Hydroxychloroquine Retinopathy Diagnosis Requires More Than Multifocal Electroretinography Parameter Alone

Hydroxychloroquine Medicine
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R1/R2 ratios are not a reliable enough indicator to predict retinal damage, according to a case report.

In monitoring for retinopathy associated with long term use of hydroxychloroquine, previous research has described an increase in multifocal electroretinography (mfERG) R1/R2 ring ratios as a sensitive test to detect toxicity. A case series presented at the annual meeting of the American Society of Retina Specialists (ASRS) suggests that, although mfERG is an appropriate screening tool, R1/R2 ratios are not a reliable indicator to predict retinal damage. 

The series retrospectively reviewed 19 eyes of 10 patients (mean age 64.6±8.5 years) who presented from 2010 to 2020 with hydroxychloroquine toxicity, and 2 eyes of 1 patient with chloroquine toxicity. The investigators took into account the patients’ demographic data, indication for hydroxychloroquine or chloroquine therapy, daily dose, cumulative dose, best corrected visual acuity (BCVA) at presentation, BCVA at diagnosis, and presence or absence of kidney disease. 

They also examined patients using fundus autofluorescence (FAF), optical coherence tomography (OCT), visual field testing, and mfERG. 

The report shows that some patients can, in fact, present normal R1/R2 ratios on mfERG, despite having signs of retinal toxicity associated with hydroxychloroquine on FAF, OCT of the retina, and visual field testing.

The patients were primarily using hydroxychloroquine for rheumatoid arthritis (50%), systemic lupus erythematosus (SLE, 40%), and graft vs host disease (10%). Patients used a mean daily dose of 5.46±1.48 mg/kg/day (mean cumulative dose 2285.5±953.2 grams).

Of these 19 eyes with  hydroxychloroquine or chloroquine toxicity, 15 (78.9%) demonstrated normal R1/R2 ratios less than 2.6 (CI 99%).  

However, 16 eyes (84.2%) demonstrated visual field loss characteristic of retinal toxicity, 11 eyes (57.9%) demonstrated abnormal OCT findings consistent with retinal toxicity, and 6 eyes (31.6%) demonstrated abnormal FAF findings.

The 1 patient who was treated with chloroquine toxicity for SLE had normal R1/R2 ratios in both eyes, despite showing signs of chloroquine toxicity on FAF, HVF, and OCT of the retina.

“A multidisciplinary approach that includes all these imaging modalities is needed to effectively screen” for hydroxychloroquine or chloroquine toxicity, the investigators report.


Shamim M, Uwaydat S. Normal R1/R2 ratios on mfERG in patients with plaquenil retinopathy. Poster presented at: The 40th annual meeting of the American Society of Retina Specialists; June 13-16, 2022; New York, NY. Poster 408.