The diagnostic utility of multifocal electroretinography in detecting chloroquine and hydroxychloroquine retinal toxicity
What:
Paper Presentation | Présentation d'article
When:
11:30 AM, Sunday 3 Jun 2018
(10 minutes)
Where:
How:
Authors: Adrian C. Tsang, Sina Ahmadi, John Hamilton, Jennifer Gao, Gianni Virgili, Stuart Coupland, Chloe Gottlieb
Author Disclosure Block: A.C. Tsang: None. S. Ahmadi: None. J. Hamilton: None. J. Gao: None. G. Virgili: None. S. Coupland: None. C. Gottlieb: None.
Abstract Body:
Purpose: To evaluate the diagnostic accuracy of the multifocal electroretinogram (mfERG) as a screening test for detecting hydroxychloroquine (HCQ) and chloroquine (CQ) toxicity.
Study Design: A prospective cross-sectional study conducted in accordance to the Standards for Reporting of Diagnostic Accuracy Studies (STARD).
Methods: Consecutive patients referred to the University of Ottawa Eye Institute for HCQ or CQ retinopathy screening from 2011-2014 underwent a 10-2 automated visual field (AVF), spectral domain optical coherence tomography (sdOCT), and mfERG testing. Patients with amblyopia, myopia or hyperopia in excess of 8 diopters, coexisting retinal disease, and prior retinal surgery were excluded. Abnormalities in parafoveal ring amplitudes (R2, R3) or parafoveal ring ratios (R2/R5, R3/R5) were considered a positive index test. mfERG was compared against the reference standard set by the 2016 AAO Recommendations on Screening for 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. Logistic regression was used to model the effect of covariates in ROC analyses. The area under the curve (AUC) for each mfERG parameter, and the sensitivity and specificity of mfERG were calculated.
Results: 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 mfERG findings suspicious for CQ/HCQ retinal toxicity. 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 decreases linearly with increasing cumulative dose (p=0.015) and daily dose (p=0.009).
Conclusions: 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.
Author Disclosure Block: A.C. Tsang: None. S. Ahmadi: None. J. Hamilton: None. J. Gao: None. G. Virgili: None. S. Coupland: None. C. Gottlieb: None.
Abstract Body:
Purpose: To evaluate the diagnostic accuracy of the multifocal electroretinogram (mfERG) as a screening test for detecting hydroxychloroquine (HCQ) and chloroquine (CQ) toxicity.
Study Design: A prospective cross-sectional study conducted in accordance to the Standards for Reporting of Diagnostic Accuracy Studies (STARD).
Methods: Consecutive patients referred to the University of Ottawa Eye Institute for HCQ or CQ retinopathy screening from 2011-2014 underwent a 10-2 automated visual field (AVF), spectral domain optical coherence tomography (sdOCT), and mfERG testing. Patients with amblyopia, myopia or hyperopia in excess of 8 diopters, coexisting retinal disease, and prior retinal surgery were excluded. Abnormalities in parafoveal ring amplitudes (R2, R3) or parafoveal ring ratios (R2/R5, R3/R5) were considered a positive index test. mfERG was compared against the reference standard set by the 2016 AAO Recommendations on Screening for 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. Logistic regression was used to model the effect of covariates in ROC analyses. The area under the curve (AUC) for each mfERG parameter, and the sensitivity and specificity of mfERG were calculated.
Results: 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 mfERG findings suspicious for CQ/HCQ retinal toxicity. 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 decreases linearly with increasing cumulative dose (p=0.015) and daily dose (p=0.009).
Conclusions: 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.
