Table 1.

Mitochondrial diseases with ocular involvement

Disease	Mutation	Impact on mitochondrial function	Ocular phenotype	Retinal ganglion cell affected?	Photoreceptor affected?
Leber’s hereditary optic neuropathy	mtDNA encoded complex 1 subunits ND1,4,6	OXPHOS complex I defects	Central or centrocecal scotomas and axonal loss in the papillomacular bundle of rapid onset; temporal atrophy of the optic nerve head	Yes	No
Autosomal dominant optic atrophy	Over 220 mutations identified, primarily in Opa1 gene	Regulation of cristae morphology and OXPHOS impairment	Insidious onset, slowly progressive disease with bilateral vision loss; central, centrocecal, paracentral scotomas, and generalized color-perception deficits	Yes	No
Neurogenic atrophy and retinitis pigmentosa syndrome	mtDNA mutation most commonly T8993G in ATPase-6 gene	OXPHOS complex V defect	Retinitis pigmentosa, cone-rod photoreceptor dystrophy, with or without optic neuropathy	Yes	Yes
Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes	Most commonly A3243G mtDNA mutation in the tRNALeu gene	Multiple OXPHOS defects	Stroke-like episodes, retrochiasmal visual loss, pigmentary retinopathy without optic atrophy	No	Yes
Maternally inherited diabetes and deafness (MIDD)	Most commonly A3243G mtDNA mutation in the tRNALeu gene	Multiple OXPHOS defects	Discontinuous circumferential perifoveal atrophy with sparing of the fovea Alternatively, a pattern dystrophy characterized by RPE changes surrounding vascular arcades with relative sparing of the fovea	No	Yes
Chronic progressive external ophthalmoplegia	Large-scale rearrangements of mtDNA Maternal inherited CPEO: point mutations in mitochondrial tRNA genes	Multiple OXPHOS defects	Bilateral ptosis, ophthalmoplegia Progressive fibrosis of extraocular muscles Pigmentary retinopathy, optic neuropathy, corneal opacity, cataracts may occur also	Yes	Yes
Kearns-Sayre syndrome	Large-scale rearrangements of mtDNA	Multiple OXPHOS defects	Severe subtype of CPEO, with ptosis, ophthalmoplegia, and pigmentary retinopathy, plus specific extraocular systemic criteria	Yes	Yes
Friedreich’s ataxia	GAA trinucleotide repeat expansion in the frataxin gene	Impairment of iron–sulfur containing mitochondrial proteins including OXPHOS complex I, II, and III	Optic atrophy and degeneration of optic radiations Slowly progressive or occasionally LHON-like subacute optic neuropathy	Yes	No
Mohr-Tranebjaerg syndrome	Deafness/dystonia peptide DDP1/TIMM8A	Mitochondrial protein import, secondary OXPHOS defects	Visual dysfunctions from loss of the visual cortex, optic atrophy and degeneration of retinal inner nuclear layer	Yes	No
Hereditary spastic paraplegia	Mutations in numerous nuclear genes, for example SPG7 (paraplegin)	Impairment of OXPHOS complex I	Pathological descriptions of the optic nerve have not been reported	Yes	No
Charcot-Marie-Tooth disease subtype CMT2A	Mfn2	Mitochondrial outer membrane fusion defects	Subacute onset of optic atrophy and subsequent slow recovery of visual acuity	Yes	No

Abbreviations: OXPHOS, oxidative phosphorylation; CPEO, chronic progressive external ophthalmoplegia; LHON, Leber’s hereditary optic neuropathy.