Retinal dysfunction characterizes subtypes of dominant optic atrophy

Acta Ophthalmol. 2018 Mar;96(2):e156-e163. doi: 10.1111/aos.13557. Epub 2017 Sep 19.


Purpose: To assess preganglionic retinal function using multifocal electroretinogram (mfERG) in patients affected by dominant optic atrophy (DOA) stratified by OPA1 gene mutation.

Methods: Multifocal electroretinogram (mfERG) was recorded in 18 DOA patients (DOA group, 35 eyes) and 25 age-matched healthy subjects (control group, 25 eyes). Patients were stratified in two groups based on gene mutation: missense mutation (DOA-M group, 11 eyes) and mutation causing haploinsufficiency (DOA-H group, 24 eyes). The mfERG N1-P1 response amplitude density (RAD) has been evaluated in five annular retinal areas with different eccentricity from the fovea (ring 1: 0-5 degrees, R1; ring 2: 5-10 degrees, R2; ring 3: 10-15 degrees, R3; ring 4: 15-20 degrees, R4; and ring 5: 20-25 degrees, R5) and in eight sectors on the basis of the retinal topography: temporal-superior (TS), temporal-inferior (TI), nasal-superior (NS) and nasal-inferior (NI), temporal (T), superior (S), nasal (N) and inferior (I).

Results: Compared to controls, DOA group revealed a significant reduction in N1-P1 RADs values in R1-R4 rings and in TI, NS and N sectors [analysis of variance (ANOVA), p < 0.01). DOA-M group showed a significant reduction in N1-P1 RADs values in R1-R5 rings and in TI, NS, NI, T, N and I sectors (p < 0.01). Dominant optic atrophy-H (DOA-H) group displayed only a significant (p < 0.01) reduction in N1-P1 RADs values, exclusively in R1 and in the NS sector.

Conclusion: Preganglionic retinal impairment occurs in DOA with a clear genotype to retinal dysfunction association. Missense mutations are characterized by a far more severe functional impairment.

Keywords: OPA1 gene; dominant optic atrophy; multifocal electroretinogram; photoreceptors; retinal topography.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Electroretinography
  • Female
  • GTP Phosphohydrolases / genetics
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Optic Atrophy, Autosomal Dominant / diagnosis*
  • Optic Atrophy, Autosomal Dominant / genetics
  • Retina / physiopathology*
  • Retinal Diseases / diagnosis*
  • Retinal Ganglion Cells / pathology*
  • Visual Fields


  • GTP Phosphohydrolases
  • OPA1 protein, human