Optic Nerve Head Morphology in Unaffected Carriers of Leber’s Hereditary Optic Neuropathy Suggests that Optic Disc Size Influences Disease Expression

Abstract

Purpose: : To analyze by OCT the Optic Nerve Head (ONH) in unaffected carriers of Leber’s Hereditary Optic Neuropathy (LHON) belonging to two different cohorts.

Methods: : 58 Italian carriers (mean age: 38.8±16.6 years) from 24 unrelated pedigrees with LHON, as defined by the presence of a pathogenic mtDNA point mutation, and 39 carriers (mean age: 39.0±13.7 years) belonging to the same Brazilian maternal lineage (SOA–BR family) of Italian ancestry were compared respectively to age–matched control groups of 88 Italian and 35 Brazilian individuals. Stratus OCT was used to analyze the ONH (Fast optic disc acquisition protocol). One randomly selected eye was considered for each carrier and control individual. Groups were compared by one–way ANOVA analysis of variance.

Results: : The ONH analysis of Italian carriers showed a significantly increased optic disk area (p=0.007) and vertical disk diameter (p=0.029) compared to Italian controls. Similarly, the ONH analysis of Brazilian carriers showed the same tendency of increased optic disk area (p=0.07) and a significantly increase vertical disk diameter (p=0.04) compared to Brazilian control.

Conclusions: : The OCT analysis of ONH morphology in unaffected LHON mutation carriers belonging to two different cohorts, the former composed by cases from unrelated Italian pedigrees and different LHON mutations and the latter composed by homogeneous series of cases from the same Brazilian family, showed a strikingly similar result. The optic disk size in unaffected carriers of LHON is larger than the mean size in the general population. The OCT objective measurement of this anatomical factor supports the previously proposed hypothesis that the anatomical size of the optic disk may influence the clinical expression of LHON.

Keywords: neuro-ophthalmology: optic nerve • optic disc