Uncovering subclinical retinal toxicity: The role of macular thickness mapping inhydroxychloroquine screening

To evaluate the value of quantitative macular thickness mapping using spectral-domain optical coherence tomography (SD-OCT) as an early screening tool for preclinical hydroxychloroquine-induced retinal toxicity.

This observational cross-sectional study included 122 patients receiving hydroxychloroquine. Established hydroxychloroquine retinal toxicity was defined according to classical structural and functional criteria, including ellipsoid zone disruption on SD-OCT and confirmatory abnormalities on 10-2 visual field testing, fundus autofluorescence, and/or multifocal electroretinography. Patients fulfilling these criteria were identified separately and excluded from intergroup quantitative analyses. The remaining patients were stratified according to treatment duration into a higher-exposure group (≥ 5 years) and a lower-exposure group (< 5 years). All participants underwent SD-OCT and 10-2 visual field testing. Macular thickness, ganglion cell complex (GCC), and retinal nerve fiber layer (RNFL) parameters were compared, and correlations with hydroxychloroquine treatment characteristics were analyzed.

Macular thickness was significantly reduced in patients with longer hydroxychloroquine exposure, particularly in the parafoveal and perifoveal regions (mean parafoveal thickness: 323.05±12.12μm vs. 311.54±16.09μm; P=0.01). Parafoveal thinning correlated negatively with cumulative dose and treatment duration (r=-0.39, P=0.038 and r=-0.46, P=0.041, respectively). GCC thinning reached statistical significance only in the hemi-inferior quadrant, while RNFL parameters showed no significant differences or correlations.

Quantitative macular thickness reduction, particularly in the parafoveal region, is associated with hydroxychloroquine exposure and may precede classical structural signs of retinal toxicity. Macular thickness mapping by SD-OCT should be interpreted as a complementary early screening tool rather than a diagnostic criterion for established hydroxychloroquine maculopathy.