Reliability and Agreement Between Metrics of Cone Spacing in Adaptive Optics Images of the Human Retinal Photoreceptor Mosaic

PURPOSE. To assess reliability and agreement among three metrics used to evaluate the distribution of cell distances in adaptive optics (AO) images of the cone mosaic. METHODS. Using an AO flood illumination retinal camera, we acquired images of the cone mosaic in 20 healthy subjects and 12 patients with retinal diseases. The three spacing metrics studied were the center-to-center spacing (Scc), the local cone spacing (LCS), and the density recovery profile distance (DRPD). Each metric was calculated in sampling areas of different sizes (64 3 64 lm and 204 3 204 lm) across the parafovea. RESULTS. Both Scc and LCS were able to discriminate between healthy subjects and patients with retinal diseases; DRPD did not reliably detect any abnormality in the distribution of cell distances in patients with retinal diseases. The agreement between Scc and LCS was high in healthy subjects (intraclass correlation coefficient [ICC] ? 0.79) and moderate in patients with retinal diseases (ICC 0.51). The DRPD had poor agreement with Scc (ICC 0.47) and LCS (ICC 0.37). The correlation between the spacing metrics of the two sampling areas was greater in healthy subjects than in patients with retinal diseases. CONCLUSIONS. The Scc and LCS provided interchangeable estimates of cone distance in AO retinal images of healthy subjects but could not be used interchangeably when investigating retinal diseases with significant cell reflectivity loss (?30%). The DRPD was unreliable for describing cell distance in a human retinal cone mosaic and did not correlate with Scc and LCS. Caution is needed when comparing spacing metrics evaluated in sampling areas of different sizes.