Childhood-Onset Leber Hereditary Optic Neuropathy - Clinical and Prognostic Insights

Purpose: To investigate the clinical and molecular genetic features of childhood-onset Leber hereditary optic neuropathy (LHON) to gain a better understanding of the factors influencing the visual outcome in this atypical form of the disease. Design: Retrospective cohort study. Methods: We retrospectively included two cohorts of LHON patients with onset of visual loss before the age of 12 years old from Italy and the United Kingdom. Ophthalmological evaluation, including best-corrected visual acuity, orthoptic evaluation, slit-lamp biomicroscopy, visual field testing and optical coherence tomography (OCT) were considered. Patients were classified based both on the age of onset and the pattern of visual loss. Results: 68 PATIENTS WERE STRATIFIED BASED ON THE AGE OF ONSET OF VISUAL LOSS: GROUP 1 (< 3YRS): : 14 patients (20.6%); Group 2 (≥ 3 - < 9yrs): 27 patients (39.7%); and Group 3 (≥ 9 - ≤ 12yrs): 27 patients (39.7%). Patients in Group 2 achieved a better visual outcome compared with those in Group 3. Patients in Group 1 and Group 2 had better mean deviation on visual field testing compared with those in Group 3. The mean ganglion cell layer thickness on OCT was higher in Group 2 compared with those in Group 1 and Group 3. Patients were also categorized based on the pattern of visual loss as: Subacute Bilateral: 54 patients (66.7%); Insidious Bilateral: 14 patients (17.3%); Unilateral: 9 patients (11.1%); and Subclinical Bilateral: 4 patients (4.9%). Conclusions: Children who lose vision from LHON before the age of 9 years old have a better visual prognosis compared with those who become affected in later years, likely representing a "form frustre" of the disease.