Blue-Yellow VEP with Projector-Stimulation in Glaucoma

Abstract

Background and aim: In the past, increased latencies of the blue-on-yellow pattern visually evoked potentials (BY-VEP), which predominantly originate in the koniocellular pathway, have proven to be a sensitive biomarker for early glaucoma. However, a complex experimental setup based on an optical bench was necessary to obtain these measurements because computer screens lack sufficient temporal, spatial, spectral, and luminance resolution. Here, we evaluated the diagnostic value of a novel setup based on a commercially available video projector.

Methods: BY-VEPs were recorded in 126 participants (42 healthy control participants, 12 patients with ocular hypertension, 17 with "preperimetric" glaucoma, and 55 with perimetric glaucoma). Stimuli were created with a video projector (DLP technology) by rear projection of a blue checkerboard pattern (460 nm) for 200 ms (onset) superimposed on a bright yellow background (574 nm), followed by an offset interval where only the background was active. Thus, predominantly S-cones were stimulated while L- and M-cone responses were suppressed by light adaptation. Times of stimulus onset to VEP onset-trough (N-peak time) and offset-peak (P-peak time) were analyzed after age-correction based on linear regression in the normal participants.

Results: The resulting BY-VEPs were quite similar to those obtained in the past with the optical bench: pattern-onset generated a negative deflection of the VEP, whereas the offset-response was dominated by a positive component. N-peak times were significantly increased in glaucoma patients (preperimetric 136.1 ± 10 ms, p < 0.05; perimetric 153.1 ± 17.8 ms, p < 0.001) compared with normal participants (123.6 ± 7.7 ms). Furthermore, they were significantly correlated with disease severity as determined by visual field losses retinal nerve fiber thinning (Spearman R = -0.7, p < 0.001).

Conclusions: Video projectors can be used to create optical stimuli with high temporal and spatial resolution, thus potentially enabling sophisticated electrophysiological measurements in clinical practice. BY-VEPs based on such a projector had a high diagnostic value for detection of early glaucoma. Registration of study Registration site: www.

Clinicaltrials: gov Trial registration number: NCT00494923.

Keywords: Blue–yellow VEP; Glaucoma; Onset–offset VEP; Projector-stimulation.

Conflict of interest statement

The authors declare that they have no conflicts of interest. The authors have no commercial interest in the equipment used in this work.

© 2021. The Author(s).

Figures

Fig. 1

A Measurement setting for rear projection with an LED-beamer. B Spectra for blue and yellow stimulation by the present beamer. C Stimulus locations of the test grid from the Octopus perimeter (G1-protocol). The 21 central test points (open symbols) overlapping with the VEP-stimulus are used for the calculation of the central MD and central SLV. D Optic disc segmentation: 4 peripapillary sectors in which the RNFL thickness was determined. The temporal optic disc sectors anatomically overlapped with the VEP test field. The ring indicates the position of the scan circle of the OCT

Fig. 2

Blue-on-yellow VEP measurements in a healthy participant with the projector comparing on-screen and back-screen projection. In on-screen stimulation, the position of the projector was between patient and the screen. The angle of field size, the spatial frequency, and the luminance was the same for both methods. The dotted lines indicate the 95% confidence interval for six repeated tests

Fig. 3

The response to a blue-on-yellow pattern-onset/offset stimulus (yellow light 571 nm, superimposed blue pattern 460 nm). The figure shows the definitions of peak times and amplitudes for the (negative) onset-component and (positive) offset response. The mean luminance was 640 cd/m2

Fig. 4

A Age-dependence of the peak time of the N component in normal participants. If both eyes were studied (open symbols above and below a cross symbol), the mean from right and left eye were calculated (cross symbol). B The data in all groups were age corrected using the regression line as shown in Fig. 4A. Symbols: normal, cross; OHT, filled box; preperimetric glaucoma, open box; perimetric glaucoma, filled circle

Fig. 5

The averaged BY-VEPs (solid line) from ten normal participants (age group 50–60 years). The thin lines indicate 95% confidence interval. Dotted and dashed line show results from a glaucoma patient (age 59 years) with perimetric defects in both eyes

Fig. 6

Mean values (± 95 confidence interval) of BY-VEPs in normal participants and three patient groups. A Amplitudes. B Peak times. P values indicate significant differences between patients and control group. Paired comparison of on and offset components with the Wilcoxon-test (*p < 0.001) reveal significant larger onset than offset amplitudes in all groups. Onset and offset peak times differed significantly (*p < 0.001) only in perimetric patients

Fig. 7

ROC-curves generated for perimetric patients. A amplitudes of on- and off-set VEP. B Peak times of the (negative) onset-component show the largest diagnostic value

Fig. 8

VEP-onset results (A amplitude N, B peak time N) as a function of thickness of the corresponding RNFL show significant associations. Symbols: normal, cross; OHT, filled box; preperimetric glaucoma, open box; perimetric glaucoma, filled circle. In control participants, the RNFL is thicker, the amplitudes are larger, and the peak times are shorter than in patients. Spearman correlation coefficients are included for all participants and for glaucoma patients only (***p < 0.001, **p < 0.01)

Fig. 9

VEP-onset results as a function of central perimetric mean defects (Spearman rho, ***p < 0.001, **p < 0.01). Symbols: normal, cross; OHT, filled box; preperimetric glaucoma, open box; perimetric glaucoma, filled circle