Adaptive optics cone arrangement in hydroxychloroquine users without signs of retinal toxicity based on current screening guidelines: a case-control study

Purpose: To describe early cone changes detected by adaptive optics (AO) in patients on chronic hydroxychloroquine (HC) treatment with no abnormalities on standard functional or structural retinal tests. Methods: Case-control study including 36 eyes of 36 female patients. Cases included 18 women on HC for autoimmune disease whose cumulative dose exceeded 1600 g and who demonstrated no evidence of retinal toxicity on visual field (VF), spectral domain optical coherence tomography (SD-OCT), or multifocal electroretinography (mfERG). Controls included 18 women with no known systemic or ocular disease and no history of HC use. For each eye of every study participant, an image was captured using a commercially available flood-illuminated AO retinal camera (rtx1^TM,Imagine Eyes, France), at 2 degrees nasal and 2 degrees temporal to the fovea. The cone density and spacing measurements were automatically detected by the software provided by the RTX1 in a region of interest (ROI). Results: The control group exhibited mean nasal and temporal cone densities of 28,967 ± 1759 and 29,446 ± 1934 cells/mm², respectively, along with mean nasal and temporal spacing of 6.47 ± 0.19 and 6.43 ± 0.21 μm, respectively. The case group showed mean nasal and temporal cone densities of 26,967 ± 1667 and 26,099 ± 2052 cells/mm², respectively, and mean nasal and temporal spacing of 6.72 ± 0.20 and 6.84 ± 0.28 μm, respectively. A significantly (p < 0.01) lower density and larger spacing of cones were observed in the case group compared to the control group. Conclusions: AO may detect retinal changes from HC toxicity before they become apparent on VF, SD-OCT, or mfERG.