Treatment of Hereditary Optic Neuropathies

Hereditary optic nerve disorders result in significant chronic visual morbidity and the minimum prevalence of affected individuals in the population has been estimated at 1 in 10,000.1 Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (DOA) are the two classical paradigms for this group of disorders and they comprise nearly half of all the inherited optic atrophy cases seen in clinical practice. LHON is caused by mitochondrial DNA (mtDNA) point mutations whereas in DOA, the majority of cases are due to pathogenic mutations in the OPA1 gene, which codes for an inner mitochondrial membrane protein. Strikingly, both LHON and DOA share the same characteristic pathological features with selective degeneration of the retinal ganglion cell (RGC) layer leading to progressive optic nerve degeneration and the onset of visual symptoms. RGCs are therefore exquisitely sensitive to mitochondrial dysfunction and the elucidation of the mechanisms involved is opening the way for therapeutic interve ions targeting different stages of the disease process. In this review, recent advances in our understanding of LHON and DOA will be discussed, in addition to the practical management of this group of patients and emerging treatment options.