Josef Finsterer1, Michelangelo Mancuso2, Davide Pareyson3, Jean-Marc Burgunder4, Thomas Klopstock5. 1. Krankenanstalt Rudolfstiftung, Vienna, Austria. Electronic address: fifigs1@yahoo.de. 2. Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, Italy. 3. Department of Clinical Neurosciences, C. Besta Neurological Institute, IRCCS Foundation, Milan, Italy. Electronic address: davide.pareyson@istituto-besta.it. 4. Department of Neurology, University of Bern, Switzerland; Department of Neurology, Sun Yat Sen University, Guangzhou, China; Department of Neurology, Sichuan University, Chendgu, China. Electronic address: jmburgunder@bluewin.ch. 5. Department of Neurology, Friedrich-Baur Institute, Ludwig-Maximilians-Universität München, Munich, Germany; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany. Electronic address: Thomas.Klopstock@med.LMU.de.
Abstract
OBJECTIVES: To summarise and discuss recent findings and future perspectives concerning mitochondrial disorders (MIDs) affecting the retinal ganglion cells and the optic nerve (mitochondrial optic neuropathy. MON). METHOD: Literature review. RESULTS: MON in MIDs is more frequent than usually anticipated. MON may occur in specific as well as non-specific MIDs. In specific and non-specific MIDs, MON may be a prominent or non-prominent phenotypic feature and due to mutations in genes located either in the mitochondrial DNA (mtDNA) or the nuclear DNA (nDNA). Clinically, MON manifests with painless, bilateral or unilateral, slowly or rapidly progressive visual impairment and visual field defects. In some cases, visual impairment may spontaneously recover. The most frequent MIDs with MON include LHON due to mutations in mtDNA-located genes and autosomal dominant optic atrophy (ADOA) or autosomal recessive optic atrophy (AROA) due to mutations in nuclear genes. Instrumental investigations for diagnosing MON include fundoscopy, measurement of visual acuity, visual fields, and color vision, visually-evoked potentials, optical coherence tomography, fluorescein angiography, electroretinography, and MRI of the orbita and cerebrum. In non-prominent MON, work-up of the muscle biopsy with transmission electron microscopy may indicate mitochondrial destruction. Treatment is mostly supportive but idebenone has been approved for LHON and experimental approaches are promising. CONCLUSIONS: MON needs to be appreciated, requires extensive diagnostic work-up, and supportive treatment should be applied although loss of vision, as the most severe outcome, can often not be prevented.
OBJECTIVES: To summarise and discuss recent findings and future perspectives concerning mitochondrial disorders (MIDs) affecting the retinal ganglion cells and the optic nerve (mitochondrial optic neuropathy. MON). METHOD: Literature review. RESULTS: MON in MIDs is more frequent than usually anticipated. MON may occur in specific as well as non-specific MIDs. In specific and non-specific MIDs, MON may be a prominent or non-prominent phenotypic feature and due to mutations in genes located either in the mitochondrial DNA (mtDNA) or the nuclear DNA (nDNA). Clinically, MON manifests with painless, bilateral or unilateral, slowly or rapidly progressive visual impairment and visual field defects. In some cases, visual impairment may spontaneously recover. The most frequent MIDs with MON include LHON due to mutations in mtDNA-located genes and autosomal dominant optic atrophy (ADOA) or autosomal recessive optic atrophy (AROA) due to mutations in nuclear genes. Instrumental investigations for diagnosing MON include fundoscopy, measurement of visual acuity, visual fields, and color vision, visually-evoked potentials, optical coherence tomography, fluorescein angiography, electroretinography, and MRI of the orbita and cerebrum. In non-prominent MON, work-up of the muscle biopsy with transmission electron microscopy may indicate mitochondrial destruction. Treatment is mostly supportive but idebenone has been approved for LHON and experimental approaches are promising. CONCLUSIONS: MON needs to be appreciated, requires extensive diagnostic work-up, and supportive treatment should be applied although loss of vision, as the most severe outcome, can often not be prevented.