The photopic negative response: an objective measure of retinal ganglion cell in patients with Leber's Hereditary Optic Neuropathy

Abstract

Purpose : The photopic negative response (PhNR) is a slow negative component of a flash photopic full field ERG which has been shown to be specific for retinal ganglion cell (RGC) activity. Direct evaluation of RGC function is desirable in patients with Leber’s Hereditary Optic Neuropathy (LHON) in which functional improvement with Idebenone and EPI-743 can take years to be clinically measurable. The purpose of this study was to evaluate the use of PhNR as a potential objective non-invasive clinical metric in patients with LHON.

Methods : Full field photopic ERG recordings using a sequence of 50 brief red flash stimulus on blue background were collected in 26 subjects with the mt.11778 LHON mutation using standard ERG recording techniques. Two sets of recording were performed per patient to ensure data reproducibility. All subjects are from a well described Brazilian pedigree (Sadun et al., 2002). The PhNR was identified using a computer based automated detection system and data was manually examined to remove movement artifacts.

Results : The PhNR was recordable in both affecteds and nonsymptomatic carriers with LHON The PhNR amplitude was significantly smaller in affected individuals (Avg -7.80 ± 1.97 µV; n=6) compared to carriers (Avg -22.56 ± 6.51 µV; n=20; p < 0.0001). There was no difference in the latency of the response (55-75 msec) between the two groups.

Conclusions : We are able to demonstrate that the PhNR is significantly decreased in patients affected by LHON compared to carriers in a well described pedigree. Unlike the Pattern ERG (pERG) the PhNR is recordable independent of fixation and refractive error. This is important in patients affected with LHON who typically have a dense central scotoma. The PhNR may be a useful objective outcome measure for future testing of pupported treatments in clinical trials.


Sadun, A. A. et al. A very large Brazilian pedigree with 11778 Leber's hereditary optic neuropathy. Transactions of the American Ophthalmological Society 100, 169-178; discussion 178-169 (2002).

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.