Purpose: We examine the interocular symmetry of foveal outer nuclear layer (ONL) thickness measurements in subjects with achromatopsia (ACHM). Methods: Images from 76 subjects with CNGA3-or CNGB3-associated ACHM and 42 control subjects were included in the study. Line or volume scans through the fovea of each eye were acquired using optical coherence tomography (OCT). Image quality was assessed for each image included in the analysis using a previously-described maximum tissue contrast index (mTCI) metric. Three foveal ONL thickness measurements were made by a single observer and interocular symmetry was assessed using the average of the three measurements for each eye. Results: Mean (6 standard deviation) foveal ONL thickness for subjects with ACHM was 79.7 6 18.3 lm (right eye) and 79.2 6 18.7 lm (left eye) compared to 112.9 6 15.2 (right eye) and 112.1 6 13.9 lm (left eye) for controls. Foveal ONL thickness did not differ between eyes for ACHM (P ¼ 0.636) or control subjects (P ¼ 0.434). No significant relationship between mTCI and observer repeatability was observed for either control (P ¼ 0.140) or ACHM (P ¼ 0.351) images. Conclusions: While foveal ONL thickness is reduced in ACHM compared to controls, the high interocular symmetry indicates that contralateral ONL measurements could be used as a negative control in early-phase monocular treatment trials. Translational Relevance: Foveal ONL thickness can be measured using OCT images over a wide range of image quality. The interocular symmetry of foveal ONL thickness in ACHM and control populations supports the use of the non-study eye as a control for clinical trial purposes.

Purpose To test the hypothesis that foveal cone topography is symmetrical between contralateral eyes. Methods We used adaptive optics scanning light ophthalmoscopy to acquire images of the foveal cone mosaic in each eye of 58 subjects with normal vision (35 female, 23 male). Cones were semiautomatically identified over a 300 × 300-µm foveal area. From these cone coordinates, maps of cone density were derived, and we extracted estimates of peak cone density from each map. Mosaic regularity was assessed using Voronoi cell area regularity (VCAR). Average roundness and average area of the 70%, 75%, 80%, 85%, and 90% of peak density isodensity contours were evaluated. Results The average peak cone density for right eyes was 180,286 cones/mm 2 ( n = 49) and for left eyes was 182,397 cones/mm 2 ( n = 45), with a mean absolute difference of 6363 cones/mm 2 ( n = 43). Peak density, cone spacing, VCAR, and average area within the isodensity contours of fellow eyes were not significantly different ( P = 0.60, P = 0.83, P = 0.30, and P = 0.39, respectively). However, the average roundness of the isodensity contours was 2% more circular in the right eyes than in the left eyes ( P = 0.02). Conclusions There is interocular symmetry of peak foveal cone density, mosaic regularity, and area encompassing the most densely packed cells in subjects with normal vision. The origin and significance of the observed interocular difference in average roundness of the isodensity contours are unclear.

The foveal cone mosaic can be directly visualized using adaptive optics scanning light ophthalmoscopy (AOSLO). Previous studies in individuals with normal vision report wide variability in the topography of the foveal cone mosaic, especially the value of peak cone density (PCD). While these studies often involve a human grader, there have been no studies examining intergrader reproducibility of foveal cone mosaic metrics. Here we re-analyzed published AOSLO foveal cone images from 44 individuals to assess the relationship between the cone density centroid (CDC) location and the location of PCD. Across 5 graders with variable experience, we found a measurement error of 11.7% in PCD estimates and higher intergrader reproducibility of CDC location compared to PCD location (p < 0.0001). These estimates of measurement error can be used in future studies of the foveal cone mosaic, and our results support use of the CDC location as a more reproducible anchor for cross-modality analyses.