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Should a patient with signs of retinal toxicity be taken off HCQ completely, or are a reduced dose and additional screening more appropriate?
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Responsibility to protect patients’ vision
Hydroxychloroquine is a drug used by many rheumatologists and dermatologists as a first-line agent to treat conditions from arthritis to lupus to alopecia. HCQ is an effective agent, but there is always a small risk for irreversible retinal toxicity.
HCQ toxicity primarily affects the macula, and patients taking more than 5 mg/kg/day (based on real body weight) are at the highest risk for having damage. The most common symptoms of toxicity are color vision changes and paracentral scotomas. We have to be especially cautious in patients with macular disease, such as age-related macular degeneration. These patients are at increased risk for HCQ toxicity, as the retinal pigment epithelium (RPE) is compromised and, thus, more sensitive to toxic agents. For these patients, we cannot apply the 5 mg/kg/day guideline and should use a lower dose.
HCQ toxicity rarely occurs in the first 5 years of treatment, but due to the permanent nature of the toxicity, we must vigilantly screen patients on HCQ annually for the earliest signs. This is most efficiently accomplished using spectral-domain OCT and 10-2 Humphrey visual field testing. Multifocal ERG can be used to corroborate these tests if abnormalities are detected.
If there are any signs of toxicity, it is imperative to recommend the cessation of HCQ immediately. I do not think that one should take the risk for continued progression of toxicity by reducing the dose. In fact, even if one stops HCQ, further progression of retinopathy can still occur, and it can be devastating. This “coasting” effect occurs because HCQ is absorbed and stored in the RPE cells and can continue to cause damage even after the patient stops taking HCQ. In fact, HCQ can be detected in the blood and urine of patients 5 years after stopping HCQ.
If you have to recommend the cessation of HCQ due to early signs of toxicity, do not fret. There are many immunomodulating agents at the disposal of our rheumatology and dermatology colleagues, and patients can be switched to other immune suppressants or biologic agents that can also have great efficacy for the conditions they treat. Our primary responsibility is to protect our patients’ vision, and the best way to do that is to lower the risk for retinal damage as much as possible at the earliest sign of trouble.
Theodore Leng, MD, FACS, is the director of clinical and translational research at Byers Eye Institute at Stanford University School of Medicine. Disclosure: Leng reports no relevant financial disclosures.
Stop medication permanently if there are toxicity signs
In my opinion, any patient taking hydroxychloroquine who shows definitive signs of retinal toxicity should have the medication stopped permanently and not reinstated again at any dose. HCQ toxicity produces permanent scotomas that can worsen even after the medication is stopped. Once toxicity begins, there is no evidence that a “safe” dose exists. Clinicians should be aware that certain co-existing factors may produce HCQ toxicity in patients on relatively lower doses. These conditions include renal and/or liver disease, concurrent retinal disease, concurrent use of tamoxifen and small body habitus. After many years of use, HCQ toxicity is not rare; about 20% of patients will manifest it after 20 years of intake.
Toxicity is best diagnosed via both structural and functional testing. The most widely available structural test that is apt to show the earliest changes is spectral-domain OCT. Clinicians should look for subtle perifoveolar thinning of the outer retina. While high-quality line scanning can detect it, the best method is to use the quantitative macular map. As the “flying saucer sign” is a late OCT manifestation of outer retinal loss, the goal should be to detect toxicity before its appearance. Patients of Asian descent may show initial evidence of HCQ toxicity outside of the perifoveolar area. Other structural testing such as fundus autofluorescence can be used, but at present, it is not quantitative like OCT. Fluorescein angiography is not a helpful screening tool as it does not reveal the earliest changes reliably. The detection of the retinal pigment epithelium loss that produces a clinical or angiographic bull’s-eye maculopathy is a late finding of HCQ toxicity and therefore is not a useful screening sign. The best functional test is multifocal ERG, but because it is not widely available and is expensive, central visual field testing should be employed.
If there are no other good systemic alternatives, cases of possible or early HCQ toxicity may be watched carefully in conjunction with rheumatologic consultation, but if subsequent examinations with testing show worsening signs, the drug should be permanently stopped.
Jay S. Duker, MD, is an OSN Retina/Vitreous Board Member. Disclosure: Duker reports no relevant financial disclosures.