Oral fluoroquinolone use may increase risk of retinal detachment

Detachments and reported tendon ruptures may be attributed to interference with collagen synthesis and repair, specialist says.

Issue: January 2013

Use of oral fluoroquinolones may be associated with an increased risk of retinal detachment, according to a large study.

“There is likely an effect between oral fluoroquinolone use and retinal detachment, with up to 4% of all detachments possibly attributed to this association. Confirmatory studies are needed but it still may be prudent to alert patients taking fluoroquinolones of the symptoms of detachment and ask them to seek attention if these symptoms develop,” David Maberley, MD, FRCS(C), told colleagues at the American Society of Retina Specialists meeting.

Oral fluoroquinolone use has been associated with tendon rupture. These ruptures have been attributed to interference with the collagen synthesis and repair processes. Fluoroquinolones are believed to have a similarly deleterious effect on collagen in the vitreous, Maberley said.

“There are animal studies showing that after 3 days of [ciprofloxacin] use, collagen in tendons decreases by 50%. And there are also recorded cases of tendon ruptures after one dose of this drug. Most Achilles ruptures actually occur within the first 7 days of fluoroquinolone use as well, which is supportive of our findings,” he said.

Fluoroquinolones are among the most commonly prescribed drugs in the U.S., with more than 40 million prescriptions dispensed annually.

“Fluoroquinolones have a broad spectrum of antibacterial coverage and high tissue distribution, especially in the eye,” Maberley said.

Study results were published in the Journal of the American Medical Association.

Patients and methods

The case-control study included 4,384 patients diagnosed with retinal detachment and 43,840 healthy age-matched controls.

Mean patient age was 61.1 years. Males comprised 58.2% of the retinal detachment group and 43.5% of controls.

Investigators assessed all oral fluoroquinolone use in the 1 year before retinal detachment diagnosis. Data on topical and intravenous fluoroquinolone use were excluded.

Current fluoroquinolone use was defined as a prescription overlapping with a diagnosis of retinal detachment. Recent use was a prescription that ended 1 to 7 days before diagnosis of retinal detachment. Past use was a prescription that ended 8 to 365 days before diagnosis.

Investigators calculated raw rate ratios for risk of retinal detachment among fluoroquinolone users and non-users. Data were also adjusted for gender, previous cataract surgery, myopia, diabetes, number of previous prescription drugs in the past year and number of ophthalmology visits in the past year.

Infections being treated at the time of retinal detachment were primarily respiratory, followed by genitourinary, skin, bone or joint, and gastrointestinal; ciprofloxacin was used in 82.7% of cases.

A sensitivity analysis of two drugs not linked to retinal detachment, oral beta-lactam antibiotics and short-acting beta-agonists, was undertaken to validate the fluoroquinolone findings.

Results and analysis

Study results showed that patients using fluoroquinolones concurrently with diagnosis had a 5.55-times greater risk of retinal detachment compared with non-users. Adjusted data showed a 4.5-times greater risk.

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“Both of these were highly significant,” Maberley said.

Patients using fluoroquinolones at any time in the year before diagnosis had a 1.55-times greater risk of developing retinal detachment compared with non-users. Adjusted data showed a 1.39-times greater risk. Both results were statistically significant.

Recent use of fluoroquinolones was associated with a 1.35-times greater risk of developing retinal detachment; adjusted data showed a 0.92-times greater risk. These results were not statistically significant.

Past use was associated with a 1.13-times greater risk of detachment, adjusted to a 1.03-times greater risk; these results were not statistically significant.

The results had statistical power for fluoroquinolones as a drug class but not for specific types of fluoroquinolones, Maberley said.

“A study designed to determine a class effect of all fluoroquinolones is not powered to study individual subsets of that class of drugs,” he said.

Data showed no association between retinal detachment and use of oral  beta-lactam antibiotics and short-acting beta-agonists, Maberley said. – by Matt Hasson

Reference:

Etminan M, Forooghian F, Brophy JM, Bird ST, Maberly D. Oral fluoroquinolones and the risk of retinal detachment. JAMA. 2012;307(13):1414-1419.

For more information:

David Maberley, MD, FRCS(C), can be reached at VGH/UBC Eye Care Centre, Section C, 2550 Willow Street, Vancouver, British Columbia, Canada V5Z 3N9; 604-875-4599; fax: 604-875-4699; email: crtg_vancouver@hotmail.com.
Disclosure: Maberley is a consultant for Genentech, Regeneron, Eyetech and QLT Therapeutics.