Natural History of Pre-Sympthomatic to Acute Stage Transition in Leber's Hereditary Optic Neuropathy

Abstract

Purpose: : To investigate by OCT the topographic pattern of fiber loss in the peripapillary Retinal Nerve Fiber Layer (RNFL) of patients with Leber’s Hereditary Optic Neuropathy (LHON) in a longitudinal follow-up.

Methods: : Six eyes of four patients (mean age: 36.2±13.3 years) with LHON, as defined by the presence of a pathogenic mtDNA point mutation, were studied during the first nine months, starting from the pre-sympthomatic stage of the disease. Measurements were carried out at different time points: pre-sympthomatic stage, time of visual loss and 1, 2, 3, 6 and 9 months later. Stratus OCT was used to analyze peripapillary RNFL thickness (3.4mm diameter). Groups were compared by un-paired Mann-Whitney test followed by box plot graphical distribution.

Results: : A significant increase of RNFL was detected in the 360° average, temporal and inferior quadrants between pre-sympthomatic stage and disease onset (p=0.02, p=0.02 and p=0.006 respectively). The superior and nasal quadrant showed a slight increase of thickness at this time. In the superior and nasal quadrants the RNFL thickening was statistically significant between onset and 3 months (p=0.018 and p=0.05 respectively) and between pre-sympthomatic and 3 months (p=0.006 and p=0.006 respectively). At 3 months, a non-significant reduction of RNFL thickness was detected in the temporal quadrant whereas no difference was evident in the inferior quadrant.A significant reduction of RNFL was detected in all quadrants between 3 and 9 months.None of the patients experienced recovery of visual acuity during this 9-months follow-up period, despite all patients underwent idebenone treatment.

Conclusions: : The temporal and inferior quadrants appeared to be the site were the RNFL thickness increase at first. Conversely, in the superior and nasal quadrants the fiber thickening was more evident at 3 months, once the temporal quadrant flattened. These findings are consistent with the well-known preferential involvement of the papillo-macular bundle. We also document the previously unrecognized simultaneous early involvement of the inferior quadrant. Moreover, the late involvement of both superior and nasal quadrants suggests a dynamic evolution of the acute stage until 3 months. This has a potential value for the therapeutic window.

Keywords: neuro-ophthalmology: optic nerve • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • nerve fiber layer