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KCNV2-Associated Retinopathy: Genetics, Electrophysiology, and Clinical Course-KCNV2 Study Group Report 1.

Authors
  • Georgiou, Michalis1
  • Robson, Anthony G1
  • Fujinami, Kaoru2
  • Leo, Shaun M1
  • Vincent, Ajoy3
  • Nasser, Fadi4
  • Cabral De Guimarães, Thales Antônio1
  • Khateb, Samer5
  • Pontikos, Nikolas1
  • Fujinami-Yokokawa, Yu6
  • Liu, Xiao7
  • Tsunoda, Kazushige7
  • Hayashi, Takaaki8
  • Vargas, Mauricio E9
  • Thiadens, Alberta A H J10
  • de Carvalho, Emanuel R11
  • Nguyen, Xuan-Thanh-An12
  • Arno, Gavin1
  • Mahroo, Omar A1
  • Martin-Merida, Maria Inmaculada13
  • And 16 more
  • 1 Moorfields Eye Hospital, London, United Kingdom; University College London Institute of Ophthalmology, London, United Kingdom. , (United Kingdom)
  • 2 Moorfields Eye Hospital, London, United Kingdom; University College London Institute of Ophthalmology, London, United Kingdom; Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan; Department of Ophthalmology, Keio University School of Medicine, Tokyo, Ontario, Japan. , (United Kingdom)
  • 3 Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. , (Canada)
  • 4 Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany. , (Germany)
  • 5 Department of Ophthalmology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. , (Israel)
  • 6 University College London Institute of Ophthalmology, London, United Kingdom; Department of Health Policy and Management, Keio University School of Medicine, Tokyo, Japan. , (United Kingdom)
  • 7 Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan; Department of Ophthalmology, Keio University School of Medicine, Tokyo, Ontario, Japan. , (Japan)
  • 8 Department of Ophthalmology, Katsushika Medical Center, The Jikei University School of Medicine, Tokyo, Japan. , (Japan)
  • 9 Department of Ophthalmology, Oregon Health and Science University, Casey Eye Institute, Portland, Oregon, USA.
  • 10 Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands. , (Netherlands)
  • 11 University College London Institute of Ophthalmology, London, United Kingdom; Department of Ophthalmology, Amsterdam UMC, Academic Medical Center, Amsterdam, the Netherlands. , (United Kingdom)
  • 12 Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands. , (Netherlands)
  • 13 Department of Genetics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital-Universidad Autónoma de Madrid, Madrid, Spain; Center for Biomedical Network Research on Rare Diseases, Instituto de Salud Carlos III, Madrid, Spain. , (Spain)
  • 14 Department of Ophthalmology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital-Universidad Autónoma de Madrid, Madrid, Spain. , (Spain)
  • 15 Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA.
  • 16 Department of Ophthalmology, Amsterdam UMC, Academic Medical Center, Amsterdam, the Netherlands; Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands. , (Netherlands)
  • 17 Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western University, Cleveland, Ohio, USA; Eye Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates. , (United Arab Emirates)
  • 18 Moorfields Eye Hospital, London, United Kingdom; University College London Institute of Ophthalmology, London, United Kingdom. Electronic address: [email protected] , (United Kingdom)
Type
Published Article
Journal
American journal of ophthalmology
Publication Date
May 01, 2021
Volume
225
Pages
95–107
Identifiers
DOI: 10.1016/j.ajo.2020.11.022
PMID: 33309813
Source
Medline
Language
English
License
Unknown

Abstract

To investigate genetics, electrophysiology, and clinical course of KCNV2-associated retinopathy in a cohort of children and adults. This was a multicenter international clinical cohort study. Review of clinical notes and molecular genetic testing. Full-field electroretinography (ERG) recordings, incorporating the international standards, were reviewed and quantified and compared with age and recordings from control subjects. In total, 230 disease-associated alleles were identified from 117 patients, corresponding to 75 different KCNV2 variants, with 28 being novel. The mean age of onset was 3.9 years old. All patients were symptomatic before 12 years of age (range, 0-11 years). Decreased visual acuity was present in all patients, and 4 other symptoms were common: reduced color vision (78.6%), photophobia (53.5%), nyctalopia (43.6%), and nystagmus (38.6%). After a mean follow-up of 8.4 years, the mean best-corrected visual acuity (BCVA ± SD) decreased from 0.81 ± 0.27 to 0.90 ± 0.31 logarithm of minimal angle of resolution. Full-field ERGs showed pathognomonic waveform features. Quantitative assessment revealed a wide range of ERG amplitudes and peak times, with a mean rate of age-associated reduction indistinguishable from the control group. Mean amplitude reductions for the dark-adapted 0.01 ERG, dark-adapted 10 ERG a-wave, and LA 3.0 30 Hz and LA3 ERG b-waves were 55%, 21%, 48%, and 74%, respectively compared with control values. Peak times showed stability across 6 decades. In KCNV2-associated retinopathy, full-field ERGs are diagnostic and consistent with largely stable peripheral retinal dysfunction. Report 1 highlights the severity of the clinical phenotype and established a large cohort of patients, emphasizing the unmet need for trials of novel therapeutics. Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

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