title: Natural History of Conversion of Leber's Hereditary Optic Neuropathy: A Prospective Case Series.
abstract: To illustrate the natural history of Leber's hereditary optic neuropathy (LHON).
  
  
  
  Prospective observational case series.
  
  
  
  The Soave-Brazil pedigree of m.11778G>A/ND4 mitochondrial DNA LHON mutation.
  
  
  
  A prospectively acquired database of the Soave-Brazil pedigree was reviewed. Data from 285 individuals were included in the database over a 15-year period. The pedigree was reviewed for unaffected mutation carriers who converted to affected status, 6 patients with LHON were identified. The medical records were reviewed 1 year preconversion to 1 year postconversion for visual acuity (logarithm of the minimum angle of resolution [logMAR]), Humphrey Visual Field (HVF) mean deviation (MD), and retinal nerve fiber layer (RNFL) thickness, as measured by Cirrus (Carl Zeiss, Oberkochen, Germany) optic coherence tomography (OCT). The RNFL thickness values were normalized for age. Visual acuity, HVF, and processed RNFL data from each of the 12 eyes were then sorted into 2-month time periods relative to the date of conversion, within which they were averaged.
  
  
  
  The main outcome measures were visual acuity, HVF MD, and RNFL thickness.
  
  
  
  Decreased visual acuity preceded conversion by up to 2 months and then declined up to 8 months postconversion. Decrease in HVF MD occurred at least 4 months preceding conversion, after which values decreased until plateau at 6 to 8 months. Average RNFL thickness was above normal baseline thickness in all 4 quadrants as measured by OCT at the time of conversion. Increase in RNFL thickness preceded conversion as early as 4 to 6 months, peaked at conversion, and decreased until individual plateaus. The temporal quadrant was first to be involved, then the inferior and superior quadrants, and the nasal quadrant showed the latest and least changes.
  
  
  
  Subclinical changes preceded the date of conversion and may reflect the complicated nature of identifying the date of conversion in LHON. Early increases in RNFL preceding conversion suggest that structural changes precede clinically significant vision loss. Asynchronous quadrant involvement supports a previously published mathematical model. The natural history of LHON is not a subacute process, as previously believed, but progresses more slowly, taking up to 8 months to plateau.
authors.affiliation: Doheny Eye Institute, University of California Los Angeles, Los Angeles, California.
authors.forename: Tiffany Jean
authors.initials: TJ
authors.lastname: Hwang
authors.affiliation: Doheny Eye Institute, University of California Los Angeles, Los Angeles, California; Doheny Eye Center, Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, California; Ottawa Eye Institute, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Health Research Institute, Ottawa, Ontario, Canada.
authors.forename: Rustum
authors.initials: R
authors.lastname: Karanjia
authors.affiliation: Instituto de Olhos de Colatina, Colatina, Espírito Santo, Brazil.
authors.forename: Milton Nunes
authors.initials: MN
authors.lastname: Moraes-Filho
authors.affiliation: Surgery and Anaesthesia, University of Otago, Wellington, New Zealand.
authors.forename: Jesse
authors.initials: J
authors.lastname: Gale
authors.affiliation: Doheny Eye Institute, University of California Los Angeles, Los Angeles, California.
authors.forename: Jeffrey Show
authors.initials: JS
authors.lastname: Tran
authors.affiliation: Doheny Eye Institute, University of California Los Angeles, Los Angeles, California.
authors.forename: Edward R
authors.initials: ER
authors.lastname: Chu
authors.affiliation: Departamento de Oftalmologia e Ciências Visuais, Escola Paulista de Medicina, Universidade Federal de São Paulo, Hospital São Paulo, São Paulo, Brasil.
authors.forename: Solange R
authors.initials: SR
authors.lastname: Salomao
authors.affiliation: Departamento de Oftalmologia e Ciências Visuais, Escola Paulista de Medicina, Universidade Federal de São Paulo, Hospital São Paulo, São Paulo, Brasil.
authors.forename: Adriana
authors.initials: A
authors.lastname: Berezovsky
authors.affiliation: Departamento de Oftalmologia e Ciências Visuais, Escola Paulista de Medicina, Universidade Federal de São Paulo, Hospital São Paulo, São Paulo, Brasil; Instituto Paulista da Visão, São Paulo, Brasil.
authors.forename: Rubens
authors.initials: R
authors.lastname: Belfort
authors.affiliation: Instituto de Olhos de Colatina, Colatina, Espírito Santo, Brazil.
authors.forename: Milton Nunes
authors.initials: MN
authors.lastname: Moraes
authors.affiliation: Department of Ophthalmology, Ospedale Parodi Delfino, Colleferro, Rome, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Sadun
authors.affiliation: Azienda Ospedaliera San Camillo-Forlanini, Roma, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: DeNegri
authors.affiliation: IRCCS Institute of Neurological Sciences of Bologna, Bellaria Hospital, Bologna, Italy; Neurology Unit, Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: La Morgia
authors.affiliation: Studio Oculistico d'Azeglio, Bologna, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Barboni
authors.affiliation: Hospital Federal da Lagoa, Rio de Janeiro, Brazil.
authors.forename: Carolina do V F
authors.initials: CDVF
authors.lastname: Ramos
authors.affiliation: Doheny Eye Institute, University of California Los Angeles, Los Angeles, California.
authors.forename: Carlos Filipe
authors.initials: CF
authors.lastname: Chicani
authors.affiliation: Doheny Eye Institute, University of California Los Angeles, Los Angeles, California; Doheny Eye Center, Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, California.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Quiros
authors.affiliation: IRCCS Institute of Neurological Sciences of Bologna, Bellaria Hospital, Bologna, Italy; Neurology Unit, Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Carelli
authors.affiliation: Doheny Eye Institute, University of California Los Angeles, Los Angeles, California; Doheny Eye Center, Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, California. Electronic address: sadun@jsei.ucla.edu.
authors.forename: Alfredo A
authors.initials: AA
authors.lastname: Sadun
mesh_terms: D000293:Adolescent; D000328:Adult; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology*; D029242:Optic Atrophy, Hereditary, Leber / Q000175:diagnosis* / Q000235:genetics; D010375:Pedigree; D011446:Prospective Studies; D012165:Retinal Ganglion Cells / Q000473:pathology*; D041623:Tomography, Optical Coherence; D014786:Vision Disorders / Q000175:diagnosis* / Q000503:physiopathology; D014792:Visual Acuity / Q000502:physiology; D058609:Visual Field Tests; D014794:Visual Fields / Q000502:physiology*; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial