Retinal dysfunction characterizes subtypes of dominant optic atrophy

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

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).

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.

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.