Optometry and Vision Sciences - Research Publications

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    Time-Frequency Analysis of ERG With Discrete Wavelet Transform and Matching Pursuits for Glaucoma.
    Sarossy, M ; Crowston, J ; Kumar, D ; Weymouth, A ; Wu, Z (Association for Research in Vision and Ophthalmology (ARVO), 2022-10-03)
    PURPOSE: To examine the performance of two time-frequency feature extraction techniques applied to electroretinograms (ERGs) for the prediction of glaucoma severity. METHODS: ERGs targeting the photopic negative response were obtained in 103 eyes of 55 patients with glaucoma. Features from the ERG recordings were extracted using two time-frequency extraction techniques based on the discrete wavelet transform (DWT) and the matching pursuit (MP) decomposition. Amplitude markers of the time-domain signal were also extracted. Linear and multivariate adaptive regression spline (MARS) models were fitted using combinations of these features to predict estimated retinal ganglion cell counts, a measure of glaucoma disease severity derived from standard automated perimetry and optical coherence tomography imaging. RESULTS: Predictive models using features from the time-frequency analyses-using both DWT and MP-combined with amplitude markers outperformed predictive models using the markers alone with linear (P = 0.001) and MARS (P ≤ 0.011) models. For example, the proportions of variance (R2) explained by the MARS model using the DWT and MP features with amplitude markers were 0.53 and 0.63, respectively, compared to 0.34 for the model using the markers alone (P = 0.011 and P = 0.001, respectively). CONCLUSIONS: Novel time-frequency features extracted from the photopic ERG substantially added to the prediction of glaucoma severity compared to using the time-domain amplitude markers alone. TRANSLATIONAL RELEVANCE: Substantial information about retinal ganglion cell dysfunction exists in the time-frequency domain of ERGs that could be useful in the management of glaucoma.
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    Prediction of glaucoma severity using parameters from the electroretinogram
    Sarossy, M ; Crowston, J ; Kumar, D ; Weymouth, A ; Wu, Z (NATURE PORTFOLIO, 2021-12-13)
    Glaucoma is an optic neuropathy that results in the progressive loss of retinal ganglion cells (RGCs), which are known to exhibit functional changes prior to cell loss. The electroretinogram (ERG) is a method that enables an objective assessment of retinal function, and the photopic negative response (PhNR) has conventionally been used to provide a measure of RGC function. This study sought to examine if additional parameters from the ERG (amplitudes of the a-, b-, i-wave, as well the trough between the b- and i-wave), a multivariate adaptive regression splines (MARS; a non-linear) model and achromatic stimuli could better predict glaucoma severity in 103 eyes of 55 individuals with glaucoma. Glaucoma severity was determined using standard automated perimetry and optical coherence tomography imaging. ERGs targeting the PhNR were recorded with a chromatic (red-on-blue) and achromatic (white-on-white) stimulus with the same luminance. Linear and MARS models were fitted to predict glaucoma severity using the PhNR only or all ERG markers, derived from chromatic and achromatic stimuli. Use of all ERG markers predicted glaucoma severity significantly better than the PhNR alone (P ≤ 0.02), and the MARS performed better than linear models when using all markers (P = 0.01), but there was no significant difference between the achromatic and chromatic stimulus models. This study shows that there is more information present in the photopic ERG beyond the conventional PhNR measure in characterizing RGC function.
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    Measuring the Photopic Negative Response: Viability of Skin Electrodes and Variability Across Disease Severities in Glaucoma
    Wu, Z ; Hadoux, X ; Gaskin, JCF ; Sarossy, MG ; Crowston, JG (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2016-03)
    PURPOSE: The purpose of this study was to determine the feasibility of measuring the photopic negative response (PhNR) of the full-field electroretinogram (ERG) using skin electrodes compared to conjunctival electrodes and its test-retest variability over a range of disease severities in open-angle glaucoma. METHODS: Recordings were performed twice (100 sweeps each) within the same session in 43 eyes of 23 participants with glaucoma to determine its intrinsic variability. The ratio between the PhNR and B-wave amplitude (PhNR/B ratio) was determined for each trace and computed across 5 to 100 sweeps of each recording. Spectral-domain optical coherence tomography was used to measure the average peripapillary retinal nerve fiber layer (RNFL) thickness. RESULTS: The PhNR/B ratio and its magnitude of variability were not significantly different between skin and conjunctival electrodes (P ≤ 0.197), and the degree of variability decreased substantially with increasing number of sweeps. For skin electrodes, the intraclass correlation coefficient was 0.89 and 0.91 for right and left eyes, respectively. The variability of the PhNR/B ratio decreased with lower RNFL thickness values and larger B-wave amplitudes (P ≤ 0.002). CONCLUSIONS: Skin electrodes are a viable alternative to conjunctival electrodes when measuring the PhNR in open angle glaucoma, and increasing the number of sweeps substantially reduced its intrinsic variability; the extent of variability was also lower with worsening disease severity. TRANSLATIONAL RELEVANCE: The feasibility of performing ERG recordings widely across a range of disease severities in glaucoma can be achieved through using skin electrodes and increasing the number of sweeps performed to improve measurement repeatability.
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    A Comparison of the RETeval Sensor Strip and DTL Electrode for Recording the Photopic Negative Response
    Tang, J ; Hui, F ; Hadoux, X ; Sarossy, M ; van Wijngaarden, P ; Coote, M ; Crowston, JG (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2018-12)
    PURPOSE: To compare the RETeval sensor strip and Dawson-Trick-Litzkow (DTL) electrodes for recording the photopic negative response (PhNR) using a portable electroretinogram (ERG) device in eyes with and without glaucoma. METHODS: Twenty-six control and 31 glaucoma or glaucoma-suspect participants were recruited. Photopic ERGs were recorded with sensor strip and DTL electrodes in random order using the LKC RETeval device. Stimuli consisted of brief, red flashes (1.7 cd.s/m2) on a blue background (photopic 10 cd/m2). The PhNR amplitude was measured from baseline to trough and also expressed as a ratio over the b-wave amplitude. RESULTS: The sensor strip-recorded PhNR amplitude was significantly attenuated (mean ± standard deviation [SD], 4.8 ± 2.1 vs. 12.7 ± 4.8 μV, P < 0.0001), with lower signal-to-noise ratio (SNR; 5.5 ± 2.1 vs. 8.1 ± 3.9, P < 0.0001), and a trend toward a larger PhNR/b-wave ratio compared with DTL electrodes. The PhNR amplitude, implicit time and PhNR/b-wave ratio correlated with visual field mean light sensitivity, although this fell short of significance for the sensor strip recorded PhNR amplitude. The electrodes demonstrated similar intersession repeatability with a coefficient of repeatability of ±27% and ±28% for the DTL and sensor strip, respectively. CONCLUSIONS: Sensor strip electrodes are a viable alternative for recording reproducible PhNRs, especially when values are normalized to the b-wave. However, DTL electrodes should be considered in cases of attenuated PhNR, or in elevated noise levels, due to its better signal-to-noise quality. TRANSLATIONAL RELEVANCE: Sensor strip electrodes can simplify PhNR recordings in the clinic, potentially eliminating the need for an experienced operator.
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    Photopic Negative Response Obtained Using a Handheld Electroretinogram Device: Determining the Optimal Measure and Repeatability
    Wu, Z ; Hadoux, X ; Hui, F ; Sarossy, MG ; Crowston, JG (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2016-07)
    PURPOSE: To determine the measure of the photopic negative response (PhNR) of the full-field electroretinogram (ERG) that exhibits the optimal level of test-retest repeatability, and examine its repeatability under different conditions using a handheld, nonmydriatic ERG system and self-adhering skin electrodes. METHODS: Multiple ERG recordings (using 200 sweeps each) were performed in both eyes of 20 normal participants at two different sessions to compare its coefficient of repeatability (CoR; where 95% of the test-retest difference is expected to lie) between different PhNR measures and under different testing conditions (within and between examiners, and between sessions). RESULTS: The ratio between the PhNR trough to b-wave peak and b-wave peak to a-wave trough amplitude (PhNR/B ratio) exhibited the lowest CoR relative to its effective dynamic range (30 ± 4%) when including three recordings. There were no significant changes in the PhNR/B ratio over seven measurements (4 right and 3 left eyes) at either session (P ≥ 0.100), or significant difference in its CoR between different testing conditions (P = 0.314). CONCLUSION: The PhNR/B ratio was the measure that minimized variability, and its measurements using a novel handheld ERG system with self-adhering skin electrodes and the protocols described in this study were comparable under different testing conditions and over multiple recordings. TRANSLATIONAL RELEVANCE: The PhNR can be measured for clinical and research purposes using a simple-to-implement technique that is consistent within and between visits, and also between examiners.
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    Test-Retest Variability of Fundus-Tracked Perimetry at the Peripapillary Region in Open Angle Glaucoma
    Wu, Z ; McKendrick, AM ; Hadoux, X ; Gaskin, JCF ; Ang, GS ; Sarossy, MG ; Crowston, JG (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2016-07)
    PURPOSE: To examine the association between the measured level and local gradient of visual sensitivity on the magnitude of test-retest variability of its measurements at the peripapillary region using fundus-tracked perimetry in eyes with glaucoma. METHODS: A total of 30 participants with open angle glaucoma underwent three examinations in one eye on fundus-tracked perimetry using a stimulus pattern that sampled the peripapillary region densely. Factors associated with the magnitude of test-retest variability at each location were examined. RESULTS: There was no significant change in average pointwise sensitivity (PWS) between tests 1 and 2 (P = 0.855), but a significant reduction between tests 2 and 3 (P < 0.001). Therefore, all subsequent analyses were performed only between tests 1 and 2. Multivariate analyses revealed that the magnitude of test-retest variability at a given location was significantly associated with its average sensitivity and gradient of sensitivity relative to the immediately adjacent locations (P ≤ 0.001), meaning that locations with low levels of sensitivity (4-18 dB) with low gradients of sensitivity (<2 dB/location) had a 90% test-retest limit of ±5.83 dB, compared to a limit of ±10.65 dB in areas of high gradients of sensitivity (>4 dB/location). CONCLUSIONS: On a pointwise basis, the test-retest variability of visual sensitivity in glaucoma is not just related to its measured level, but also its local gradient when using fundus-tracked perimetry. Locations with low sensitivity do not necessarily demonstrate very high test-retest variability, depending on the local uniformity of visual field damage.