Effects of botulinum toxin type A on the treatment of dry eye disease and tear cytokines

  • Min Gyu Choi
  • Joon Hyung Yeo
  • Jeong Woo Kang
  • Yeoun Sook Chun
  • Jeong Kyu Lee
  • Jae Chan KimEmail author



To determine the effects of botulinum toxin type A (BTX-A) injection on dry eye signs, symptoms, and tear cytokine levels in patients with intractable dry eye disease (DED).


In this prospective study, patients with intractable DED were randomized to a BTX-A (group A) or control group (group B). Patients were injected with BTX-A or normal saline in the medial part of the upper and lower eyelids. Before and at 2 weeks, 1 month, 2 months, and 4 months after injection, dry eye signs; tear film break-up time (TBUT), Schirmer I test, corneal fluorescein staining (CFS), and symptoms; ocular surface disease index (OSDI); and frequency of lubricants were assessed. The tear levels of matrix metalloproteinase (MMP)-9 and serotonin were measured before and at 1 month after injection.


Fifty-two eyes from 26 patients (mean age, 57.7 years) were included. The TBUT was higher at 2 weeks and at 1 month in group A. The Schirmer I test and OSDI scores were also better in group A for up to 2 months. The CFS grades in group A were significantly lower until 4 months. Repeated measures analysis of variance (RMANOVA) demonstrated significant differences between the two groups over time for the Schirmer I test (p = 0.002), CFS (p = 0.025), OSDI (p = 0.020), and frequency of lubricants (p = 0.029). The MMP-9 conversion rate of group A (76.92%) was significantly higher than that of group B (38.46%, p = 0.005). The tear serotonin level in group A was reduced from 2.76 ± 0.34 to 1.73 ± 0.14 ng/mL (p < 0.001). No complications were observed during the study.


BTX-A injection into the medial part of eyelid improves dry eye signs and symptoms and reduces tear cytokine levels. BTX-A is thus a potential treatment option for patients with intractable DED.


Botulinum toxin Dry eye disease Ocular surface disease index Matrix metalloproteinase-9 Serotonin 



This study was supported by a grant from Daewoong Pharmaceutical (Seoul, Korea). The funding organization had no role in the design or conduct of this research.

Compliance with ethical standards

Conflict of interest

Jae Chan Kim received research grants from Daewoong Pharmaceutical. Min Gyu Choi, Joon Hyung Yeo, Jeong Woo Kang, Yeoun Sook Chun, and Jeong Kyu Lee declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with ethical standards of the institutional and/or national research committee (Chung-Ang University Hospital Institutional Review Board) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of OphthalmologyChung-Ang University Hospital, College of MedicineSeoulSouth Korea
  2. 2.Department of Ophthalmology, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulSouth Korea
  3. 3.Cheil Eye Research InstituteCheil Eye HospitalDaeguRepublic of Korea

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