Detecting Hydroxychloroquine Retinal Toxicity using a Novel Multifocal Electroretinography Stimulus

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AbstractPurposeTo evaluate a novel 5‐ring multifocal electroretinogram (mfERG) stimulus as a screening test for detecting hydroxychloroquine (HCQ) retinopathy.Study DesignA stratified case‐control study conducted in accordance to the Standards for Reporting of Diagnostic Accuracy Studies (STARD).MethodsConsecutive patients referred to the University of Ottawa for HCQ retinopathy screening from July 2018 to September 2018 underwent testing using a novel 5‐ring mfERG stimulus and the standard 61‐hexagon mfERG stimulus. Patients with amblyopia, high myopia or hyperopia, coexisting retinal disease, and prior retinal surgery were excluded. mfERG parameters were compared between protocols and against cumulative dose (CD), dose by real body weight (RBW), and duration of HCQ therapy. Ring amplitudes (R1‐R5) and ring ratios (R1‐R4/R5) were collected for each stimulus protocol. mfERG data was collected from an additional group of controls with no previous exposure to HCQ. Stata 15.1 software was used to perform the regression analyses, and to compute Spearman correlation coefficients between variables.Results24 eyes (10 patients, 2 controls) were included in the final analysis. The novel R2 and R3 P1 amplitudes and R2/R5 were moderately correlated with the respective R2 (r = 0.434, p = 0.034) and R3 (r = 0.429, p = 0.036) P1 amplitudes and R2/R5 (r = 0.422, p = 0.040) of the 61‐hexagon stimulus. The novel R2 P1 amplitude was highly correlated with CD (r = −0.687, p < 0.001), treatment duration (r = −0.687, p < 0.001), and dose by RBW (r = −0.763, p < 0.001). Similarly, novel R2/R5 was highly correlated with CD (r = −0.743, p < 0.001), treatment duration (r = −0.743, p < 0.001), and dose by RBW (r = −0.567, p = 0.004). The correlations between the 61‐hexagon stimulus R2/R5 and HCQ risk factors also reached significance but were not as robust. Linear regression analysis showed that CD may account for almost half of the variance in the novel R2/R5. (r2 = 0.486, R2/R5 = 9.68063 + cumulative dose ‐0.00286)ConclusionsThe 2016 AAO guidelines focused primarily on the use of subjective functional testing and objective structural testing and relegated mfERG based on a lack of accessibility. This pilot study describes a new 5‐ring mfERG protocol specific for HCQ retinopathy screening and suggests equivalence to the 61‐hexagon protocol at characterizing parafoveal function. This novel 5‐ring stimulus has a significantly shorter acquisition period and the ring design may be more sensitive to HCQ induced electrophysiologic change in the parafoveal region. R2 P1 amplitude and R2/R5 ring ratios acquired using this novel mfERG stimulus are strongly correlated to treatment duration and HCQ dosing. Additional prospective cohort studies are needed to validate this novel stimulus which may decrease the resource burden associated with objective functional testing.