PhNR and peripapillary RNFL changes in Leber hereditary optic neuropathy with m.G11778A mutation

To analyze the functional and structural changes in retinal ganglion cells (RGCs) and their axons that occur during Leber's hereditary optic neuropathy (LHON) using photopic negative response (PhNR) and spectral domain optical coherence tomography (SD-OCT).

Individuals diagnosed with LHON and their family members were invited to participate in this cross-sectional study. PhNR and OCT were used. The PhNR amplitude and peripapillary retinal nerve fiber layer (pRNFL) thicknesses were compared among the three groups. In addition, affected individuals were divided into subacute, dynamic and chronic phases based on disease duration in order to evaluate the decay in RGCs function and structure.

73 affected and 30 carriers with a m.11778G > A mutation were included. PhNR amplitude and the thickness of pRNFL significantly decreased in affected individuals and carriers compared to that of the controls (P＜0.001). However, there was no difference between the carriers and the controls (P＞0.05). There was no difference in the PhNR amplitude of different phases (P = 0.464). In the subacute phase, only temporal pRNFL thickness decreased significantly (P＜0.001). PRNFL thickness decreased significantly in dynamic phase (P＜0.001). Temporal pRNFL thickness continued to decrease in the chronic phase (P = 0.042).

In the subacute phase, the function of RGCs was severely impaired. Thickness of pRNFL decreased significantly in four quadrants during disease progression. In the chronic phase, pRNFL thickness decreased slightly. Carriers have shown RGCs dysfunction before pathological changes occur, suggesting subclinical abnormalities.