Residual Foveal Cone Structure in CNGB3-Associated Achromatopsia. Invest Ophthalmol Vis Sci 2016 Aug 01;57(10):3984-95
Date
08/02/2016Pubmed ID
27479814Pubmed Central ID
PMC4978151DOI
10.1167/iovs.16-19313Scopus ID
2-s2.0-84980378557 (requires institutional sign-in at Scopus site) 104 CitationsAbstract
PURPOSE: Congenital achromatopsia (ACHM) is an autosomal recessive disorder in which cone function is absent or severely reduced. Gene therapy in animal models of ACHM have shown restoration of cone function, though translation of these results to humans relies, in part, on the presence of viable cone photoreceptors at the time of treatment. Here, we characterized residual cone structure in subjects with CNGB3-associated ACHM.
METHODS: High-resolution imaging (optical coherence tomography [OCT] and adaptive optics scanning light ophthalmoscopy [AOSLO]) was performed in 51 subjects with CNGB3-associated ACHM. Peak cone density and inter-cone spacing at the fovea was measured using split-detection AOSLO. Foveal outer nuclear layer thickness was measured in OCT images, and the integrity of the photoreceptor layer was assessed using a previously published OCT grading scheme.
RESULTS: Analyzable images of the foveal cones were obtained in 26 of 51 subjects, with nystagmus representing the major obstacle to obtaining high-quality images. Peak foveal cone density ranged from 7,273 to 53,554 cones/mm2, significantly lower than normal (range, 84,733-234,391 cones/mm2), with the remnant cones being either contiguously or sparsely arranged. Peak cone density was correlated with OCT integrity grade; however, there was overlap of the density ranges between OCT grades.
CONCLUSIONS: The degree of residual foveal cone structure varies greatly among subjects with CNGB3-associated ACHM. Such measurements may be useful in estimating the therapeutic potential of a given retina, providing affected individuals and physicians with valuable information to more accurately assess the risk-benefit ratio as they consider enrolling in experimental gene therapy trials. (www.clinicaltrials.gov, NCT01846052.).
Author List
Langlo CS, Patterson EJ, Higgins BP, Summerfelt P, Razeen MM, Erker LR, Parker M, Collison FT, Fishman GA, Kay CN, Zhang J, Weleber RG, Yang P, Wilson DJ, Pennesi ME, Lam BL, Chiang J, Chulay JD, Dubra A, Hauswirth WW, Carroll J, ACHM-001 Study GroupAuthors
Joseph J. Carroll PhD Director, Professor in the Ophthalmology and Visual Sciences department at Medical College of WisconsinChristopher Langlo MD, PhD Assistant Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AdolescentAdult
Child
Color Vision Defects
Cyclic Nucleotide-Gated Cation Channels
DNA
DNA Mutational Analysis
Electroretinography
Fovea Centralis
Humans
Middle Aged
Mutation
Ophthalmoscopy
Retinal Cone Photoreceptor Cells
Tomography, Optical Coherence
Visual Acuity
Young Adult
