Hereditary optic neuropathies result from genetic defects that cause vision loss and occasionally cardiac or neurologic abnormalities. There is no effective treatment.
Hereditary optic neuropathies include dominant optic atrophy and Leber hereditary optic neuropathy, which are both mitochondrial cytopathies (1). These disorders typically manifest in childhood or adolescence with bilateral, symmetric central vision loss. Optic nerve damage is usually permanent and in some cases progressive. By the time optic atrophy is detected, substantial optic nerve injury has already occurred.
Dominant optic atrophy
Dominant optic atrophy is inherited in an autosomal dominant fashion. It is believed to be the most common of the hereditary optic neuropathies, with prevalence in the range of 1:10,000 to 1:50,000. It is thought to be optic abiotrophy, premature degeneration of the optic nerve leading to progressive vision loss. Onset is in the 1st decade of life.
Leber hereditary optic neuropathy
Leber hereditary optic neuropathy involves a mitochondrial DNA abnormality that affects cellular respiration. Although mitochondrial DNA throughout the body is affected, vision loss is the primary manifestation. Most cases (80 to 90%) occur in males. The disease is inherited with a maternal inheritance pattern, meaning that all offspring of a woman with the abnormality inherit the abnormality, but only females can pass on the abnormality because the zygote receives mitochondria only from the mother.
General reference
1. Kisilevsky E, Freund P, Margolin E: Mitochondrial disorders and the eye. Surv Ophthalmol 65(3):294-311, 2020. doi: 10.1016/j.survophthal.2019.11.001
Symptoms and Signs of Hereditary Optic Neuropathies
Dominant optic atrophy
Most patients with dominant optic atrophy have no associated neurologic abnormalities, although nystagmus and hearing loss have been reported. The only symptom is slowly progressive bilateral vision loss, usually mild until late in life. The entire optic disk or, at times, only the temporal portion is pale without visible vessels. A blue-yellow color vision deficit is characteristic.
Leber hereditary optic neuropathy
Some patients with Leber hereditary optic neuropathy have cardiac conduction defects. Other patients have minor neurologic abnormalities, such as a postural tremor, loss of ankle reflexes, dystonia, spasticity, or a multiple sclerosis–like illness.
Diagnosis of Hereditary Optic Neuropathies
Clinical evaluation
Molecular genetic testing
Diagnosis of dominant optic atrophy and Leber hereditary optic atrophy is mainly clinical. Molecular genetic testing is available to confirm many mutations responsible for both disorders. However, results can be falsely negative because mutations may exist for which molecular testing does not yet test.
If Leber hereditary optic neuropathy is suspected, electrocardiography (ECG) should be done to diagnose occult cardiac conduction defects.
Treatment of Hereditary Optic Neuropathies
Symptomatic treatment
There is no effective treatment for the hereditary optic neuropathies. Low-vision aids (eg, magnifiers, large-print devices, talking watches) may be helpful. Genetic counseling is suggested.
Leber hereditary optic neuropathy
In patients with Leber hereditary optic neuropathy, corticosteroids, vitamin supplements, and antioxidants have been tried without success. A small study found benefits from quinone analogs (ubiquinone and idebenone) during the early phase (1). Suggestions to avoid agents that might stress mitochondrial energy production (eg, tobacco, alcohol, particularly if excessive) have no proven benefit but are theoretically reasonable. Patients with cardiac and neurologic abnormalities should be referred to a specialist.
Treatment reference
1. Peragallo JH, Newman NJ: Is there treatment for Leber hereditary optic neuropathy? Curr Opin Ophthalmol 26(6):450-457, 2015. doi: 10.1097/ICU.0000000000000212
