Leber Hereditary Optic Neuropathy

What is it?

Subacute—usually irreversible--visual loss affecting both eyes sequentially and sometimes simultaneously
Caused by a mitochondrial mutation usually at positions 11778, 3460, 14484, or 14459
Transmitted maternally (because the mother provides the mitochondria)
Men aged 15 to 40 years are most at risk, but women and older men are also vulnerable
Vision loss is usually the only clinical manifestation
No effective treatment
Cardiac conduction defects occur sometimes

Core features
- One eye loses vision, then the other eye loses vision, usually with a delay of weeks to months
- Central or centrocecal scotomas
- In the active phase, the affected optic disc may appear hyperemic and show a thickened nerve fiber layer and dilated papillary capillaries
- Late after the active phase, the affected optic disc will show temporal pallor
Trap: an afferent pupil defect is not always present—even when only one eye is affected—leading to a misdiagnosis of psychogenic vision loss, especially if the optic discs appear normal
Tip: the optic discs do not leak fluorescein because the optic disc elevation is based on axoplasmic stasis, not on blood-brain barrier breakdown
MRI may show multifocal high T2/FLAIR abnormalities of uncertain significance

Look for the classic peripapillary nerve fiber layer thickening and telangiectasia in the acutely affected eye and even in the unaffected eye (“pre-eruptive stage”)
Order fluorescein angiography to exclude optic disc leakage, which would indicate inflammatory or ischemic optic neuropathy
Order orbit-based MRI to exclude inflammatory or compressive optic neuropathy
Order the blood test for the mitochondrial DNA mutations, realizing that laboratory results may be delayed for months
Advise cessation of smoking and alcohol ingestion, which generate free radicals that exacerbate mitochondrial dysfunction
Offer treatment with idebenone, coenzyme Q10, vitamin E, and B vitamins, although evidence of benefit is weak
Provide genetic counseling, advising males that they cannot transmit the disease, and advising mothers that all children--especially males—are at risk at any age

Visual loss is usually irreversible, but some visual recovery may occur in mitochondrial DNA mutations at loci 14484 and 3460
Tip: mutations at loci 11778, 3460, 14484, and 14459 account for only 80% of LHON cases; if mutations are not present at those loci, and clinical features strongly suggest LHON, laboratories will provide a more expanded investigation of other potential loci
Evidence of treatment benefit is still lacking
Patients who suffer apparent nutritional-deficiency or alcoholism-related optic neuropathy may carry a Leber mitochondrial DNA mutation