Personalised therapies for mitochondrial optic neuropathies – myth or reality?

Summary Mitochondrial optic neuropathies affect an estimated 1 in 10,000 individuals in the population and as a group, it represents an important cause of chronic visual morbidity among children and young adults. The pathological hallmark is the preferential loss of retinal ganglion cells (RGCs) within the inner retina, which results in progressive optic nerve degeneration and the onset of visual symptoms. The past decade has seen tremendous progress in our understanding of the molecular genetic basis and pathophysiology of this group of disorders, providing at the same time invaluable insight into the shared disease pathways that precipitate RGC loss. The two classical paradigms are Leber hereditary optic neuropathy (LHON), which is a primary mitochondrial DNA (mtDNA) disorder, and autosomal dominant optic atrophy (DOA) secondary to pathogenic mutations within the nuclear gene OPA1 that encodes for a mitochondrial inner membrane protein. The stark reality is that the majority of patients with mitochondrial optic neuropathies are eventually registered legally blind and management remains largely supportive. The translational gap for this group of disorders still remains to be bridged, but the development of effective disease‐modifying treatments is now within tantalising reach helped by major advances in drug discovery and targeted genetic manipulation.