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Graefe's Archive for Clinical and Experimental Ophthalmology

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01-02-2019 | Cornea

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

Authors: Min Gyu Choi, Joon Hyung Yeo, Jeong Woo Kang, Yeoun Sook Chun, Jeong Kyu Lee, Jae Chan Kim

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 2/2019

Abstract

Purpose

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).

Methods

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.

Results

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.

Conclusion

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.

Craig JP, Nichols KK, Akpek EK, Caffery B, Dua HS, Joo CK, Liu Z, Nelson JD, Nichols JJ, Tsubota K, Stapleton F (2017) TFOS DEWS II definition and classification report. Ocul Surf 15:276–283. https://doi.org/10.1016/j.jtos.2017.05.008 CrossRefPubMed

Donald C, Hamilton L, Doughty M (2003) A quantitative assessment of the location and width of Marx’s line along the marginal zone of the human eyelid. Optom Vis Sci 80:564–572CrossRefPubMed

Bron AJ, de Paiva CS, Chauhan SK, Bonini S, Gabison EE, Jain S, Knop E, Markoulli M, Ogawa Y, Perez V, Uchino Y, Yokoi N, Zoukhri D, Sullivan DA (2017) TFOS DEWS II pathophysiology report. Ocul Surf 15:438–510. https://doi.org/10.1016/j.jtos.2017.05.011 CrossRefPubMed

Horwath-Winter J, Bergloeff J, Floegel I, Haller-Schober EM, Schmut O (2003) Botulinum toxin A treatment in patients suffering from blepharospasm and dry eye. Br J Ophthalmol 87:54–56CrossRefPubMedPubMedCentral

Scott AB (1980) Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery. Ophthalmology 87:1044–1049CrossRefPubMed

Kaltreider SA, Kennedy RH, Woog JJ, Bradley EA, Custer PL, Meyer DR, American Academy of O, Ophthalmic Technology Assessment Committee Oculoplastics P (2005) Cosmetic oculofacial applications of botulinum toxin: a report by the American Academy of Ophthalmology. Ophthalmology 112:1159–1167. https://doi.org/10.1016/j.ophtha.2005.03.021 CrossRefPubMed

Kaynak-Hekimhan P (2010) Noncosmetic periocular therapeutic applications of botulinum toxin. Middle East Afr J Ophthalmol 17:113–120. https://doi.org/10.4103/0974-9233.63069 CrossRefPubMedPubMedCentral

Chun YS, Kim JC (2009) Treatment of superior limbic keratoconjunctivitis with a large-diameter contact lens and botulium toxin A. Cornea 28:752–758. https://doi.org/10.1097/ICO.0b013e3181967006 CrossRefPubMed

Schiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL (2000) Reliability and validity of the ocular surface disease index. Arch Ophthalmol 118:615–621CrossRefPubMed

10.

Messmer EM, von Lindenfels V, Garbe A, Kampik A (2016) Matrix metalloproteinase 9 testing in dry eye disease using a commercially available point-of-care immunoassay. Ophthalmology 123:2300–2308. https://doi.org/10.1016/j.ophtha.2016.07.028 CrossRefPubMed

11.

Chhadva P, Lee T, Sarantopoulos CD, Hackam AS, McClellan AL, Felix ER, Levitt RC, Galor A (2015) Human tear serotonin levels correlate with symptoms and signs of dry eye. Ophthalmology 122:1675–1680. https://doi.org/10.1016/j.ophtha.2015.04.010 CrossRefPubMed

12.

Martin XD, Brennan MC (1994) Serotonin in human tears. Eur J Ophthalmol 4:159–165CrossRefPubMed

13.

Sahlin S, Chen E, Kaugesaar T, Almqvist H, Kjellberg K, Lennerstrand G (2000) Effect of eyelid botulinum toxin injection on lacrimal drainage. Am J Ophthalmol 129:481–486CrossRefPubMed

14.

Fouda SM, Mattout HK (2017) Comparison between botulinum toxin a injection and lacrimal punctal plugs for the control of post-LASIK dry eye manifestations: a prospective study. Ophthalmol Therapy 6:167–174. https://doi.org/10.1007/s40123-017-0079-5 CrossRef

15.

Serna-Ojeda JC, Nava-Castaneda A (2017) Paralysis of the orbicularis muscle of the eye using botulinum toxin type A in the treatment for dry eye. Acta Ophthalmol 95:e132–e137. https://doi.org/10.1111/aos.13140 CrossRefPubMed

16.

Spiera H, Asbell PA, Simpson DM (1997) Botulinum toxin increases tearing in patients with Sjogren’s syndrome: a preliminary report. J Rheumatol 24:1842–1843PubMed

17.

Isshiki Y, Ishikawa H, Mimura O (2016) Changes in ocular higher-order aberrations following botulinum toxin treatment in patients with blepharospasm : BTX improves dry eye in patients with BEB. Jpn J Ophthalmol 60:486–491. https://doi.org/10.1007/s10384-016-0469-6 CrossRefPubMed

18.

Ho MC, Hsu WC, Hsieh YT (2014) Botulinum toxin type A injection for lateral canthal rhytids: effect on tear film stability and tear production. JAMA Ophthalmol 132:332–337. https://doi.org/10.1001/jamaophthalmol.2013.6243 CrossRefPubMed

19.

Sambursky R, Davitt WF 3rd, Latkany R, Tauber S, Starr C, Friedberg M, Dirks MS, McDonald M (2013) Sensitivity and specificity of a point-of-care matrix metalloproteinase 9 immunoassay for diagnosing inflammation related to dry eye. JAMA Ophthalmol 131:24–28. https://doi.org/10.1001/jamaophthalmol.2013.561 CrossRefPubMed

20.

Galor A, Zlotcavitch L, Walter SD, Felix ER, Feuer W, Martin ER, Margolis TP, Sarantopoulos KD, Levitt RC (2015) Dry eye symptom severity and persistence are associated with symptoms of neuropathic pain. Br J Ophthalmol 99:665–668. https://doi.org/10.1136/bjophthalmol-2014-306057 CrossRefPubMed

21.

Sommer C (2004) Serotonin in pain and analgesia: actions in the periphery. Mol Neurobiol 30:117–125. https://doi.org/10.1385/MN:30:2:117 CrossRefPubMed

22.

Bardin L (2011) The complex role of serotonin and 5-HT receptors in chronic pain. Behav Pharmacol 22:390–404. https://doi.org/10.1097/FBP.0b013e328349aae4 CrossRefPubMed

23.

Moalem G, Grafe P, Tracey DJ (2005) Chemical mediators enhance the excitability of unmyelinated sensory axons in normal and injured peripheral nerve of the rat. Neuroscience 134:1399–1411. https://doi.org/10.1016/j.neuroscience.2005.05.046 CrossRefPubMed

24.

Sandrini G, De Icco R, Tassorelli C, Smania N, Tamburin S (2017) Botulinum neurotoxin type A for the treatment of pain: not just in migraine and trigeminal neuralgia. J Headache Pain 18:38. https://doi.org/10.1186/s10194-017-0744-z CrossRefPubMedPubMedCentral

25.

Burstein R, Zhang X, Levy D, Aoki KR, Brin MF (2014) Selective inhibition of meningeal nociceptors by botulinum neurotoxin type A: therapeutic implications for migraine and other pains. Cephalalgia 34:853–869. https://doi.org/10.1177/0333102414527648 CrossRefPubMedPubMedCentral

26.

Bourkiza R, Lee V (2012) A review of the complications of lacrimal occlusion with punctal and canalicular plugs. Orbit 31:86–93. https://doi.org/10.3109/01676830.2011.648802 CrossRefPubMed

27.

Lanza NL, Valenzuela F, Perez VL, Galor A (2016) The matrix metallopreteinase 9 point-or-care test in dry eye. Ocul Surf 14:189–195. https://doi.org/10.1016/j.jtos.2015.10.004 CrossRefPubMedPubMedCentral

28.

van Haeringen NJ (1997) Aging and the lacrimal system. Br J Ophthalmol 81:824–826CrossRefPubMed

Title: Effects of botulinum toxin type A on the treatment of dry eye disease and tear cytokines
Authors: Min Gyu Choi
Joon Hyung Yeo
Jeong Woo Kang
Yeoun Sook Chun
Jeong Kyu Lee
Jae Chan Kim
Publication date: 01-02-2019
Publisher: Springer Berlin Heidelberg
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 2/2019
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-018-4194-3

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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