Understanding the onset of Leber's Hereditary Optic Neuropathy

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.