July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Understanding the onset of Leber's Hereditary Optic Neuropathy
Author Affiliations & Notes
  • Rustum Karanjia
    Ophthalmology, University of Ottawa, Ottawa, Ontario, Canada
    Ophthalmology, UCLA, Los Angeles, California, United States
  • Henry Liu
    Ophthalmology, University of Ottawa, Ottawa, Ontario, Canada
  • Chiara La Morgia
    IRCCS Institute of Neurologica Sciences of Bologna, Bologna, Italy
  • Samir Nazarali
    Ophthalmology, University of Ottawa, Ottawa, Ontario, Canada
  • Milton Moraes Filho
    Instituto de Olhos de Colatina, Colatina, Brazil
  • Michele Carbonelli
    IRCCS Institute of Neurologica Sciences of Bologna, Bologna, Italy
  • Adriana Berezovsky
    Departamento de Oftalmologia e Ciências Visuais, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), Sao Paulo, Brazil
  • Lidia Di Vito
    IRCCS Institute of Neurologica Sciences of Bologna, Bologna, Italy
  • Anna Maria De Negri
    S. Camillo-Forlanini Hospital, Rome, Italy
  • Carolina Ramos
    Hospital Federal da Lagoa, Rio de Janeiro, Brazil
  • Alexander Liam
    Ophthalmology, University of Ottawa, Ottawa, Ontario, Canada
  • Rubens Belfort Jr
    Departamento de Oftalmologia e Ciências Visuais, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), Sao Paulo, Brazil
  • Solange Salomao
    Departamento de Oftalmologia e Ciências Visuais, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), Sao Paulo, Brazil
  • Patrick Yu-Wai-Man
    University of Cambridge, Cambridge, United Kingdom
  • Alfredo A Sadun
    Ophthalmology, UCLA, Los Angeles, California, United States
  • Valerio Carelli
    IRCCS Institute of Neurologica Sciences of Bologna, Bologna, Italy
  • Footnotes
    Commercial Relationships   Rustum Karanjia, None; Henry Liu, None; Chiara La Morgia, None; Samir Nazarali, None; Milton Moraes Filho, None; Michele Carbonelli, None; Adriana Berezovsky, None; Lidia Di Vito, None; Anna Maria De Negri, None; Carolina Ramos, None; Alexander Liam, None; Rubens Belfort Jr, None; Solange Salomao, None; Patrick Yu-Wai-Man, None; Alfredo Sadun, None; Valerio Carelli, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3356. doi:
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      Rustum Karanjia, Henry Liu, Chiara La Morgia, Samir Nazarali, Milton Moraes Filho, Michele Carbonelli, Adriana Berezovsky, Lidia Di Vito, Anna Maria De Negri, Carolina Ramos, Alexander Liam, Rubens Belfort Jr, Solange Salomao, Patrick Yu-Wai-Man, Alfredo A Sadun, Valerio Carelli; Understanding the onset of Leber's Hereditary Optic Neuropathy. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3356.

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

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Abstract

Purpose : Leber’s hereditary optic neuropathy (LHON) is an inherited mitochondrial disease characterized by asynchronous subacute vision loss. The purpose of this study was to determine if there was a correlation between age of onset and synchronicity of vision loss and the different mutation types.

Methods : Age of onset, unilateral versus bilateral presentation, interval between first and second eye involvement, and the mtDNA mutations were retrieved from clinical registries at the investigators' institutions.

Results : Clinical data from 370 LHON patients with classical LHON mutations were evaluated (m.11778G>A, n = 245; m.3460G>A, n = 40; m.14484T>C, n = 47; non-dominant mutations, n = 38). Bilateral eye involvement was clinically documented in 98.3% of cases with 50.3% of all patients demonstrating sequential onset. In these latter cases the median inter-eye delay was 12 weeks. The m.14484T>C mutation resulted in the lowest age at onset (19.1 ± 10.5 years) compared to m.11778G>A (26.2 ± 15.0 years), m.3460G>A (20.9 ± 14.5 years) and non-dominant mutations (22.9 ± 12.1 years) (p < 0.05). The M:F ratio for m.11778G>A, m.3460G>A, m.14484T>C and non-dominant mutations were 3.6:1, 1.7:1, 4.9:1 and 3.8:1 respectively. Interestingly, the m.14484T>C mutation exhibited more simultaneous onset than sequential onsets compared with the other mutation subtypes (p <0.001). Moreover, m.14484T>C showed a shorter and more reproducible interval between eyes (inter-eye onset range = 1–44 weeks) versus m.11778G>A (range = 1–2016 weeks), m.3460G>A (range = 2–816 weeks), non-dominant mutations (range = 1–108 weeks) for sequential presentations.

Conclusions : The m.14484T>C mutation, though least penetrant, manifested at an earlier age and resulted in a smaller inter-eye delay interval range and higher incidence of simultaneous involvement compared to the other classical and non-dominant mutations in LHON.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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