OPA1 sequencing analysis and detailed ophthalmic examinations including the investigation of microcystic macular edema in 18 patients with bilateral optic atrophy

Abstract

Purpose: Autosomal dominant optic atrophy (ADOA), also known as Kjer’s disease, is the most common hereditary ocular neuropathy. ADOA is characterized by a decrease in the visual acuity that develops in childhood, temporal palor of the optic discs, centrocecal scotoma, and color vision defects. The purpose of this study was to distinguish patients with ADOA and optic atrophy with unknown origin by comparing the results of OPA1 sequencing analysis and clinical characteristics of the patients.

Methods: 18 patients with bilateral optic atrophy underwent detailed ophthalmic examinations. The ophthalmological examinations included measurements of the best-corrected visual acuity, fundus photography, perimetry, SD-OCT analysis of nerve fiber layer thickness, color vision test, differences of severity between right and left eyes, and investigation of microcystic macular edema (MME) in SD-OCT. 12 patients underwent an adaptive optics analysis for detailed examination of MME. Mutational screening of all coding and flanking intron sequences of the OPA1 gene in 18 patients was performed by sanger DNA sequencing.

Results: We have identified pathological mutations of OPA1 gene in 7 patients from 5 families. All patients with OPA1 mutation revealed temporal palor of optic discs, centrocecal scotoma or blind spot enlargement binoculary. 6 patients with OPA1 mutation showed color vision deficiency. All patients with OPA1 mutation revealed very thin retinal nerve fiber layer between optic nerve and macular by a vertical SD-OCT scan at about 1 mm from the edge of optic disc. Majority of patients without OPA1 mutation lack some of these observations commonly found in patients with OPA1 mutation. MME in SD-OCT was found in 2 patients with OPA1 mutation and 2 patients without OPA1 mutation. Adaptive optics analysis revealed MME in 2 patients with OPA1 mutation and 2 patients without OPA1 mutation.

Conclusions: A vertical SD-OCT scan at about 1 mm from the edge of optic disc is useful way to visualize and evaluate the temporal palor of optic disc that is a remarkable feature of ADOA. MME were identified in both groups with and without OPA1 mutation. Since sanger sequencing could not detect a large deletion of the gene, further studies such as multiplex ligation-dependent probe amplification will be needed.