A 2-Year Longitudinal Study of Normal Cone Photoreceptor Density

Despite the potential for adaptive optics scanning light ophthalmoscopy (AOSLO) to quantify retinal disease progression at the cellular level, there remain few longitudinal studies investigating changes in cone density as a measure of disease progression. Here, we undertook a prospective, longitudinal study to investigate the variability of cone density measurements in normal subjects during a 2-year period. Fourteen eyes of nine subjects with no known ocular pathology were imaged both at a baseline and a 2-year follow-up visit by using confocal AOSLO at five retinal locations. Two-year affine-registered images were created to minimize the effects of intraframe distortions. Regions of interest were cropped from baseline, 2-year manually aligned, and 2-year affine-registered images. Cones were identified (graded masked) and cone density was extracted. Mean baseline cone density (cones/mm2) was 87,300, 62,200, 45,500, 28,700, and 18,200 at 190, 350, 500, 900, and 1500 μm, respectively. The mean difference (± standard deviation [SD]) in cone density from baseline to 2-year affine-registered images was 1400 (1700), 100 (1800), 300 (800), 400 (800), and 1000 (2400) cones/mm2 at the same locations. The mean difference in cone density during the 2-year period was lower for affine-registered images than manually aligned images. There was no meaningful change in normal cone density during a 2-year period. Intervisit variability in cone density measurements decreased when intraframe distortions between time points were minimized. This variability must be considered when planning prospective longitudinal clinical trials using changes in cone density as an outcome measure for assessing retinal disease progression.