Intraobserver Repeatability and Interobserver Reproducibility of Foveal Cone Density Measurements in CNGA3- and CNGB3-Associated Achromatopsia. Transl Vis Sci Technol 2020 Jun;9(7):37
Date
08/25/2020Pubmed ID
32832242Pubmed Central ID
PMC7414701DOI
10.1167/tvst.9.7.37Scopus ID
2-s2.0-85090673745 (requires institutional sign-in at Scopus site) 9 CitationsAbstract
PURPOSE: To examine repeatability and reproducibility of foveal cone density measurements in patients with CNGA3- and CNGB3-associated achromatopsia (ACHM) using split-detection adaptive optics scanning light ophthalmoscopy (AOSLO).
METHODS: Thirty foveae from molecularly confirmed subjects with ACHM, half of whom harbored disease-causing variants in CNGA3 and half in CNGB3, underwent nonconfocal split-detection AOSLO imaging. Cone photoreceptors within the manually delineated rod-free zone were manually identified twice by two independent observers. The coordinates of the marked cones were used for quantifying foveal cone density. Cone density and difference maps were generated to compare cone topography between trials.
RESULTS: We observed excellent intraobserver repeatability in foveal cone density estimates, with intraclass correlation coefficients (ICCs) ranging from 0.963 to 0.991 for CNGA3 and CNGB3 subjects. Interobserver reproducibility was also excellent for both CNGA3 (ICC = 0.952; 95% confidence interval [CI], 0.903-1.0) and CNGB3 (ICC = 0.968; 95% CI, 0.935-1.0). However, Bland-Altman analysis revealed bias between observers.
CONCLUSIONS: Foveal cone density can be measured using the described method with good repeatability and reproducibility both for CNGA3- and CNGB3-associated ACHM. Any degree of bias observed among the observers is of uncertain clinical significance but should be evaluated on a study-specific basis.
TRANSLATIONAL RELEVANCE: This approach could be used to explore disease natural history, as well as to facilitate stratification of patients and monitor efficacy of interventions for ongoing and upcoming ACHM gene therapy trials.
Author List
Georgiou M, Litts KM, Singh N, Kane T, Patterson EJ, Hirji N, Kalitzeos A, Dubra A, Michaelides M, Carroll JAuthor
Joseph J. Carroll PhD Director, Professor in the Ophthalmology and Visual Sciences department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Color Vision DefectsCyclic Nucleotide-Gated Cation Channels
Fovea Centralis
Humans
Reproducibility of Results
Retinal Cone Photoreceptor Cells