Leber hereditary optic neuropathy

Leber hereditary optic neuropathy is a maternally inherited bilateral optic neuropathy that typically affects teenage males with acute vision loss first in one eye and then the other within days or weeks. The etiology involves a point mutation in the mitochondrial DNA at 1 of 3 main loci: 11778, 14484, or 3460. There are some distinctive changes in the ocular fundus appearance at various stages of the process that make specific diagnosis possible clinically. At the time the patient presents with vision loss, there is apparent swelling of the optic disc but there is no leakage of fluorescein dye as is usually present with other forms of optic nerve head swelling. Other distinctive changes include small peripapillary telangiectatic vessel changes that go away shortly after the acute phase and retinal venous tortuosity that may persist indefinitely as a marker. The author updates progress on developing a virus vector delivering DNA restorative therapy for patients with Leber hereditary optic neuropathy, citing a phase I clinical trial that demonstrated safety and even some visual improvement in a few subjects. He also reviews an OCT-based imaging study in which thinning of the retinal ganglion cell layer and the retinal nerve fiber layer were demonstrated prior to vision loss, which may provide a basis for early intervention to prevent vision loss when it becomes available.