Just How Common Is Hydroxychloroquine Retinopathy?

Brianne N. Hobbs, OD


April 07, 2015

The Risk of Toxic Retinopathy in Patients on Long-term Hydroxychloroquine Therapy

Melles RB, Marmor MF
JAMA Ophthalmol. 2014;132:1453-1460

Established Risk, Lingering Questions

Most rheumatologists, optometrists, and ophthalmologists are aware of the risk for patients developing toxic retinopathy after hydroxychloroquine (HCQ) use. However, there remains considerable debate about the safety of HCQ and the exact prevalence of retinopathy resulting from its use.

The American Academy of Ophthalmology's eye care guidelines regarding patients taking HCQ, which were first released in 2002 and later revised in 2011, are considered the standard of care. These guidelines are more relevant than ever, owing to the increasing use of HCQ for a broader spectrum of diseases (including autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis) and novel applications in oncology and dermatology.

It is unknown what the "safe" dose for any given patient is, because a wide variety of patient factors and a large range of daily and cumulative doses may influence tolerance. Prior studies have emphasized the importance of cumulative dose and body weight in determining the ideal dosage, but the identification of all risk factors for toxic retinopathy remains an important step in addressing the eye care needs of this patient population.

Study Summary

In a study published in JAMA Ophthalmology, Melles and Marmor sought to provide an estimate of the true prevalence of HCQ retinopathy and to identify additional risk factors associated with its development. Their investigation was a retrospective medical record review of patients with documented use of HCQ for at least 5 years. Although the most effective means for detecting HCQ retinopathy remains debated, in this study the condition was diagnosed using the parameters of visual field loss or spectral-domain optical coherence tomography (SD-OCT) abnormalities, including thinning or photoreceptor damage.

The results of this study should change our perspective on the likelihood of patients developing HCQ retinopathy. Although previous studies have estimated the risk for HCQ retinopathy to be in the relatively low range of 0.5%-2%, the current study found that 7.5% of patients taking HCQ for at least 5 years developed toxic retinopathy. The high-resolution quality of SD-OCT has also enhanced the ability to detect even subtle changes in the integrity of the retina, thus increasing the sensitivity of diagnosing retinopathy.

Previously identified risk factors that are predictive of retinopathy development include daily dose and duration of dose, both of which were reconfirmed in this study. Unexpected, however, was the identification in this study of a new risk factor for retinopathy: concurrent use of tamoxifen. The precise mechanism of this association was not determined, but certainly deserves further exploration.

This investigation also proposed that dose calculations based on actual body weight rather than ideal weight are more effective at identifying risk for retinopathy and can protect underweight patients from receiving excessive doses.


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