The development of novel electroretinogram stimuli to detect glaucoma using a handheld device

Abstract

Purpose : Glaucoma is a progressive optic neuropathy that involves damage and subsequent death of retinal ganglion cells (RGCs). Functional assessment involves perimetry to quantify the degree of visual field loss, but this test is prone to subjectivity. Our laboratory has previously demonstrated that glaucoma results in the differential impairment of specific RGC types, with OFF-RGCs more vulnerable than ON-RGCs. Retinal function can be assessed with an electroretinogram (ERG), but standard ERG equipment is bulky and requires substantial testing time. In this study, we asked whether a handheld ERG recording device could be used in glaucoma patients to objectively detect relative changes to ON- and OFF-pathways.

Methods : Control and open-angle glaucoma subjects were recruited from UCSF glaucoma and comprehensive ophthalmology clinics. Patients with retinal diseases or significant cataracts were excluded. Data was recorded using the handheld ERG RETeval (LKC Technologies). We tested each eye with several standard electrophysiology paradigms set by the International Society for Clinical Electrophysiology of Vison (ISCEV). We also utilized a novel custom-written sinusoidal wave pattern of light in order to separate ON vs. OFF responses. The sinusoidal stimulus was modulated between 0.3 Hz and 50 Hz. Data was analyzed with a Wilcoxon rank-sum test.

Results : In total, 62 glaucoma eyes and 21 control eyes were tested. Baseline demographics were similar between the groups. The ERG results for the standard ISCEV protocols were largely similar to previous findings (e.g., PhNR amplitudes were depressed in glaucoma eyes). Our novel sinusoidal stimulus showed that for frequencies between 15 and 50 Hz, glaucoma eyes had significantly lower response amplitudes than control eyes. Most notably at 50 Hz, glaucoma eyes had a 48% reduction in ERG amplitude (control eyes: 3.50 ± 0.49 mV, glaucoma eyes: 1.82 ± 0.19 mV, p = 0.0012).

Conclusions : Our study is novel in that we utilized a sinusoidal light stimulus of varying frequencies. Studies in mice suggest that ERG responses to stimulus frequencies greater than 18 Hz reflect OFF pathway activity while 5 to 15 Hz reflect ON pathway activity. We found that the higher stimulus frequencies showed a greater decrease in response. A handheld ERG device using a sinusoidal wave pattern may provide an objective, fast, portable, and more comfortable diagnostic test to detect glaucoma.

This is a 2020 ARVO Annual Meeting abstract.