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You are here: Home / Articles / Hydroxychloroquine Retinopathy Still Alive and Well

Hydroxychloroquine Retinopathy Still Alive and Well

May 16, 2011 • By Michael F. Marmor, MD

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Hydroxychloroquine Retinopathy Still Alive and Well

Hydroxychloroquine (Plaquenil; HCQ) has been an important and effective drug for the treatment of lupus erythematosus and related autoimmune and inflammatory diseases for half a century, although its potential to cause retinal damage continues to raise concern among rheumatologists and ophthalmologists. Further, despite the overall safety profile of HCQ, some patients with preexisting vision problems (e.g., glaucoma, cataracts) may be reluctant to take a medication with any potential for ocular toxicity, thus depriving them of a valuable therapy.

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Explore This Issue
May 2011

It is important to know the facts. Retinal complications from HCQ are actually rare (at proper dosage) and, with good screening, the risk for visual loss is very low. Nevertheless, retinopathy begins to appear with long-term use, and retinopathy is serious insofar as there is no known treatment. It can progress for a year or more after stopping the drug and, if not recognized early (at the point of screening), it can lead to functional blindness. The classic clinical picture of HCQ toxicity is a “bull’s eye” maculopathy (see Figure 1)—but as I’ll later note, this is a late finding.

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Data on retinal complications associated with HCQ and recommendations for screening for HCQ toxicity from the American Academy of Ophthalmology (AAO) have been published recently, and they have important clinical and legal implications for the rheumatologist.1,2 This article is intended to highlight new knowledge about how this toxic effect develops and can be recognized.

Figure 1.
Figure 1. Retinal photograph showing classic “bull’s eye” retinopathy of hydroxychloroquine toxicity, which represents atrophy of the retinal pigment epithelium. This is a relatively late change, and good screening can detect toxicity before any bull’s eye is visible.
Figure 2: Automated visual field.
click for large version
Figure 2: Automated visual field. Automated 10-2 visual field from the left eye of a patient with moderate HCQ toxicity, showing nasal paracentral scotomas. However, the patient showed a complete bull’s eye ring on SD-OCT and mfERG.

TABLE 1: Ideal Weight

Women: 100 lb + 5 lbs per inch over 5 ft

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Men: 110 lb + 5 lbs per inch over 5 ft

Figure 3: SD-OCT cross-sectional images of the retina.
Figure 3: SD-OCT cross-sectional images of the retina. A: Normal eye showing the foveal pit and thickening of photoreceptor layers in the central fovea (vertical bars are blood vessel shadows).
B: Eye with well-developed HCQ toxicity. There is marked thinning of the retina just outside the fovea (making the bull’s eye). Central vision will be preserved until the ring widens to close off the center. Damage can be recognized at an earlier stage.
B: Eye with well-developed HCQ toxicity. There is marked thinning of the retina just outside the fovea (making the bull’s eye). Central vision will be preserved until the ring widens to close off the center. Damage can be recognized at an earlier stage.
Figure 4: mfERG showing a set of electrical responses to light topographically across the macula.
Figure 4: mfERG showing a set of electrical responses to light topographically across the macula. A: Normal eye.
B: Eye with early HCQ toxicity. The parafoveal responses are smaller than those in either the center or periphery.
B: Eye with early HCQ toxicity. The parafoveal responses are smaller than those in either the center or periphery.

Incidence

The best data on HCQ toxicity are from the National Data Bank for Rheumatic Diseases.1 They suggest that, in an unselected population, the risk is below 1% for toxicity within the first five to seven years of treatment as long as dosage is within general guidelines. However, frequency of toxicity rises thereafter, probably reaching several percentage points by 15 to 20 years of use, although there were not enough cases in the data bank to give a firm number. From anecdotal data and the large number of overdose cases among published reports of toxicity, the risk is clearly accelerated and higher with overdose. Further, the recognition of toxicity may rise with the use of more sensitive diagnostic tools for screening. I have seen a dozen cases of toxicity in the past year, which is rather high for a suburban area, even when considering referral patterns.

Daily Dose

The new AAO recommendations focus more on the duration of treatment rather than a daily dose but emphasize that overdosage is dangerous.2 Most patients receive two tablets (400 mg) per day, which is fine for women taller than 5 ft. 7 in. or men taller than 5 ft. 5 in. Why is height important? Because the drug does not distribute in fatty tissues, so an “ideal” weight is a critical parameter for dose calculation. Many of the overdose cases I have seen have received dosage by weight, and these patients were overweight. The ideal weight formula is show in Table 1.

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Pages: 1 2 3 4 | Single Page

Filed Under: Conditions, SLE (Lupus), Systemic Inflammatory Syndromes Tagged With: HYDROXYCHLOROQUINE, Lupus, patient care, Plaquenil, retinal, toxicityIssue: May 2011

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  • Ocular Disease Monitoring Critical to Avoid Retinal Toxicity from Hydroxychloroquine
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  • HCQ Debate: Should Dose Be No More Than 5 mg/kg in All SLE Patients?

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