Leber hereditary optic neuropathy: current perspectives

Abstract

Leber hereditary optic neuropathy (LHON) is one of the most common inherited optic neuropathies causing bilateral central vision loss. The disorder results from point mutations in mitochondrial DNA and subsequent mitochondrial dysfunction. The primary cell type that is lost in LHON is the retinal ganglion cell, which is highly susceptible to disrupted ATP production and oxidative stress. Inheritance of LHON follows that of mitochondrial genetics, and it has a highly variable clinical phenotype, as other genetic and environmental factors also play a role. Although LHON usually presents with isolated vision loss, some patients suffer other neurological sequelae. For ill-defined reasons, male LHON mutation carriers are more affected than females. Most LHON patients remain legally blind, but a small proportion can experience spontaneous partial recovery, often within the first year of symptom onset. Unfortunately, at this time there are no established curative interventions and treatment is largely supportive. Patients should be offered low vision services and counseled on mitigating risk factors for additional vision loss, such as smoking and consuming alcohol. Encouraging treatments currently undergoing investigation includes ubiquinone analogs, such as idebenone, as well as gene therapy and stem cells to restore ATP synthesis and provide neuroprotection to surviving retinal ganglion cells.

Keywords: Leber hereditary optic neuropathy; mitochondria; mitochondrial DNA; neuro-ophthalmology.

Figure 1

Automated 30-2 protocol Humphrey visual field study of the right eye showing a dense cecocentral scotoma on the grayscale (A) and total deviation map (B) in a patient with acute LHON-related vision loss. Abbreviation: LHON, Leber hereditary optic neuropathy.

Figure 2

Right optic nerve (A) of a patient with acute LHON-related vision loss showing mild hyperemia, blurring of the disc margin, and elevation of the optic nerve head from swelling of the peripapillary retinal nerve fiber layer. LHON-related vision loss in the left eye had occurred 6 months prior leading to prominent temporal optic nerve pallor (B) from atrophy of the retinal nerve fiber layer. Abbreviation: LHON, Leber hereditary optic neuropathy.