Abstract
Purpose :
Choroideremia (CHM) is an X-linked inherited retinal degeneration affecting the photoreceptors, retinal pigment epithelium and choriocapillaris. Previous studies have reported local regions of reduced and normal cone density in CHM, but density measurements alone do not fully quantify the cone phenotype. Here, we compare cone inner segment (IS) area and circularity in CHM images to cones in images from normal-sighted controls.
Methods :
Nonconfocal split-detection images of the photoreceptor IS mosaic in 13 CHM and 12 normal controls were acquired at 1, 2, and 4° temporal to the fovea using a custom-built, multimodal adaptive optics scanning light ophthalmoscope. Cone centers were manually identified (JIWM) and cone borders segmented (PX). A custom MATLAB script was used to extract perimeter and area for each cone. Cone circularity was calculated as 4π * cone area / cone perimeter2. Regularities of each metric [defined as mean / standard deviation (stdev)] were calculated for each image. Unbalanced two-way ANOVA and Bonferroni post hoc were used to assess statistical differences between disease states (CHM vs. control) and along retinal eccentricity.
Results :
There was an effect of disease [ANOVA; F(1,65) = 31.88, p < 0.001] and eccentricity [F(2,65) = 63.23, p < 0.001] on cone area, though there was no significant interaction between disease state and eccentricity [F(2,65) = 0.02, p = 0.981]. Cones were significantly larger in CHM than control (mean ± stdev: 20.4 ± 8.8 µm2 vs. 14.5 ± 7.3 µm2; p < 0.001) and larger with eccentricity from the fovea (p < 0.001). There was an effect of disease state on cone circularity [F(1,65) = 4.31, p = 0.042] and circularity regularity [F(1,65) = 14.72, p < 0.001]. Compared to control, cones in CHM were more circular (p = 0.042) and circularity regularity was higher (p< 0.001). There was no significant effect of disease state on cone area regularity [F(1,65) = 1.27, p = 0.264].
Conclusions :
Cones are larger and more circular in CHM compared to normal, consistent with the idea that cones expand to form a contiguous mosaic in areas of reduced photoreceptor density. The increase in circularity in CHM was surprising, but one possible explanation may be that the tight packing of normal parafoveal cones result in a lack of intra-cone space and thus adjacent cones’ borders abut.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.