Abstract
Purpose :
Leber’s Hereditary Optic Neuropathy (LHON) is a rare, mitochondrially inherited disease, typically recognized as a disease of young men between 15-35 years of age. We performed a retrospective observational clinical study to learn about the visual outcome of patients with an age of onset before 16 years with and without treatment with Idebenone..
Methods :
277 LHON patients were analysed regarding gender, age of onset before the age of 16 years, genetic mutation and best corrected visual acuity (BCVA). Molecular and clinical characteristics of Idebenone-treated patients were correlated to an age-adjusted patient cohort without treatment.
Results :
We identified 63 patients with an age of onset between 4 and 16 years. Of those, 32 had been treated with Idebenone, 31 were untreated. In the Idebenone group, 17 had an age of onset ≤ 12 years and 70.5% were male. All patients affected at an age older than 13 years (n = 15) were male. Median disease duration until Idebenone treatment was 5.6 months (range 1.9 - 20.8). In the untreated cohort, 16 had onset ≤ 12 years of age and 15 between 13 - 16 years. In the untreated childhood onset group (n = 16), 63% were male. In the older group, 87% were male. Median disease duration was 9 years (range 3 – 34). The main mtDNA mutations in the Idebenone cohort were mt.11778 (53.1%), mt.14484 (15.6%), and mt.3460 (21.9%), 9.4% had rare mutations. In the natural course group 77.7% had mt.11778, 11.1% mt.3460, 7.7% mt.14484 and mt.11778, and 7.7% had rare mutations. In patients treated with Idebenone mean BCVA was 1.05 logMAR before and 0.85 logMAR after 12 months of treatment. After 24 months patients of the older group had a mean BCVA of 1.35 logMAR and 0.65 logMAR in the younger group. No severe side effects were reported. In natural course of the disease bilateral BCVA was 0.78 logMAR in the younger and 0.87 logMAR in the older age group after 9 years median (range 3 – 34).
Conclusions :
LHON should be considered as a differential diagnosis of subacute vision loss in young patients. The high rate of males in the early onset age group between 13 and 16 years suggests protective factors in females upon reaching puberty. Idebenone is a safe treatment in children between 4 and 16 years of age. Longer follow-up is required for correlation with the natural course.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.