Longitudinal Adaptive Optics Scanning Laser Ophthalmoscopy Reveals Regional Variation in Cone and Rod Photoreceptor Loss in Stargardt Disease

Abstract

Purpose: To investigate the temporal sequence of changes in the photoreceptor cell mosaic in patients with Stargardt disease type 1 (STGD1), using adaptive optics scanning laser ophthalmoscopy (AOSLO). Methods: Two brothers with genetically confirmed STGD1 underwent comprehensive eye exams, spectral-domain optical coherence tomography (SD-OCT), fundus auto fluorescence (FAF) and AOSLO imaging 3 times over the course of 28 months. Confocal images of the cones and rods were obtained from the central fovea to 10 degrees inferiorly. Photoreceptors were counted in sampling windows at 100 µm intervals of 200 µm × 200 µm for cones and 50 µm × 50 µm for rods, using custom cell marking software with manual correction. Photoreceptor density and spacing were measured and compared across imaging sessions using one-way ANOVA. Results: AOSLO revealed the younger brother had a 30% decline in foveal cone density after 8 months, followed by 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 spacings were greater than normal in both patients. The ratio of the cone spacing to rod spacing was greater than normal across all eccentricities, with a greater divergence closer to the foveal center. Conclusions: Cone cell loss may be an early pathogenetic step in Stargardt disease. AOSLO provides the capability to track individual photoreceptor changes longitudinally in Stargardt disease. Summary statement: The pathogenetic mechanism of Stargardt disease remains poorly understood. We used high resolution AOSLO to track the progression of the disease and found cone cell loss may be an early pathogenetic step in Stargardt disease.