Background/purpose Despite effectiveness and favourable safety profile, antimalarials have the potential to cause irreversible macular retinopathy. Screening methods have evolved over the last decade and the optimal dose of hydroxychloroquine (HCQ) is now set at under 5 mg/kg real body weight. HCQ in Portugal comes only as a 400 mg pill and in 10 pills per package, which is neither friendly for optimising safe dosing nor for promoting compliance. This study aims to test the frequency of retinal hydroxychloroquine toxicity in a single-centre cohort.

Methods Cross-sectional study conducted between January-2016 and May-2017, of a convenience sample of chronically compliant and well characterised patients. The screening strategy consisted of automated threshold visual fields and objective test: spectral-domain optical coherence tomography, fundus autofluorescence and multifocal electroretinogram. Toxicity was diagnosed on the basis of compatible visual fields defects together with at least one positive objective test. Univariate statistical analysis was performed using the Wilcoxon Mann-Whitney (WMW) and Chi-Square (CS) tests for non-parametric distributed data.

Results Of the 62 patients screened, 32 (51%) had no prior ophthalmological examination. Median age was 46 years (y), IQR 37–60; range 27–83; 59 (95%) were female; the majority, 28 (45%) took HCQ due to SLE, 4 (6%) for Sjögren syndrome, 12 (19%) for UCTD, 11 (18%) for incomplete/cutaneous forms of lupus and 7 (11%) for other CTD. No patient had concomitant renal or liver disease. Median duration and cumulative dose were respectively 8 y (IQR 3–12; range 0.4–31) and 1168 g (IQR 584–2044; range 36–8760). Retinal toxicity was confirmed in 6 SLE and 1 non-SLE patient; in all HCQ was stopped (2/7 screen-naïve; 1/7 on tamoxifen; 1/7 with visual loss). Toxicity correlated to disease (p=0,003) and HCQ therapy (p=0,002) duration, cumulative HCQ dose (p=0,001) and SLE (p=0,04). Table 1 dose adjustments were performed in 13 patients.

Conclusion Using a standardised referral protocol for HCQ retinopathy screening led to cessation of therapy due to toxicity (11%) and adjustment of daily dosing (21%). This study highlights that regular adjustment of dose and retinal toxicity screening is mandatory in patients on prolonged HCQ therapy and reinforces lobbying for more flexible dosages. In addition, HCQ toxicity raises the need for alternative therapies in patients with CTD.