The effect of inter-stimulus frequency on the photopic negative response in glaucoma and healthy eyes

Abstract

Purpose : Clinical electroretinogram (ERG) recording of the photopic negative response (PhNR), a measure of retinal ganglion cell activity, is gaining attention due to the introduction of handheld recording devices to aid clinical translation in glaucoma. To date, there are no clinical standards for recording PhNR. Due to inherent noise in the ERG, multiple flash sweeps are required, making flash stimulus frequency of importance for its potential to shorten patient test times by reducing the amount of time between flashes. Here we examined the effect of stimulus frequency on the PhNR in glaucoma and healthy eyes.

Methods : Full-field ERGs were recorded in one dilated eye using a red on blue flash (1 cd.s/m² on 10 cd/m²) in glaucoma (n=15, 69±3 years, visual field mean defect: -4.6±1.0dB, mean±SEM) and age-matched controls (n=20, 58±5 years) using the RETeval^TM (LKC Technologies Inc, USA). Five flash frequencies were tested in random order (1-5Hz). 100 sweeps (50 sweeps at 1Hz to cap test duration to <1min) were acquired per frequency and band-pass filtered (0.3-300Hz). Amplitudes and implicit times for a-wave, b-wave and PhNR (measured baseline to trough) were analysed via two-way analysis of variance. Coefficient of variation (CoV) was used to examine variability of the PhNR amplitude.

Results : The PhNR was highly sensitive to increasing stimulus frequency with reduced amplitude from 1Hz (controls: -19.6±2.1µV, mean±SEM; glaucoma: -18.8±2.7µV) to 5Hz (controls: -10.7±1.0µV, glaucoma: -7.0±0.8µV, F_4,132=28.6, p<0.0001) and faster implicit times (1 to 5Hz, controls: 70.8±1.8 to 66.2±0.9ms; glaucoma: 72.8±2.2 to 69.4±1.1ms; F_4,132=6.4, p<0.0001). PhNR amplitudes were significantly smaller in the glaucoma group (F_4,132=4.8, p=0.03). The a-wave (F_4,132=0.2, p=0.91), b-wave (F_4,132=1.8, p=0.14) amplitudes and implicit times (a-wave: F_4,132=2.2, p=0.07; b-wave: F_4,132=1.8, p=0.14) did not change and was not different between groups. Whilst 1Hz delivered the largest PhNR, it was most variable in both groups (CoV: 68.8±14.7%, mean±95%CI). CoV significantly improved from 2Hz onwards (39.9±8.5%, F_4,132=7.2, p<0.0001). However, compared to 2Hz, PhNR amplitudes were significantly smaller at 3-5Hz in both groups (F_2,66=5.8, p=0.005).

Conclusions : Of the frequencies tested, 2Hz provides a good balance between testing times and ensuring quality of PhNR recording for photopic ERG to have clinical utility in glaucoma.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.