Hydroxychloroquine retinopathy — implications of research advances for rheumatology care


Despite advances in therapy for rheumatic diseases, hydroxychloroquine remains almost universally recommended for the treatment of systemic lupus erythematosus (SLE), and is often used in the management of other rheumatic diseases such as rheumatoid arthritis (RA). However, the major dose-limiting toxicity of hydroxychloroquine is retinopathy that can lead to loss of vision. New highly sensitive screening methods can identify early stages of retinopathy, and studies that include these modalities have indicated a substantially higher prevalence of hydroxychloroquine retinopathy than was previously recognized, resulting in revisions to ophthalmology guidelines and the recommendation of a low dose of hydroxychloroquine for many patients. However, the efficacy of low-dose hydroxychloroquine for treating SLE and other rheumatic diseases is unknown. Further studies are required to establish the effectiveness and retinal safety of the latest hydroxychloroquine treatment recommendations.

Key points

  • Hydroxychloroquine is almost universally recommended for patients with systemic lupus erythematosus (SLE) and has wide-ranging benefits, but risks include toxic retinopathy.

  • A proposed mechanism of hydroxychloroquine retinopathy is impaired lysosomal degradation of photoreceptor outer segments by the retinal pigment epithelium.

  • Early changes associated with hydroxychloroquine retinopathy can be detected by modern highly sensitive screening modalities.

  • Hydroxychloroquine retinopathy prevalence is lower in studies of older screening modalities than in studies of highly sensitive screening methods that include early stages of disease (<2% versus ≤8%).

  • The most important predictors of hydroxychloroquine retinopathy are thought to be high-dose (>5 mg/kg) and long-term (>5 years) use, but existing evidence is limited to retrospective studies of prevalence data.

  • Despite the wide-ranging benefits of hydroxychloroquine therapy for patients with SLE, rheumatoid arthritis (RA) or other conditions, data on the dose–response relationship with outcomes are scarce.

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Fig. 1: Techniques for assessing hydroxychloroquine retinopathy.
Fig. 2: Mechanisms of hydroxychloroquine retinopathy.


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The authors would like to thank A. Thanos of Legacy Devers Eye Institute in Portland, OR, USA, for assistance with the formulation of figure 2.

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Nature Reviews Rheumatology thanks N. Costedoat-Chalumeau, J. Rosenbaum and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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All authors researched data for the article, made substantial contributions to discussions of the content, wrote the article and contributed to reviewing and editing of the manuscript before submission.

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Correspondence to Hyon K. Choi.

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Region of the retina that surrounds the central fovea, within the macula. The macula is the region responsible for high-acuity central vision.

Visual field

The entire area that can be seen with the eyes fixed in one region.

Actual body weight

(ABW).True (measured) body weight.

Ideal body weight

(IBW). An estimate of body weight based on lean mass, calculated from factors including height and sex.


A specialized test measuring differences in electrical potential in the eyes.

Retinal pigment epithelium

(RPE). A monolayer of pigmented cells that coats the outer retina.

Bull’s eye damage

The classic late-stage finding of hydroxychloroquine retinopathy, seen as a ring of retinal damage in the parafoveal region.

Visual cycle

The biological conversion of a photon into an electrical signal in the retina.

Loading dose

The short-term (typically ~3 months) use of a higher dose of a medication than will be used as the maintenance dose.

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Jorge, A., Ung, C., Young, L.H. et al. Hydroxychloroquine retinopathy — implications of research advances for rheumatology care. Nat Rev Rheumatol 14, 693–703 (2018). https://doi.org/10.1038/s41584-018-0111-8

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