Change in cone structure over 24 months in USH2A-related retinal degeneration.

PURPOSE: To describe cone structure changes using adaptive optics scanning laser ophthalmoscopy (AOSLO) in the Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) study.

METHODS: AOSLO images were acquired at 4 centers, twice at baseline and annually for 24 months in this natural history study. For each eye, at least 10 regions of interest (ROIs) with ≥ 50 contiguous cones were analyzed by masked, independent graders. Cone spacing Z-scores, standard deviations from the normal mean at the measured location, were compared between graders and tests at baseline. The association of cone spacing with clinical characteristics was assessed using linear mixed effects regression models weighted by image quality score. Annual rates of change were calculated based on differences between visits.

RESULTS: Fourteen eyes of 14 participants were imaged, with 192 ROIs selected at baseline. There was variability among graders, which was greater in images with lower image quality score (P < 0.001). Cone spacing was significantly correlated with eccentricity, quality score and disease duration (P < 0.02). On average, cone spacing Z-score increased 0.14 annually (about 9%, P < 0.001). We observed no significant differences in rate of change between disease type (Usher syndrome or retinitis pigmentosa), imaging site, or grader.

CONCLUSIONS: Using current methods, analysis of quantitative measures of cone structure showed some challenges, yet showed promise that AOSLO images can be used to characterize progressive change over 24 months. Additional multicenter studies utilizing AOSLO are needed to advance cone mosaic metrics as sensitive outcome measures for clinical trials.