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  • Review Article
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Treatment of hereditary optic neuropathies

Nature Reviews Neurology volume 8, pages 545–556 (2012)Cite this article

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Abstract

The hereditary optic neuropathies are inherited disorders in which optic nerve dysfunction is a prominent feature in the phenotypic expression of disease. Optic neuropathy may be primarily an isolated finding, such as in Leber hereditary optic neuropathy and dominant optic atrophy, or part of a multisystem disorder. The pathophysiological mechanisms underlying the hereditary optic neuropathies involve mitochondrial dysfunction owing to mutations in mitochondrial or nuclear DNA that encodes proteins essential to mitochondrial function. Effective treatments are limited, and current management includes therapies directed at enhancing mitochondrial function and preventing oxidative damage, as well as genetic counselling, and supportive and symptomatic measures. New therapies, including gene therapy, are emerging via animal models and human clinical trials. Leber hereditary optic neuropathy, in particular, provides a unique model for testing promising treatments owing to its characteristic sequential bilateral involvement and the accessibility of target tissue within the eye. Lessons learned from treatment of the hereditary optic neuropathies may have therapeutic implications for other disorders of presumed mitochondrial dysfunction. In this Review, the natural history of the common inherited optic neuropathies, the presumed pathogenesis of several of these disorders, and the literature to date regarding potential therapies are summarized.

Key Points

  • Hereditary optic neuropathies include those disorders in which optic nerve dysfunction is typically isolated and those in which optic neuropathy features prominently within a multisystem neurological or systemic disorder

  • The two most common hereditary optic neuropathies are Leber hereditary optic neuropathy (caused by point mutations in mitochondrial DNA) and dominant optic atrophy (caused by nuclear DNA abnormalities)

  • Mitochondrial dysfunction has a central role in the pathogenesis of most, if not all, of the inherited optic neuropathies

  • Current treatments for hereditary optic neuropathies are limited, but include therapies that purportedly enhance mitochondrial function and prevent oxidative damage, such as idebenone

  • Gene therapy seems promising, and may be particularly suited for patients with Leber hereditary optic neuropathy who exhibit a 'window of opportunity' for directed ocular treatment before second eye involvement

  • Supportive, preventive and symptomatic measures, combined with informed genetic counselling, remain of paramount importance in the management of patients with hereditary optic neuropathies

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Figure 1: Clinical investigation in a patient with dominant optic atrophy.
Figure 2: Nuclear and mitochondrial DNA influences on mitochondrial function.

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Acknowledgements

This study was supported in part by an unrestricted departmental grant (Department of Ophthalmology, Emory University, Atlanta, GA, USA) from Research to Prevent Blindness Inc., New York. N. Newman is a recipient of the Research to Prevent Blindness Lew R. Wasserman Merit Award.

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  1. Department of Ophthalmology, Neuro-ophthalmology Unit, Neurology and Neurological Surgery, Emory University School of Medicine, 1365-B Clifton Road NE, Atlanta, 30322, GA, USA

    Nancy J. Newman

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N. J. Newman has acted as a consultant for Santhera Pharmaceuticals.

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Newman, N. Treatment of hereditary optic neuropathies. Nat Rev Neurol 8, 545–556 (2012). https://doi.org/10.1038/nrneurol.2012.167

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