Retinal Damage in Chloroquine Maculopathy, Revealed by High Resolution Imaging: A Case Report Utilizing Adaptive Optics Scanning Laser Ophthalmoscopy
A 53-year-old Asian woman with a history of lupus erythematosus was initially treated with hydroxychloroquine (Plaquenil, unknown dose) for 5 years. Approximately 3 years ago, the patient's medication was changed to chloroquine (400 mg daily). Within a few years of taking chloroquine, she noticed a circular shadow in her central vision, which she described as an arch surrounding her central vision. At first, she only noticed a superiorly oriented half-moon shadow that lasted for a few seconds during reading. The shadow was seen while both eyes were open and disappeared after a few seconds. Because of these symptoms and the presence of bull's eye maculopathy on fundus examination, chloroquine was discontinued and the patient's medication was changed to dapsone (unknown dose).\nThe best-corrected visual acuity (corrected with current spectacles) of the highly myopic patient during her most recent examination was 20 / 25 in both eyes, with no evidence of an afferent pupillary defect. Slit-lamp examination indicated that the anterior segment was unremarkable and Goldmann applanation intraocular pressure was normal (16 mmHg) in both eyes. However, a significant central defect was noted on Humphrey visual field (HVF) examination (Humphrey Visual Field Analyzer 10-2; Humphrey Instruments, San Leandro, CA, USA) in both eyes. Dilated fundoscopy revealed tilting of the optic nerves in both eyes, consistent with myopia, and a ring-shaped area of RPE depigmentation in the parafoveal area of the left eye (). Fundus autofluorescence (FAF) imaging revealed a hypofluorescent lesion in the foveal and perifoveal areas correspond with the bull's eye retinopathy. In the left eye, a prominent hypofluorescent lesion was also noticed on FAF imaging, reflecting marked atrophy of the RPE layer ().\nCross-sectional retinal scans, obtained with SD-OCT (Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany) showed obvious thinning of the macula and disruptions in the outer retina. More specifically, loss of the photoreceptor inner/outer segment (IS/OS) junction corresponded to the location of the maculopathy as identified on fundus photography, FAF, and HVF 10-2. The outer retinal layer had a moth-eaten appearance at the IS/OS junction, but the thickness and appearance of the inner retina were within normal limits. Additionally, a downward displacement of the overlying retina was seen in perifoveal areas and corresponded to the hypofluorescent lesion in FAF images. Unlike the anatomically disrupted areas, which corresponded to the bull's eye lesion, the central fovea had normal thickness and structure on SD-OCT in both eyes ().\nInstead of using a deformable mirror to correct for wavefront aberrations, the AO system used in the current study utilized a dual liquid crystal on silicon spatial light modulators (LCOS-SLMs; X10468-02, Hamamatsu Photonics, Morimoto, Japan) first introduced by Hirose et al. []. Although deformable mirrors have been widely used, their performance is limited with respect to compensating large amounts of aberration of human eyes. Meanwhile, although LCOS-SLM is able to compensate large amounts of aberration by the phase wrapping method utilizing a continuity of the wavefront of a laser beam, it is only capable of compensating a particular polarization component. Most AO systems simultaneously process the measurement/compensation of aberration and SLO imaging. This system is very efficient at following changes in aberration of a subject according to change in imaging location, but is not suitable for obtaining high contrast images because the power of the lights used for simultaneous imaging and measurement/compensation of time is limited for safety. In this study, we overcame these problems by adopting dual LCOS-SLM to compensate the two orthogonal polarization components and sequential processing of SLO imaging and measurement/compensation of aberrations [].\nAO-SLO images were obtained and cone density was measured 0.5, 1.0, and 1.5 mm from the center of the fovea in each of the 4 major directions (superior, inferior, nasal, and temporal). A montage was then created and verified by checking the correspondence between the AO-SLO and wide-field images. Cone density was calculated using photoreceptor analysis software (Canon, Tokyo, Japan). To obtain an accurate cone density, the axial length, anterior chamber depth, and keratometry values were all considered when counting cone cells, which were represented in images as bright spots 2 to 5 µm in size. We manually selected areas of interest, and excluded retinal vessels and artifacts that obscured the underlying cone mosaic. AO-SLO images showed patch cone mosaic lesions, indicating abnormal regions of missing or lost cones. In addition, the observed cones were asymmetrical in shape and size and varied in brightness ().\nCone densities in the right eye were 14,927, 10,377, and 11,853 cones/mm2 at 0.5, 1.0, and 1.5 mm from the center of the fovea, respectively. The corresponding cone densities in the left eye were 16,692, 12,564, and 13,100 cones/mm2, respectively. The cone density at 1.5 mm from the center of the fovea was closer to normal than the other distances; however, the photoreceptors located 1.5 mm from the foveal center exhibited asymmetrical shapes and sizes, and varied in brightness in AO-SLO images. Additionally, SD-OCT images showed an abnormal IS/OS cytoarchitecture 1.5 mm from the foveal center. When we matched the disrupted areas on the AO-SLO images with the visual field test, the areas with abnormal cone mosaic patterns and low cone density corresponded with the location of visual field defects on HVF ().