007;48:3216–22.

    Article  PubMed  Google Scholar 

  5. Isobe T, Mizuno K, Kaneko Y, Ohta M, Koide T, Tanabe S. Effects of K-115, a Rho-kinase inhibitor on aqueous humor dynamics in rabbits. Curr Eye Res. 2014;39:813–22.

    CAS  Article  PubMed  Google Scholar 

  6. Tanihara H, Inoue T, Yamamoto T, Kuwayama Y, Abe H, Araie M, K-115 Clinical Study Group. Phase I clinical trials of a selective Rho kinase inhibitor K-115. JAMA Ophthalmol. 2013;131:1288–95.

    CAS  Article  PubMed  Google Scholar 

  7. Tanihara H, Inoue T, Yamamoto T, Kuwayama Y, Abe H, Araie M, K-115 Clinical Study Group. Phase 2 randomized clinical study of a rho kinase inhibitor, K-115, in primary open-angle glaucoma and ocular hypertension. Am J Ophthalmol. 2013;156:731–6.

    CAS  Article  PubMed  Google Scholar 

  8. Tanihara H, Inoue T, Yamamoto T, Kuwayama Y, Abe H, Araie M, K-115 Clinical Study Group. Intra-ocular pressure-lowering effects of a Rho kinase inhibitor, ripasudil (K-115), over 24 hours in primary open-angle glaucoma and ocular hypertension: a randomized, open-label, crossover study. Acta Ophthalmol. 2015;93:e254–60.

    CAS  Article  PubMed  Google Scholar 

  9. Tanihara H, Inoue T, Yamamoto T, et al. Additive intraocular pressure-lowering effects of the rho kinase inhibitor ripasudil (K-115) combined with timolol or latanoprost. JAMA Ophthalmol. 2015;133:755–61.

    Article  PubMed  Google Scholar 

  10. Hodapp E, Parrish RK II, Anderson DR. Clinical detection in glaucoma. St. Louis: Mosby; 1993. p. 52–61.

    Google Scholar 

  11. Tanihara H, Inoue T, Yamamoto T, et al. One-year clinical evaluation of 0.4% ripasudil (K-115) in patients with open-angle glaucoma and ocular hypertension. Acta Ophthalmol. 2016;94:e26–34.

    CAS  Article  PubMed  Google Scholar 

Download references

Acknowledgments

Sponsorship and article processing charges for this study were funded by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (26462689).

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.

Data collection and analysis of this manuscript was provided by Dr. Shino Sato.

Writing of this manuscript was provided by Dr. Kazuyuki Hirooka.

Editing assistance of this manuscript was provided by Dr. Eri Nitta, Dr. Kaori Ukegawa and Dr. Akitaka Tsujikawa.

Disclosures

Shino Sato, Kazuyuki Hirooka, Eri Nitta, Kaori Ukegawa, and Akitaka Tsujikawa have nothing to disclose.

Compliance with Ethics Guidelines

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1964, as revised in 2013. Informed consent was obtained from all patients for being included in the study.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki, Kagawa, 761-0793, Japan

    Shino Sato, Kazuyuki Hirooka, Eri Nitta, Kaori Ukegawa & Akitaka Tsujikawa

Authors
  1. Shino Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kazuyuki Hirooka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eri Nitta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kaori Ukegawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Akitaka Tsujikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kazuyuki Hirooka.

Additional information

Enhanced content

To view enhanced content for this article go to http://www.medengine.com/Redeem/74E4F0604FDDABAE.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Sato, S., Hirooka, K., Nitta, E. et al. Additive Intraocular Pressure Lowering Effects of the Rho Kinase Inhibitor, Ripasudil in Glaucoma Patients Not Able to Obtain Adequate Control After Other Maximal Tolerated Medical Therapy. Adv Ther 33, 1628–1634 (2016). https://doi.org/10.1007/s12325-016-0389-3

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12325-016-0389-3

Keywords

  • Glaucoma
  • Intraocular pressure
  • Ophthalmology
  • Ripasudil