Objective: Hydroxychloroquine (HCQ) retinopathy is of concern because of the potential seriousness of visual loss and the medicolegal consequences of failure to detect toxicity. However, there have been limited demographic data on which to base recommendations for screening. We have studied the largest unselected series of patients to date to evaluate the risk of toxicity and the relevance of purported risk factors.
Methods: We studied 3,995 patients with rheumatoid arthritis or systemic lupus erythematosus who had used HCQ, including 1,538 current users. We screened for self-reported toxicity, and followed up on positive cases with detailed interviews and specialist confirmation. We categorized cases as "definite or probable" if there was bull's eye maculopathy or visual field loss.
Results: Of the lifetime users of HCQ, 6.5% discontinued therapy because of an eye problem, including 1.8% who reported HCQ retinal problems. However, definite or probable toxicity was documented in only 0.65% (95% confidence interval 0.31-0.93). The risk of toxicity was low in the initial 7 years of exposure, and was approximately 5 times greater after 7 years of usage (or 1,000 gm total exposure). Toxicity was unrelated to age, weight, or daily dosage. Eye examinations were obtained annually by 50.5% and every 6 months by 40.4% of patients.
Conclusion: HCQ toxicity remains uncommon, but increases markedly with the duration of therapy and exceeds 1% after 5-7 years. Toxicity was unassociated with age, daily dosage, or weight. These findings will aid the reformulation of screening guidelines.