Hydroxychloroquine-Induced Retinopathy in Systemic Lupus Erythematosus: Predictors of Progression Following Drug Discontinuation.

BACKGROUND: Hydroxychloroquine (HCQ) is a cornerstone of systemic lupus erythematosus (SLE) management. However, the medication can accumulate within organs and cause toxicity including retinopathy. HCQ is usually discontinued once ocular toxicity is diagnosed, but this is not always sufficient to avoid further damage. Whether retinal injury progresses following HCQ cessation, and which patients are at risk, is of great interest. Prior studies examining progression after HCQ discontinuation are sparse and limited by small sample sizes, and none specifically examine patients with SLE. This study aimed to identify predictors of progression of HCQ-induced retinopathy in SLE patients after medication discontinuation. METHODS: We queried the NYU Lupus Cohort to identify patients with documented HCQ-induced retinopathy who discontinued HCQ and had at least one optical coherence tomography (OCT) follow-up to assess for progression. Demographic information, cumulative HCQ dose, duration of therapy, presence of chronic kidney disease or tamoxifen use, SLE disease activity, and ophthalmologic follow-up intervals were collected. Two ophthalmologists independently reviewed OCT and Humphrey visual field data to confirm retinopathy, grade its severity, and determine progression following drug discontinuation. Statistical analysis was performed using Student's t-test or Wilcoxon rank-sum test for continuous variables and Chi-square or Fisher's exact test for categorical variables. RESULTS: Twenty-one patients with confirmed HCQ retinopathy were included. The mean duration of HCQ therapy preceding diagnosis was 16.2 years and the mean cumulative exposure was 1884 g. Retinal toxicity progressed in 6 patients (28.6%) despite HCQ discontinuation. There appeared to be a trend towards a greater likelihood of progression with more severe retinal toxicity at the time of diagnosis. However, there were no differences between progressors and non-progressors with respect to age at diagnosis, duration or cumulative HCQ exposure, SLE disease activity, tamoxifen use, chronic kidney disease, or guideline-concordant care. CONCLUSIONS: Nearly thirty percent of patients with SLE and HCQ retinopathy progressed despite drug discontinuation. No baseline clinical predictors were associated with progression, though there was a descriptive trend toward greater risk with more severe baseline retinopathy. These data emphasize the importance of continued ocular surveillance for progression of toxicity after discontinuation.