According to Yvonne Ou, MD, the test can objectively detect relative changes in the on and off pathways.
Reviewed by Yvonne Ou, MD
The retina has many different subtypes of ganglion cells that respond to different stimuli. For example, some types are more sensitive to gradations or contrast, some respond to motion or specific directions, or to local edges.
“When all of that information is put together,” Yvonne Ou, MD, explained, “the retina can process all the visual information being presented.”
In addition to those subtypes, retinal ganglion cells (RGCs) can be classified as on- or off-center types. Off RGCs respond to decreases in light and on RGCs to increases in light,1 according to Ou, who is academic director, Glaucoma Division, and vice chair for postgraduate education in the Department of Ophthalmology at University of California San Francisco.
Experimental glaucoma studies have demonstrated that preferential damage occurs in the off RGCs in loss of synapses, dendritic retraction, and RGC responses. “We believe that there is selective vulnerability of alpha-off-transient RGCs in glaucoma, which has been identified in mice,” she said.
The next step was to determine what happens in humans. It seems that the off cells provide clues to ongoing damage from glaucoma in the retina, the so-called canary in the coal mine.
“Are the on cells the coal miners, ie, very hardy and resilient, and less susceptible to glaucomatous damage?” she queried, which then brought her to the next stage, assessment of visual function.
Visual field tests are subjective, uncomfortable, and difficult for patients. In addition, they require costly equipment. Ou suggested that using an objective measurement of the visual fields with a handheld electroretinography (ERG) device may be a better mousetrap for identifying any changes in the on and off RGC pathways.
“The on and off pathways have been explored with other ERG modalities in glaucoma and there is evidence that a flicker stimulus can separate the on and off pathways in mice and perhaps in nonhuman primates and humans,” she said.
Ou recounted a study in which a genetic glaucoma murine model had a decreased ERG response to a flicker stimulus that was more notable at the higher frequencies.2
“We found this to be especially interesting because it suggested that the off pathway is more vulnerable,” she said.
A new look at ERG
This technology is not currently standard of practice to assess visual function in patients with glaucoma because of the need for corneal electrodes, the equipment is bulky, and the examination is time-consuming.
When considering the practical application of the handheld device in the clinic, Ou and colleagues questioned if the handheld ERG can objectively detect relative changes in the on and off pathways.
In their study, the investigators tested photopic flash, flicker stimulus, photopic negative response, and the sinusoidal custom-written wave stimulus, the last of which is a sinusoidal wave at varying frequencies ranging from 50 to 0.3 Hz. The study included 59 eyes in the glaucoma group and 19 control eyes; the mean participant age was 69 years. The demographics of both groups were similar. The ERG response was measured using the RETeval device (LKC Technologies. The participants were presented with higher and lower sinusoidal frequency stimuli and the data analyzed.
Ou demonstrated the sinusoidal response obtained from the controls and patients using both 25- and 5-Hz frequency stimuli. She reported that at 25 Hz there was a clear decrease in the ERG amplitudes in the glaucoma patients compared with the controls. However, at 5 Hz no difference was seen between the 2 groups.
“Quantitation of the ERG response as a function of the sinusoidal stimulus frequency, showed separation between the controls and the glaucoma patients especially at the higher frequencies,” Ou said. “When we evaluated the percent difference from the controls, we saw about a 20% to 25% reduction in the higher frequencies in the ERG amplitudes.”
When patients were asked their opinions of the handheld ERG test compared with the standard visual field test, 55% of patients reported no discomfort performing the test compared with 27% of patients who reported no discomfort with the visual field test.
“When evaluating the on and off pathways using a novel stimulus and a handheld ERG device in patients with glaucoma compared with controls, the handheld ERG using a sinusoidal stimulus may provide an objective assessment that demonstrates greater off pathway susceptibility in glaucoma,” Ou concluded.
Yvonne Ou, MD
This article was adapted from Ou’s presentation at the 2021 virtual meeting of the 25th Annual Glaucoma Symposium. She has no financial interest in this subject matter.
1. Ou Y, Ullian EM, Wong ROL, et al. Selective vulnerability of specific retinal ganglion cell types and synapses after transient ocular hypertension. J Neurosci 2016;36:9240-9252.
2. Harazny K, Scholz M, Buder T, et al. Electrophysiological deficits in the retina of the DBA/2J mouse. Doc Ophthalmol Adv Ophthalmol 2009;119:181-197.