Diagnostic Performance of a Handheld Electroretinography Test for Glaucoma.

Purpose: To evaluate the diagnostic performance of a sinusoidal flicker stimulus test at various frequencies using a handheld electroretinography (ERG) device in glaucoma versus control participants. Design: A cross-sectional study conducted between June 2019 and October 2022 at the University of California, San Francisco. Participants: Participants with glaucoma were recruited from glaucoma clinics if they had a diagnosis of open-angle glaucoma, as demonstrated by optic nerve damage or reproducible visual field defects. Control participants had normal optic nerves and intraocular pressures of ≤21 mmHg and were recruited from optometry clinics. Methods: The RETeval device (LKC Technologies), a handheld ERG recording system, was used to administer a sinusoidal flicker stimulus modulated at 14 frequencies from 1 to 50 Hz, and the first harmonic frequency response amplitudes were collected. Logistic regression models with glaucoma diagnosis as the outcome were trained using data from 67% of participants; models were then tested on the remaining 33%. Main Outcome Measures: Receiver operating characteristic curves demonstrating model performance on the testing set were generated, and area under the receiver operating characteristic curve (AUC) was calculated. The improved DeLong algorithm was used to compare diagnostic performance of the models and differences in performance in dilated versus nondilated eyes. Results: The study included 117 eyes from 72 participants (18 control, 54 glaucoma; mean age [standard deviation {SD}] = 70.4 [12.2] years; 51.4% female). Among glaucomatous eyes, average (SD) mean deviation was -4.61 (5.55) decibels. In a model assessing the combined effects of amplitude responses across all frequencies, the AUC was 0.57 (95% confidence interval [CI]: 0.37-0.78). However, in a model focusing on frequencies of ≥30 Hz, where the OFF pathway may be more affected, the AUC improved to 0.81 (95% CI: 0.66-0.97). In this higher frequency model, sensitivity was 80% and specificity was 74% at the Youden J cutoff. Conclusions: These findings provide evidence of the potential use of handheld ERG in diagnosing glaucoma by assessing retinal amplitude responses to sinusoidal flicker stimuli at frequencies between 30 and 50 Hz. This supports the hypothesis that the OFF pathway may be more vulnerable in glaucoma. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.