Ocular Disease Monitoring Critical to Avoid Retinal Toxicity from Hydroxychloroquine

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Both due to its efficacy and favorable side effect profile when compared with alternative drugs for rheumatologic conditions, hydroxychloroquine is an important agent in rheumatologists’ armamentarium. However, one barrier to hydroxychloroquine use can be its effects on the eye (also see “Revised Retinopathy Screening Guidelines,”). Ocular side effects of hydroxychloroquine can include impact on the cornea, ciliary body, lens and retina.¹ Corneal deposits, fortunately, rarely affect vison.² However, the concern of retinal toxicity and the need for monitoring must be reviewed with patients prior to and during its use.^2,3

Monitoring is intended to identify separate ocular disease that would interfere with identifying changes or baseline retinal disease that could increase hydroxychloroquine’s risk, as well as to detect the earliest changes related to hydroxychloroquine. The concern with retinal toxicity is that this may be irreversible and may progress even after hydroxychloroquine discontinuation. Identifying toxicity prior to changes affecting the fundus limits potential for further deterioration.⁴ Despite this, a significant proportion of individuals receive hydroxychloroquine without eye examinations.⁵

Prevalence

Estimates of prevalence are variable among studies, with differences likely representing the increasing availability of more sensitive testing and case ascertainment by the studies. Further, the impairment experienced by patients was variable. Initial studies demonstrated the risk as low as 0.5% and no events of retinal toxicity when dosing was below 6.5 mg/kg/day of ideal body weight.⁶ Further a prospective cohort demonstrated incidence of 0.5% in patients all treated with less than 6.5 mg/kg/day with no events occurring until after six years of treatment.⁷

Wolfe et al, in a study of patient-reported toxicity with review of medical records by experts, identified overall prevalence as 0.65%. However, the probability of toxicity was 0.29% after five years and further increased after 10 years (1%) and 15 years (2.1%).⁸ In a study published in 2014 by Melles and Marmor that included only patients who had been assessed with visual field examination or Spectral Domain-Optical Coherence Tomography (SD-OCT), the prevalence was 7.5%.⁹

Fortunately, thus far, studies have not identified clear risk to children who had an in utero exposure.¹⁰ In certain scenarios particularly systemic lupus erythematosus, hydroxychloroquine is felt to be an important treatment option for pregnant women.¹¹

Ideal Body Weight Vs. Real Body Weight

In terms of daily dose, initial studies emphasized a cut-off of 6.5 mg/kg of ideal body weight in terms of toxicity risk.¹² However, due to the typical dosing of either 200 or 400 mg of hydroxychloroquine, it is rare for individuals to receive higher than this cut-off. More recent studies suggest that real body weight predicts retinal toxicity better than ideal body weight.⁹ Further, a cut-off of 5 mg/kg/day based on real body weight has been proposed.