Longitudinal Imaging of the Parafoveal Cone Mosaic in Congenital Achromatopsia

To assess longitudinal changes in parafoveal cone density in individuals with congenital achromatopsia (ACHM).

Retrospective longitudinal study.

Nineteen individuals (7 women and 12 men) with genetically confirmed ACHM. To be eligible, each had adaptive optics scanning light ophthalmoscope (AOSLO) images of the photoreceptor mosaic from ≥2 time points.

For each individual, follow-up AOSLO montages were aligned to their baseline montage. Notably, 100 × 100 μm regions of interest (ROIs) were extracted from the split-detection modality at locations 1°, 5°, and 10° temporal (T) from the peak cone density in each montage. All ROIs from follow-up visits were then manually aligned to their respective baseline ROI for that location. Cones were identified in each ROI by one observer, reviewed by a second observer, and confirmed together 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 the cone density changes were statistically significant.

Parafoveal cone spacing (at 1°, 5°, and 10° T) as a function of time.

The mean (± standard deviation [SD]) age at baseline was 21.6 ± 10.7 years and the mean (±SD) follow-up period was 3.83 ± 2.93 years (range, 0.46-8.66 years). 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 nonstatistically significant decrease of 58 cones/mm² per year (P = 0.504). At 10° T, we observed a significant decrease of 139 cones/mm² per year (P = 0.0188). For a 100 × 100 μm ROI, these density changes correspond to a reduction of between about 0.5 and 4 cones per year, depending on the location.

Parafoveal cone density estimates in ACHM show a small decrease over time. These observed changes are within the previously reported longitudinal repeatability values for normal retinas, suggesting the observed average cone loss may not be clinically meaningful. Further studies with longer follow-up times and more genetically heterogeneous and age-diverse populations are needed to better understand factors contributing to changes in foveal and parafoveal cone structure in ACHM over time.

Proprietary or commercial disclosures may be found in the Footnotes and Disclosures at the end of this article.