Portable S-cone electroretinography recordings in healthy participants and in a patient with NR2E3-associated retinopathy

Author: Clara Valor Suarez (United Kingdom)

Co-authors: Xiaofan Jiang, Isabelle Chow, Shaun Leo, Chang Ning Lee, Andrew Webster, Omar A Mahroo

Purpose

To explore use of an S-cone specific setting on a portable hand-held electroretinogram (ERG) device to detect differences in ERG waveform between healthy participants and a patient with NR2E3-associated Enhanced S-cone Syndrome.

Setting/Venue

Recordings were obtained from a patient with NR2E3-associated Enhanced S-cone Syndrome whilst in the retinal genetics clinic, and from healthy control participants in clinic or office settings.

Methods

ERG waveforms were recorded using the portable RETeval device (LKC technologies, Gaithersburg, MD, USA) together with skin electrodes following pharmacological mydriasis. The stimulus was a blue flash (0.25 photopic m-2 s then 1.0 photopic cd m-2 s) delivered at 4.2 Hz in the presence of a red background (560 cd m-2). Averaged traces from up to 500 stimulus presentations were obtained. The patient was a 35 year old female who was homozygous for the c.119-2A>C variant in NR2E3. Healthy control participants of similar age with no known ocular disorders were recruited and underwent the same testing. All study participants gave informed consent and the study had ethics committee approval.

Results

Recordings from 5 healthy participants (including 3 females and 2 males) were analysed. Mean (SD) age was 32 (6.8) years (median 30; range 24 to 42 years). ERG waveforms from these participants were similar, with a-wave amplitudes of less than 5 microvolts and less than 8 microvolts for the 0.25 and 1.0 cd m-2 s flashes respectively, and a-wave peak times of 15-18 ms. B-waves were larger than a-waves, and usually showed 2 or more peaks. Responses from the patient showed a much larger a-wave (>10 microvolts and >15 microvolts for the two stimuli respectively) with a simplified waveform. The patient’s ERG b-waves were of similar size to the a-waves, and the b-waves peaked at a markedly later time point (>50 ms after the flash) in comparison with the control traces.

Conlusions

Using a hand-held portable ERG device and S-cone specific setting, we were able to detect characteristic waveform features of Enhanced S-cone Syndrome in a patient with variants in NR2E3. This ERG waveform was clearly distinguishable from healthy control participants. The recording procedure was well-tolerated, simple to conduct and completed in 5 minutes or less per eye. Large S-cone ERGs are quite specific for disease associated with bi-allelic pathogenic variants in NR2E3 (or more rarely bi-allelic variants in NRL). This technique can be of value in guiding genetic screening. Where genetic testing has already been performed, these recordings can help establish the likely pathogenicity of variants of uncertain significance in these genes.

Financial Disclosure

No financial disclosures