Photoreceptor Outer Segment Reflectivity With Ultrahigh-Resolution Visible-Light Optical Coherence Tomography in Systemic Hydroxychloroquine Use

Purpose: To evaluate outer retinal organization in normal subjects and those using hydroxychloroquine (HCQ) with ultrahigh-resolution visible-light optical coherence tomography (VIS-OCT). Methods: Forty eyes of 22 adult subjects were recruited from a tertiary-care retina practice, including controls (20 eyes, 12 subjects, 40 +/- 22 years old) and subjects with a history of HCQ use (20 eyes, 10 subjects, 62 +/- 17 years old). Each subject was imaged using a custom-built VIS-OCT device (axial resolution 1.3 mu m) and U.S. Food and Drug Administration-approved OCT devices. Results: With the use of VIS-OCT, control subjects demonstrated five and six hyperreflective bands in the foveal and parafoveal regions, respectively, between the outer nuclear layer and Bruch's membrane. These bands demonstrated intensity profiles complementary to the known histopathologic distribution of rods and cones. In comparison to controls, subjects taking HCQ demonstrated reduced intensity of all bands, particularly bands two to four. In all cases of suspected or known toxicity, VIS-OCT demonstrated attenuation of band 3i, and in no cases was there attenuation of other bands that was more severe than band 3i, suggesting that changes in the reflectivity of band 3i may be the earliest identifiable sign of HCQ toxicity. Conclusions: VIS-OCT of the outer retina revealed a unique outer retinal banding pattern corresponding to photoreceptor density distributions. Notable attenuation of the photoreceptor outer segment reflectivity profile was associated with early HCQ toxicity. This finding may be an early, and possibly reversible, sign of HCQ toxicity, primarily impacting the cones. Translational Relevance: VIS-OCT is useful in detecting subclinical outer retinal structural changes found in subjects using hydroxychloroquine.