S-cone electroretinograms recorded with a portable device in a series of patients with bi-allelic pathogenic variants in NR2E3

Abstract

Purpose : Patients with recessive NR2E3-retinopathy can show enhanced S-cone electroretinogram (ERG) responses. We investigated use of a portable ERG device to record S-cone ERGs with skin electrodes in the clinic or office setting from patients and healthy participants.

Methods : Consecutive patients in the retinal genetics clinic with bi-allelic variants in NR2E3 were recruited as well as healthy controls. ERGs were recorded using a portable device (RETeval with Sensor Strip skin electrodes, LKC technologies, Gaithersburg, MD) following pupil dilation. Stimuli were blue flashes (0.25 and 1.0 photopic cd m-2 s) delivered in the presence of a red background (560 cd m-2). Averages from up to 500 responses were analysed.

Results : Recordings were well tolerated (completed in <5 min per eye). Recordings from 5 healthy participants (3 females) and 5 patients (3 females) were analysed. Mean (SD) age of the healthy participants was 32 (6.8) years (median 30). ERGs from healthy participants were similar with small a-wave amplitudes (<3 and <6 microvolts for the two stimuli respectively), and a-wave peak times of approximately 15-18 ms. B-waves were larger than a-waves, usually with 2 or more peaks. Mean (SD) age of the patients was 44 (8.9) years (median 39). In 3 patients, typical “enhanced” S-cone responses were seen, with simplified waveforms. These patients had larger a-waves (typically >4 and >8 microvolts for the two stimuli) than the healthy participants. The b-waves were of similar size to the a-waves (b: a ratio close to 1) and showed single broad peaks at 50 ms or later (delayed compared to controls). In 1 patient, similar ERGs were recorded from one eye, but the fellow eye, which had a dense brunescent cataract, showed attenuated responses. In the 5^th patient, responses were severely attenuated; this patient had widespread retinal degeneration (and attenuated responses on conventional recordings).

Conclusions : The characteristic S-cone waveform features were observable using the portable device and skin electrodes in the majority of the patients tested; these were clearly distinct from the waveform obtained in control participants. S-cone ERGs may be more attenuated by brunescent cataract than standard white light ERGs. The technique may be useful in supporting the diagnosis of NR2E3-associated retinopathy when this is suspected.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.