{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T11:42:41Z","timestamp":1769514161110,"version":"3.49.0"},"reference-count":28,"publisher":"American Veterinary Medical Association (AVMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["javma"],"published-print":{"date-parts":[[2023,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:sec>\n<jats:title>OBJECTIVE<\/jats:title>\n<jats:p>To characterize the clinical course and long-term prognosis of a suspected novel cause of neurogenic keratoconjunctivitis sicca (nKCS) secondary to florfenicol, terbinafine hydrochloride, mometasone furoate (Claro and Neptra) or florfenicol, terbinafine, betamethasone acetate (Osurnia).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>ANIMALS<\/jats:title>\n<jats:p>29 client-owned dogs.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>PROCEDURES<\/jats:title>\n<jats:p>Online survey and word-of-mouth recruitment were conducted to identify dogs that developed clinical signs of nKCS after application of otitis externa medication containing terbinafine and florfenicol. A retrospective analysis of medical records of dogs meeting inclusion criteria was then conducted. Included dogs had onset of clinical signs of nKCS within 1 day after application of otitis externa medications containing terbinafine and florfenicol and had documentation of low Schirmer tear test value (&lt; 15 mm\/min) of affected eyes.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>RESULTS<\/jats:title>\n<jats:p>29 dogs with medical records available for review met the inclusion criteria. Documented return of clinically normal tear production was identified in 24 of 29 dogs, with a median time from application of ear medication to documented return of clinically normal tear production of 86 days (range, 19 to 482 days). A corneal ulcer was diagnosed in 68% (20\/29). Multivariable Cox regression analysis showed being referred to an ophthalmologist (<jats:italic>P<\/jats:italic> = .03) and having a deep ulcer (<jats:italic>P<\/jats:italic> = .02) were associated with a longer time to documentation of Schirmer tear test \u2265 15 mm\/min.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>CLINICAL RELEVANCE<\/jats:title>\n<jats:p>Dogs that developed nKCS within 1 day after application of otitis externa medications containing terbinafine and florfenicol had a good prognosis for return of normal tear production within 1 year.<\/jats:p>\n<\/jats:sec>","DOI":"10.2460\/javma.22.07.0301","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T17:25:17Z","timestamp":1667928317000},"page":"97-103","source":"Crossref","is-referenced-by-count":1,"title":["Long-lasting otic medications may be a rare cause of neurogenic keratoconjunctivitis sicca in dogs"],"prefix":"10.2460","volume":"261","author":[{"given":"Genia R.","family":"Bercovitz","sequence":"first","affiliation":[{"name":"Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annora M.","family":"Gaerig","sequence":"additional","affiliation":[{"name":"Eye Care for Animals, Chicago, IL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily D.","family":"Conway","sequence":"additional","affiliation":[{"name":"VCA Great Lakes Veterinary Specialists, Warrensville Heights, OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane Ashley","family":"Huey","sequence":"additional","affiliation":[{"name":"Memphis Veterinary Specialists & Emergency, Cordova, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary R.","family":"Telle","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renata","family":"Stavinohova","sequence":"additional","affiliation":[{"name":"Lumbry Park Veterinary Specialists, Hampshire, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giunio Bruto","family":"Cherubini","sequence":"additional","affiliation":[{"name":"Dick White Referrals, Cambridgeshire, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo","family":"Capasso","sequence":"additional","affiliation":[{"name":"Lumbry Park Veterinary Specialists, Hampshire, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathern E.","family":"Myrna","sequence":"additional","affiliation":[{"name":"Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1272","reference":[{"key":"ref1","series-title":"Veterinary Ophthalmology","first-page":"2285","article-title":"Neuro-ophthalmology","volume":"Vol 2","author":"Webb AA","year":"2021","unstructured":"Webb AA, Cullen CL. Neuro-ophthalmology. In: Gelatt KN, Ben-Shlomo G, Gilger BC, Hendrix DVH, Kern TJ, Plummer CE, eds. Veterinary Ophthalmology. 6th ed. Vol 2. Wiley Blackwell; 2021:2285\u20132286."},{"issue":"6","key":"ref2","series-title":"Vet Clin North Am Small Anim Pract","first-page":"1143","article-title":"Neurological manifestations of ear disease in dogs and cats","volume":"42","author":"Garosi LS","year":"2012","unstructured":"Garosi LS, Lowrie ML, Swinbourne NF. Neurological manifestations of ear disease in dogs and cats. Vet Clin North Am Small Anim Pract. 2012;42(6):1143\u20131160. doi:10.1016\/j.cvsm.2012.08.00623122174"},{"issue":"2","key":"ref3","series-title":"Vet Dermatol","first-page":"146","article-title":"Occult otitis media in dogs with chronic otitis externa\u2014magnetic resonance imaging and association with otoscopic and cytological findings","volume":"31","author":"Lorek A","year":"2020","unstructured":"Lorek A, Dennis R, van Dijk J, Bannoehr J. Occult otitis media in dogs with chronic otitis externa\u2014magnetic resonance imaging and association with otoscopic and cytological findings. Vet Dermatol. 2020;31(2):146\u2013153. doi:10.1111\/vde.1281731858646"},{"issue":"3","key":"ref4","series-title":"Vet Clin North Am Small Anim Pract","first-page":"777","article-title":"Nonhypotensive autonomic agents in veterinary ophthalmology","volume":"34","author":"Klauss G","year":"2004","unstructured":"Klauss G, Constantinescu GM. Nonhypotensive autonomic agents in veterinary ophthalmology. Vet Clin North Am Small Anim Pract. 2004;34(3):777\u2013800. doi:10.1016\/j.cvsm.2003.12.01115110984"},{"issue":"4","key":"ref5","series-title":"Vet Ophthalmol","first-page":"288","article-title":"Canine neurogenic keratoconjunctivitis sicca: 11 cases (2006\u20132010)","volume":"15","author":"Matheis FL","year":"2012","unstructured":"Matheis FL, Walser-Reinhardt L, Spiess BM. Canine neurogenic keratoconjunctivitis sicca: 11 cases (2006\u20132010). Vet Ophthalmol. 2012;15(4):288\u2013290. doi:10.1111\/j.1463-5224.2011.00968.x22051024"},{"issue":"2","key":"ref6","series-title":"Vet Ophthalmol","first-page":"341","article-title":"A retrospective evaluation of systemic and\/or topical pilocarpine treatment for canine neurogenic dry eye: 11 cases","volume":"23","author":"Wegg ML","year":"2020","unstructured":"Wegg ML. A retrospective evaluation of systemic and\/or topical pilocarpine treatment for canine neurogenic dry eye: 11 cases. Vet Ophthalmol. 2020;23(2):341\u2013346. doi:10.1111\/vop.12731"},{"issue":"2","key":"ref7","series-title":"Vet Ophthalmol","first-page":"140","article-title":"Neurogenic keratoconjunctivitis sicca in 34 dogs: a case series","volume":"25","author":"Galley AP","year":"2022","unstructured":"Galley AP, Beltran E, Tetas Pont R. Neurogenic keratoconjunctivitis sicca in 34 dogs: a case series. Vet Ophthalmol. 2022;25(2):140\u2013152. doi:10.1111\/vop.1294934870366"},{"issue":"4","key":"ref8","series-title":"Can Vet J","first-page":"368","article-title":"Suspected hypothyroid-associated neuropathy in a female Rottweiler dog","volume":"54","author":"Rushton JO","year":"2013","unstructured":"Rushton JO, Leschnik M, Nell B. Suspected hypothyroid-associated neuropathy in a female Rottweiler dog. Can Vet J. 2013;54(4):368\u2013372."},{"issue":"5","key":"ref9","series-title":"J Small Anim Pract","first-page":"252","article-title":"Reduced tear production in three canine endocrinopathies","volume":"48","author":"Williams DL","year":"2007","unstructured":"Williams DL, Pierce V, Mellor P, Heath MF. Reduced tear production in three canine endocrinopathies. J Small Anim Pract. 2007;48(5):252\u2013256.17425694"},{"issue":"11","key":"ref10","series-title":"J Am Vet Med Assoc","first-page":"1761","article-title":"Keratoconjunctivitis sicca attributable to parasympathetic facial nerve dysfunction associated with hypothyroidism in a horse","volume":"233","author":"Schwarz BC","year":"2008","unstructured":"Schwarz BC, Sallmutter T, Nell B. Keratoconjunctivitis sicca attributable to parasympathetic facial nerve dysfunction associated with hypothyroidism in a horse. J Am Vet Med Assoc. 2008;233(11):1761\u20131766. doi:10.2460\/javma.233.11.1761"},{"issue":"5","key":"ref11","series-title":"Cornea","first-page":"627","article-title":"Unilateral dry eye due to possible isolated parasympathetic denervation of the lacrimal gland in a woman with hypothyroidism","volume":"41","author":"Singh S","year":"2022","unstructured":"Singh S, Basu S. Unilateral dry eye due to possible isolated parasympathetic denervation of the lacrimal gland in a woman with hypothyroidism. Cornea. 2022;41(5): 627\u2013629. doi:10.1097\/ICO.0000000000002867"},{"issue":"3","key":"ref12","series-title":"Vet Ophthalmol","first-page":"284","article-title":"Retrospective analysis of ocular neuropathies in diabetic dogs following cataract surgery","volume":"22","author":"Foote BC","year":"2019","unstructured":"Foote BC, Michau TM, Welihozkiy A, Stine JM. Retrospective analysis of ocular neuropathies in diabetic dogs following cataract surgery. Vet Ophthalmol. 2019;22(3): 284\u2013293. doi:10.1111\/vop.12589"},{"issue":"6","key":"ref13","series-title":"Vet Ophthalmol","first-page":"472","article-title":"Retrospective study of the prevalence of keratoconjunctivitis sicca in diabetic and nondiabetic dogs after phacoemulsification","volume":"18","author":"Gemensky-Metzler AJ","year":"2015","unstructured":"Gemensky-Metzler AJ, Sheahan JE, Rajala-Schultz PJ, Wilkie DA, Harrington J. Retrospective study of the prevalence of keratoconjunctivitis sicca in diabetic and nondiabetic dogs after phacoemulsification. Vet Ophthalmol. 2015;18(6):472\u2013480.25429857"},{"key":"ref14","article-title":"Package insert. Bayer HealthCare LLC","year":"2018","unstructured":"Claro. Package insert. Bayer HealthCare LLC; 2018."},{"key":"ref15","series-title":"Elanco","article-title":"Package insert","year":"2021","unstructured":"Neptra. Package insert. Elanco; 2021."},{"key":"ref16","series-title":"Dechra Veterinary Products","article-title":"Package insert","year":"2020","unstructured":"Osurnia. Package insert. Dechra Veterinary Products; 2020."},{"key":"ref17","series-title":"NADA 141\u2013437","article-title":"Original new animal drug application. Osurnia otic gel for dogs","unstructured":"Corrected Freedom of Information summary. Original new animal drug application. Osurnia otic gel for dogs. NADA 141\u2013437. Regulations.gov. Accessed May 26, 2022. https:\/\/www.regulations.gov\/document\/FDA-2014-N-0002-0076"},{"issue":"2","key":"ref18","series-title":"J Otolaryngol Head Neck Surg","first-page":"78","article-title":"Ototoxic effect of topical oxiconazole and terbinafine in rats","volume":"41","author":"Ayd\u0131n E","year":"2012","unstructured":"Ayd\u0131n E, Ta\u015ftan E, Aydo\u01e7an F, Karaca G, As\u0131m \u015eafak M. Ototoxic effect of topical oxiconazole and terbinafine in rats. J Otolaryngol Head Neck Surg. 2012;41(2):78\u201383.22569007"},{"issue":"1","key":"ref19","series-title":"J R Stat Soc Series B Stat Methodol","first-page":"289","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini Y","year":"1995","unstructured":"Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodol. 1995;57(1): 289\u2013300. doi:10.1111\/j.2517-6161.1995.tb02031.x"},{"issue":"10","key":"ref20","series-title":"Invest Ophthalmol Vis Sci","first-page":"4468","article-title":"Evaluation of novel dry eye model: preganglionic parasympathetic denervation in rabbit","volume":"48","author":"Toshida H","year":"2007","unstructured":"Toshida H, Nguyen DH, Beuerman RW, Murakami A. Evaluation of novel dry eye model: preganglionic parasympathetic denervation in rabbit. Invest Ophthalmol Vis Sci. 2007;48(10):4468\u20134475. doi:10.1167\/iovs.06-148617898267"},{"issue":"5","key":"ref21","series-title":"Am J Pathol","first-page":"1068","article-title":"Identification of lacrimal gland postganglionic innervation and its regulation of tear secretion","volume":"190","author":"Jin K","year":"2020","unstructured":"Jin K, Imada T, Hisamura R, et al. Identification of lacrimal gland postganglionic innervation and its regulation of tear secretion. Am J Pathol. 2020;190(5):1068\u20131079. doi:10.1016\/j.ajpath.2020.01.00732084368"},{"issue":"4","key":"ref22","series-title":"Clin Pharmacol Ther","first-page":"491","article-title":"Drug-induced ototoxicity: mechanisms, pharmacogenetics, and protective strategies","volume":"101","author":"Lanvers-Kaminsky C","year":"2017","unstructured":"Lanvers-Kaminsky C, Zehnhoff-Dinnesen AA, Parfitt R, Ciarimboli G. Drug-induced ototoxicity: mechanisms, pharmacogenetics, and protective strategies. Clin Pharmacol Ther. 2017;101(4):491\u2013500. doi:10.1002\/cpt.60328002638"},{"key":"ref23","article-title":"US FDA","unstructured":"Animal Drug Safety-Related Labeling Changes. US FDA. Accessed May 26, 2022. https:\/\/www.fda.gov\/animal-veterinary\/drug-labels\/animal-drug-safety-related-labeling-changes"},{"key":"ref24","series-title":"Veterinary Ophthalmology","first-page":"1121","article-title":"Diseases and surgery of the canine cornea and sclera","volume":"Vol 1","author":"Whitley RD","year":"2021","unstructured":"Whitley RD, Hamor RE. Diseases and surgery of the canine cornea and sclera. In: Gelatt KN, Ben-Shlomo G, Gilger BC, Hendrix DVH, Kern TJ, Plummer CE, eds. Veterinary Ophthalmology. 6th ed. Vol 1. Wiley Blackwell; 2021:1121."},{"key":"ref25","series-title":"Veterinary Ophthalmology","first-page":"1010","article-title":"Diseases and surgery of the canine lacrimal secretory system","volume":"Vol 1","author":"Giuliano EA","year":"2021","unstructured":"Giuliano EA. Diseases and surgery of the canine lacrimal secretory system. In: Gelatt KN, Ben-Shlomo G, Gilger BC, Hendrix DVH, Kern TJ, Plummer CE, eds. Veterinary Ophthalmology. 6th ed. Vol 1. Wiley Blackwell; 2021:1010."},{"issue":"8","key":"ref26","series-title":"Int J Mol Sci","first-page":"4256","article-title":"The role of metalloproteinases and their tissue inhibitors on ocular diseases: focusing on potential mechanisms","volume":"23","author":"Caban M","year":"2022","unstructured":"Caban M, Owczarek K, Lewandowska U. The role of metalloproteinases and their tissue inhibitors on ocular diseases: focusing on potential mechanisms. Int J Mol Sci. 2022;23(8):4256. doi:10.3390\/ijms2308425635457074"},{"issue":"3","key":"ref27","series-title":"Am J Vet Res","first-page":"333","article-title":"Impact of synthetic canine cerumen on in vitro penetration of auricular skin of dogs by florfenicol, terbinafine, and betamethasone acetate","volume":"79","author":"Ehling S","year":"2018","unstructured":"Ehling S, Baynes RE, B\u00e4umer W. Impact of synthetic canine cerumen on in vitro penetration of auricular skin of dogs by florfenicol, terbinafine, and betamethasone acetate. Am J Vet Res. 2018;79(3):333\u2013341. doi:10.2460\/ajvr.79.3.33329466046"},{"key":"ref28","series-title":"Muller and Kirk\u2019s Small Animal Dermatology","first-page":"757","article-title":"Diseases of eyelids, claws, anal sacs, and ears","author":"Miller WH","year":"2013","unstructured":"Miller WH, Griffin C, Campbell K. Diseases of eyelids, claws, anal sacs, and ears. Muller and Kirk\u2019s Small Animal Dermatology. 7th ed. Elsevier Mosby; 2013:757\u2013767."}],"container-title":["Journal of the American Veterinary Medical Association"],"original-title":[],"link":[{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/javma\/261\/1\/javma.22.07.0301.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/javma\/261\/1\/javma.22.07.0301.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/javma\/261\/1\/javma.22.07.0301.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T12:59:33Z","timestamp":1741352373000},"score":1,"resource":{"primary":{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/javma\/261\/1\/javma.22.07.0301.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,1]]},"references-count":28,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.2460\/javma.22.07.0301","relation":{},"ISSN":["0003-1488"],"issn-type":[{"value":"0003-1488","type":"print"}],"subject":[],"published":{"date-parts":[[2023,1,1]]}}}