{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T02:59:58Z","timestamp":1776826798737,"version":"3.51.2"},"reference-count":24,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T00:00:00Z","timestamp":1611187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004470","name":"Daewoong Pharmaceutical Company","doi-asserted-by":"publisher","award":["1100045"],"award-info":[{"award-number":["1100045"]}],"id":[{"id":"10.13039\/501100004470","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>The purpose of this study was to determine and compare the effects between injecting botulinum toxin A (BTX-A) transconjunctivally into the palpebral lobe and transcutaneously into the orbital lobe of the lacrimal gland in patients with epiphora due to lacrimal outflow obstruction. This randomized controlled study included 53 eyes of 31 patients with unilateral or bilateral epiphora. Patients were randomly allocated to receive an injection of BTX-A (3 units) either transconjunctivally (n = 15, 25 eyes) or transcutaneously (n = 16, 28 eyes). For objective assessments, the tear meniscus height and Schirmer\u2019s I test with topical anesthesia were measured at baseline and after 2, 6, 12, and 24 weeks of follow-up. Subjective evaluations were performed using the Munk score. After BTX-A injection, patients in both groups experienced significant objective and subjective reductions in tearing at all follow-up times compared to pre-injection (success rate 86.8%), and the effect lasted for a mean duration of 5.63 months. The two delivery routes showed similar clinical effectiveness for a single injected dose of BTX-A. In conclusion, injecting BTX-A via either a transconjunctival or transcutaneous route helps to reduce normal tear production and results in significant improvements in the symptoms in patients with epiphora.<\/jats:p>","DOI":"10.3390\/toxins13020077","type":"journal-article","created":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T11:49:40Z","timestamp":1611229780000},"page":"77","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Transconjunctival versus Transcutaneous Injection of Botulinum Toxin into the Lacrimal Gland to Reduce Lacrimal Production: A Randomized Controlled Trial"],"prefix":"10.3390","volume":"13","author":[{"given":"Andrew G.","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, Houston, TX 77030, USA"},{"name":"Department of Ophthalmology, Neurology, Neurosurgery, Weill Cornell Medicine, New York, NY 10021, USA"},{"name":"Department of Ophthalmology, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Department of Ophthalmology, UT MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"Department of Ophthalmology, Texas A and M College of Medicine, College Station, TX 77807, USA"},{"name":"Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA"},{"name":"Department of Ophthalmology, Baylor College of Medicine and the Center for Space Medicine, Houston, TX 77030, USA"},{"name":"Department of Ophthalmology, University of Buffalo, Buffalo, New York, NY 14214, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shin-Hyo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minsu","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Research Institute of Medical Science, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul 05030, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang Jae","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Medicine, Konkuk University, Seoul 05029, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3563-8042","authenticated-orcid":false,"given":"Hyun Jin","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Research Institute of Medical Science, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul 05030, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,21]]},"reference":[{"key":"ref_1","first-page":"1751","article-title":"Etiology, diagnosis, management and outcomes of epiphora referrals to an oculoplastic practice","volume":"9","author":"Shen","year":"2016","journal-title":"Int. J. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1097\/IOP.0b013e318230b110","article-title":"Silicone Intubation for the treatment of epiphora in adults with presumed functional nasolacrimal duct obstruction","volume":"28","author":"Moscato","year":"2012","journal-title":"Ophthalmic Plast. Reconstr. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1136\/bjo.86.7.792","article-title":"Analysis of the results of surgical endoscopic dacryocystorhinostomy: Effect of the level of obstruction","volume":"86","author":"Yung","year":"2002","journal-title":"Br. J. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ajo.2003.08.002","article-title":"Lacrimal canalicular bypass surgery with the Lester Jones tube","volume":"137","author":"Lim","year":"2004","journal-title":"Am. J. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1136\/bjo.87.1.54","article-title":"Botulinum toxin A treatment in patients suffering from blepharospasm and dry eye","volume":"87","author":"Bergloeff","year":"2003","journal-title":"Br. J. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1016\/j.bjps.2008.03.023","article-title":"Botulinum Toxin for Treatment of Glandular Hypersecretory Disorders","volume":"61","author":"Laing","year":"2008","journal-title":"J. Plast. Reconstr. Aesthetic Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/sj.eye.6700230","article-title":"Treatment of gustatory hyperlacrimation (crocodile tears) with injection of botulinum toxin into the lacrimal gland","volume":"16","author":"Montoya","year":"2002","journal-title":"Eye"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1097\/IOP.0b013e318201d1d3","article-title":"Results of lacrimal gland botulinum toxin injection for epiphora in lacrimal obstruction and gustatory tearing","volume":"27","author":"Wojno","year":"2011","journal-title":"Ophthalmic Plast. Reconstr. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1076\/orbi.22.3.193.15622","article-title":"The use of botulinum toxin A in the treatment of functional epiphora","volume":"22","author":"Whittaker","year":"2003","journal-title":"Orbit"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1136\/bjo.2008.155887","article-title":"Transconjunctival botulinum toxin offers an effective, safe and repeatable method to treat gustatory lacrimation","volume":"94","author":"Falzon","year":"2010","journal-title":"Br. J. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Hofmann, R.J. (2008). Botox Injection to the Lacrimal Gland for Treatment of Epiphora: Pearls and Pitfalls in Cosmetic Oculoplastic Surgery, Springer.","DOI":"10.1007\/978-0-387-69007-0_109"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.jfo.2017.03.006","article-title":"Botulinum neurotoxin injection for the treatment of epiphora in nasolacrimal duct obstruction","volume":"40","author":"Girard","year":"2017","journal-title":"J. Fr. Ophtalmol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/eye.2015.18","article-title":"Botulinum toxin injection for the treatment of epiphora in lacrimal outflow obstruction","volume":"29","author":"Ziahosseini","year":"2015","journal-title":"Eye"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.jfo.2017.11.010","article-title":"Botulinum neurotoxin A injection for the treatment of epiphora with patent lacrymal ducts","volume":"41","author":"Girard","year":"2018","journal-title":"J. Fr. Ophtalmol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1136\/jnnp.65.1.111","article-title":"Botulinum toxin treatment of synkinesia and hyperlacrimation after facial palsy","volume":"65","author":"Boroojerdi","year":"1998","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_16","first-page":"43.e6","article-title":"Botulinum toxin treatment for hyperlacrimation: Gustatory lacrimation and salivary gland transplant","volume":"86","author":"Keegan","year":"2001","journal-title":"Br. J. Ophthalmol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1111\/j.1755-3768.2010.01873.x","article-title":"Efficacy of dye disappearance test and tear meniscus height in diagnosis and postoperative assessment of nasolacrimal duct obstruction","volume":"88","author":"Roh","year":"2010","journal-title":"Acta Ophthalmol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1097\/01.iop.0000244515.07925.99","article-title":"Duration of botulinum toxin effect in the treatment of crocodile tears","volume":"22","author":"Boullosa","year":"2006","journal-title":"Ophthalmic Plast. Reconstr. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1097\/IOP.0b013e31826e8a86","article-title":"Intraglandular injection of Botulinum Toxin A reduces tear production in rabbits","volume":"29","author":"Demetriades","year":"2013","journal-title":"Ophthalmic Plast. Reconstr. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1097\/00002341-200007000-00007","article-title":"Treatment of Frey\u2019s Syndrome (gustatory sweating) and \u2018Crocodile Tears\u2019 (gustatory epiphora) with purified botulinum toxin","volume":"16","author":"Hofmann","year":"2000","journal-title":"Ophthalmic Plast. Reconstr. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1136\/bjo.2003.029181","article-title":"Long term efficacy and safety of botulinum toxin A injection for crocodile tears syndrome","volume":"88","author":"Miller","year":"2004","journal-title":"Br. J. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1097\/SCS.0b013e31829ac655","article-title":"Functional and histologic changes in the lacrimal gland after botulinum toxin injection","volume":"24","author":"Kim","year":"2013","journal-title":"J. Craniofacial Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e15","DOI":"10.1016\/j.jaapos.2011.12.060","article-title":"Use of botulinum toxin injections to the lacrimal gland for epiphora in children with proximal obstruction of lacrimal drainage system","volume":"16","author":"Eustis","year":"2012","journal-title":"J. Pediatr. Ophthalmol. Strabismus"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1038\/eye.2012.188","article-title":"Patient-reported benefit from oculoplastic surgery","volume":"26","author":"Smith","year":"2012","journal-title":"Eye"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/13\/2\/77\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:13:36Z","timestamp":1760159616000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/13\/2\/77"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,21]]},"references-count":24,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["toxins13020077"],"URL":"https:\/\/doi.org\/10.3390\/toxins13020077","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,21]]}}}