{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T15:38:20Z","timestamp":1791819500603,"version":"4.3.4"},"reference-count":34,"publisher":"American Veterinary Medical Association (AVMA)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["javma"],"published-print":{"date-parts":[[2015,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:p><jats:bold>Case Description<\/jats:bold>\u20146 dogs (10 eyes) with keratitis following long-term topical treatment with a carbonic anhydrase inhibitor (CAI) were evaluated. In 4 dogs (6 eyes), CAI treatment was discontinued. Three dogs (4 eyes) underwent enucleation because of end-stage corneal disease. One dog was treated differently in each eye and thus was represented in both aforementioned groups.<\/jats:p>\n<jats:p><jats:bold>Clinical Findings<\/jats:bold>\u2014Following initiation of treatment with a CAI (ie, brinzolamide or dorzolamide), the median time to development of severe ocular signs was 266 days (range, 133 to 679 days). Clinically severe ocular signs included ulcerative and nonulcerative perilimbal keratitis or severe diffuse keratitis with marked vascularization. The keratitis was refractory to treatment with anti-inflammatory medications. Histologic and immunohistochemical examination of enucleated globes was performed in 3 affected dogs and in 1 dog with keratitis that recovered. Corneal lesions included 2 distinct inflammatory infiltrates with plasma cells predominating in the anterior stroma and both T cells and neutrophils in the epithelium. Stromal plasma cells and overlying epithelium exhibited strong positive immunoreactivity for IgG.<\/jats:p>\n<jats:p><jats:bold>Treatment and Outcome<\/jats:bold>\u2014Topical CAI treatment was discontinued in 4 dogs after a median of 209 days (range, 44 to 433 days), and in these dogs, clinical improvement was evident within 2 to 4 days of CAI treatment cessation. Signs of keratitis resolved in 12 to 25 days in these 4 dogs, and median follow-up time after CAI discontinuation was 25.5 months (range, 6 to 42 months), during which time signs of corneal disease did not recur.<\/jats:p>\n<jats:p><jats:bold>Clinical Relevance<\/jats:bold>\u2014On the basis of this small series, presumed topical CAI-associated keratitis in dogs appeared to be an uncommon immune-mediated disease that was not responsive to corticosteroid treatment. Affected patients improved rapidly, but only after discontinuation of CAI treatment. In dogs with glaucoma, clinicians should consider the development of punctate keratopathy and severe diffuse keratitis as potential adverse effects related to topical administration of CAIs, even after previously uneventful long-term use.<\/jats:p>","DOI":"10.2460\/javma.247.12.1419","type":"journal-article","created":{"date-parts":[[2015,12,7]],"date-time":"2015-12-07T18:56:13Z","timestamp":1449514573000},"page":"1419-1426","source":"Crossref","is-referenced-by-count":11,"title":["Keratitis in six dogs after topical treatment with carbonic anhydrase inhibitors for glaucoma"],"prefix":"10.2460","volume":"247","author":[{"given":"Billie","family":"Beckwith-Cohen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellison","family":"Bentley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Gasper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian J.","family":"McLellan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard R.","family":"Dubielzig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1272","reference":[{"key":"ref1","series-title":"Vet Ophthalmol","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1046\/j.1463-5216.2001.00202.x","article-title":"Advances in topical glaucoma therapy","volume":"5","author":"Willis","year":"2002"},{"key":"ref2","series-title":"Vet Ophthalmol","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1111\/vop.12069","article-title":"Efficacy of prophylactic antiglaucoma and anti-inflammatory medications in canine primary angle-closure glaucoma: a multicenter retrospective study (2004\u20132012)","volume":"17","author":"Dees","year":"2014"},{"key":"ref3","series-title":"Isr Med Assoc J","first-page":"260","article-title":"Switching from systemic to the topical carbonic anhydrase inhibitor dorzolamide: effect on the quality of life of glaucoma patients with drug-related side effects","volume":"5","author":"Nesher","year":"2003"},{"key":"ref4","series-title":"Curr Pharm Des","doi-asserted-by":"publisher","first-page":"649","DOI":"10.2174\/138161208783877866","article-title":"The development of topically acting carbonic anhydrase inhibitors as antiglaucoma agents","volume":"14","author":"Mincione","year":"2008"},{"key":"ref5","series-title":"Vet Ophthalmol","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1046\/j.1463-5224.2001.00141.x","article-title":"Changes in intraocular pressure associated with topical dorzolamide and oral methazolamide in glaucomatous dogs","volume":"4","author":"Gelatt","year":"2001"},{"key":"ref6","series-title":"Am J Vet Res","doi-asserted-by":"publisher","first-page":"859","DOI":"10.2460\/ajvr.2001.62.859","article-title":"Effects of topical application of a 2% solution of dorzolamide on intraocular pressure and aqueous humor flow rate in clinically normal dogs","volume":"62","author":"Cawrse","year":"2001"},{"key":"ref7","series-title":"Br J Ophthalmol","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.1136\/bjo.87.8.1052","article-title":"Topical dorzolamide and metabolic acidosis in a neonate","volume":"87","author":"Morris","year":"2003"},{"key":"ref8","series-title":"Am J Contact Dermat","first-page":"217","article-title":"Contact dermatitis to topical drugs for glaucoma","volume":"12","author":"Holdiness","year":"2001"},{"key":"ref9","series-title":"Am J Ophthalmol","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/S0002-9394(98)00095-6","article-title":"Clinical efficacy and safety of brinzolamide (Azopt), a new topical carbonic anhydrase inhibitor for primary openangle glaucoma and ocular hypertension. Brinzolamide Primary Therapy Study Group","volume":"126","author":"Silver","year":"1998"},{"key":"ref10","series-title":"Med Lett Drugs Ther","first-page":"76","volume":"37","year":"1995"},{"key":"ref11","series-title":"Am J Ophthalmol","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/S0002-9394(00)00478-5","article-title":"Marginal keratitis: an uncommon form of topical dorzolamide allergy","volume":"130","author":"Taguri","year":"2000"},{"key":"ref12","series-title":"Ophthalmology","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/j.ophtha.2006.09.032","article-title":"Drug-induced ectropion: what is best practice?","volume":"114","author":"Hegde","year":"2007"},{"key":"ref13","series-title":"Am J Ophthalmol","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/S0002-9394(98)00438-3","article-title":"Irreversible corneal decompensation in patients treated with topical dorzolamide","volume":"127","author":"Konowal","year":"1999"},{"key":"ref14","series-title":"J Ocul Pharmacol Ther","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1089\/jop.2007.0058","article-title":"Erythema multiforme after use of topical dorzolamide","volume":"24","author":"Munshi","year":"2008"},{"key":"ref15","series-title":"J Glaucoma","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1097\/00061198-200104000-00011","article-title":"Dorzolamide-induced immune thrombocytopenia: a case report and literature review","volume":"10","author":"Martin","year":"2001"},{"key":"ref16","series-title":"West Indian Med J","first-page":"102","article-title":"Skin eruption and thrombocytopaenia in a woman with glaucoma: a case report","volume":"59","author":"Santos","year":"2010"},{"key":"ref17","series-title":"Australas J Dermatol","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1111\/j.1440-0960.2004.00074.x","article-title":"Lichenoid drug eruption secondary to topical timolol and dorzolamide eye-drops","volume":"45","author":"Mullins","year":"2004"},{"key":"ref18","series-title":"Contact Dermat","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1111\/j.1600-0536.2007.01143.x","article-title":"Systemic contact dermatitis to dorzolamide eye drops","volume":"58","author":"Kluger","year":"2008"},{"key":"ref19","series-title":"Ophthalmology","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.ophtha.2003.05.002","article-title":"Thygeson's superficial punctate keratitis: ten years' experience","volume":"111","author":"Nagra","year":"2004"},{"key":"ref20","series-title":"Cornea","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1097\/00003226-199903000-00002","article-title":"Classification of herpes simplex virus keratitis","volume":"18","author":"Holland","year":"1999"},{"key":"ref21","series-title":"Clin Ophthalmol","first-page":"2131","article-title":"Preservative toxicity in glaucoma medication: clinical evaluation of benzalkonium chloride-free 0.5% timolol eye drops","volume":"7","author":"Rosin","year":"2013"},{"key":"ref22","series-title":"Vet Ophthalmol","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1111\/j.1463-5224.2009.00709.x","article-title":"Outbreak of ocular disease associated with naturally-acquired canine herpesvirus-1 infection in a closed domestic dog colony","volume":"12","author":"Ledbetter","year":"2009"},{"key":"ref23","series-title":"Graefes Arch Clin Exp Ophthalmol","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1007\/s00417-004-0955-2","article-title":"Efficacy of topical nerve growth factor treatment in dogs affected by dry eye","volume":"243","author":"Coassin","year":"2005"},{"key":"ref24","series-title":"Vet Clin North Am Small Anim Pract","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.cvsm.2007.11.007","article-title":"Immune-mediated canine and feline keratitis","volume":"38","author":"Andrew","year":"2008"},{"key":"ref25","series-title":"Graefes Arch Clin Exp Ophthalmol","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1007\/s00417-010-1397-7","article-title":"Comparison of the efficacy and tolerability of preservative-free and preservative-containing formulations of the dorzolamide\/timolol fixed combination (COSOPT) in patients with elevated intraocular pressure in a randomized clinical trial","volume":"248","author":"Shedden","year":"2010"},{"key":"ref26","series-title":"Curr Eye Res","doi-asserted-by":"publisher","first-page":"391","DOI":"10.3109\/02713683.2011.562340","article-title":"Ocular surface disease in patients with ocular hypertension and glaucoma","volume":"36","author":"Stewart","year":"2011"},{"key":"ref27","series-title":"J Glaucoma","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1097\/00061198-200312000-00007","article-title":"Ocular factors relevant to antiglaucomatous eyedrop-related keratoepitheliopathy","volume":"12","author":"Inoue","year":"2003"},{"key":"ref28","series-title":"Curr Eye Res","doi-asserted-by":"publisher","first-page":"101","DOI":"10.3109\/02713683.2011.631722","article-title":"A comparison of active ingredients and preservatives between brand name and generic topical glaucoma medications using liquid chromatographytandem mass spectrometry","volume":"37","author":"Kahook","year":"2012"},{"key":"ref29","series-title":"Neurology","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1212\/WNL.43.5.1045","article-title":"Double-blind controlled study of methazolamide in the treatment of essential tremor","volume":"43","author":"Busenbark","year":"1993"},{"issue":"Suppl 2","key":"ref30","series-title":"Surv Ophthalmol","doi-asserted-by":"publisher","first-page":"S141","DOI":"10.1016\/S0039-6257(99)00111-3","article-title":"Ocular comfort of brinzolamide 1.0% ophthalmic suspension compared with dorzolamide 2.0% ophthalmic solution: results from two multicenter comfort studies. Brinzolamide Comfort Study Group","volume":"44","author":"Silver","year":"2000"},{"key":"ref31","series-title":"Expert Opin Pharmacother","doi-asserted-by":"publisher","first-page":"2425","DOI":"10.1517\/14656566.2011.589384","article-title":"From dorzolamide 2%\/timolol 0.5% to brinzolamide 1%\/timolol 0.5% fixed combination: a 6-month, multicenter, open-label tolerability switch study","volume":"12","author":"Rossi","year":"2011"},{"key":"ref32","series-title":"J Am Acad Dermatol","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1067\/mjd.2002.120908","article-title":"The clinical and histopathologic spectrum of \u201cdermal hypersensitivity reactions,\u201d a nonspecific histologic diagnosis that is not very useful in clinical practice, and the concept of a \u201cdermal hypersensitivity reaction pattern","volume":"47","author":"Fung","year":"2002"},{"key":"ref33","series-title":"Eur J Ophthalmol","doi-asserted-by":"publisher","first-page":"296","DOI":"10.5301\/ejo.5000220","article-title":"Risk factors to develop ocular surface disease in treated glaucoma or ocular hypertension patients","volume":"23","author":"Rossi","year":"2013"},{"key":"ref34","series-title":"Drugs Aging","doi-asserted-by":"publisher","first-page":"267","DOI":"10.2165\/11588830-000000000-00000","article-title":"Effects of common topical antiglaucoma medications on the ocular surface, eyelids and periorbital tissue","volume":"28","author":"Servat","year":"2011"}],"container-title":["Journal of the American Veterinary Medical Association"],"original-title":[],"link":[{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/javma\/247\/12\/javma.247.12.1419.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/javma\/247\/12\/javma.247.12.1419.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/javma\/247\/12\/javma.247.12.1419.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T11:46:00Z","timestamp":1741347960000},"score":1,"resource":{"primary":{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/javma\/247\/12\/javma.247.12.1419.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,15]]},"references-count":34,"journal-issue":{"issue":"12"},"URL":"https:\/\/doi.org\/10.2460\/javma.247.12.1419","relation":{},"ISSN":["0003-1488"],"issn-type":[{"value":"0003-1488","type":"print"}],"subject":[],"published":{"date-parts":[[2015,12,15]]}}}