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Adrian C Tsang, Sina Ahmadi, John Hamilton, Jennifer Gao, Chloe Gottlieb, Stuart G Coupland; Multifocal Electroretinography: An Objective Functional Test for Detecting Chloroquine and Hydroxychloroquine Retinal Toxicity. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4442.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the diagnostic accuracy of the multifocal electroretinogram (mfERG) as a screening test for detecting hydroxychloroquine (HCQ) and chloroquine (CQ) toxicity.
This is a prospective cross-sectional study conducted in accordance to the Standards for Reporting of Diagnostic Accuracy Studies (STARD). Patients referred to the University of Ottawa Eye Institute for HCQ or CQ retinopathy screening underwent a 10-2 AVF, sdOCT, and mfERG testing. Patients with amblyopia, extreme myopia or hyperopia, and coexisting retinal disease were excluded. Abnormalities in parafoveal ring amplitudes or ring ratios were considered a positive index test. mfERG was compared against the 2016 AAO Recommendations on CQ and HCQ Retinopathy. Toxicity was defined as presence of a 10-2 AVF defect with localized thinning of the photoreceptor layers in the parafoveal region on sdOCT. Receiver operating characteristic (ROC) analyses was used to determine diagnostic performance of mfERG parameters. The area under the curve (AUC) for each mfERG parameter, and the sensitivity and specificity of mfERG were calculated.
Sixty-three patients (47 females, 16 males) were included in the final analysis. 8 patients had evidence of retinal toxicity according to the 2016 AAO guidelines and 20 patients had positive mfERG findings. mfERG was found to have a sensitivity of 1.00 (95%CI: 0.79 to 1.00) and a specificity of 0.78 (95%CI: 0.69 to 0.85). Ring 2 amplitude had the best performance among all parameters (AUC: 0.97, 95%CI: 0.94 to 1.00). R2 amplitude decreased linearly with increasing cumulative dose (p=0.015) and daily dose (p=0.009).
The 2016 AAO guidelines focuses primarily on the use of subjective functional testing and objective structural testing through its endorsement of 10-2 AVF and sdOCT respectively. The high sensitivity of parafoveal (R2) amplitude depression on mfERG and its linear relationship to cumulative and daily dose in this study illustrates an important role for objective documentation of visual function. The false positive rate suggests a potential period where physiologic dysfunction maybe detected objectively on mfERG prior to demonstrable structural change on sdOCT. The progressive and irreversible course of the disease warrants further prospective trials to establish criteria to detect dysfunction prior to established retinopathy.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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