title: Natural history of Leber's hereditary optic neuropathy: longitudinal analysis of the retinal nerve fiber layer by optical coherence tomography.
abstract: OBJECTIVE
  To investigate by optical coherence tomography (OCT) the topographic pattern and temporal sequence of fiber loss in the peripapillary retinal nerve fiber layer (RNFL) of patients with Leber's hereditary optic neuropathy (LHON) in a longitudinal follow-up.
  
  
  METHODS
  Cohort study.
  
  
  METHODS
  Six eyes of 4 patients with molecularly defined LHON were enrolled before the subacute period of visual loss.
  
  
  METHODS
  Subjects were studied by StratusOCT (Carl Zeiss Meditec, Inc., Dublin, CA) during a 9-month follow-up starting from the presymptomatic stage of the disease. Examinations were carried out at 4 different time points: presymptomatic stage, time of visual loss, and 3 and 9 months later.
  
  
  METHODS
  Peripapillary RNFL thickness for each quadrant of the optic nerve. Statistical comparisons were performed by ordinary analysis of variance with Dunnett's post-test.
  
  
  RESULTS
  A significant increase of RNFL thickness was detected in the temporal and inferior quadrants between the presymptomatic stage and the disease onset (P<0.05). The 360-degree average and the superior and nasal quadrants showed a nonstatistically significant increase of thickness at this time. In the 360-degree average (P<0.01), superior (P<0.01), nasal (P<0.05), and inferior (P<0.01) quadrants, RNFL thickening showed statistically significant changes between the presymptomatic stage and the 3-month follow-up. At 3 months, a nonsignificant reduction of RNFL thickness was detected in the temporal quadrant. A significant reduction of RNFL was detected in all but the nasal quadrants between the presymptomatic stage and the 9-month Follow-up.
  
  
  CONCLUSIONS
  The RNFL thickness increase first appeared at the temporal and inferior quadrants. Conversely, at 3 months the thickening fibers were more evident in the superior and nasal quadrants. These findings are consistent with the established preferential early involvement of the papillomacular bundle in LHON. We also demonstrated the previously unrecognized simultaneous early involvement of the inferior quadrant. The late involvement of both superior and nasal quadrants suggests a dynamic evolution of the acute stage that continues for 3 months and may represent a therapeutic window of opportunity.
authors.affiliation: Studio Oculistico d'Azeglio, Bologna, Italy. p.barboni@studiodazeglio.it
authors.forename: Piero
authors.initials: P
authors.lastname: Barboni
authors.forename: Michele
authors.initials: M
authors.lastname: Carbonelli
authors.forename: Giacomo
authors.initials: G
authors.lastname: Savini
authors.forename: Carolina do V F
authors.initials: Cdo V
authors.lastname: Ramos
authors.forename: Arturo
authors.initials: A
authors.lastname: Carta
authors.forename: Adriana
authors.initials: A
authors.lastname: Berezovsky
authors.forename: Solange R
authors.initials: SR
authors.lastname: Salomao
authors.forename: Valerio
authors.initials: V
authors.lastname: Carelli
authors.forename: Alfredo A
authors.initials: AA
authors.lastname: Sadun
mesh_terms: D000328:Adult; D005500:Follow-Up Studies; D006801:Humans; D009412:Nerve Fibers / Q000473:pathology*; D029242:Optic Atrophy, Hereditary, Leber / Q000175:diagnosis*; D009900:Optic Nerve / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000473:pathology*; D041623:Tomography, Optical Coherence; D014792:Visual Acuity