title: Cone responses in Usher syndrome types 1 and 2 by microvolt electroretinography.
abstract: OBJECTIVE
  Progressive decline of psychophysical cone-mediated measures has been reported in type 1 (USH1) and type 2 (USH2) Usher syndrome. Conventional cone electroretinogram (ERG) responses in USH demonstrate poor signal-to-noise ratio. We evaluated cone signals in USH1 and USH2 by recording microvolt level cycle-by-cycle (CxC) ERG.
  
  
  METHODS
  Responses of molecularly genotyped USH1 (n = 18) and USH2 (n = 24) subjects (age range, 15-69 years) were compared with those of controls (n = 12). A subset of USH1 (n = 9) and USH2 (n = 9) subjects was examined two to four times over 2 to 8 years. Photopic CxC ERG and conventional 30-Hz flicker ERG were recorded on the same visits.
  
  
  RESULTS
  Usher syndrome subjects showed considerable cone flicker ERG amplitude losses and timing phase delays (P < 0.01) compared with controls. USH1 and USH2 had similar rates of progressive logarithmic ERG amplitude decline with disease duration (-0.012 log μV/y). Of interest, ERG phase delays did not progress over time. Two USH1C subjects retained normal response timing despite reduced amplitudes. The CxC ERG method provided reliable responses in all subjects, whereas conventional ERG was undetectable in 7 of 42 subjects.
  
  
  CONCLUSIONS
  Cycle-by-cycle ERG showed progressive loss of amplitude in both USH1 and USH2 subjects, comparable to that reported with psychophysical measures. Usher subjects showed abnormal ERG response latency, but this changed less than amplitude with time. In USH syndrome, CxC ERG is more sensitive than conventional ERG and warrants consideration as an outcome measure in USH treatment trials.
authors.affiliation: National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Wadih M
authors.initials: WM
authors.lastname: Zein
authors.affiliation: National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Benedetto
authors.initials: B
authors.lastname: Falsini
authors.affiliation: National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Ekaterina T
authors.initials: ET
authors.lastname: Tsilou
authors.affiliation: National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Turriff
authors.affiliation: Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Schultz
authors.affiliation: Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Friedman
authors.affiliation: Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Carmen C
authors.initials: CC
authors.lastname: Brewer
authors.affiliation: Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Zalewski
authors.affiliation: Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: King
authors.affiliation: Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Muskett
authors.affiliation: Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Atteeq U
authors.initials: AU
authors.lastname: Rehman
authors.affiliation: Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Morell
authors.affiliation: Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Griffith
authors.affiliation: National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Sieving
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004596:Electroretinography / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology*; D052245:Usher Syndromes / Q000235:genetics / Q000503:physiopathology*; D055815:Young Adult
keywords: Usher genes; Usher syndrome; cone function; microvolt electroretinogram