Objectives: To observe the long-term effects of hydroxychloroquine sulfate on retinal electrical activity by multifocal electroretinography (mfERG) and to evaluate the regional variation of retinal dysfunction in subjects with hydroxychloroquine retinopathy. Methods: Multifocal ERG with 103-hexagon stimulation was performed on 19 patients (36 eyes) treated with hydroxychloroquine for systemic lupus erythematosus, rheumatoid arthritis, or localized atypical scleroderma. Visual acuity testing, Amsler grid testing, and Ishihara color vision testing were also performed. In 2 of the patients, hydroxychloroquine was discontinued due to concerns about toxicity. Both of these patients had additional mfERG performed after discontinuation of medication. Results: Twelve patients (19 eyes) had a normal response density in one or both eyes, including 6 patients (12 eyes) with a low lifetime dose (≤438 g) of hydroxychloroquine who had normal response densities in both eyes. Eleven patients (17 eyes) had abnormal response densities in one or both eyes, and 2 of these patients (4 eyes) had significant attenuation of response densities in almost the whole tested field; 4 patients had a normal mfERG result for one eye but had a slight decrease of response densities for the other eye. There were 4 patterns of abnormal mfERG amplitude change observed: (1) paracentral loss, (2) foveal loss, (3) peripheral loss, and (4) generalized loss. Implicit times were abnormal for pericentral responses in 3 patients. The results of color vision and Amsler grid testing were normal, except for one patient with a generalized loss pattern. In 2 subjects in whom hydroxychloroquine toxicity was suspected, response densities improved after termination of hydroxychloroquine. Conclusions: Long-term hydroxychloroquine use may be associated with mfERG abnormalities. The mfERG appears to detect retinal physiological change earlier than visual acuity testing, color vision testing, or Amsler grid testing can. The greatest value of the mfERG is in differentiating a retinal cause and, hence, providing important evidence for hydroxychloroquine toxicity, for whatever visual field loss is apparent on perimetry.
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