June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Baseline characteristics of patients with Usher Syndrome due to MYO7A mutations enrolled in a prospective natural history study
Author Affiliations & Notes
  • Francesco Testa
    Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
  • Ester Carreño
    CIBERER, ISCIII, Madrid, Spain
    Department of Ophthalmology, University Hospital Fundacion Jimenez Diaz, Madrid, Spain
  • Koen Vermeer
    Rotterdam Eye Hospital, Rotterdam, Netherlands
  • Valentina Di lorio
    Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
  • Belen Jimenez-Rolando
    CIBERER, ISCIII, Madrid, Spain
    Department of Ophthalmology, University Hospital Fundacion Jimenez Diaz, Madrid, Spain
  • Marianthi Karali
    Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
    Telethon Institute of Genetics and Medicine, Pozzuoli, Italy
  • Blanca Garcia Sandoval
    CIBERER, ISCIII, Madrid, Spain
    Department of Ophthalmology, University Hospital Fundacion Jimenez Diaz, Madrid, Spain
  • Irene Perea Romero
    CIBERER, ISCIII, Madrid, Spain
    Department of Genetics, University Hospital Fundacion Jimenez Diaz, Madrid, Spain
  • José Millán Salvador
    CIBERER, ISCIII, Madrid, Spain
    Unit of Genetics, University Hospital La Fe – IIS La Fe, Valencia, Spain
  • Paolo Melillo
    Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
  • Sandro Banfi
    Telethon Institute of Genetics and Medicine, Pozzuoli, Italy
    Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, Italy
  • Alberto Auricchio
    Telethon Institute of Genetics and Medicine, Pozzuoli, Italy
    Medical Genetics, Department of Translational Medicine, University of Naples Federico II, Naples, Italy
  • L. Ingeborgh van den Born
    Rotterdam Eye Hospital, Rotterdam, Netherlands
  • Carmen Ayuso
    CIBERER, ISCIII, Madrid, Spain
    Department of Genetics, University Hospital Fundacion Jimenez Diaz, Madrid, Spain
  • Francesca Simonelli
    Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
  • Footnotes
    Commercial Relationships   Francesco Testa, None; Ester Carreño, None; Koen Vermeer, None; Valentina Di lorio, None; Belen Jimenez-Rolando, None; Marianthi Karali, None; Blanca Garcia Sandoval, None; Irene Perea Romero, None; José Millán Salvador, None; Paolo Melillo, None; Sandro Banfi, None; Alberto Auricchio, None; L. Ingeborgh van den Born, None; Carmen Ayuso, None; Francesca Simonelli, None
  • Footnotes
    Support  European Union - Horizon 2020 Grant Number 754848 (Ushther Project)
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 1905. doi:
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      Francesco Testa, Ester Carreño, Koen Vermeer, Valentina Di lorio, Belen Jimenez-Rolando, Marianthi Karali, Blanca Garcia Sandoval, Irene Perea Romero, José Millán Salvador, Paolo Melillo, Sandro Banfi, Alberto Auricchio, L. Ingeborgh van den Born, Carmen Ayuso, Francesca Simonelli; Baseline characteristics of patients with Usher Syndrome due to MYO7A mutations enrolled in a prospective natural history study. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1905.

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

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Abstract

Purpose : Natural history data of Usher Syndrome (USH) due to MYO7A mutations are scarce. In view of future gene therapy studies, we assessed the natural course and investigated potential clinical endpoints in patients with USH due to MYO7A mutations.

Methods : a multicenter prospective longitudinal (two-year) natural history study was designed within Ushther project (www.ushther.eu/). Patients aged 8 years or older with USH due to MYO7A mutations and a visual acuity ≥ 20/640 in at least one eye were recruited. We assessed: best-corrected visual acuity (BCVA, ETDRS), kinetic Visual field (VF, Octopus 900), spectral domain optical coherence tomography (OCT), microperimetry (MP, MAIA), and full-field electroretinogram (ERG). Regression analysis on baseline data was performed to estimate progression with age.

Results : Forty-four patients aged 9-72 years (34.7 ± 16.1 years) were enrolled at the 3 centers. At baseline, patients showed a reduced BCVA (0.47 ± 0.30 logMAR in RE; 0.43 ± 0.32 logMAR in LE) and a constricted visual field (using V4e stimulus size: 5,436°2 ± 878°2 in RE; 5,722°2 ± 903°2 in LE). Moreover, MP showed a reduced macular sensitivity (8.2 ± 1.7 dB in RE; 8.2 ± 1.7 in LE). From preliminary analysis of OCT scans, we observed a disrupted Ellipsoid Zone (EZ) band with a mean width of 1,880 ± 329 µm in RE and of 1,842 ± 307 µm in LE. ERG responses were below noise level in all patients but five who showed markedly reduced responses in a rod-cone pattern.
Cross-sectional analysis showed a decline with age of the BCVA (at a mean annual rate of 0.015 logMAR/year equivalent to about 1 EDTRS letter / year; P<0.001), of VF (3.8%/year; P<0.001) and of macular sensitivity (-3.8%/year; P=0.003). We observed a less pronounced (P=0.099) decline of the EZ band width (-1.7%/year).
NGS analysis revealed 20 novel variants in MYO7A out of the 45 identified mutations. Missense mutations (16) were the most frequent, followed by nonsense (13). Other truncating mutations include: frameshift (8), splice variants (6) and two deletions.

Conclusions : Based on our cross-sectional data, BCVA and VF appear good outcome measures to assess progression with age in patients with USH due to MYO7A mutations. Follow-up data will be required to assess consistency of the data and further explore the role of MP and OCT, particularly, to evaluate a window of opportunity for innovative therapies.

This is a 2020 ARVO Annual Meeting abstract.

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