Sir,

Retinopathy associated with hydroxychloroquine treatment in patients with rheumatologic diseases has been well-documented, but findings can be subtle. Spectral domain optical coherence tomography (SD-OCT) can be helpful to demonstrate early toxicity and predict future progression; SD-OCT typically demonstrates perifoveal disruption of the photoreceptor inner/outer segment (IS/OS) junction line and thinning of the outer nuclear layer.1, 2 Preservation of the external limiting membrane was recently shown be associated with the preservation and possible regeneration of the IS/OS junction.3 We report a case of early hydroxychloroquine retinopathy detected with SD-OCT, where subtle thinning of the IS/OS junction and the outer segment photoreceptor/RPE interdigitation layer are the only anatomic indicators of hydroxychloroquine toxicity.

Case report

A 58-year-old female with psoriatic arthritis and a 10-year history of hydroxychloroquine use was referred for evaluation of possible toxic maculopathy (daily dose of 400 mg for 6 years, weight 58.1 kg (6.9 mg/kg/day; 8.3 mg/ideal body weight (IBW) (48 kg)/day) and decreased to 300 mg for 4 years after a 3 kg weight loss (7.3 mg/kg/day to 5.4 mg/kg/day; 6.25 mg/IBW/day); cumulative dose of 1314 grams). The patient had undergone Humphrey 10–2 visual field testing with a white stimulus revealing bilateral central scotomas, which have been noted in hydroxycholoroquine toxicity3 (Figures 1c and d). Upon further review, the visual fields were of low reliability. Visual acuity was 20/20 in both eyes. The patient was asymptomatic at the time of presentation. There was no history of renal insufficiency. Fundus exam was notable for mild, central mottling of the retinal pigment epithelium (RPE) bilaterally. Fundus autofluorescence (FAF) was significant for mild parafoveal hyperautofluorescence in both eyes, suggestive of early damage to the RPE (Figures 1a and b). SD-OCT showed subtle parafoveal thinning of the IS/OS junction and interdigitation layer, as well as hyperreflective, granular appearance of the RPE (Figure 2). The ELM was preserved in both eyes. A blunted parafoveal response was detected bilaterally on multifocal electroretinogram (mfERG) (Figures 1e and f). These findings were suggestive of hydroxychloroquine retinopathy, and the patient was advised to discontinue hydroxychloroquine. At 6-month follow-up, the patient’s visual acuity remained 20/20 bilaterally. Visual fields were repeated and more reliably showed bilateral paracentral scotomas. SD-OCT images and multifocal ERG were unchanged.

Figure 1
figure 1

(a–f): Fundus autofluorescence (a, b) with mild hyperautofluorescence in both eyes. Automated visual fields (c, d) showed central scotomas bilaterally. Multifocal electroretinogram trace array (e, f) showed bilateral parafoveal depression more pronounced in the left eye.

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Figure 2
figure 2

High-resolution spectral domain optical coherence tomography images showing parafoveal and mild perifoveal thinning on thickness map. There is an outer layer thinning between the IS/OS junction (white arrows) and the outer segment/RPE interdigitation layer (black arrows). Top: right eye; Bottom: left eye.

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Comment

At present, no treatment exists for hydroxychloroquine retinopathy. The American Academy of Ophthalmology recently emphasized the use of objective screening tests, including SD-OCT, FAF, and mfERG, to be evaluated along with 10–2 automated fields in an effort to minimize retinal damage.4 SD-OCT is a valuable screening and diagnostic modality for the detection of anatomical changes associated with early hydroxychloroquine toxicity, however these changes can be subtle. In this case, the only anatomic changes visible are thinning of the IS/OS junction and disruption of the photoreceptor/RPE interdigitation line with very subtle changes on the FAF. Changes to these outer retinal layers may easily be missed, therefore careful examination of high-resolution SD-OCT images is critical when screening for hydroxychloroquine toxicity.