Optic Nerve Head Morphology in Patients With OPA1-Related Dominant Optic Atrophy Suggests That OPA1 Influences Its Anatomical Conformation

Abstract

Purpose:: To analyze by OCT the Optic Nerve Head (ONH) morphology and retinal nerve fiber layer (RNFL) thickness in patients with Dominant Optic Atrophy (DOA) associated with mutations in the OPA1 gene.

Methods:: We have investigated 30 patients with DOA (mean age: 37.4±20.1 years) from 15 pedigrees, which were positive for the presence of OPA1 gene mutations, and compared them with to an age-matched control group of 57 individuals. Stratus OCT was used to detect the peripapillary RNFL thickness (RNFL thickness 3.4 acquisition protocol) and measure the ONH morphology (Fast optic disc acquisition protocol). One randomly selected eye was considered for each patient and control individual. RNFL thickness values and ONH measurements were compared by one-way analysis of variance (ANOVA) and multiple comparisons post-test.

Results:: The ONH analysis of DOA patients showed a significantly smaller optic disc area (p<0.0001), vertical (p<0.0001) and horizontal disc diameter (p<0.0001), and rim area (p<0.0001) compared to controls. The cup area was significantly increased (p=0.001) compared to controls. Furthermore, the DOA patients showed decreased RNFL thickness values in the temporal (p<0,0001), superior (p<0,0001), nasal (p<0,0001) and inferior (p<0,0001) quadrants compared to the control group.

Conclusions:: Our results with atrophic DOA patients indicate a loss of axons involving all quadrants. This pattern is different from optic atrophy in LHON, which was shown to partially spare the nasal quadrant. The ONH measurements showed that DOA patients present with a significantly smaller anatomical conformation of ONH compared to the size variability observed in a control population. This observation may suggest that OPA1 gene is involved in the ONH anatomical conformation. Recent studies emphasized the relevance of OPA1 gene in regulating apoptosis. Thus physiological apoptosis during optic nerve embryonic development may result altered by mutations in the OPA1 gene, ultimately leading to a smaller ONH.

Keywords: neuro-ophthalmology: optic nerve • optic disc • mitochondria