Recent evidence from small animal models and human electrophysiology suggests that the OFF-pathway is more vulnerable to glaucomatous insult than the ON-pathway. Thus, OFF-pathway based measurements of visual function may be useful in the diagnosis of Glaucoma. The steady-state visually evoked potential (SSVEP) can be used to non-invasively make such functional measurements. Here, we examine whether OFF- and ON-pathway biasing SSVEP measurements differently predict glaucoma diagnosis using a large cohort of 98 glaucoma patients and 71 controls. Using both a logistic regression with k-fold cross-validation and a random forest classifier, we show that OFF-pathway biasing features produce a small improvement in predictive accuracy over ON-pathway biasing features. However, despite our inclusion of many more response features and the retention of both participants' eyes, our classifier did not perform as well as previous reports that used the isolated-check VEP. This is likely a result of the relatively small amount of data we collected for each participant, but may also be explained by the absence of any train-test splitting in preexisting work. Nevertheless, our results support further exploration of the diagnostic potential of OFF-pathway biasing functional biomarkers for glaucoma.

The authors have declared no competing interest.

This study was funded by the Glaucoma Research Foundation, the National Eye Institute (P30-EY026877 and R01-EY030361-01) and Research to Prevent Blindness, Inc.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Institutional Review Board of Stanford University gave ethical approval for this work.

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Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors