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Change in Cone Structure Over 24 Months in USH2A-Related Retinal Degeneration. Am J Ophthalmol 2023 Aug;252:77-93



Pubmed ID




Scopus ID

2-s2.0-85154059408 (requires institutional sign-in at Scopus site)   2 Citations


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.

DESIGN: Multicenter, longitudinal natural history 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 < .001). Cone spacing was significantly correlated with eccentricity, quality score, and disease duration (P < .02). On average, the cone spacing Z-score increased 0.14 annually (about 9%, P < .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, the 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 using AOSLO are needed to advance cone mosaic metrics as sensitive outcome measures for clinical trials. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Author List

Duncan JL, Liang W, Maguire MG, Porco TC, Wong J, Audo I, Cava JA, Grieve K, Kalitzeos A, Kreis J, Michaelides M, Norberg N, Paques M, Carroll J, Foundation Fighting Blindness Consortium Investigator Group


Joseph J. Carroll PhD Director, Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Extracellular Matrix Proteins
Retinal Cone Photoreceptor Cells
Retinal Degeneration
Tomography, Optical Coherence
Usher Syndromes