Skip to main content
SpringerLink
Log in

Efficacy of Ripasudil as a Second-line Medication in Addition to a Prostaglandin Analog in Patients with Exfoliation Glaucoma: A Pilot Study

  • Original Research Article
  • Published:
Clinical Drug Investigation Aims and scope Submit manuscript

Abstract

Objective

This study aimed to assess the intraocular pressure (IOP)-lowering effects of ripasudil, a Rho kinase inhibitor, as a second-line medication in patients with exfoliation glaucoma.

Methods

This retrospective cohort study included patients with exfoliation glaucoma who received ripasudil as the second-line drug in addition to prostaglandin analogs, and were followed-up for at least 5 months. Twenty-seven eyes of 16 patients were enrolled; the mean (±standard deviation) age was 76.1 ± 7.2 years (range 63–91 years). Baseline IOPs were the averages of three IOP measurements performed before ripasudil treatment. Statistical analyses used the paired t test with the Bonferroni correction. Relevant background factors were analyzed via stepwise, multiple regression analysis.

Results

The mean (±standard deviation) IOP levels prior to commencement of ripasudil, 1–2 months later, and 5–6 months later were 16.2 ± 2.1, 14.7 ± 2.8, and 13.1 ± 2.6 mmHg, respectively. These levels differed significantly (p = 0.00019 for 0 versus 1–2 months, 0.00087 for 1–2 vs. 5–6 months, and <0.00001 for 0 vs. 5–6 months). Stepwise multiple regression analysis on data from all 27 eyes showed that the change in IOP at 5–6 months was associated with the treatment time with prostaglandin analogs and age, but not with baseline IOP, the severity of the visual field defect, the timing of IOP measurement, or pseudophakic status.

Conclusions

Ripasudil significantly lowered IOP in patients with exfoliation glaucoma, and the effect thereof increased over time within 5 months.

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
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Investigators AGIS. The Advanced Glaucoma Intervention Study (AGIS), 7: the relationship between control of intraocular pressure and visual field deterioration. Am J Ophthalmol. 2000;130:429–40.

    Article  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. Garway-Heath DF, Crabb DP, Bunce C, et al. Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial. Lancet. 2015;385:1295–304.

    Article  CAS  PubMed  Google Scholar 

  4. Li T, Lindsley K, Rouse B, et al. Comparative effectiveness of first-line medications for primary open-angle glaucoma: a systematic review and network meta-analysis. Ophthalmology. 2016;123:129–40.

    Article  PubMed  Google Scholar 

  5. Lippa EA, Carlson LE, Ehinger B, et al. Dose response and duration of action of dorzolamide, a topical carbonic anhydrase inhibitor. Arch Ophthalmol. 1992;110:495–9.

    Article  CAS  PubMed  Google Scholar 

  6. Katz LJ, Simmons ST, Craven ER. Efficacy and safety of brimonidine and dorzolamide for intraocular pressure lowering in glaucoma and ocular hypertension. Curr Med Res Opin. 2007;23:2971–83.

    Article  CAS  PubMed  Google Scholar 

  7. Tanihara H, Inoue T, Yamamoto T, K-115 Clinical Study Group, et al. Additive intraocular pressure-lowering effects of the Rho kinase inhibitor ripasudil (K-115) combined with timolol or latanoprost: a report of 2 randomized clinical trials. JAMA Ophthalmol. 2015;133:755–61.

    Article  PubMed  Google Scholar 

  8. Tanihara H, Inoue T, Yamamoto T, K-115 Clinical Study Group, 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.

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  10. Kameda T, Inoue T, Inatani M, et al. The effect of Rho-associated protein kinase inhibitor on monkey Schlemm’s canal endothelial cells. Invest Ophthalmol Vis Sci. 2012;53:3092–103.

    Article  CAS  PubMed  Google Scholar 

  11. Inoue T, Tanihara H. Rho-associated kinase inhibitors: a novel glaucoma therapy. Prog Retin Eye Res. 2013;37:1–12.

    Article  CAS  PubMed  Google Scholar 

  12. Kaneko Y, Ohta M, Inoue T, et al. Effects of K-115 (Ripasudil), a novel ROCK inhibitor, on trabecular meshwork and Schlemm’s canal endothelial cells. Sci Rep. 2016;6:19640.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Thorleifsson G, Magnusson KP, Sulem P, et al. Common sequence variants in the LOXL1 gene confer susceptibility to exfoliation glaucoma. Science. 2007;317:1397–400.

    Article  CAS  PubMed  Google Scholar 

  14. Ritch R, Schlötzer-Schrehardt U, Konstas AG. Why is glaucoma associated with exfoliation syndrome? Prog Retin Eye Res. 2003;22:253–75.

    Article  PubMed  Google Scholar 

  15. Miglior S, Bertuzzi F. Exfoliative glaucoma: new evidence in the pathogenesis and treatment. Prog Brain Res. 2015;221:233–41.

    Article  PubMed  Google Scholar 

  16. Tanihara H, Inoue T, Yamamoto T, Kuwayama Y, Abe H, Araie M, K-115 Clinical Study Group. Phase 1 clinical trials of a selective Rho kinase inhibitor, K-115. JAMA Ophthalmol. 2013;131:1288–95.

    Article  CAS  PubMed  Google Scholar 

  17. 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.

    Article  CAS  PubMed  Google Scholar 

  18. Tanihara H, Inoue T, Yamamoto T, K-115 Clinical Study Group, et al. 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.

    Article  CAS  PubMed  Google Scholar 

  19. Sato S, Hirooka K, Nitta E, Ukegawa K, Tsujikawa A. 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. 2016;33:1628–34.

    Article  CAS  PubMed  Google Scholar 

  20. Inazaki H, Kobayashi S, Anzai Y, et al. Efficacy of the additional use of ripasudil, a Rho-kinase inhibitor, in patients with glaucoma inadequately controlled under maximum medical therapy. J Glaucoma. 2017;. doi:10.1097/IJG.0000000000000552.

    PubMed  Google Scholar 

  21. Koga T, Koga T, Awai M, Tsutsui J, Yue BY, Tanihara H. Rho-associated protein kinase inhibitor, Y-27632, induces alterations in adhesion, contraction and motility in cultured human trabecular meshwork cells. Exp Eye Res. 2006;82:362–70.

    Article  CAS  PubMed  Google Scholar 

  22. Fujimoto T, Inoue T, Kameda T, et al. Involvement of RhoA/Rho-associated kinase signal transduction pathway in dexamethasone-induced alterations in aqueous outflow. Invest Ophthalmol Vis Sci. 2012;53:7097–108.

    Article  CAS  PubMed  Google Scholar 

  23. Inoue-Mochita M, Inoue T, Fujimoto T, et al. p38 MAP kinase inhibitor suppresses transforming growth factor-β2-induced type 1 collagen production in trabecular meshwork cells. PLoS One. 2015;10:e0120774.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan

    Riyo Matsumura, Toshihiro Inoue & Hidenobu Tanihara

  2. Matsumura Eye Clinic, Kumamoto, Japan

    Riyo Matsumura & Akira Matsumura

Authors
  1. Riyo Matsumura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Toshihiro Inoue
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Akira Matsumura
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hidenobu Tanihara
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Toshihiro Inoue.

Ethics declarations

Funding

No external sources of funding were used to conduct this study.

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 for publication of this version.

Disclosures

HT has received consulting fees from Kowa and MSD, and board membership fees from Senju Pharmaceutical, Santen Pharmaceutical, Alcon Japan, and Pfizer Japan. RM, TI, and AM certify that they have no conflict of interest.

Compliance with ethics guidelines

All procedures followed the ethical standards of relevant committees on human experimentation (both institutional and national) and the Declaration of Helsinki of 1964, as revised in 2013. Written informed consent was obtained from all patients prior to inclusion in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Matsumura, R., Inoue, T., Matsumura, A. et al. Efficacy of Ripasudil as a Second-line Medication in Addition to a Prostaglandin Analog in Patients with Exfoliation Glaucoma: A Pilot Study. Clin Drug Investig 37, 535–539 (2017). https://doi.org/10.1007/s40261-017-0509-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40261-017-0509-0

Keywords

Search

Navigation