title: Retinal nerve fiber layer thickness variability in Leber hereditary optic neuropathy carriers.
abstract: OBJECTIVE
  Recent investigations suggested that unaffected carriers of Leber hereditary optic neuropathy (LHON) may show subclinical visual alterations. Structural changes have also been detected by optical coherence tomography (OCT), which revealed a temporal thickening of the retinal nerve fiber layer (RNFL). These changes may reflect compensatory effects such as mitochondria accumulation within the RNFL axons. This study aimed to investigate whether the RNFL of LHON carriers shows greater than expected thickness variations, which may reflect transient subclinical changes, over the course of years.
  
  
  METHODS
  Using Stratus OCT, the RNFL thickness was measured yearly from 2005 to 2008 in 24 Brazilian LHON carriers, all with homoplasmic 11778/ND4 mtDNA mutation. An Italian sample of 20 healthy subjects served as a control. Data were compared also to a previously published sample (n=59) of glaucomatous eyes.
  
  
  RESULTS
  The LHON carriers showed test-retest standard deviations that were larger than normal controls in the temporal (p=0.004), superior (p&lt;0.0001), and inferior quadrants (p=0.019). Compared to the glaucoma cases, no statistical differences were observed.
  
  
  CONCLUSIONS
  The RNFL thickness in LHON carriers, when measured at different time points, has higher variability than in normal subjects. Transitory RNFL swelling may be caused either by compensatory mechanisms (increased mitochondrial biogenesis) or by axonal stasis preceding decompensation of retinal ganglion cells. In both situations, these changes may represent the origin of the visual alterations previously detected in LHON carriers. Alternatively, increased variability of RNFL thickness may be influenced by the LHON microangiopathy, as retinal blood vessels contribute to the OCT RNFL thickness measurements.
authors.affiliation: 2 Dipartimento di Scienze Neurologiche, Università di Bologna, Bologna - Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Barboni
authors.forename: Giacomo
authors.initials: G
authors.lastname: Savini
authors.forename: William J
authors.initials: WJ
authors.lastname: Feuer
authors.forename: Donald L
authors.initials: DL
authors.lastname: Budenz
authors.forename: Michele
authors.initials: M
authors.lastname: Carbonelli
authors.forename: Filipe
authors.initials: F
authors.lastname: Chicani
authors.forename: Carolina Do V F
authors.initials: Cdo V
authors.lastname: Ramos
authors.forename: Solange R
authors.initials: SR
authors.lastname: Salomao
authors.forename: Annamaria De
authors.initials: AD
authors.lastname: Negri
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Parisi
authors.forename: Valerio
authors.initials: V
authors.lastname: Carelli
authors.forename: Alfredo A
authors.initials: AA
authors.lastname: Sadun
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009412:Nerve Fibers / Q000473:pathology*; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics* / Q000473:pathology*; D009929:Organ Size; D012165:Retinal Ganglion Cells / Q000473:pathology*; D041623:Tomography, Optical Coherence / Q000379:methods; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial