Hydroxychloroquine May Put Eyes at Risk

By Linda Rath | July 15, 2022

Up to half of patients treated with the arthritis drug hydroxychloroquine (Plaquenil) are prescribed more than the recommended maximum amount, according to new research. In separate studies, Canadian and U.S. researchers found that 30% to 50% of patients didn’t receive the dose outlined in treatment guidelines; a smaller percentage didn’t get recommended eye exams.
Hydroxychloroquine is an antimalarial drug commonly used to treat rheumatoid arthritis (RA), lupus and other autoimmune diseases, either alone or in combination with one or more other medications. Unlike some other conventional disease-modifying antirheumatic drugs (DMARDs) and biologics, it affects the immune response without suppressing it or increasing the risk of infection.

Hydroxychloroquine is generally safe at normal doses, but higher amounts can damage the retina, the light-sensitive tissue at the back of the eye, and could result in partial or complete blindness. Hydroxychloroquine-related eye problems were once considered rare, but better detection methods now show they occur in a greater proportion of patients — more than the 7% originally thought. More recent data show retinal toxicity occurs in more than 10% of patients who have taken hydroxychloroquine for more than 10 years, and in anywhere from 20% to 50% of those who have taken the drug more than 20 years. The risk increases not only with a higher dose and more years taking it but also in African Americans and people who are slender.

Vision Risks

The appropriate dose of hydroxychloroquine depends on the patient’s body weight. The American Academy of Ophthalmology (AAO) currently defines an overdose of hydroxychloroquine as more than 5 milligrams (mg) per kilogram (2.2 pounds) of body weight or more than 400 mg a day.

An eye exam is recommended at the start of treatment to detect any existing vision problems; follow-up tests are needed to catch retinal damage in the earliest stages, before symptoms appear. If found later, damage to the eye is irreversible and may continue even after the medication is stopped.

Yet Canadian researchers found in a study that approximately one-third of 90 arthritis patients at eight different rheumatology clinics were not prescribed appropriate weight-based doses of hydroxychloroquine, and 12% failed to have an eye exam in the first year of treatment.

This is “significantly below the standard of care,” says Sahil Koppikar, MD, a rheumatologist at Women’s College Hospital in Toronto, Canada.

In a separate study, published in Ophthalmology in early 2017, Rebekah Braslow, MD, and colleagues at NorthShore University HealthSystem in Chicago reviewed the records of more than 550 rheumatology patients seen by NorthShore ophthalmologists between 2009 and 2016. About half had been prescribed too much hydroxychloroquine, and dosing errors continued at the same rate even after the AAO issued revised treatment guidelines in 2016.

Why Dosing Goes Wrong

Dr. Braslow says several things probably account for prescribing errors. Some of the blame falls on drug manufacturers, who offer only 200 mg pills, which are hard to calibrate to body weight. As Dr. Koppikar points out, it’s easier and faster to prescribe a 400 mg pill than calculate an exact dose, but that puts patients at risk.

Changing and conflicting guidelines may also cause confusion. The 2011 AAO guidelines recommended dosing hydroxychloroquine based on ideal body weight — what a patient should weigh for their height rather than their actual weight. This was supposed to ensure that people who were very short or overweight got the right amount of drug. The proposed daily dose was 6.5 mg per kilogram (kg) of ideal body weight. That recommendation was lowered in March 2016 to 5 mg per kg of actual body weight, up to a maximum of 400 mg a day.  

“It behooves rheumatologists to adopt the recommendations of the American Academy of Ophthalmology because there is more toxicity [from hydroxychloroquine] than we previously appreciated,” says James Rosenbaum, MD, chief of ophthalmology at Devers Eye Institute and chief of arthritis and rheumatic diseases at Oregon Health & Science University, both in Portland, Oregon.

Prior to the coronavirus pandemic, the American College of Rheumatology (ACR) hadn’t taken a formal stand on hydroxychloroquine dosing. But when some COVID-19 patients developed heart problems after receiving high doses of hydroxychloroquine, the ACR issued a white paper endorsing weight-based dosing up to a maximum of 400 mg a day. (Hydroxychloroquine was later found to be ineffective for COVID-19). Both the AAO and ACR recommend that patients starting hydroxychloroquine have a baseline eye exam using newer imaging technologies like  optical coherence tomography (OCT).

Dr. Rosenbaum says that the AAO’s guidelines are based on emerging data that show the value of OCT screening, and he points out that “since rheumatologists refer patients to ophthalmologists for screening, presumably the AAO guidelines will be the ones that tend to be actually followed.”

Protect Yourself

It’s not clear what it will take to prevent incorrect dosing of hydroxychloroquine. One Canadian hospital instituted three simple interventions: dosing charts and scales in all clinic offices and a requirement that patients receiving hydroxychloroquine have their weight entered in their electronic medical records. Ten months after these changes were introduced, the percentage of patients receiving the right dose of hydroxychloroquine increased from 30% to 89% and the percentage undergoing eye screening tests increased from 51% to 91%.

If your provider doesn’t have those kinds of measures in place, be proactive. Make sure you receive a baseline eye exam when starting hydroxychloroquine and talk to your doctor to make sure your dose isn’t too high. Also, keep in mind that the chance of eye disease increases the longer you take the drug.