Imaging video plethysmography shows reduced signal amplitude in glaucoma patients in the area of the microvascular tissue of the optic nerve head

Abstract

Purpose: To measure parameters of the cardiac cycle-induced pulsatile light absorption signal (plethysmography signal) of the optic nerve head (ONH) and to compare parameters between normal subjects and patients with different stages of glaucoma.

Patients and methods: A recently developed video ophthalmoscope was used to acquire short video sequences (10 s) of the ONH. After image registration and trend correction, the pulsatile changing light absorption at the ONH tissue (excluding large vessels) was calculated. The changing light absorption depends on the pulsatile changing blood volume. Various parameters, including peak amplitude, steepness, time-to-peak, full width at half maximum (FWHM), and pulse duration, were calculated for averaged individual pulses (heartbeats) of the plethysmography signal. This method was applied to 19 healthy control subjects and 91 subjects with ocular hypertension, as well as different stages of primary open-angle glaucoma (17 subjects with ocular hypertension, 24 with preperimetric glaucoma, and 50 with perimetric glaucoma).

Results: Compared to the normal subjects, significant reductions (p < 0.001) in peak amplitude and steepness were observed in the group of perimetric glaucoma patients, but no significant difference was found for time-to-peak, FWHM, and pulse duration. Peak amplitude and steepness showed high correlations with RNFL thickness (p < 0.001).

Conclusions: The presented low-cost video-ophthalmoscope permits measurement of the plethysmographic signal of the ONH tissue and calculation of different blood flow-related parameters. The reduced values of the amplitude and steepness parameters in perimetric glaucoma patients suggest decreased ONH perfusion and blood volume. This outcome is in agreement with results from other studies using OCT angiography and laser speckle flowgraphy, which confirm reduced capillary density in these patients. Registration site: www.clinicaltrials.gov , Trial registration number: NCT00494923.

Keywords: Blood flow; Blood volume; Glaucoma; Perfusion; Retinal plethysmography.

Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Fig. 1

Flowchart to calculate pulse parameters of the plethysmographic signal of the ONH from video sequences. The different steps (1) to (9) are explained in the text

Fig. 2

Calculation of averaged pulse from raw (intensity) signal of a normal subject. (A) original pulsatile signal (thick blue line) and calculated trend (red thin line). (B) Calculated plethysmographic signal after trend correction (dotted line) and manually selected pulses (solid parts). (C) Averaged image with segmented ONH ROI (green). (D) Five selected individual single pulses. (E) Averaged pulse was calculated from selected single pulses (red line) and standard deviation (reddish area). Twenty-five frames correspond to 1 s

Fig. 3

Graphical explanation of calculated parameters from averaged pulse

Fig. 4

Examples of calculated averaged pulses. Upper row: averaged fundus images of the entire sequence and segmented ONH ROIs (green area). Middle row: averaged pulses (red line) and standard deviations (reddish areas) calculated from the green ROIs shown in the upper row. Lower row: calculated pulse parameters (the bright semicircle on the right side in image B is due to a not correct aligned aperture during this measurement, but it has no influence on the result.) A corresponding example of a normal subject (amplitude 7.6%A, steepness 34%A/s, FWHM 44%) is shown in Fig. 2C and E. Patient groups: OHT, ocular hypertension; prep, preperimetric glaucoma; perim, perimetric glaucoma

Fig. 5

Boxplots showing medians and quartiles of peak amplitude and steepness for the different subject groups. Significant differences (p < 0.001) between groups (Mann-Whitney test) in comparison with normal subjects are indicated by asterisks (*). Patient groups: OHT, ocular hypertension; prep, preperimetric glaucoma; perim, perimetric glaucoma; norm, normal subjects

Fig. 6

Scatterplots of peak amplitude and steepness as functions of RNFL mean thickness, including regression lines. The Spearman test indicates a significant association between peak amplitude and steepness with RNFL thickness. Patient groups: OHT, ocular hypertension; prep, preperimetric glaucoma; perim, perimetric glaucoma; norm, normal subjects