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Randomized Controlled Study to Investigate the Effect of Topical Diquafosol Tetrasodium on Corneal Sensitivity in Short Tear Break-Up Time Dry Eye

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Abstract

Introduction

Complex mechanisms underlie dry eye (DE) symptom provocation. In particular, corneal hypersensitivity may provoke symptoms in short tear break-up time (BUT) DE characterized by tear film instability. We hypothesized that improved tear film stability may alleviate corneal sensitivity in patients with short tear BUT DE. Therefore, we investigated the effect of topical diquafosol tetrasodium (DQS) on corneal sensitivity in unstable tear film DE.

Methods

This prospective, randomized study included 27 subjects (age: 39.1 ± 8.4 years; range: 25–59 years) with short tear BUT DE, defined based on the presence of DE symptoms and tear film instability. Subjects were randomly divided into DQS (3% DQS, 12 subjects) and artificial tear (AT; preservative-free AT, 15 subjects) groups. Subjects applied the medication 6 times a day for 5 weeks. The perception of touch (S-touch) and pain (S-pain) sensitivity was measured using a Cochet—Bonnet esthesiometer. Tear evaluation, corneal sensitivity, and DE symptoms were compared before and after DQS or AT administration. The correlation between the improvement degrees of corneal sensitivity and DE symptoms following medication was analyzed.

Results

DQS significantly improved tear BUT and tear meniscus height (TMH) scores (p < 0.05), while AT significantly improved tear BUT (p < 0.05) but not TMH score. Mean S-pain and DE symptom scores were lower after medication use in the DQS (S-pain and DE symptoms: p  < 0.05) and AT groups (S-pain: p  = 0.05; DE symptoms: p  < 0.05). However, S-touch did not change significantly in either group. A positive correlation was observed between the improvement degrees of S-pain and DE symptoms in the overall subjects studied.

Conclusion

Both DQS and AT alleviate corneal hypersensitivity and DE symptoms in eyes with short tear BUT DE. However, DQS seems to be more effective to adjust tear environment, leading to the normalization of corneal sensitivity and DE symptoms.

Trial Registration

UMIN Clinical Trials Registry Identifier, UMIN000014536

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Acknowledgements

Funding

Facility provisions and equipment transport were funded by Santen Pharmaceutical Co., Ltd. The funding organization had no role in data analyses or in the conduct of this research. The article processing charges were funded by the authors.

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. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis.

Author Contribution statement

Conception and design of the study: Minako Kaido, Kazuo Tsubota. Analysis and interpretation of results: Minako Kaido. Manuscript preparation: Minako Kaido. Critical review of the article: Motoko Kawashima, Yoshiaki Yamada, Kazuo Tsubota. Data acquisition: Minako Kaido, Yuta Shigeno. Provision of materials, patients, or resources: Minako Kaido, Yoshiaki Yamada. Statistical expertise, literature searches: Minako Kaido. Administrative, technical, or logistic support: Minako Kaido, Kazuo Tsubota

Thanking Patient Participants

We thank all the study participants for their participation in the study.

Data Management

We wish to thank the Biostatistical Research Co. (Tokyo, Japan) for their assistance in data management.

Disclosures

Kazuo Tsubota is a consultant for Santen Pharmaceutical Co., Ltd. (Osaka, Japan). The Department of Ophthalmology, Keio University School of Medicine receives research funds from Santen Pharmaceutical Co., Ltd., and Kazuo Tsubota is a member of Santen’s Speaker’s Bureau. However, Santen Pharmaceutical Co., Ltd. was not involved with the scientific content of the research projects run by the department. Yoshiaki Yamada is an employee at Santen Pharmaceutical Co., Ltd. Minako Kaido, Motoko Kawashima and Yuta Shigeno have nothing to disclose.

Compliance with Ethics Guidelines

This study protocol was reviewed and approved by the Ethics Committee of the Institutional Review Board at the Shinanozaka Clinic. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964, as revised in 2013. Informed consent was obtained from all patients for being included in the study. This study was registered in the University hospital Medical Information Network (UMIN) (Registries No. UMIN000014536).

Data Availability

All data generated or analyzed during this study are included in this published article/as supplementary information files.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan

    Minako Kaido, Motoko Kawashima, Yuta Shigeno & Kazuo Tsubota

  2. Shinanozaka Clinic, Tokyo, Japan

    Minako Kaido

  3. Medical Affairs Department, R&D Division, Santen Pharmaceutical Co., Ltd., Osaka, Japan

    Yoshiaki Yamada

Authors
  1. Minako Kaido
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  2. Motoko Kawashima
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Corresponding author

Correspondence to Minako Kaido.

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Kaido, M., Kawashima, M., Shigeno, Y. et al. Randomized Controlled Study to Investigate the Effect of Topical Diquafosol Tetrasodium on Corneal Sensitivity in Short Tear Break-Up Time Dry Eye. Adv Ther 35, 697–706 (2018). https://doi.org/10.1007/s12325-018-0685-1

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