Medical Management of Hereditary Optic Neuropathies

Abstract

Hereditary optic neuropathies are diseases affecting the optic nerve. The most common are mitochondrial hereditary optic neuropathies, i.e., the maternally inherited Leber’s hereditary optic neuropathy (LHON) and dominant optic atrophy (DOA). They both share a mitochondrial pathogenesis that leads to the selective loss of retinal ganglion cells and axons, in particular of the papillo-macular bundle. Typically, LHON is characterized by an acute/subacute loss of central vision associated with impairment of color vision and swelling of retinal nerve fibers followed by optic atrophy. DOA, instead, is characterized by a childhood-onset and slowly progressive loss of central vision, worsening over the years, leading to optic atrophy. The diagnostic workup includes neuro-ophthalmologic evaluation and genetic testing of the three most common mitochondrial DNA mutations affecting complex I (11778/ND4, 3460/ND1, and 14484/ND6) for LHON and sequencing of the nuclear gene OPA1 for DOA. Therapeutic strategies are still limited including agents that bypass the complex I defect and exert an antioxidant effect (idebenone). Further strategies are aimed at stimulating compensatory mitochondrial biogenesis. Gene therapy is also a promising avenue that still needs to be validated.

Macular nerve fibre and ganglion cell layer changes in acute Leber's hereditary optic neuropathy

“…The central scotoma enlarges over a few months, usually reaching a stable and profound defect within a year, leading to the transition to the chronic stage 6–8. Some patients may undergo spontaneous or treatment-related recovery that is usually of modest degree and affects various visual functions and with different timings 1 9…”

Auditory neuropathy — neural and synaptic mechanisms

“…Neuropathic hear ing impairments are common findings among indivi duals with syndromic dominant optic atrophy caused by mutations in the gene optic atrophy 1 (OPA1) 74,75 . Dominant optic atrophy is one of the most frequent genetic optic atrophies, and OPA1 mutations are causal in the majority of the cases 76 . The OPA1 protein is a mitochondria targeted dynaminrelated GTPase 77,78 that is critical for mitochondrial shaping 79 .…”

Trauma-Associated Leber Hereditary Optic Neuropathy

“…1 Head or eye trauma has rarely been reported as a trigger of LHON conversion. Redmill et al described an 18-year-old man who experienced vision loss 6 days after being punched in the face and was later diagnosed as LHON.…”