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LHON is caused by mutations in mitochondrial DNA, which is maternally inherited. The three most common mutations are located at nucleotide positions 11778 (over 50 per cent of cases), 3460 and 14484. The penetrance and severity of LHON are highly variable, and may be influenced by the relative proportions of mutated and normal mitochondrial DNA (ie 'heteroplasmy'). Carrier mothers transmit the mutation to all of their sons, of whom at least 50 per cent develop LHON. All daughters of carrier mothers are carriers, and approximately 10 per cent develop LHON themselves. Males cannot transmit the disease.
Symptoms
The patient experiences painless, rapidly progressive and severe monocular visual loss, often with a central scotoma. It usually begins unilaterally and involves the other eye within days to weeks.
Signs
In the acute stage, there is often mild optic disc swelling and hyperaemia however, the disc may appear normal. Acuity varies from 6/60 to counting fingers, with a centrocaecal visual field defect (ie in the field of vision corresponding to the space between the macula and optic disc). After several weeks, the acute changes resolve and the optic disc becomes flat, pale and atrophic. In asymptomatic members of affected families, the presence of dilated peripapillary capillaries may suggest an increased risk of developing LHON.
Prevalence
Rare. Men are affected more often than women (approximately 7 to 1), particularly in the second to third decades of life. Rarely, cases are diagnosed at the extremes of age.
Significance
LHON causes severe, painless loss of vision of rapid onset that fails to improve.
Differential diagnosis
Optic neuritis, Papilloedema, Anterior ischaemic optic neuropathy (arteritic or non-arteritic), Toxic optic neuropathy.
Management
Additional investigations
Fluorescein angiography is often useful when the diagnosis is uncertain. Characteristically, the optic nerve head does not stain, and the dilated peripapillary blood vessels do not leak fluorescein.
Genetics
See above for genetic inheritance. Laboratory tests for the mitochondrial DNA mutations associated with LHON are performed on blood and hair specimens. Genetic counselling is offered to patients and their families.
Advice and referral
Unfortunately, no treatment is known to improve the visual prognosis of LHON. Various vitamin and enzyme supplements have been employed to alleviate this proposed metabolic deficiency. To date, however, no treatment has been shown to improve the visual prognosis of LHON in a prospective clinical trial. Avoidance of cigarette smoking and excessive alcohol consumption is advised, with the intention of minimising mitochondrial metabolic stress. Cardiology consultation is recommended, since patients with LHON have an increased incidence of cardiac abnormalities.
Refractive correction or LVAs
Most patients are left with acuity of 6/60 or worse. (In general, patients with the 11778 mutation carry the worst prognosis.) Partial restoration of vision rarely occurs later in life. The patient's remaining vision is optimised with correction of refractive errors, and provision of low vision aids and vocational rehabilitation.