Effect of Disease Stage on Progression of Hydroxychloroquine Retinopathy

Abstract

IMPORTANCE Hydroxychloroquine sulfate retinopathy can progress after the drug is stopped. It is not clear how this relates to the stage of retinopathy or whether early screening with modern imaging technology can prevent progression and visual loss. OBJECTIVE To determine the relationship between progression of retinopathy and the severity of disease using objective data from optical coherence tomography and assess the value of early screening for the toxic effects of hydroxychloroquine. DESIGN, SETTING, AND PARTICIPANTS Clinical findings in patients with hydroxychloroquine retinopathy were monitored with repeated anatomical and functional examinations for 13 to 40 months after the drug was stopped in a referral practice in a university medical center. Eleven patients participated, with the severity of toxic effects categorized as early (patchy parafoveal damage shown on field or objective testing), moderate (a 50%-100% parafoveal ring of optical coherence tomography thinning but intact retinal pigment epithelium), and severe (visible bull's-eye damage). MAIN OUTCOMES AND MEASURES Visual acuity, white 10-2 visual field pattern density plots, fundus autofluorescence, spectral-density optical coherence tomography cross sections, thickness (from cube diagrams), and ellipsoid zone length. RESULTS Visual acuity and visual fields showed no consistent change. Fundus autofluorescence showed little or no change except in severe cases in which the bull's-eye damage expanded progressively. Optical coherence tomography cross sections showed little visible change in early and moderate cases but progressive foveal thinning (approximately 7 μm/y) and loss of ellipsoid zone (in the range of 100 μm/y) in severe cases, which was confirmed by quantitative measurements. The measurements also showed some foveal thinning (approximately 4 μm/y) and deepening of parafoveal loss in moderate cases, but the breadth of the ellipsoid zone remained constant in both early and moderate cases. A few cases showed a suggestion of ellipsoid zone improvement. CONCLUSIONS AND RELEVANCE Patients with hydroxychloroquine retinopathy involving the retinal pigment epithelium demonstrated progressive damage on optical coherence tomography for at least 3 years after the drug was discontinued, including loss of foveal thickness and cone structure. Cases recognized before retinal pigment epithelium damage retained foveal architecture with little retinal thinning. Early recognition of hydroxychloroquine toxic effects before any fundus changes are visible, using visual fields and optical coherence tomography (along with fundus autofluorescence and multifocal electroretinography as indicated), will greatly minimize late progression and the risk of visual loss.

Structural and Functional Characterization of the Retinal Effects of Hydroxychloroquine Treatment in Healthy Eyes

“…Unlike other studies that quantified the overall retinal thickness or isolated retinal layers [3, 17-19, 27], or subjectively graded for changes in the outer retina, photoreceptor layer, and inner segment/outer segment junction [8, 9, 22], we performed a systematic full-thickness automatic layer segmentation. This allowed us to have a consistent and thorough amount of raw data to objectively characterize, quantify, and locate the long-term effects of hydroxychloroquine.…”

“…Despite its overall favourable systemic safety profile, retinal toxicity has been increasingly recognized and associated with irreversible visual loss, which might be progressive after drug cessation [3]. The mechanism underlying retinal toxicity is still poorly understood [1, 4].…”

Pericentral Hydroxychloroquine Retinopathy in Korean Patients

“…Our series is too small for firm conclusions, but these observations are consistent with prior reports that there is little or no progression of EZ-IZ loss in patients with parafoveal retinopathy before RPE disruption. 12 Hydroxychloroquine binds to melanin in the RPE and causes lipid complex accumulation, enzyme inhibition, free radical generation, and ion disturbances in the retina. 13e19 However, the pathophysiology of the retinal toxicity and its central distribution are not clearly understood, nor is there an obvious explanation for the disparity in the retinal location between white and Asian patients.…”

Delayed progression of bull’s eye maculopathy

“…In particular, it appears to be less in cases recognised before RPE damage, highlighting the benefits of early detection 8. The late progression is unlikely to be due to remaining drug, which is cleared in a matter of months, but it may represent a decompensation of cells initially affected by the drug 2…”