Leber's hereditary optic neuropathy (LHON) is a disease of optic atrophy first reported by Theodor Leber in 1871.⁹ This disease has an acute or subacute onset in both eyes, and it typically appears in young men in their teens and twenties. It causes a severe optic atrophy with severe visual loss within one year. The disease was considered to be hereditary because their patients showed a similar family history, in which male patients did not seem to transit the disease to their offspring, while children of female carriers always inherit the disease. Its hereditary type was unknown until in 1936. Imai and Moriwaki reported that it was a cytoplasmic inheritance.⁶ Nikoskelainen and his group proposed that mitochondrial DNA inheritance explained the hereditary patterns seen in LHON families.^17,18

In 1988, Wallace et al. reported a new mutation of 11778 base pairs of mtDNA of patients with LHON.²² Since then, more than 20 primary or secondary mtDNA mutations have been associated with LHON. The 3460, 11778, and 14484 mtDNA mutations are considered to be the most important in the pathogenesis of this disease and are classified as primary mutations.^1,4,5,8 Among the three mutations, the 11778 mutation is most frequently seen in patients with LHON. But the frequencies of the primary LHON mutations reportedly differ among ethnic groups.^15,23

The characteristics of fundus are blurred disk margins, tortuous retinal vessels, irregular telangiectatic dilation of capillaries in peripapillary and prepapillary networks in the acute stage. In spite of such microangiopathy, fluorescein angiography shows no leakage around the optic nervehead. As the disease progresses, the microangiopathy disappears, and optic atrophy develops after at least two months. In the visual field, a relative centrocecal scotoma is detected in the acute stage, and then a large central scotoma is observed. In LHON, spontaneous recovery has been well known, but it does not occur often. Johns et al. have reported that patients with the 14484 mutation show a higher incidence of visual recovery than did patients with the 11778 or 3460 mutations and that visual loss may depend more on epigenetic factors in patients with the 14484 mutation than in patients with the other primary mutations.⁷ At the present time, no effective treatment is known for LHON.

In 1992, the authors reported the results of treatment with idebenone, a quinol compound that may contribute to stimulation of the formation of ATP, in a 10-year-old Japanese boy with LHON and homoplasmic 11778 mutation.¹⁰ The authors studied the effectiveness of idebenon combined with vitamin B2, vitamin C, and isopropyl unoprostone (Rescula) for recovery of the circulation of the optic nervehead for patients in the acute stage.¹³ In patients with visual acuity of 0.3 or more, there was no statistical difference between treated and untreated groups. But the recovery interval up to 0.3 was significantly shorter in the treated group than in the untreated group.