Retinal dysfunction characterizes subtypes of dominant optic atrophy

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.