Leber Hereditary Optic Neuropathy

    • 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
    • In the chronic phase, MRI will show small caliber optic nerves
    • Optic neuritis
    • Compressive optic neuropathy
    • Posterior ischemic optic neuropathy
    • Non-arteritic ischemic optic neuropathy
    • Paraneoplastic optic neuropathy
    • Infiltrative optic neuropathy
    • Maculopathy
    • Psychogenic visual loss
    • 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

    Optic Nerve And Chiasm Disorders

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