Pattern of retinal ganglion cell loss in dominant optic atrophy due to OPA1 mutations

Abstract

The majority of patients with autosomal dominant optic atrophy (DOA) harbour pathogenic OPA1mutations. Although DOA is characterised by the preferential loss of retinal ganglion cells (RGCs), about 20% of patients with OPA1mutations will develop a more severe disease variant (DOA+), with additional neuromuscular features. In this prospective, observational case series, optical coherence tomography (OCT) was used to define the pattern of retinal nerve fibre layer (RNFL) loss in patients with both the pure and syndromal forms of DOA. Forty patients with a molecular diagnosis of DOA due to OPA1mutations were prospectively recruited from our neuro-ophthalmology clinic: 26 patients with isolated optic atrophy and 14 patients manifesting DOA+ features. Peripapillary RNFL thickness was measured with the Fast RNFL (3.4) acquisition protocol on a Stratus OCT. There was a statistically significant reduction in average RNFL thickness in the OPA1group compared with normal controls (PP<0.0001). RGC loss in DOA is characterised by severe involvement of the temporal papillomacular bundle, with relative sparing of the nasal fibres. RNFL thinning is more pronounced in patients with DOA+ phenotypes.