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Maxwell A Reback, Hongxin Song, Lisa R. Latchney, Mina M Chung; Longitudinal adaptive optics imaging reveals regional variation in cone and rod loss in Stargardt disease. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4929.
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© ARVO (1962-2015); The Authors (2016-present)
Stargardt disease (SD) is defined clinically by lipofuscin deposition and atrophy of the retinal pigment epithelium (RPE), but the causative ABCA4 gene encodes a protein uniquely expressed in cone and rod outer segments. How mutations in ABCA4 lead to clinically detectable RPE changes, or whether photoreceptors are affected prior to the RPE remains unclear. Using adaptive optics scanning laser ophthalmoscopy (AOSLO), we investigated the sequence of changes in the photoreceptor mosaic in the macular atrophy phenotype of SD.
Two brothers with genetically confirmed SD underwent comprehensive eye exams and AOSLO imaging 3 times in a 28-month period. Reflectance images of the cone and rod photoreceptors were obtained from the central fovea to 10 degrees inferior. Photoreceptors were counted in sampling windows at 100μm intervals of 200x200µm for cones and 50x50µm for rods, using custom semi-automated software. Photoreceptor density and spacing were measured and compared across imaging sessions using one-way ANOVA.
Over 28 months, visual acuity declined from 20/30 to 20/150 with an expanding bull’s eye lesion in the younger, more mildly affected brother; the older brother maintained 20/150 visual acuity with a central scotoma and expanding macular RPE atrophy. In the younger brother, AOSLO showed a 30% decline in peak foveal cone density after 8 months, and complete loss of foveal cones at 28 months; the older brother had no detectable foveal cones at baseline. In the peripheral macula, cone and rod spacing was greater than normal in both patients. Rod spacing increased significantly in the younger brother after 28 months (p<0.01) and remained unchanged in the older brother. There was no change in peripheral cone spacing in either patient over 28 months. The ratio of cone to rod spacing was greater than normal over all eccentricities tested, with greater divergence closer to the foveal center.
AOSLO demonstrates early foveal cone loss and increasing rod spacing in the peripheral macula in SD. Cones and rods are reduced in the peripheral macula in areas that appear normal by conventional imaging methods. The ratio of cone to rod spacing is increased, particularly near the foveal center. These findings suggest that central cone loss may be an early pathogenetic step in SD. AOSLO provides the capability to track individual cone and rod changes in SD longitudinally.
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