Longitudinal imaging of the parafoveal cone mosaic in congenital achromatopsia

Abstract

Purpose : Using adaptive optics to assess longitudinal changes in parafoveal cone density in individuals with congenital achromatopsia (ACHM).

Methods : 19 individuals (7F, 12M) with genetically confirmed ACHM (1 CNGA3; 18 CNGB3) and viable split-detector adaptive optics scanning laser ophthalmoscope (AOSLO) montages from at least 2 timepoints were included in this study. Peak cone density in follow-up montages were aligned to the baseline montage for each subject. Individual 100 x 100 µm regions of interests (ROIs) were further manually aligned to baseline images. ROIs were extracted at locations 1°, 5°, and 10° temporal (T) from the location of peak cone density in each montage. A total of 86 montages were utilized which resulted in 187 ROIs included in this study. At 1°, 5°, and 10° T, 77 ROIs from 19 subjects, 62 ROIs from 18 subjects, and 48 ROIs from 14 subjects were analyzed, respectively. Cones were identified in each ROI by one observer, reviewed by a second observer, and confirmed together by both observers in a masked fashion. Cone density was calculated, and a linear mixed model was used to assess changes in density over time. A Wald test was performed to determine if there was a statistically significant change in cone density over time for each parafoveal locations.

Results : The mean age (± SD) at baseline was 21.6 ± 10.6 years and the mean follow-up period (± SD) was 42.8 ± 34.9 months (range: 5.5 - 103.8 months). At 1°T, we observed a significant decrease of 352 cones/mm² per year (p=0.0003). At 5° T, the linear mixed model showed a decrease of 58 cones/mm² per year, though this was not significant (p=0.504). At 10° T, we observed a significant decrease of 139 cones/mm² per year (p=0.0188). For the 100 x 100 µm ROIs used here, these changes in density correspond to an average decrease of between 0.5-4 cones per year, depending on the location.

Conclusions : Parafoveal cone density estimates in ACHM show a small but statistically significant decrease over time. These observed changes are within the previously reported longitudinal repeatability values for normal retinas (PMC6736277), suggesting the observed average cone loss may not be pathological in nature. Further parafoveal and foveal cone density studies with longer follow-up times and more genetically heterogenous and age-diverse populations is needed to better understand factors contributing to changes in cone structure in ACHM over time.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.