Taking oral fluoroquinolones appears to raise the risk that patients will develop a detached retina, according to a report in the April 4 issue of JAMA.
Fluoroquinolones have been linked to several forms of ocular toxicity, including corneal perforations, optic neuropathy, and retinal hemorrhages. "A class-wide warning also has been issued for tendon rupture, which raises concerns for the effect of these drugs on connective tissue in the eye," said Mahyar Etminan, Pharm.D., of the Child and Family Research Institute of British Columbia, Vancouver, and his associates.
In an epidemiologic case-control study examining a possible link between the drugs and retinal detachment, Dr. Etminan and his colleagues found that patients taking fluoroquinolones to treat an infection were nearly five times more likely to develop a detached retina than were nonusers.
They noted, however, that the absolute risk for the disorder remained small and estimated that 1,440 cases of retinal detachment diagnosed each year in the United States may be attributable to fluoroquinolone use.
The investigators studied the issue using information from a medical database covering approximately 4.5 million residents of British Columbia. They first identified all 989,591 patients who had visited an ophthalmologist in the province between 2000 and 2007, then identified all 4,384 incident cases of retinal detachment in that cohort.
Each case was matched for age with 10 control subjects from the cohort who did not have retinal detachment and all the subjects’ pharmacy records were searched for the use of ciprofloxacin, gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, or trovafloxacin for any indication except ocular infections in the preceding year. Such patients were excluded from the study because ocular infections themselves could raise the risk of retinal detachment.
The most common indications for fluoroquinolone use in this study were respiratory and genitourinary infections. Patients also took the drugs to treat gastrointestinal, skin, joint, bone, or other infections.
Patients currently using fluoroquinolones were found to be at significantly higher risk of developing a retinal detachment than were nonusers, with a rate ratio of 4.5, the investigators said (JAMA 2012;307:1414-9).
The mean length of the interval between the prescription of a fluoroquinolone and development of a retinal detachment was 4.8 days.
Patients who had used fluoroquinolones in the recent past (2 weeks before the index date) or the remote past (up to 1 year before the index date) showed no such increased risk. This indicates that the drugs’ adverse effect on the eye is acute.
Among the 445 fluoroquinolone users who developed retinal detachment, ciprofloxacin was the drug implicated in most cases (82.7%), followed by levofloxacin (7.2%), norfloxacin (4.9%), moxifloxacin (4.0%), and gatifloxacin (1.1%).
However, Dr. Etminan and his associates cautioned that the absolute risk of retinal detachment in fluoroquinolone users remained small at 4 per 10,000 person-years. They calculated that the number needed to harm was 2,500 patients.
"Given an approximate exposure prevalence of 10%, and assuming a similar risk increase in the general population, the population attributable risk would be estimated to be approximately 4%. We estimate that 1,440 cases of retinal detachment diagnosed annually in the United States may be attributed to oral fluoroquinolone use," they wrote.
"As a quality measure, we [also] tested the risk of retinal detachment in our study population with two distinct classes of medications that have not been associated with retinal detachment," namely oral beta-lactam antibiotics (penicillins and cephalosporins) and short-acting beta-agonists. No increase in risk for retinal detachment was found with either class of drugs.
"It is unlikely that treating retina surgeons suspected a possible link [between] oral fluoroquinolone use and retinal detachment, which may explain why more cases of retinal detachment secondary to fluoroquinolone use have not been reported," Dr. Etminan and his colleagues suggested.
The exact mechanism by which the drugs exert this adverse effect on the eye is not known, but it may involve their known ability to disrupt collagen and connective tissue. Medical conditions that are known to interfere with connective tissue and collagen formation "also increase vitreous liquefaction and have been shown to increase the risk of retinal detachment," the researchers said.
In addition, several large epidemiologic studies have demonstrated a link between fluoroquinolones and tendon rupture or detachment, usually within a median of 7 days of exposure to the drugs, which is similar to the 5-day interval noted in this study.
Further research is needed to confirm the association identified in this study, they added.
This study was funded by the Canadian National Institute for the Blind. No financial conflicts of interest were reported.