Clinical electroretinograms (ERGs) are gaining more widespread attention due to the introduction of handheld recording devices, the use of which has broadened the possibility of using ERG as a screening tool and for longitudinal patient monitoring.
Previous studies have shown that the PhNR is reduced in eyes with glaucoma, similar to the pattern electroretinogram (PERG).
There is some advantage in recording the PhNR compared to other electrophysiological measures such as the PERG and scotopic threshold response in the clinic as it is more robust to cataract, does not require refractive correction, and does not require dark adaptation, thus increasing its potential for clinical translation.
This is of particular interest in glaucoma management, where the PhNR may provide additional objective information on RGC function and may be utilized as an alternative for people who do not perform well on perimetry.
Objective measures of RGC function in glaucoma would be attractive if such measures were clinically feasible, with demonstrated good utility.
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, 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. “We found this to be especially interesting because it suggested that the off pathway is more vulnerable,” she said.
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.