Table 1.

Salient clinical features of isolated optic neuropathies and diseases associated with optic neuropathies

Disease entity	Clinical manifestations
Isolated optic neuropathies
LHON	Severe subacute bilateral, often sequential, painless, central vision loss. Second eye involvement in >97% of cases by 1 year
DOA (Kjers disease)	Slowly progressive, insidious, symmetric painless bilateral visual loss with central or cecocentral scotomas, usually detected in the first two decades of life or incidentally found
Optic neuropathies with multisystem involvement
DOA plus	Optic neuropathy with one or more of: SNHL, ophthalmoplegia, myopathy, peripheral neuropathy and ataxia
LHON plus (dystonia)	Dystonia, bulbar dysfunction, pyramidal tract involvement and cognitive impairment
Wolfram syndrome	Optic neuropathy with childhood-onset diabetes mellitus, SNHL, diabetes insipidus, cataracts, nystagmus, glaucoma and pigmentary maculopathy. May have neurologic and urologic signs and symptoms. May be pauci-symptomatic with just optic neuropathy or optic neuropathy and hearing loss
MELAS	Hemianopia, seizures, stroke-like episodes, lactic acidosis, optic neuropathy, salt-and-pepper retinopathy, progressive ophthalmoplegia and macular pattern dystrophy
MERRF	Generalized seizures, myoclonus, ataxia, myopathy, peripheral neuropathy, cognitive impairment, and rarely optic neuropathy
MNGIE	Gastrointestinal dysmotility, peripheral neuropathy, progressive leukoencephalopathy, ophthalmoparesis, ptosis, pigmentary retinopathy and optic atrophy
MILS	Severe subacute necrotizing encephalomyelopathy with early death. Dystonia, optic atrophy, pigmentary retinopathy, ataxia, nystagmus, seizures and central respiratory hypoventilation
FRDA	Progressive ataxia, dysarthria, loss of deep tendon reflexes, loss of joint position and vibration sense, pes cavus, cardiomyopathy and scoliosis. Mild optic neuropathy
CMT/HMSN VI	Axonal peripheral neuropathy with optic atrophy
Complicated HSP (SPG7)	Progressive spastic paraparesis, optic atrophy

LHON=Leber hereditary optic neuropathy, DOA=Dominant optic atrophy, MELAS=Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes, MERRF=Myoclonic epilepsy with ragged red fibers, MNGIE=Mitochondrial neurogastrointestinal encephalopathy, MILS=Maternally inherited Leigh syndrome, FRDA=Friedreich’s ataxia, HSP=Hereditary spastic paraparesis, SPG7=Spastic paraplegia 7, CMT=Charcot-Marie-Tooth, SNHL=Sensorineural hearing loss, HMSN=Hereditary motor and sensory neuropathy