Assessing Early Stage Open-Angle Glaucoma in Patients by Isolated-Check Visual Evoked Potential
May 25th, 2020
The isolated-check visual evoked potential (icVEP) method is implemented here to assess the magnocellular ON pathway that is initially damaged in glaucoma. The study shows standard operative procedures using icVEP to obtain reliable results. It is proved to serve as a useful objective diagnosing technology for the early detection of glaucoma.
This method can help answer how this unique objective electrophysiologic radio field functional measure work in the diagnosis of early stage open-angle glaucoma. This technique can selectively stimulate aim on pathway, which initially is damaged in glaucoma, especially for early stage. To set up the icVEP system, click the setting button, and confirm that the frame rate is set to 6 Hertz.
The luminance of the static background of the display is set to 51 candela's per square meter. And the total cycles are set to 20. To differentiate the OAG patients and control subjects, confirm that the sign and total temperature signals are set to 10 Hertz at six frames per cycle with a 15%positive contrast.
To ensure the acquisition of reliable results, confirm that the refractive error is corrected to adapt for a distance of 114 centimeters, that the intraocular pressure is no more than 30 millimeters of mercury on the day of examination, that the pupil diameters are at least two millimeters and without mydriasis, and that each subject is at rest and is quiet at least 30 minutes before the examination. To avoid the influence of a study curve, check the right and the left eyes. Then, check the right and left eyes again and record the second result.
Initiate a retest after at least a 30 minute rest when the R value between both eyes shows a difference of greater 0.2, indicating that the result is unreliable. To accrue facilitated and careful fixation on the center of the screen, click the IC button to confirm that the spacial pattern is a 24 by 24 array of isolated checks to sub 10 and 11 degree visual field. With a two by two array fixation cross, without sinusoidal temporal signals, place the gold cup electrodes, filled with electrolytic water-soluble paste, at the midline sites on the scalp, based on the international 10/20 system.
And note that the grounding electrode can be the parietal midline electrode or the frontal parietal midline electrode. Take care that the testing distance is 114 centimeters. When all of the electrodes have been placed, click the start button.
One run will last for two seconds. With the first second presenting half of the test contrast level as an adaptation condition. And the second second presenting the full test contrast.
Note the prompt from the program and repeat the run when noise is detected and the EEG epoch is rejected. The EEG data will be displayed with the monitor when the run is determined to be valid after prompting to either accept or reject the data based on the reliability. Once the data has been accepted, the program will indicate what the next run should be until a set of 8 valid runs are accumulated.
Each run will produce a fundamental frequency component. When all eight runs have been completed, the program will calculate the mean fundamental frequency component and the radius of a 95%confidence circle using the T squared circular statistic that is automatically produced from the eight fundamental frequency components within less than one minute after the end of the test. The changing of retinal nerve fiber layer thickness in the temporal superior and inferior quadrants were calculated by subtracting the retinal nerve fiber layer thickness value from the standard value obtained from a database of healthy individuals.
In this representative analysis, a total of 44 OAG patients and 39 control subjects were included. No statistical differences in age, sex, right, or left eye, best corrected visual acuity, spherical equivalent, or pupil diameter were measured between patients and controls. But the signal to noise ratio was significantly lower in patients.
Using an A priori signal to noise ratio criteria on 0.93, the specificity of the receiver operating characteristic analysis reached 100%with a sensitivity of 65.9%For the patients, abnormalities in the central 11 degree visual field test were calculated by the numbers of abnormal points with different possibility criteria. With a criteria level of p 0.5, the amount of abnormal test points in the central 11 degree visual field was significantly negatively correlated with the signal to noise ratio. Thickness changing at the retinal nerve fiber layer in the temporal superior quadrant was significantly positively correlated with the signal to noise ratio, while the standard automated perimetry mean deviation of the other eye, thickness changing of the retinal nerve fiber layer in the temporal inferior quadrant, and the baseline interocular pressure, and central corneal thickness, were not correlated.
If you find a person who may be diagnosed as glaucoma suspect or open-angle glaucoma, you can use this procedure and make sure that step 1.2 and 1.3, sitting for isolated check, Ocular hypertension, or subjects with extension of a cap to distal ratio can also be performed with this procedure to differentiate open-angle glaucoma. Fortunately, the second generation of icVEP has been designed. It was developed for smaller screen and HD display.
Also, shorter exam distance. The machine is much smaller than first generation, which is much more convenient.
Overview
This study implements the isolated-check visual evoked potential (icVEP) method to assess the initial damage in the magnocellular ON pathway due to glaucoma. It outlines standard operating procedures to ensure reliable results, highlighting icVEP as a valuable objective technology for the early diagnosis of glaucoma.
Key Study Components
Area of Science
- Neuroscience
- Electrophysiology
- Ophthalmology
Background
- Glaucoma primarily affects the magnocellular ON pathway.
- Early detection is crucial for effective management of the disease.
- Objective diagnostic methods can enhance patient outcomes.
Purpose of Study
- To validate the icVEP method for diagnosing early-stage open-angle glaucoma.
- To assess the reliability and effectiveness of this electrophysiological technique.
- To differentiate between open-angle glaucoma patients and control subjects.
Methods Used
- The icVEP system involves a specific display setup and electrode arrangement.
- Electrodes are placed according to the international 10/20 system to record visual evoked potentials.
- Retinal nerve fiber layer thickness is measured and compared with a database of healthy individuals.
- Specific signal-to-noise ratios are analyzed to ensure data reliability.
Main Results
- The study reported significant differences in signal-to-noise ratios between patients and controls.
- Abnormalities in visual field tests correlated with retinal nerve fiber layer thickness changes.
- High specificity (100%) and moderate sensitivity (65.9%) were achieved using defined signal criteria.
Conclusions
- The icVEP method demonstrates utility for early glaucoma detection.
- This technique can facilitate timely intervention in open-angle glaucoma patients.
- Findings enhance understanding of glaucomatous processes and inform future diagnostic approaches.
Frequently Asked Questions
Executive Industry Relevance
Early detection of open-angle glaucoma remains a critical unmet need in ophthalmic drug development, where objective biomarkers can de-risk target validation and support go/no-go decisions in preclinical pipelines. The isolated-check visual evoked potential (icVEP) method provides a quantifiable electrophysiological readout that selectively probes the magnocellular ON pathway, which is preferentially damaged in early glaucoma. By correlating signal-to-noise ratio (SNR) with retinal nerve fiber layer (RNFL) thinning, icVEP offers a translational biomarker with predictive confidence for mechanistic de-risking in glaucoma therapeutics discovery.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Scientific Value: Enables interrogation of therapeutic hypotheses by isolating magnocellular ON pathway function, a key site of early glaucomatous damage.
- Operational Value: Supports biological de-risking through objective, pathway-specific functional assessment independent of structural measures alone.
- Predictive Value: Correlates SNR abnormalities with RNFL thickness changes, providing a quantifiable metric for target engagement and pathway modulation in preclinical models.
Screening & Assay Development
- Assay Readiness: Delivers standardized, quantitative SNR outputs derived from eight valid runs with automated T-squared circular statistic analysis, enabling reproducible compound screening.
- Scalability: Features a defined SOP with fixed parameters (10 Hz, 15% positive-contrast, 20 total cycles, 2-second runs) suitable for high-throughput adaptation in discovery settings.
- Platform Reuse: Electrode placement per international 10/20 system and automated EEG epoch acceptance/rejection ensure cross-lab consistency and reduced variability in longitudinal studies.
Translational & Preclinical Research
- Disease Relevance: Detects glaucomatous visual function abnormality in the central 11-degree visual field, aligning with early functional deficits in OAG.
- Translational Continuity: SNR directly correlates with RNFL thickness thinning in temporal superior and inferior quadrants, bridging functional electrophysiology with structural biomarkers.
- Risk-Adjusted Advancement: ROC analysis shows high classification accuracy (specificity 100%, sensitivity 65.9% at SNR ≤ 0.93), supporting go/no-go decisions based on predictive confidence in target modulation.
Pipeline & Workflow Integration
icVEP fits within the discovery continuum from target validation through lead identification to preclinical efficacy, offering a mechanistic readout that supports pathway-specific de-risking before advancing to phenotypic screening or in vivo models.
- Discovery Biology: Tests hypotheses about magnocellular ON pathway integrity by measuring VEP fundamental frequency components and deriving SNR from multivariate statistics.
- Screening: Provides assay-ready, quantitative electrophysiological outputs with automated signal validation and noise rejection, suitable for evaluating compound effects on visual pathway function.
- Analytics: Generates SNR as a primary dependent variable, with 95% confidence circles from T-squared statistics enabling group comparison and effect size estimation.
- Translational Research: Links functional SNR changes to RNFL thickness alterations, supporting biomarker qualification efforts in glaucoma therapeutic development.
- Enterprise Reuse: SOP-driven workflow with fixed stimulus parameters and automated analysis allows reuse across studies, sites, and compound series with minimal retraining.
Operational & Enterprise Impact
- Scientific Value: Reduces mechanistic ambiguity by isolating afferent activity in the magnocellular ON pathway, improving target confidence in glaucoma mechanisms.
- Operational Value: Ensures reproducibility through standardized SOP, automated EEG epoch acceptance, and SNR derivation via multivariate statistics.
- Strategic Value: Enhances go/no-go decision-making by providing an objective, quantifiable biomarker linked to both functional and structural glaucoma endpoints.
- Portfolio Impact: Enables risk-adjusted prioritization of compounds based on SNR modulation, reducing late-stage failure due to lack of target engagement in early pathophysiology.
Implementation Considerations
- Requires expertise in electrophysiology, EEG electrode placement (international 10/20 system), and visual stimulus calibration.
- Dependent on calibrated display capable of 6 Hz frame rate, 51 cd/m² background luminance, and precise 10 Hz temporal frequency with 15% positive-contrast isolated checks.
- Necessitates standardized pre-test conditions: 30-minute rest, corrected refractive error at 114 cm, IOP ≤ 30 mmHg, pupil ≥ 2 mm without mydriasis.
- Involves adaptation considerations for varying visual field extents (24x24 isolated checks subtending 10-11 degrees) and fixation monitoring via 2x2 array cross.
- Limited by need for reliable EEG signal acquisition; retest required if inter-eye R-value difference > 0.2, and epochs rejected upon noise detection.
