Leber Hereditary Optic Neuropathy (LHON)

Rare hereditary form of optic atrophy that usually affects young males. Characterized by sudden bilateral cloudiness of vision, followed by scotoma, rapid deterioration of central vision, and occasional color vision disorders. Associated with atrophy of the optic nerve fibers and retinae. Considered a mitochondrial disease. Cardiac conduction defects have been reported with this condition.

Leber Disease; Leber Optic Atrophy.

NB: Do not confuse with Leber congenital amaurosis, another inherited condition (without mitochondrial DNA involvement), resulting from a mutation in the CRX gene.

Originally described by Theodore von Leber, a German Ophthalmologist, in the 19th century.

Incidence is not established, however, the disease is present worldwide. Male predominance (2:1).

Genetic disorder related to mitochondrial DNA transmission (i.e., exclusively from mother to child, either male or female). At least four mutations in mitochondrial DNA (including G11778A, T14484C, and G3460A) are associated with this clinical abnormality. Different family pedigrees show different mutations but with clinically similar pictures. The pattern of transmission within a kindred are not in accordance with mendelian principles, and it is apparent that a complex mechanism of inheritance is in operation. The disease is never transmitted by affected men; it is transmitted by affected women or, most frequently, by female carriers of the gene.

The mutation in mitochondrial DNA results in lowering of the amount of energy available to the cells of the optic nerve and retina, thus leading to severe cell damage. Fundal changes are described as opacification of the disc margin, hyperemia of the disc vessels, circumpapillary telangiectatic microangiopathy, and swelling of the peripapillary nerve fiber layer.

Visual field testing reveals enlarging centrocecal scotoma. Fluorescein angiography shows pseudoedema of the nerve fiber layer, peripapillary telangiectasia, and increased tortuosity of the retinal vessels. Pattern electroretinogram and visual-evoked potentials show optic nerve dysfunction not associated with retinal disease. Magnetic resonance imaging may reveal a high signal within the optic nerves. Molecular genetic testing for the mutations can be decisive.

There is a wide spectrum of ages at onset of the disorder. However, the most frequent age at onset is in the late teens. Typically, vision fails from normal to severely impaired over a period of weeks, beginning with one eye and then the other eye a few weeks later. Some improvement may occur over months or years, however, vision is permanently impaired. There is probably no association between this disorder and other organ systems. A link between this and multiple sclerosis has been suggested but remains unproved. Similarly, some patients have demonstrated both optic neuropathy and cardiac preexcitation, but any link may be purely chance.

Thorough history and examination should exclude any coexisting pathology. A 12-lead electroencephalogram should be performed to exclude cardiac preexcitation or conduction defects.

No specific anesthetic techniques are recommended or contraindicated. As with all neurologic conditions, it is prudent to demonstrate the extent of disability before anesthesia in order to be confident in making postoperative assessments.

Use of sodium nitroprussiate should be avoided because of the increase in cyanide anions in this specific condition. The mechanism is unknown.

Other forms of optic atrophy: coloboma and other congenital defects of optic nerve, congenital optic atrophy, juvenile optic atrophy, Behr optic atrophy (with ataxia), demyelinating neuropathies.