This article is more than 5 years old. Information may no longer be current.
Ophthalmologists play important role for patients treated with hydroxychloroquine
Click Here to Manage Email Alerts
Hydroxychloroquine has been used in American medicine since 1955. It is primarily prescribed to treat chloroquine-sensitive malaria, rheumatoid arthritis, lupus erythematosus, porphyria cutanea tarda and post-Lyme disease arthritis. It is an anti-inflammatory that interferes with toll-like receptors, especially toll-like receptor 9, reducing the activation of plasmacytoid dendritic cells.
Typical doses are in the range of 200 mg to 400 mg per day, and the medicine is conveniently taken by mouth. Like all medicines with potential side effects, the lowest effective dose is preferred, and many patients are treated with higher doses than required. The typical toxicity is gastrointestinal, including nausea and vomiting.
The vision-threatening side effect we ophthalmologists are asked to screen for is so-called “bull’s-eye maculopathy,” which involves damage and death of retinal pigment epithelial cells. Hydroxychloroquine toxicity resembles dry age-related macular degeneration in its pathology, but the pattern is different. If hydroxychloroquine maculopathy is allowed to progress, the macular damage often continues despite discontinuation of the medication. The other ocular finding is cornea verticillata, or vortex keratopathy, secondary to deposits in the corneal epithelium. Cornea verticillata is not sight-threatening and is not necessarily accompanied by hydroxychloroquine-induced bull’s-eye maculopathy.
The maculopathy is rare with less than 5 years of continuous therapy, so many experts suggest that an annual eye examination is unnecessary until the patient has been treated for at least 5 years. Most patients, however, are sent by their primary physicians for a baseline eye examination when the drug is initiated. At 5 years, about 1% of patients will demonstrate maculopathy, at 10 years 2%, and at 20 years as many as 20%.
The examination recommended by most experts includes a careful fundus examination. If retinal photography is available, fundus autofluorescence can be useful. Many comprehensive ophthalmologists do not have retinal cameras. If a retinal camera is not available, the ophthalmologist can do fundoscopy with the standard white as well as a green light. All comprehensive ophthalmologists have access to Humphrey perimetry or its equivalent, and a visual field is mandatory. A 30-2, 24-2 or 10-2 can be performed looking for a bull’s-eye or perifoveal central scotoma. The 10-2 is a good visual field choice for Caucasian patients, but the 24-2 or 30-2 is a superior screening test for Asian patients. OCT is also useful, and the lesion is perifoveal at the RPE level.
If toxicity is discovered, the treating physician needs to be notified, and in most cases hydroxychloroquine is discontinued and an alternative antimetabolite such as methotrexate is substituted. In the older patient, it can be difficult to differentiate hydroxychloroquine-induced maculopathy from standard AMD. The bull’s-eye pattern is usually diagnostic. Antioxidant vitamins have not been proven to be protective, but they are not harmful. Some doctors recommend them.
At one time or another, nearly all of us are called upon to examine a patient being treated with hydroxychloroquine. For me, key points are educating the patient regarding the low but important risk of maculopathy, appreciating that the cornea verticillata is benign and requires no therapy nor discontinuation of the drug, and screening with careful fundus examination, visual field and OCT. The frequency of examination for me is once per year up to 10 years of therapy, but I then increase it to every 6 months.
If the retinal findings are identified early and the drug discontinued, the maculopathy usually does not progress. If the maculopathy is not identified early, it may progress despite stopping the medication, so we ophthalmologists play an important role in reducing the incidence of meaningful visual loss in patients treated with hydroxychloroquine.