Association of optic disc size with development and prognosis of Leber's hereditary optic neuropathy

Invest Ophthalmol Vis Sci. 2009 Apr;50(4):1666-74. doi: 10.1167/iovs.08-2695. Epub 2008 Dec 20.


Purpose: To study the optic nerve head (ONH) morphology of patients with Leber's hereditary optic neuropathy (LHON) in a large family from Brazil carrying the 11778/ND4 mutation and in a case series of unrelated Italian families bearing different mitochondrial DNA (mtDNA) pathogenic mutations.

Methods: Enrolled in the study were 15 LHON-affected patients (LHON-affected) and 45 LHON unaffected mutation carriers (LHON carriers) belonging to the previously reported Brazilian SOA-BR LHON pedigree and 56 LHON-affected and 101 LHON carriers from 45 unrelated LHON Italian pedigrees molecularly defined. The LHON-affected were subgrouped according to the extent of visual recovery. All individuals underwent optic nerve head (ONH) analysis by optical coherence tomography.

Results: In the Brazilian sample, the mean optic disc area was significantly larger in LHON carriers than in the control group (P=0.002). In the Italian sample, the mean optic disc area and vertical disc diameter were significantly higher in LHON carriers than in both LHON-affected (respectively, P=0.008 and P<0.001) and control subjects (P<0.001 in both cases). The LHON-affected with visual recovery had a significantly larger vertical disc diameter when compared with those without visual recovery (P=0.03).

Conclusions: The results, revealing that the ONH size is larger in LHON carriers than in LHON-affected, suggest a protective role for this anatomic trait. Such a hypothesis is reinforced by the observation that, among the LHON-affected, larger discs correlated with visual recovery and better visual outcome. The findings may be relevant for prognosis and provide a mechanism for identifying nuclear-modifying genes implicated in the variability of penetrance in LHON.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • DNA Mutational Analysis
  • DNA, Mitochondrial / genetics
  • Disease Progression
  • Female
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Optic Atrophy, Hereditary, Leber / diagnosis*
  • Optic Atrophy, Hereditary, Leber / genetics
  • Optic Disk / pathology*
  • Pedigree
  • Penetrance
  • Prognosis
  • Tomography, Optical Coherence


  • DNA, Mitochondrial