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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. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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.
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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