Commercial Quinolone Ear Drops Cause Perforations in Intact Rat Tympanic Membranes , Hypothesis: Commercial quinolone ear drops may promote the development of perforations (TMPs) in intact tympanic membrane (TMs). Background: Quinolone ear drops have been associated with TMPs after myringotomy +/- tube placement in a drug-specific manner and potentiation by steroids. Methods: Rats were randomized to six groups (10/group), with one ear receiving otic instillation of dexamethasone, ofloxacin, ciprofloxacin, ofloxacin + dexamethasone, ciprofloxacin + dexamethasone, or neomycin + polymyxin + hydrocortisone—all commercial formulations and at standard clinical concentrations—and the contralateral ear receiving saline, twice daily for 10 days. TMs were assessed over 42 days. Results: No TMPs were seen in ears treated with saline, dexamethasone, or neomycin. At day 10, TMPs were seen in one of 10 ofloxacin- and three of 10 ciprofloxacin + dexamethasone-treated ears (p = 0.038). At day 14, the ofloxacin TMP healed. In contrast, the three ciprofloxacin + dexamethasone TMPs remained and one new TMP developed in this group. A ciprofloxacin and an ofloxacin + dexamethasone-treated ears also had TMPs (p = 0.023). By day 21, the ofloxacin + dexamethasone TMP and two of four of the ciprofloxacin + dexamethasone TMPs healed but two new TMPs were seen in ciprofloxacin + dexamethasone ears (p = 0.0006). At day 28, 1 of 10 ciprofloxacin and 4 of 10 ciprofloxacin + dexamethasone-treated ears had TMPs (p = 0.0006). By day 35, only one ciprofloxacin + dexamethasone had TMP (p = 0.42). All TMPS were healed at day 42. Conclusions: Application of commercial quinolone ear drops can cause TMPs in intact TMs. This effect appears to be drug-specific and potentiated by steroids. Address correspondence and reprint requests to Carolyn O. Dirain, Ph.D., Department of Otolaryngology, University of Florida, Box 100264, 1345 Center Drive MSB M2-228, Gainesville, FL 32610-0264; E-mail: ojanoc@ent.ufl.edu None of these commercial entities was involved in the design and conduct of the study or in the interpretation of the data and preparation of the manuscript. Financial support for this study was provided solely by the University of Florida. Dr. Antonelli discloses research support from Alcon Laboratories, Edison Pharmaceuticals, Otonomy, Next Science, and Medtronic ENT; service on Otonomy and Metarmor advisory boards; and speaker sponsorship by Alkem Laboratories and Vindico Medical Education. Dr. Dirain discloses research support from Next Science and Medtronic ENT. Mr. Karnani has no relevant conflicts to disclose. Supplemental digital content is available in the text. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://journals.lww.com/otology-neurotology). Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company