Background/Purpose:

Despite effectiveness and favourable safety profile, antimalarials have the potential to cause irreversible macular retinopathy and vision loss. Screening methods still vary among clinicians but have evolved over the last decade (1, 2) and the optimal dose of hydroxychloroquine (HCQ) is now set at ≤5 mg/kg real body weight, above which the risk of retinal toxicity increases (3). HCQ in Portugal comes only as a 400 mg pill and in 10 pills per package, both of which, are neither friendly for optimizing safe dosing nor for promoting compliance. Once a patient is in a high risk group, yearly follow-up is recommended. The aim of the study is 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 patients, characterized according to demographic and clinical phenotype, duration, current and cumulative dose of HCQ. The screening strategy consisted of automated threshold visual fields and objective test: spectral domain-OCT, fundus autofluorescence and multifocal electroretinogram. Toxicity was diagnosed on the basis of compatible visual fields defects together with at least one positive objective test, upon confirmation. 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 further diagnosed in 1 non-SLE-patients; in all HCQ was stopped (overall: 2/7 screen naïve; 1/7 on tamoxifen; 1/7 with visual loss). Toxicity was 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 I. Dose adjustments to ≤ 5 mg/kg 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 serves as a reminder that regular adjustment of dose and retinal toxicity screening is mandatory in patients subjected to prolonged HCQ therapy and reinforces lobbying for more flexible dosages. In addition, HCQ toxicity raises the need for alternative therapies in patients with CTD.

Table I. Univariate analysis comparing patients according to retinal toxicity