title: Association of optic disc size with development and prognosis of Leber's hereditary optic neuropathy.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Ophthalmology, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Carolina do V F
authors.initials: Cdo V
authors.lastname: Ramos
authors.forename: Costantino
authors.initials: C
authors.lastname: Bellusci
authors.forename: Giacomo
authors.initials: G
authors.lastname: Savini
authors.forename: Michele
authors.initials: M
authors.lastname: Carbonelli
authors.forename: Adriana
authors.initials: A
authors.lastname: Berezovsky
authors.forename: Celina
authors.initials: C
authors.lastname: Tamaki
authors.forename: Rafael
authors.initials: R
authors.lastname: Cinoto
authors.forename: Paula Y
authors.initials: PY
authors.lastname: Sacai
authors.forename: Milton N
authors.initials: MN
authors.lastname: Moraes-Filho
authors.forename: Hevillin M P P
authors.initials: HM
authors.lastname: Miura
authors.forename: Maria Lucia
authors.initials: ML
authors.lastname: Valentino
authors.forename: Luisa
authors.initials: L
authors.lastname: Iommarini
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: De Negri
authors.forename: Federico
authors.initials: F
authors.lastname: Sadun
authors.forename: Pietro
authors.initials: P
authors.lastname: Cortelli
authors.forename: Pasquale
authors.initials: P
authors.lastname: Montagna
authors.forename: Solange R
authors.initials: SR
authors.lastname: Salomao
authors.forename: Alfredo A
authors.initials: AA
authors.lastname: Sadun
authors.forename: Valerio
authors.initials: V
authors.lastname: Carelli
authors.forename: Piero
authors.initials: P
authors.lastname: Barboni
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D018450:Disease Progression; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D029242:Optic Atrophy, Hereditary, Leber / Q000175:diagnosis* / Q000235:genetics; D009898:Optic Disk / Q000473:pathology*; D010375:Pedigree; D019683:Penetrance; D011379:Prognosis; D041623:Tomography, Optical Coherence
chemical_list: D004272:DNA, Mitochondrial