New Guidelines for Hydroxychloroquine Visual Screening

Christina M. Sorenson, OD


November 11, 2016

Optometry has a long history of providing complete eye care. "Look at everything—every time" is a mantra many of us have humming in the background as we go through our clinical day. Accordingly, providing screening examinations for high-risk medications, such as hydroxychloroquine, is a natural service for our profession.

Hydroxychloroquine is an analogue to the much older drug chloroquine. Chloroquine was first used as an antimalaria drug. Hydroxychloroquine is most frequently used for the management of lupus and rheumatoid arthritis; however, it is now being applied to treatments in adjunctive cancer therapy, diabetes, and heart disease.[1] Given the broader applications of hydroxychloroquine, primary care clinicians may see more patients in need of ongoing screening services.

Hydroxychloroquine is associated with long-recognized retinal toxicity.[2,3,4] The retinopathy is hallmarked by parafoveal changes within the retina. Early toxicity may be asymptomatic, detected only with specialized testing of the retina, such as spectral domain optical coherence tomography (SD-OCT) and macular visual field evaluation. The clinician may note scotomatous areas within the macular and paramacular areas on visual field testing, skip lesions in the retinal pigmented layer, or macular edema on SD-OCT.

As the toxic effects increase, patients may note a paracentral scotoma or a disturbance in their color vision. Advanced retinal toxicity is seen by the clinician as a bull's-eye maculopathy, presenting as concentric rings of hyperpigmentation and hypopigmentation, or possibly as an extramacular pattern of damage, as may be seen in patients of broadly Asian descent. These changes are classified as a true maculopathy because they are irreversible and can progress after cessation of the medication.[5]

Lesser known side effects of this drug include corneal toxicity, which presents as an intraepithelial deposition of the drug in the cornea. This deposit seldom affects vision and is fully reversible.[6] In addition, there is a rare effect on the accommodation of the ciliary body.

Screening guidelines were updated this year, with some pertinent changes for our profession to note.[1] Cumulative dose is no longer a risk factor, but more of a tool in the screening of our patients. The actual body weight rather than the ideal body weight is used to determine the threshold dose. The maximum safe dose is 5 mg/kg of actual body weight. For example, a patient who weighs 175 lb would be at a threshold dose when taking 400 mg daily.

Screening interval has also been updated. All patients will need a baseline screening before or within 1 year of initiation of hydroxychloroquine. The baseline examination includes a fundus examination. SD-OCT and visual field testing are added to the initial examination if a concurrent maculopathy is present.

If, and only if, the patient is at the recommended maximum daily dose and does not fall into a higher risk category, the screening interval is 5 years after the initial evaluation. This is because the incidence of retinopathy is less than 1% at 5 years and only 2% at 10 years. The incidence increases to 20% at 20 years of treatment. Of note, however, if a patient makes it to 20 years of treatment and does not have retinopathy, the risk of converting to hydroxychloroquine retinopathy is 4% every year thereafter.

Subsequent screening examinations should include fundus examination, visual field testing (ie, macular testing or central testing), and SD-OCT. Additional testing as needed should include fundus autofluorescence and multifocal electroretinography.

Patients who fall into a high-risk category include those who exceed the maximum daily dose on the basis of their actual weight, patients with renal disease, patients on tamoxifen (concurrent tamoxifen and hydroxychloroquine use increases the risk for retinopathy fivefold), and patients with concurrent macular disease. Patients with these risks will benefit from annual or more frequent screening intervals. Of interest, hepatic disease and age are no longer considered risk factors.

Moreover, some tests are no longer recommended. The recent guidelines recommend against biomicroscopy alone, fundus photography, time-domain optical coherence tomography, fluorescein angiography, full-field electroretinography, Amsler grid, color vision testing, and electro-oculography.[1,7] All of these tests are thought to have inadequate sensitivity to detect hydroxychloroquine toxicity at a stage to prevent significant vision loss.

In a demographic study, the rate of hydroxychloroquine-induced retinal toxicity was thought to be near 7.5%.[8] In addition, years of hydroxychloroquine treatment even at a "safe dose" can still lead to toxicity.[9] Moreover, retinal toxicity is irreversible and can progress after cessation of hydroxychloroquine. Therefore, ongoing screening is recommended. Screening examinations that include SD-OCT, multifocal electroretinography, or autofluorescence provide sensitive adjuncts to macular visual field evaluation in the detection of early hydroxychloroquine toxicity.


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