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JCR: Journal of Clinical Rheumatology:
doi: 10.1097/RHU.0b013e31826d2f2d
Concise Reports

Advances in Ophthalmic Monitoring for Hydroxychloroquine Toxicity

Gorovoy, Ian MD; Gorovoy, Jaclyn B. BS, MS

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From the University of California, San Francisco, CA.

The authors declare no conflict of interest.

Correspondence: Ian Gorovoy, MD, University of California, San Francisco, CA. E-mail:

A 59-year-old woman with a history of sarcoidosis on hydroxychloroquine 200 mg twice daily for 15 years presented for routine hydroxychloroquine ophthalmologic monitoring. She denied visual complaints with normal best corrected visual acuity of 20/20 and normal central automated visual fields in both eyes. However, fundus autofluorescence revealed a classic bilateral bull’s-eye maculopathy (Fig. 1). A control autofluorescence is also shown for comparison (Fig. 2). Given these findings, the patient discontinued her hydroxychloroquine to prevent further retinal damage.

Figure 1
Figure 1
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Figure 2
Figure 2
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Currently, the American Academy of Ophthalmology and the American College of Rheumatology recommend that patients on hydroxychloroquine undergo baseline and annual screening beginning after 5 years of treatment, unless high risk factors are present.1,2 Screening consists of 10-2 automated visual fields, which tests the visual function of the macula as this is the central region at risk for hydroxychloroquine toxicity, in addition to spectral domain optical coherence tomography (SD-OCT), multifocal electroretinogram (mfERG), or fundus autofluorescence. Spectral domain optical coherence tomography and fundus autofluorescence are photographic methods that demonstrate cross-sectional images of the retina and a topographic map of the distribution of lipofuscin and other pigments in the retina, respectively. Multifocal electroretinogram measures the bioelectric potential of the different parts of the retina when stimulated by light.

The approximate expense and time for these tests are listed in Table 1. Toxicity in the first 5 years of hydroxychloroquine use is exceedingly rare unless patients have risk factors, which include high daily dosage, renal or liver disease, older than 60 years, or previous retinal disease. Newer techniques such as autofluorescence better detect toxicity than dilated fundus examinations, which is critical because visible findings occur late and may progress even after drug cessation. Of these additional options, further work is needed to identify the ideal modality. Fundus autofluorescence may prove to be superior because it is easier to interpret the image compared with SD-OCT, where subtle loss of the photoreceptor inner segment/outer segment of the perifoveal retina is observed in hydroxychloroquine toxicity. In addition, the technology is more widespread and faster to use compared with mfERG.

Table 1
Table 1
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Although hydroxychloroquine toxicity is likely rare, recent work suggests it may be underrecognized. Symptoms include decreased night vision, decreased central vision, loss of color discrimination, metamorphopsia, and photopsias. A recent study of 4000 patients found a prevalence of 6.8 per 1000 patients.3 Daily doses of greater than 6.5 mg/kg (ideal body weight) place patients at increased risk, but lower daily doses for many years can also cause toxicity. Furthermore, many physicians incorrectly calculate this dosage based on a patient’s actual weight instead of their ideal weight. A cumulative dose of greater than 1000 g of hydroxychloroquine is likely the largest risk factor, usually occurring at 5 to 7 years of a typical dosage.4

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2. Marmor MF, Kellner U, Lai TY, et al.. American Academy of Ophthalmology. Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy. Ophthalmology. 2011; 118: 415–422.

3. Wolfe F, Marmor MF. Rates and predictors of hydroxychloroquine retinal toxicity in patients with rheumatoid arthritis and systemic lupus erythematosus. Arthritis Care Res. 2010; 62: 775–784.

4. Lyons JS, Severns ML. Detection of early hydroxychloroquine retinal toxicity enhanced by ring ratio analysis of multifocal electroretinography. Am J Ophthalmol. 2007.

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© 2013 Lippincott Williams & Wilkins, Inc.

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