Original article
Detection of Early Hydroxychloroquine Retinal Toxicity Enhanced by Ring Ratio Analysis of Multifocal Electroretinography

https://doi.org/10.1016/j.ajo.2006.12.042Get rights and content

Purpose

To assess decreased retinal function associated with high cumulative doses of hydroxychloroquine using multifocal electroretinography (mfERG).

Design

Retrospective cross-sectional study.

Methods

Sixty-two patients referred for evaluation of hydroxychloroquine retinal toxicity. Controls were 67 normal eyes of 67 patients referred for a variety of conditions in the other eye. Visual symptoms, duration of treatment, daily hydroxychloroquine dose (milligrams and milligrams per kilogram), cumulative dose, condition for which the drug was taken, visual acuity, retinal examination, visual fields, and mfERG amplitude. The average mfERG amplitude was calculated for five concentric rings. The age-corrected amplitude of the central hexagon (R1) and the ratios of R1 to each of the other rings (e.g., R1/R2, R1/R3) were compared with limits derived from control eyes.

Results

The incidence of characteristic mfERG abnormalities in patients referred for evaluation with cumulative hydroxychloroquine doses of more than 1250 g was nearly 50%. It was 2.8 times that found in patients with cumulative doses less than 1250 g. Significant abnormalities were seen with cumulative doses as low as 400 g. The mfERG abnormality most commonly detected was an increased R1/R2 ratio. Cumulative dose was more predictive of mfERG abnormalities than daily dose (either in milligrams or milligrams per kilogram) or duration of treatment.

Conclusions

Functional testing of the retina with mfERG shows locally decreased retinal function in a large fraction of patients referred for evaluation who have taken high cumulative doses of hydroxychloroquine. A prudent mfERG testing strategy is proposed.

Section snippets

Methods

All data were collected in the course of routine clinical practice. Institutional Review Board approval was obtained and the study is in accordance with the Health Insurance Portability and Accountability Act (HIPAA) regulations.

Normal Data

Linear regression was used to determine the change of each parameter value with age. The R1 and the other raw ring amplitudes (R2–R5) all change significantly with age (P < .007 for all rings, t test), in agreement with reports by other investigators.17, 18 This change with age was greatest in the central ring (R1) and least in the peripheral ring (R5). In contrast, R1/R2, R1/R3, and R1/R4 did not change significantly with age (P > .14 for all ratios, t test). The R1/R5 values changed with age (

Discussion

Because there were few early reports of loss of retinal function in patients taking hydroxychloroquine, it was assumed that the drug would not present a serious danger even after many years of use.1 Because of the years-long delay in onset and the subtlety of early symptoms, hydroxychloroquine retinotoxicity is still considered by many practitioners to be a relatively rare event.5 Readily available tests such as funduscopy, fluorescein angiography, perimetry, Amsler grid evaluation, and color

Jonathan S. Lyons, MD is a specialist in Medical Retina (Retinal Electrophysiology) in private practice in Silver Spring, Maryland. Dr Lyons is a lecturer and consultant in retinal electrophysiology at the Georgetown University/Washington Hospital Center Program in Ophthalmology and a Senior Attending Surgeon at the Washington National Eye Center.

References (22)

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    Multifocal electroretinographic evaluation of long-term hydroxychloroquine users

    Arch Ophthalmol

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    Jonathan S. Lyons, MD is a specialist in Medical Retina (Retinal Electrophysiology) in private practice in Silver Spring, Maryland. Dr Lyons is a lecturer and consultant in retinal electrophysiology at the Georgetown University/Washington Hospital Center Program in Ophthalmology and a Senior Attending Surgeon at the Washington National Eye Center.

    Matthew L. Severns, PhD is a Biomedical Engineer who develops methods to diagnose retinal disorders. Currently with LKC Technologies, Inc (a manufacturer of visual diagnostic systems), he was on the faculties of the Wilmer Eye Institute, Johns Hopkins University Medical School from 1986 to 1997 and George Washington University Medical School from 1980 to 1982.

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