Objective To compare subjective and objective clinical tests used in the screening for hydroxychloroquine retinal toxicity to multifocal electroretinography (mfERG) reference testing. Design Prospective, single-center, case control study. Participants Fifty-seven patients with a previous or current history of hydroxychloroquine treatment of more than 5 years' duration. Methods Participants were evaluated with a detailed medical history, dilated ophthalmologic examination, color fundus photography, fundus autofluorescence (FAF) imaging, spectral-domain (SD) optical coherence tomography (OCT), automated visual field testing (10-2 visual field mean deviation [VFMD]), and mfERG testing. We used mfERG test parameters as a gold standard to divide participants into 2 groups: those affected by hydroxychloroquine-induced retinal toxicity and those unaffected. Main Outcome Measures We assessed the association of various imaging and psychophysical variables in the affected versus the unaffected group. Results Fifty-seven study participants (91.2% female; mean age, 55.7±10.4 years; mean duration of hydroxychloroquine treatment, 15.0±7.5 years) were divided into affected (n = 19) and unaffected (n = 38) groups based on mfERG criteria. Mean age and duration of hydroxychloroquine treatment did not differ statistically between groups. Mean OCT retinal thickness measurements in all 9 macular subfields were significantly lower (<40 μm) in the affected group (P < 0.01 for all comparisons) compared with those in the unaffected group. Mean VFMD was 11 dB lower in the affected group (P < 0.0001). Clinical features indicative of retinal toxicity were scored for the 2 groups and were detected in 68.4% versus 0.0% using color fundus photographs, 73.3% versus 9.1% using FAF images, and 84.2% versus 0.0% on the scoring for the perifoveal loss of the photoreceptor ellipsoid zone on SD-OCT for affected and unaffected participants, respectively. Using a polynomial modeling approach, OCT inner ring retinal thickness measurements and Humphrey 10-2 VFMD were identified as the variables associated most strongly with the presence of hydroxychloroquine as defined by mfERG testing. Conclusions Optical coherence tomography retinal thickness and 10-2 VFMD are objective measures demonstrating clinically useful sensitivity and specificity for the detection of hydroxychloroquine toxicity as identified by mfERG, and thus may be suitable surrogate tests.
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