title: Axonal loss occurs early in dominant optic atrophy.
abstract: OBJECTIVE
  This study set out to investigate retinal nerve fibre layer (RNFL) thickness and best corrected visual acuity (BCVA) in relation to age in healthy subjects and patients with OPA1 autosomal dominant optic atrophy (DOA).
  
  
  METHODS
  We carried out a cross-sectional investigation of RNFL thickness and ganglion cell layer density in 30 healthy subjects and 10 patients with OPA1 DOA using optical coherence tomography (OCT). We then performed a regression analysis of RNFL thickness and BCVA versus age.
  
  
  RESULTS
  Both healthy subjects and DOA patients demonstrated a gradual reduction in RNFL thickness with age; the relationship was best described statistically by a model that assumed a constant offset between the two groups. Best corrected VA decreased significantly with age in DOA patients, in whom BCVA was correlated with peripapillary RNFL thickness in the inferior and superior peripapillary quadrants and with total macular thickness at eccentricities of 500-3000 microm. The observations were best described by a constant offset of 41.9 microm separating the two groups and an annual decrease in RNFL thickness of 0.48 microm (p < 0.0001). In patients with DOA, increasing age was associated with decreasing BCVA (p = 0.046).
  
  
  CONCLUSIONS
  This cross-sectional study found evidence of comparable age-related decreases in RNFL thickness in healthy subjects and in DOA patients, where the deficit in DOA patients is best described using a model that assumes the deficit between the groups does not vary with age. The gradual reduction of BCVA with age may be a consequence of a relative deficit in RNFL thickness that is established before the second decade of life.
authors.affiliation: Department of Ophthalmology, Glostrup Hospital, University of Copenhagen, Denmark. danmil01@glo.regionh.dk <danmil01@glo.regionh.dk>
authors.forename: Dan
authors.initials: D
authors.lastname: Milea
authors.forename: Birgit
authors.initials: B
authors.lastname: Sander
authors.forename: Marianne
authors.initials: M
authors.lastname: Wegener
authors.forename: Hanne
authors.initials: H
authors.lastname: Jensen
authors.forename: Birgit
authors.initials: B
authors.lastname: Kjer
authors.forename: Thomas Martini
authors.initials: TM
authors.lastname: Jørgensen
authors.forename: Henrik
authors.initials: H
authors.lastname: Lund-Andersen
authors.forename: Michael
authors.initials: M
authors.lastname: Larsen
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000502:physiology; D001369:Axons / Q000473:pathology*; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D016368:Frameshift Mutation; D020558:GTP Phosphohydrolases / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D029241:Optic Atrophy, Autosomal Dominant / Q000235:genetics / Q000473:pathology*; D009898:Optic Disk / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000473:pathology*; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology; D055815:Young Adult
chemical_list: D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human