JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS Volume 23, Number 1, 2007 © Mary Ann Liebert, Inc. DOI: 10.1089/jop.2006.0071 Effects of Topical Anti-Inflammatory Agents in a Botulinum Toxin B–Induced Mouse Model of Keratoconjunctivitis Sicca KAEVALIN LEKHANONT, 1 CHOUL YONG PARK, 1 JANINE A. SMITH, 1,2 JUAN CASTRO COMBS, 1 PISIT PREECHAWAT, 1 OLAN SUWAN-APICHON, 3 RAM RANGSIN, 4 and ROY S. CHUCK 1 ABSTRACT Purpose: The aim of this study was to compare the effects of topical nonsteroidal anti-in- flammatory drugs (NSAIDs), corticosteroid, doxycycline, and artificial tears for the treatment of ocular surface damage in the Botulinum toxin B (BTX-B)–induced mouse model of dry eye. Methods: CBA/J mice were randomized into 2 experimental groups of 35 animals each. The control group received a transconjunctival injection of 0.05 mL of saline into the left lacrimal gland, and another group was injected with 0.05 mL of 20 milliunits BTX-B solution (SPSS, Inc., Chicago, IL). Three (3) days after intralacrimal gland injections, each group was equally randomized into 7 subgroups (n  5 each) to receive treatment unilaterally into their left eyes with topical artificial tears (0.5% carboxymethylcellulose sodium), 0.1% fluorometholone, 0.1% nepafenac, 0.4% ketorolac, 0.09% bromfenac, 0.1% diclofenac, or 0.025% doxycycline. Tear vol- ume, ocular surface changes, and spontaneous blink rate were evaluated in each of the 14 ex- perimental subgroups. Results: Topical fluorometholone, nepafenac, and doxycycline significantly improved corneal surface staining in the BTX-B-injected mice within 2 weeks of treatment. Topical ke- torolac, diclofenac, and bromfenac, applied twice-daily, partially reduce corneal staining, and did so more slowly by the 4-week time point. In comparison, topical artificial tear-treated mice did not demonstrate significant improvement of the corneal surface at any time point. Aqueous tear production in the BTX-B-injected fluorometholone-treated group started to re- turn to baseline level within 2 weeks, although not significantly. Meanwhile, BTX-B-injected mice treated with artificial tears, topical NSAIDs, and doxycycline still exhibited a reduction in tear production up to 4 weeks. No significant differences in blink rate between the con- trol and study groups undergoing the various treatments were noted at all time points. Conclusions: This study suggests the potential usefulness of topical NSAIDs, corticosteroid, and doxycycline for the clinical treatment of ocular surface epithelial disorders associated with dry eye. 27 1 Wilmer Ophthalmological Institute, Johns Hopkins University, Baltimore, MD. 2 National Eye Institute, National Institutes of Health, Bethesda, MD. 3 Department of Ophthalmology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. 4 Department of Military and Community Medicine, Phramongkutklao College of Medicine, Bangkok, Thailand. Dr. Roy S. Chuck: Speaker’s Bureau and previous research funding from Allergan, Alcon, Novartis, and Ista. No research funding for this current study.