Progression of hydroxychloroquine-induced retinopathy after drug cessation

Hydroxychloroquine (HCQ) is a frequently used drug for a variety of rheumatological conditions. One significant adverse effect is HCQ retinopathy, which irreversibly affects the photoreceptor layer and retinal pigment epithelium, causing paracentral scotomas and potential visual loss. Retinal impairment is irreversible, even after termination of therapy. This study investigates the progression of the retinal destruction after drug cessation.

The study was performed at the Departments of Ophthalmology at Zurich University Hospital and Tel Aviv Sourasky Medical Center from January 2012 - December 2020.

In a multicenter retrospective observational design, we analyzed 25 lesions in 18 eyes of 11 patients with HCQ retinopathy. Patients were examined for retinal alterations using spectral-domain (SD) optical coherence tomography (OCT) scans (Heidelberg Engineering, Heidelberg Germany) at first diagnosis of HCQ retinopathy and at least one follow-up (minimum follow up 2 months duration, maximum follow up 5.5 years). Demographics and clinical aspects including age, ethnicity, therapy duration, indication, cumulative dosage, and follow-up interval were recorded. The lengths of the structural damage including ellipsoid zone defect and photoreceptor alterations were analyzed on OCT images.

Demographically, the average patient age was 53.0 years at time of enrollment. All patients were female. The cohort consisted of 54.5% non-Ashkenazi Caucasian and 18.2% Ashkenazi. Roughly half (54.5%) of the cohort held systemic lupus erythematosus (SLE) as a main diagnosis. The average daily dose of HCQ was 310 mg, with an average treatment duration of 15.6 years. Absolute increases in lesion size ranged from 7 to 552 μm (median change 99 μm). The average rate of progression in this cohort was 131.6 μm/year in across all included eyes.

Our data elucidates the progression of HCQ-induced retinopathy in regard to SD-OCT detected structural changes of the retina after drug cessation. The study highlights the pivotal role of an early detection of retinopathy to reduce the potential risk of fovea-threatening progression as an irreversible side effect of the prevalent drug HCQ.