EDITORIAL Association Between Oral Fluoroquinolones and Retinal Detachment THOMAS A. ALBINI, PETROS C. KARAKOUSIS, ASHKAN M. ABBEY, JOHN G. BARTLETT, AND HARRY W. FLYNN, JR I N A RECENT ISSUE OF THE JOURNAL OF THE AMERICAN Medical Association (JAMA), Etminan and associates report in a case-control study that the use of oral fluo- roquinolones is associated with a significantly higher risk of rhegmatogenous retinal detachment (RRD), with an adjusted rate ratio (ARR) of 4.5. 1 Oral fluoroquinolones are one of the most commonly prescribed classes of anti- biotics in the United States. 2 The study has important potential ramifications, including: 1) increased patient referrals to retina specialists for evaluation of retinal complications of fluoroquinolone use; 2) decreased use of fluoroquinolones in patients otherwise at risk for retinal detachment; and 3) medicolegal risks for physicians and pharmaceutical companies. Given these dramatic potential implications, a critical appraisal of the clinical findings of this article is warranted. Fluoroquinolones provide broad-spectrum coverage for a number of infectious diseases, including sinus/respira- tory tract infections and genitourinary tract infections. The mechanism of action of fluoroquinolones involves inhibition of deoxyribonucleic acid (DNA) gyrase and topoisomerase IV, which are essential enzymes in bacte- rial DNA replication. The fluoroquinolones are bacteri- cidal agents since drug binding to the enzyme-DNA complex blocks progression of DNA polymerase, ulti- mately leading to bacterial DNA damage and cell death. 3 Common nonocular adverse effects associated with fluoroquinolone use include gastrointestinal toxicity, typically manifesting as mild anorexia, nausea, vomiting, abdominal discomfort, or diarrhea; and central nervous system toxicity, presenting predominantly as mild headache, dizziness, insomnia, or mood alterations. Other adverse effects include tendinitis and tendon rupture, prolongation of the QT interval, hypoglycemia and hyperglycemia, elevated transaminases and liver failure, rashes and other allergic reactions, and hemato- logic toxicity. 4 Reported ocular adverse events include corneal perforation 5 from topical use and toxic optic neuropathy. 6 Retinal toxicity and degeneration, but not RRD, have been associated with the use of oral fluoroquinolones in animals. 7 Albino mice that were administered oral fluo- roquinolones followed by 4 hours of ultraviolet radiation demonstrated histologic vacuolation of photoreceptor segments and swelling of retinal pigment epithelium (RPE) cells. 7 These changes eventually resulted in atrophy and disorganization of retinal architecture. Intravitreal trovafloxacin resulted in dose-dependent injury to the RPE and photoreceptors in rabbits. 8 Retinal hemorrhages were a reported adverse event associated with the use of gemifloxacin. 9 However, there have been no documented reports in the literature of RRD associated with the use of oral fluoroquinolones. In their JAMA article, Etminan and associates cite 1 case of unspecified retinal detachment associated with oral ciprofloxacin that was reported in the 1999 Health Canada Adverse Reaction Report. 1,10 Sirbat and associates reported 3 cases of bilateral serous retinal detachments (not RRD) related to an older fluoroquinolone known as flumequine. 11 All 3 patients had chronic renal failure and were being treated for urinary tract infections, which may have increased the amount of active drug in their circulation. Within 2 days of drug cessation, the patients’ vision returned to baseline, and their serous retinal detachments completely resolved within 5 days of drug cessation. The authors noted that a quinolone treatment (nalidixic acid) has been shown to result in transient bullae on young animals’ articular cartilage. 12 The direct cytotoxic effect of quinolones on the cartilage leads to interstitial edema and subsequent bullae. It was postu- lated that a similar cytotoxic effect occurred within the retina, resulting in serous retinal detachments. It is important to consider that these serous retinal detach- ments are not rhegmatogenous (ie, not caused by a break in the retina). In their case-control study, Etminan and associates utilized the British Columbia Linked Health Database to Accepted for publication Sep 18, 2012. From the Department of Ophthalmology, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, Florida (T.A.A., A.M.A., H.W.F.); and the Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland (P.C.K., J.G.B.). Inquiries to Thomas A. Albini, 900 NW 17 Street, Suite #245, Miami, FL 33136; e-mail: talbini@med.miami.edu 0002-9394/$36.00 http://dx.doi.org/10.1016/j.ajo.2012.09.016 919 Ó 2012 BY ELSEVIER INC.ALL RIGHTS RESERVED.