June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Hearing Loss as a Prognostic Indicator of Visual Function in USH2A-associated Retinal Degeneration.
Author Affiliations & Notes
  • Jesse D Sengillo
    Ophthalmology, Columbia University, New York, New York, United States
    College of Medicine, SUNY Downstate Medical Center, Brooklyn, New York, United States
  • Thiago Cabral
    Ophthalmology, Federal University of Espírito Santo, Vitória, Brazil
    Ophthalmology, Federal University of São Paulo, São Paulo, Brazil
  • Kaspar Schuerch
    Ophthalmology, Columbia University, New York, New York, United States
  • Jimmy K Duong
    Biostatistics, Columbia University, New York, New York, United States
  • Winston Lee
    Ophthalmology, Columbia University, New York, New York, United States
  • Katherine Boudreault
    Ophthalmology, Columbia University, New York, New York, United States
    Ophthalmology, University of Montreal, Montreal, Quebec, Canada
  • Sally Justus
    Ophthalmology, Columbia University, New York, New York, United States
  • Yu Xu
    Ophthalmology, Columbia University, New York, New York, United States
    Ophthalmology, Xin Hua Hospital, affiliate of Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • Janet R Sparrow
    Ophthalmology, Columbia University, New York, New York, United States
  • Vinit B Mahajan
    Ophthalmology & Visual Sciences, University of Iowa, Iowa City, Iowa, United States
    Omics Laboratory, University of Iowa, Iowa City, Iowa, United States
  • Stephen H Tsang
    Ophthalmology, Columbia University, New York, New York, United States
    Pathology & Cell Biology, Institute of Human Nutrition, Columbia University, New York, New York, United States
  • Footnotes
    Commercial Relationships   Jesse Sengillo, None; Thiago Cabral, None; Kaspar Schuerch, None; Jimmy Duong, None; Winston Lee, None; Katherine Boudreault, None; Sally Justus, None; Yu Xu, None; Janet Sparrow, None; Vinit Mahajan, None; Stephen Tsang, None
  • Footnotes
    Support  Jonas Children’s Vision Care, and Bernard & Shirlee Brown Glaucoma Laboratory are supported by the National Institute of Health [5P30EY019007, R01EY018213, R01EY024698, R01EY026682, R21AG050437], National Cancer Institute Core [5P30CA013696], the Research to Prevent Blindness (RPB) Physician-Scientist Award, unrestricted funds from RPB, New York, NY, USA. J.D.S is supported by the RPB medical student research fellowship. T.C is supported by the International Council of Ophthalmology - Retina Research Foundation Helmerich Fellowship, honoring Mr. W. H. Helmerich III. V.B.M is supported by NIH grants [R01EY026682, R01EY024665, R01EY025225, R01EY024698 and R21AG050437]. S.H.T. is a member of the RD-CURE Consortium and is supported by the Tistou and Charlotte Kerstan Foundation, the Schneeweiss Stem Cell Fund, New York State [C029572], the Foundation Fighting Blindness New York Regional Research Center Grant [C-NY05-0705-0312], the Crowley Family Fund, and the Gebroe Family Foundation.
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 3223. doi:
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    • Get Citation

      Jesse D Sengillo, Thiago Cabral, Kaspar Schuerch, Jimmy K Duong, Winston Lee, Katherine Boudreault, Sally Justus, Yu Xu, Janet R Sparrow, Vinit B Mahajan, Stephen H Tsang; Hearing Loss as a Prognostic Indicator of Visual Function in USH2A-associated Retinal Degeneration.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3223.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Mutations in Usherin 2A (USH2A) cause Usher syndrome (USH), which manifests as retinitis pigmentosa (RP) with neurosensory hearing loss, or autosomal recessive non-syndromic RP (NSRP). However, few studies have characterized natural disease phenotype for patients with USH2A-associated retinal degenerations. Thus, we performed a cross-sectional analysis comparing electroretinography (ERG) data, retinal structure, and distribution of severe mutations between NSRP and USH patients harboring compound heterozygous or homozygous mutations in USH2A.

Methods : A total of 15 RP patients with two pathogenic mutations in USH2A were included, specifically eight USH patients and seven age-matched NSRP patients. Patients were diagnosed with USH if subjective hearing loss was present or NSRP if hearing loss was denied. To evaluate visual function prognosis, 30 Hz-flicker ERG was compared between groups. Ellipsoid zone (EZ) line length on SD-OCT and autofluorescent (AF) ring diameters on fundus AF imaging were compared. To determine the distribution of alleles containing severe mutations between each group, logistic regression models were utilized.

Results : NSRP patients had higher mean 30 Hz-flicker amplitudes of 21.1 ± 8.0 µV (mean ± SE) compared to USH patients, who had a mean of 2.1 ± 0.5 µV (p = 0.02). Of USH patients, 75% (6/8) had at least one severe mutation, defined as a frameshift or nonsense mutation, compared to 29% (2/7) of NSRP patients (p=0.13). The proportion of total alleles containing a severe mutation was 50% in the USH group compared to 14% of NSRP patients, with an odds ratio of 6.0 (confidence intervals: 1.1, 32) (p=0.04). There was no statistically significant difference in EZ-line length or AF ring diameters between groups.

Conclusions : NSRP patients had superior visual function prognoses as predicted by 30 Hz-flicker ERG and a higher proportion of alleles with severe mutations in this cohort. Our data suggests USH manifests as a more severe phenotype compared to NSRP patients with mutations in the same Usherin gene. A genetic threshold in which mutation burden relates to visual and auditory phenotype may exist. Larger cohort studies that compare visual function and audiometry of USH2A patients with their genotype are necessary to address this hypothesis. The presence or absence of hearing loss in USH2A patients may allow specialists to provide a more accurate prognosis.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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