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.
Hydroxychloroquine retinopathy primarily involves outer retina (photoreceptors). Outer retinal thinning while using HCQ initially involves the parafovea, but becomes diffuse across the macula as damage progresses or after drug cessation. When HCQ is stopped at an early or moderate stage (before RPE damage), progression seems to be limited to the first year.
IMPORTANCE Retinopathy is a known risk of long-term use of hydroxychloroquine sulfate. However, whether the inner as well as outer retina are involved before retinopathy develops and whether changes in the retina might signal impending toxic effects during screening remain unknown. OBJECTIVE To determine the degree of inner and outer retinal involvement in short-and long-term use of hydroxychloroquine before the development of retinopathy. DESIGN, SETTING, AND PARTICIPANTS This retrospective medical record review of spectral-domain optical coherence tomography (SD-OCT) findings was performed at an academic medical center. Thirty-two patients without retinopathy and with high-quality SD-OCT images were studied. Twenty-seven patients were age matched (49-65 years old) for comparison of retinal layers among patients who used the drug less than 5 years (n = 12) or longer than 15 years (n = 15) at the initial visit. Populations were also defined (without age limitation) for comparison of change during 25 to 52 months of follow-up among patients with initial use of less than 5 years (n = 7) or longer than 15 years (n = 8). Data were collected from 2010 to 2015. MAIN OUTCOMES AND MEASURES Measurements of inner and outer retinal thickness in SD-OCT images using commercial software and a Stanford pixel-by-pixel segmentation software that also provided topographic maps of thickness dimensions and change. RESULTS Thirty-two patients (5 men and 27 women) were included in the analysis. Measurements of inner retinal thickness between short-and long-term hydroxychloroquine users (n = 27) in different retinal regions, and during a median 39 months of follow-up (n = 15), showed no statistically significant differences or change. Similarly, no significant differences or changes were identified in outer retinal thickness except for the final visit of 1 patient who developed focal parafoveal thinning, a toxic effect of hydroxychloroquine use. Cirrus ganglion cell analysis measurements were inaccurate in the presence of outer retinal damage. CONCLUSIONS AND RELEVANCE The inner retina appears not to be involved in hydroxychloroquine-induced retinopathy to any clinically relevant degree within the limitations of our sample size. No clinically apparent warning of outer retinal damage was seen in the SD-OCT images of long-term hydroxychloroquine users until the actual appearance of focal retinopathy. Early detection of hydroxychloroquine-induced retinopathy is known to prevent visual acuity loss and serious progression after the therapy is stopped, and these data suggest that screening should seek distinct new areas of retinopathy (shown by topographic thickness maps) rather than long-term progressive thinning.
A lowering extent of EZ band defects in the foveal and parafoveal regions is a good indicator of postsurgery VA recovery. Attention should also be given to postsurgical alterations in the inner retina, as patients with more extensive atrophic changes appear to have slower or worse VA recovery despite closure of the macular hole.
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