Two Different Nuclear Mitochondrial DNA Mutations Associated with Retinal Abnormalities

Abstract

Purpose: To report the posterior pole imaging characteristics of two patients with pathogenic nuclear mitochondrial mutations. Methods: Case reports Results: The first case, a 61-year-old patient, initially diagnosed with age-related macular degeneration, exhibited focal hyperpigmentation and increased autofluorescence in the parafoveal macula, along with geographic atrophy and mild optic nerve pallor. Optical coherence tomography (OCT) showed ellipsoid zone (EZ) attenuation, hyperreflective foci colocalizing to the hyperpigmentation, subretinal deposits, and hypertransmission defects. He was found to have a pathogenic mutation of MFN2, a gene defect associated with Charcot-Marie-Tooth disease. The second case, a 65-year-old patient presented with loss of central vision with pallor of the optic nerve. OCT imaging showed widespread loss of the interdigitation zone and EZ attenuation peripheral to the foveal region. There was thinning of the ganglion cell and nerve fiber layers. A pathogenic OPA1 mutation, the leading cause of autosomal dominant optic atrophy, was found. Both MFN2 and OPA1 produce proteins integral in mitochondrial fusion. Conclusions: The findings of these cases suggest ocular examinations may be helpful in evaluating patients with nuclear mitochondrial mutations using the near microscopic resolution of OCT. Retinal imaging may highlight structural abnormalities related to mitochondrial problems and allows direct imaging of the EZ, a layer dominated by mitochondria and a place where direct imaging of mitochondria is possible, in vivo.