Fluoroquinolone Antibiotics Associated With Increased Risk of Retinal Detachment

Imagine going to see your doctor for symptoms suggesting you have cystitis (a bladder infection). Your doctor diagnoses a urinary tract infection and prescribes a 10-day course of the antibiotic levofloxacin (LEVAQUIN), a fluoroquinolone antibiotic. Five days later, you suddenly have difficulty seeing with your left eye.

Could your acute vision problem be related to the antibiotic? A recent Journal of the American Medical Association (JAMA) study suggests the answer may be yes.

The study found that patients taking oral fluoroquinolones, a commonly prescribed class of antibiotics, appear to have an increased risk for developing retinal detachment, a medical emergency that can result in permanent visual loss unless promptly treated by an ophthalmologist. (See Table 1 for a list of fluoroquinolones.) The authors of this study estimated that as many as 1,400 cases of retinal detachment each year in the U.S. may be due to the use of these drugs.

* Do Not Use
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What is retinal detachment?

The retina is the inner lining of the back of the eye. It is composed of special nerve cells that sense light passing through the lens of the eye. Retinal detachment occurs when part of the retina becomes separated from the back of the eye, forming a bubble. Because the detached part of the retina is separated from its blood supply, the retinal tissue can die due to a lack of oxygen unless the patient is promptly treated. Without treatment, retinal detachment can gradually progress to the entire retina, resulting in complete blindness in the affected eye.

Patients with retinal detachment can experience the sudden onset of a wide range of visual symptoms affecting one eye, including having blurred vision and seeing various abnormalities (for example, bright flashes of light particularly in the peripheral vision, floating objects, or shadows or blind spots in parts of the visual field).

Retinal detachment can be easily diagnosed by a simple examination of the eye. The condition requires prompt surgical treatment by an ophthalmologist.

JAMA study overview

In a carefully designed study, published on April 4, 2012, Dr. Mahyar Etminan and his co-authors used computerized medical and pharmacy records for all patients in the Canadian province of British Columbia to assess the risk of developing retinal detachment following exposure to an oral fluoroquinolone antibiotic.

The source population for this study included nearly 1 million patients who visited an ophthalmologist between January 2000 and December 2007.

From this population, the researchers identified 4,384 patients who were diagnosed with and underwent surgical treatment for retinal detachment (these patients are referred to as “index cases”). The research team compared these cases to a randomly selected, age-matched control group of 43,840 patients who did not have retinal detachment (10 control patients for each retinal-detachment patient).

Among the patients with retinal detachment, the average age was 61, and 58 percent were men. In comparison to control patients, index cases were more likely to have had nearsightedness (difficulty seeing distant objects), diabetes and prior cataract surgery, all three of which are risk factors for retinal detachment. The researchers adjusted for these differences between the groups so they could calculate the relative risk of developing retinal detachment following fluoroquinolone use that would more likely be attributable to the drugs rather than these other risk factors.

The researchers then identified among all patients in both groups those who had been prescribed an oral fluoroquinolone during the year preceding the diagnosis of retinal detachment in the index case.

To check the quality of their study methods, the researchers also looked at all patient exposures to two other classes of medications that have not been associated with an increased risk of retinal detachment: a different class of commonly used oral antibiotics known as beta-lactams (oral penicillins and cephalosporins, e.g., amoxicillin [AMOXIL] and cefaclor [CECLOR], respectively) and a nonantibiotic class of drugs called inhaled short-acting beta-agonists (e.g., albuterol [PROVENTIL]), which are used to treat patients with asthma and chronic obstructive pulmonary disease and have little absorption from the lungs into the bloodstream.

Effect of timing of fluoroquinolone exposure on risk of retinal detachment

The researchers assessed how the use of any oral fluoroquinolone, as well as the timing of that use, affected the risk for retinal detachment.

Of the 4,384 patients diagnosed with retinal detachment, 445 (10 percent) had been exposed to a fluoroquinolone antibiotic during the year preceding diagnosis. Of this subgroup with prior fluoroquinolone exposure, 368 (83 percent) had taken ciprofloxacin (CIPRO, PROQUIN), 32 (7 percent) levofloxacin, 22 (5 percent) norfloxacin (NOROXIN), 18 (4 percent) moxifloxacin (AVELOX), and 5 (1 percent) gatifloxacin (TEQUIN, a drug not available in the U.S.).

To assess the effect of the timing of fluoroquinolone use on the risk of retinal detachment, the patients were categorized into three user groups — current users, recent users and past users — based on how recently they took an oral fluoroquinolone prior to the diagnosis of retinal detachment in the index case.

Current users were those patients whose prescribed course of a fluoroquinolone antibiotic overlapped with the date of the index case’s retinal-detachment diagnosis. Recent users were those patients whose prescribed course ended between one and seven days before the date of the index case’s diagnosis, and past users were those patients whose prescribed course ended between eight and 365 days before that date.

The researchers used this same categorization when assessing the risk of retinal detachment in patients exposed to oral beta-lactams or inhaled short-acting beta-agonists.

After adjusting for age, sex and various known risk factors for retinal detachment, the researchers found that current fluoroquinolone users had a 3.6- to 5.7-fold higher risk of developing a detached retina than patients who had not been treated with a fluoroquinolone. For current users diagnosed with retinal detachment, the average time between the start of the fluoroquinolone prescription and the diagnosis of the detachment was about five days.

In contrast, the researchers found no increased risk of retinal detachment in recent or past users of fluoroquinolones. Further, as expected, they saw no increased risk of retinal detachment in any group of patients who had been exposed to either a beta-lactam antibiotic or an inhaled beta-agonist, indicating that the study design likely was valid and of good quality.

It is important to note that, although the increase in the relative risk of retinal detachment in current users of fluoroquinolone antibiotics was more than quadruple the risk in people who had not taken these drugs, the absolute increase in risk was much less dramatic. For example, the authors noted that if 10,000 patients took a fluoroquinolone for one year, there would be four extra cases of retinal detachment diagnosed in comparison to the number of cases in 10,000 patients who did not take these antibiotics over that same year.

Since oral fluoroquinolones typically are prescribed for several days to a few weeks, the occurrence of retinal detachment during a course of such antibiotics is a rare event.

How could fluoroquinolones cause retinal detachment?

The exact mechanism by which fluoroquinolone antibiotics may cause retinal detachment is unclear. Prior studies have shown that these antibiotics may interfere with the formation of collagen, a protein that forms strong fibers that provide structural support to many connective tissues, including those that hold the retina in place. Disruption of collagen formation by fluoroquinolones thus could weaken the connective tissues that support the retina and predispose patients to retinal detachment.

Potential danger of tendon rupture

The disruption of collagen formation may play a role in the occurrence of another well-documented adverse effect of fluoroquinolones: tendinitis and tendon rupture.

In response to an August 2006 Health Research Group petition — and subsequent successful lawsuit — the Food and Drug Administration added a warning for doctors to the labeling or package for all fluoro-quinolone antibiotics about the risk of tendinitis, including the possibility of complete tendon rupture. This adverse reaction most frequently involves the Achilles tendon, the tendon that runs from the back of the heel to the calf. Collagen is a key structural component of tendons, and disruption of collagen likewise may explain why fluoroquinolones cause tendon injuries.

What You Can Do

One of the biggest-selling and most overprescribed classes of drugs in the U.S., fluoroquinolones are commonly misprescribed for viral infections (such as the common cold, for which antibiotics are useless) and for bacterial infections (for which, in many cases, other safer, cheaper alternative antibiotics would likely be as or more effective). Therefore, whenever your doctor prescribes a fluoroquinolone, you should ask whether your illness requires any antibiotic and, if so, whether an alternative antibiotic would be effective.

When taking a fluoroquinolone, you should be alert for the previously mentioned visual symptoms that could indicate retinal detachment, particularly if you have other risk factors, such as nearsightedness, diabetes or recent cataract surgery. If such symptoms occur (whether or not you are taking a fluoroquinolone), you should seek immediate medical attention from an ophthalmologist or an emergency department so that you can be examined for possible retinal detachment. Without prompt treatment, permanent visual loss may result.

Also, if you develop tendon pain while taking a fluoroquinolone, you should promptly contact the prescribing doctor or your primary health care provider so that you can be switched to a different antibiotic in order to decrease your risk of a tendon rupture.

You should not discontinue the use of any medication without first consulting your prescribing doctor.