The most frequent mitochondrial eye diseases are Leber's Hereditary Optic Neuropathy (LHON) and Dominant Optic Atrophy (DOA). They are both characterized by optic atrophy due to retinal ganglion cell loss. Extra‐ocular features have been described in both diseases. In particular, neurological involvement has been reported even though, for some of the neurological features in LHON, the possibility of a chance association is still debated.
In LHON the main neurological features are: 1) Multiple Sclerosis “like” phenotype 2) Movement disorders including dystonia, parkinsonism and myoclonus 3) Peripheral neuropathy 5) Migraine 6) Hearing loss 6) “LHON‐MELAS‐Leigh” overlap.
In DOA, the “plus” subtype is a well‐recognized entity characterized by the occurrence, over the decades, of optic atrophy and sensorineural deafness, polyneuropathy and myopathy with chronic external ophthalmoplegia, and in some families Parkinsonism and dementia. DOA “plus” is typically associated with missense mutations affecting the OPA1 GTPase domain, and skeletal muscle is remarkable for COX deficient fibers and mtDNA multiple deletions. More recently, a Multiple Sclerosis “like” phenotype has been described also in DOA.