Functional and structural analysis in relation to age at onset of Leber hereditary optic neuropathy: a Swedish cohort

Purpose To evaluate macular ganglion cell complex (GCC) thickness, retinal vessel tortuosity, visual function, and treatment effects in chronic Leber hereditary optic neuropathy (LHON) stratified by age at onset. Methods Thirty-one chronic LHON subjects from the Swedish LHON registry were enrolled and grouped by age at onset: <15 years, ≥15 to ≤35 years, and ≥36 years. Visual acuity (VA), visual fields, optical coherence tomography (OCT), and fundus images were assessed. Vessel tortuosity was qualitatively graded. Idebenone treatment history was obtained from the registry. Results Fifty-nine eyes were analysed. Six eyes exhibited no to mild visual impairment, of which four belonged to individuals with age at onset <15 years. This group demonstrated significantly better VA (0.7 ± 0.8 vs 1.5 ± 0.5 and 1.3 ± 0.5 logMAR), higher visual field score (76.9 ± 25.8 vs 47.1 ± 27.7 and 29.7 ± 21.1%), and thicker average GCC (72.3 ± 30.8 vs 49.9 ± 11.6 and 48.7 ± 4.5 µm) compared with older-onset groups. Moderate to severe tortuosity was more prevalent in the youngest-onset group. Among individuals with onset ≥15 to ≤35 years, GCC thickness correlated with visual function. Overall, 68% received Idebenone and majority of them were treated within six months of onset (68%), but no significant outcome differences were observed between the treated and untreated subjects. Conclusions LHON onset before 15 years of age is associated with better preserved retinal structure and visual function in the chronic stage.