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Recovery of deepening of the upper eyelid sulcus after switching from prostaglandin FP receptor agonists to EP2 receptor agonist: a 3-month prospective analysis



To examine the effect of switching from a prostanoid FP receptor agonists to EP2 receptor agonist (omidenepag isopropyl) on the deepening of the upper eyelid sulcus (DUES) and intraocular pressure (IOP) in Japanese glaucoma patients over 3 months post treatment.

Study design

Prospective observational study.


Patients with glaucoma who received FP receptor agonists treatment and had complained of DUES-related reduction in quality of life were included. Their FP receptor agonists was switched to omidenepag isopropyl without a drug holiday. At baseline and 1 and 3 months post-switch, photographs were taken and the changes in DUES were assessed by three independent observers. IOP and adverse events were also assessed.


The study included 23 eyes of 23 patients (6 men, 17 women; average age, 60.6 years). After switching, DUES improved in 12 eyes at 1 month and in 16 eyes at 3 months; eyes in the remaining patients showed no worsening of the condition. The mean IOP before switching was 15.3 ± 3.3 mmHg (95% confidence interval 13.9–16.7 mmHg). Following the switch, the mean IOP values were 15.6 ± 3.3 mmHg (14.1–17.0 mmHg) at 1 month and 15.5 ± 3.3 mmHg (14.1–16.9 mmHg) at 3 months (P = 1.0 at 1 month, P = 1.0 at 3 months; both adjusted by Bonferroni correction). No adverse effects were observed.


Omidenepag isopropyl improved DUES while maintaining IOP in over 70% of Japanese patients with glaucoma who exhibited DUES caused by FP receptor agonists; the improvement was observed within 3 months after switching from FP receptor agonists.

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  1. 1.

    The Japan Glaucoma Society. Glaucoma Practice Guidelines (4th edition). Nippon Ganka Gakkai Zasshi. 2018;122:5–53 (in Japanese).

    Google Scholar 

  2. 2.

    Kashiwagi K, Furuya T. Persistence with topical glaucoma therapy among newly diagnosed Japanese patients. Jpn J Ophthalmol. 2014;58:68–74.

    Article  Google Scholar 

  3. 3.

    Li T, Lindsley K, Rouse B, Hong H, Shi Q, Friedman DS, 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  Google Scholar 

  4. 4.

    Cheng JW, Cai JP, Wei RL. Meta-analysis of medical intervention for normal tension glaucoma. Ophthalmology. 2009;116:1243–9.

    Article  Google Scholar 

  5. 5.

    Alm A, Grierson I, Shields MB. Side effects associated with prostaglandin analog therapy. Surv Ophthalmol. 2008;53(Suppl 1):S93-105.

    Article  Google Scholar 

  6. 6.

    Tan P, Malhotra R. Oculoplastic considerations in patients with glaucoma. Surv Ophthalmol. 2016;61:718–25.

    Article  Google Scholar 

  7. 7.

    Aihara M, Shirato S, Sakata R. Incidence of deepening of the upper eyelid sulcus after switching from latanoprost to bimatoprost. Jpn J Ophthalmol. 2011;55:600–4.

    Article  Google Scholar 

  8. 8.

    Kucukevcilioglu M, Bayer A, Uysal Y, Altinsoy HI. Prostaglandin associated periorbitopathy in patients using bimatoprost, latanoprost and travoprost. Clin Exp Ophthalmol. 2014;42:126–31.

    Article  Google Scholar 

  9. 9.

    Park J, Cho HK, Moon JI. Changes to upper eyelid orbital fat from use of topical bimatoprost, travoprost, and latanoprost. Jpn J Ophthalmol. 2011;55:22–7.

    CAS  Article  Google Scholar 

  10. 10.

    Taketani Y, Yamagishi R, Fujishiro T, Igarashi M, Sakata R, Aihara M. Activation of the prostanoid FP receptor inhibits adipogenesis leading to deepening of the upper eyelid sulcus in prostaglandin-associated periorbitopathy. Invest Ophthalmol Vis Sci. 2014;55:1269–76.

    CAS  Article  Google Scholar 

  11. 11.

    Lee YK, Lee JY, Moon JI, Park MH. Effectiveness of the ICare rebound tonometer in patients with overestimated intraocular pressure due to tight orbit syndrome. Jpn J Ophthalmol. 2014;58:496–502.

    Article  Google Scholar 

  12. 12.

    Miki T, Naito T, Fujiwara M, Araki R, Kiyoi R, Shiode Y, et al. Effects of pre-surgical administration of prostaglandin analogs on the outcome of trabeculectomy. PLoS ONE. 2017;12:e0181550.

    Article  Google Scholar 

  13. 13.

    Sakata R, Shirato S, Miyata K, Aihara M. Incidence of deepening of the upper eyelid sulcus in prostaglandin-associated periorbitopathy with a latanoprost ophthalmic solution. Eye (Lond). 2014;28:1446–51.

    CAS  Article  Google Scholar 

  14. 14.

    Jayaram A, Wladis E, Akkara JD, Yen MT, Seibold LK, Burkat CN. Prostaglandin associated periorbitopathy. In: EyeWiki. American Academy of Ophthalmology.

  15. 15.

    Kirihara T, Taniguchi T, Yamamura K, Iwamura R, Yoneda K, Odani-Kawabata N, et al. Pharmacologic characterization of omidenepag isopropyl, a novel selective EP2 receptor agonist, as an ocular hypotensive agent. Invest Ophthalmol Vis Sci. 2018;59:145–53.

    CAS  Article  Google Scholar 

  16. 16.

    Aihara M, Lu F, Kawata H, Iwata A, Odani-Kawabata N, Shams NK. Omidenepag isopropyl versus latanoprost in primary open-angle glaucoma and ocular hypertension: the phase 3 AYAME study. Am J Ophthalmol. 2020;220:53–63.

    CAS  Article  Google Scholar 

  17. 17.

    Yamamoto Y, Taniguchi T, Inazumi T, Iwamura R, Yoneda K, Odani-Kawabata N, et al. Effects of the selective EP2 receptor agonist omidenepag on adipocyte differentiation in 3T3-L1 cells. J Ocul Pharmacol Ther. 2020.

    Article  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Sakata R, Shirato S, Miyata K, Aihara M. Recovery from deepening of the upper eyelid sulcus after switching from bimatoprost to latanoprost. Jpn J Ophthalmol. 2013;57:179–84.

    Article  Google Scholar 

  19. 19.

    Sakata R, Shirato S, Miyata K, Aihara M. Incidence of deepening of the upper eyelid sulcus on treatment with a tafluprost ophthalmic solution. Jpn J Ophthalmol. 2014;58:212–7.

    CAS  Article  Google Scholar 

  20. 20.

    Breslow NE, Clayton DG. Approximate inference in generalized linear mixed models. J Am Stat Assoc. 1993;88:9–25.

    Google Scholar 

  21. 21.

    Jayaprakasam A, Ghazi-Nouri S. Periorbital fat atrophy—an unfamiliar side effect of prostaglandin analogues. Orbit. 2010;29:357–9.

    Article  Google Scholar 

  22. 22.

    Nakakura S. Icare((R)) rebound tonometers: review of their characteristics and ease of use. Clin Ophthalmol. 2018;12:1245–53.

    Article  Google Scholar 

  23. 23.

    Whitson JT, Trattler WB, Matossian C, Williams J, Hollander DA. Ocular surface tolerability of prostaglandin analogs in patients with glaucoma or ocular hypertension. J Ocul Pharmacol Ther. 2010;26:287–92.

    CAS  Article  Google Scholar 

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This study was funded by Santen Pharmaceutical Co., Ltd, Osaka.

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Corresponding author

Correspondence to Rei Sakata.

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Conflicts of interest

R. Sakata, None; T. Fujishiro, None; H. Saito, None; N. Nakamura, None; M. Honjo, None; S. Shirato, None; E. Miyamoto, Employee (Santen); Y. Yamada, Employee (Santen); M. Aihara, None.

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Corresponding Author: Rei Sakata

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Sakata, R., Fujishiro, T., Saito, H. et al. Recovery of deepening of the upper eyelid sulcus after switching from prostaglandin FP receptor agonists to EP2 receptor agonist: a 3-month prospective analysis. Jpn J Ophthalmol 65, 591–597 (2021).

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  • Omidenepag isoproryl
  • EP2 receptor agonist
  • Glaucoma
  • Upper eyelid sulcus
  • Prostaglandin FP receptor agonists