Secondary Post-geniculate Involvement In Leber’s Hereditary Optic Neuropathy

Abstract

Purpose: : Leber’s hereditary optic neuropathy (LHON) is characterized by retinal ganglion cell (RGC) degeneration with the preferential involvement of fibers forming the papillomacular bundle. The optic nerve is considered the main pathological target for LHON. Our aim was to investigate the possible involvement of the lateral geniculate nucleus (LGN) and the optic radiation (OR) in LHON patients.

Methods: : We used diffusion-weighted imaging for in vivo evaluation. Mean diffusivity maps from 22 LHON visually impaired, 11 unaffected LHON mutation carriers and 22 healthy subjects were generated and compared at the level of the OR. Furthermore, we studied the optic nerve and the LGN in postmortem specimens obtained from a severe case of LHON compared to an age-matched control.

Results: : Mean diffusivity values of affected patients were higher than unaffected mutation carriers (P< 0.05) and healthy subjects (P < 0.01). Increased diffusivity was associated with both disease duration (B = 0.002; P < 0.05) and lack of recovery of visual acuity (B = 0.060; P < 0.01). Post-mortem investigation in LHON detected atrophy (41.9% decrease of neuron soma size in the magnocellular layers and 44.7% decrease in the parvocellular layers) and, to a lesser extent, degeneration (28.5% decrease of neuron density in the magnocellular layers and 28.7% decrease in the parvocellular layers) in the LGN as well as severe axonal loss (99%) in the optic nerve.

Conclusions: : The geniculate and optic radiations involvement in LHON patients is probably a secondary post-synaptic phenomenon, reflecting de-afferentation rather than a primary neurodegeneration due to mitochondrial dysfunction of LGN neurons.

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