title: Residual Foveal Cone Structure in CNGB3-Associated Achromatopsia.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.).
authors.affiliation: Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Langlo
authors.affiliation: Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Patterson
authors.affiliation: Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Higgins
authors.affiliation: Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
authors.forename: Phyllis
authors.initials: P
authors.lastname: Summerfelt
authors.affiliation: Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States 3Alexandria Faculty of Medicine, University of Alexandria, Alexandria, Egypt.
authors.forename: Moataz M
authors.initials: MM
authors.lastname: Razeen
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States.
authors.forename: Laura R
authors.initials: LR
authors.lastname: Erker
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States.
authors.forename: Maria
authors.initials: M
authors.lastname: Parker
authors.affiliation: Pangere Center for Inherited Retinal Diseases, The Chicago Lighthouse, Chicago, Illinois, United States.
authors.forename: Frederick T
authors.initials: FT
authors.lastname: Collison
authors.affiliation: Pangere Center for Inherited Retinal Diseases, The Chicago Lighthouse, Chicago, Illinois, United States.
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Fishman
authors.affiliation: Vitreoretinal Associates, Gainesville, Florida, United States.
authors.forename: Christine N
authors.initials: CN
authors.lastname: Kay
authors.affiliation: Vitreoretinal Associates, Gainesville, Florida, United States.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Weleber
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Yang
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States.
authors.forename: David J
authors.initials: DJ
authors.lastname: Wilson
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Pennesi
authors.affiliation: Bascom Palmer Eye Institute, University of Miami, Miami, Florida, United States.
authors.forename: Byron L
authors.initials: BL
authors.lastname: Lam
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States.
authors.forename: John
authors.initials: J
authors.lastname: Chiang
authors.affiliation: Applied Genetics Technologies Corporation (AGTC), Alachua, Florida, United States.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Chulay
authors.affiliation: Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, United States 2Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States 9Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, Un.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Dubra
authors.affiliation: Ophthalmology, University of Florida, Gainesville, Florida, United States.
authors.forename: William W
authors.initials: WW
authors.lastname: Hauswirth
authors.affiliation: Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, United States 2Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States 9Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, Un.
authors.forename: Joseph
authors.initials: J
authors.lastname: Carroll
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003117:Color Vision Defects / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005584:Fovea Centralis / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009887:Ophthalmoscopy; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology*; D041623:Tomography, Optical Coherence / Q000379:methods*; D014792:Visual Acuity; D055815:Young Adult
chemical_list: C415904:CNGB3 protein, human; D054815:Cyclic Nucleotide-Gated Cation Channels; D004247:DNA