Prediction of glaucoma severity using parameters from the electroretinogram

AbstractGlaucoma 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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Clinical Applications of the Photopic Negative Response to Optic Nerve and Retinal Diseases

Journal of Ophthalmology ◽

10.1155/2012/397178 ◽

2012 ◽

Vol 2012 ◽

pp. 1-11 ◽

Cited By ~ 20

Author(s):

Shigeki Machida

Keyword(s):

Optic Nerve ◽

Ganglion Cells ◽

Objective Assessment ◽

Visual Sensitivity ◽

Negative Response ◽

Photopic Negative Response ◽

Retinal Diseases ◽

Automated Perimetry ◽

Retinal Ganglion ◽

Standard Automated Perimetry

The photopic negative response (PhNR) in response to a brief flash is a negative-going wave following the b-wave of the cone electroretinogram (ERG) that is driven by retinal ganglion cells (RGCs). The function of RGCs is objectively evaluated by analysing the PhNR. We reviewed articles regarding clinical use of the PhNR. The PhNR was well correlated with the visual sensitivity obtained by standard automated perimetry and morphometric parameters of the inner retina and optic nerve head in optic nerve and retinal diseases. Moreover, combining the PhNR with focal or multifocal ERG techniques enables the objective assessment of local function of RGCs. The PhNR is therefore likely to become established as an objective functional test for optic nerve and retinal diseases involving RGC injury.

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Ganglion cell complex scan in the early prediction of glaucoma

Nepalese Journal of Ophthalmology ◽

10.3126/nepjoph.v4i2.6538 ◽

2012 ◽

Vol 4 (2) ◽

pp. 236-241

Author(s):

S Ganekal

Keyword(s):

Ganglion Cell ◽

Cell Complex ◽

P Value ◽

Ganglion Cell Complex ◽

Automated Perimetry ◽

Standard Automated Perimetry ◽

Fiber Layer ◽

Color Code ◽

Rnfl Thickness ◽

Significant Difference

Objective: To compare the macular ganglion cell complex (GCC) with peripapillary retinal fiber layer (RNFL) thickness map in glaucoma suspects and patients. Subjects and methods: Forty participants (20 glaucoma suspects and 20 glaucoma patients) were enrolled. Macular GCC and RNFL thickness maps were performed in both eyes of each participant in the same visit. The sensitivity and specificity of a color code less than 5% (red or yellow) for glaucoma diagnosis were calculated. Standard Automated Perimetry was performed with the Octopus 3.1.1 Dynamic 24-2 program. Statistics: The statistical analysis was performed with the SPSS 10.1 (SPSS Inc. Chicago, IL, EUA). Results were expressed as mean ± standard deviation and a p value of 0.05 or less was considered significant. Results: Provide absolute numbers of these findings with their units of measurement. There was a statistically significant difference in average RNFL thickness (p=0.004), superior RNFL thickness (p=0.006), inferior RNFL thickness (p=0.0005) and average GCC (p=0.03) between the suspects and glaucoma patients. There was no difference in optic disc area (p=0.35) and vertical cup/disc ratio (p=0.234) in both groups. While 38% eyes had an abnormal GCC and 13% had an abnormal RNFL thickness in the glaucoma suspect group, 98% had an abnormal GCC and 90% had an abnormal RNFL thickness in the glaucoma group.Conclusion: The ability to diagnose glaucoma with macular GCC thickness is comparable to that with peripapillary RNFL thickness. Macular GCC thickness measurements may be a good alternative or a complementary measurement to RNFL thickness assessment in the clinical evaluation of glaucoma.DOI: http://dx.doi.org/10.3126/nepjoph.v4i2.6538 Nepal J Ophthalmol 2012; 4 (2): 236-241

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A simplified combined index of structure and function for detecting and staging glaucomatous damage

Scientific Reports ◽

10.1038/s41598-021-82756-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Zhichao Wu ◽

Felipe A. Medeiros

Keyword(s):

Clinical Utility ◽

Mean Deviation ◽

Automated Perimetry ◽

Measurement Scales ◽

Empirical Formulas ◽

Fiber Layer ◽

Glaucomatous Damage ◽

Functional Changes ◽

Cell Counts ◽

Better Than

AbstractGlaucomatous damage results in characteristics structural and functional changes on optical coherence tomography (OCT) imaging and standard automated perimetry (SAP) testing. The clinical utility of these measures differs based on disease severity, as they are evaluated along different measurement scales. This study therefore sought to examine if a simplified combined structure–function index (sCSFI) could improve the detection and staging of glaucomatous damage, compared to the use of average retinal nerve fiber layer thickness (RNFL) measurements from OCT and mean deviation (MD) values from SAP alone, and also an estimated retinal ganglion cell counts (eRGC) measure derived using empirical formulas described previously. Examining 577 eyes from 354 participants with perimetric glaucoma and 241 normal eyes from 138 healthy participants, we found that the sCSFI performed significantly better than average RNFL, MD and eRGC count for discriminating between glaucoma and healthy eyes (P ≤ 0.008 for all). The sCSFI also performed significantly better than RNFL and eRGC count at discriminating between different levels of visual field damage in glaucoma eyes (P < 0.001 for both). These findings highlight the clinical utility of combining structural and functional information for detecting and staging glaucomatous damage using the simplified index developed in this study.

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Electrophysiological markers of preclinical diagnosis of glaucomatous optic neuropathy

Russian Ophthalmological Journal ◽

10.21516/2072-0076-2021-14-1-35-41 ◽

2021 ◽

Vol 14 (1) ◽

pp. 35-41

Author(s):

M. O. Kirillova ◽

M. V. Zueva ◽

I. V. Tsapenko ◽

A. N. Zhuravleva

Keyword(s):

Optic Neuropathy ◽

Ganglion Cells ◽

Open Angle Glaucoma ◽

Statistical Significance ◽

Photopic Negative Response ◽

Glaucomatous Optic Neuropathy ◽

Functional Changes ◽

Bright Flash ◽

Pattern Size ◽

Group 2

Purpose: to evaluate the changes in electrophysiological indicators reflecting various aspects of the function of retinal ganglion cells (RGC) and their axons in the early diagnosis of glaucomatous optic neuropathy (GON).Material and methods. Two clinical groups, (1) 35 patients (60 eyes) aged 49 to 70 with suspected glaucoma and (2) 16 patients (30 eyes) aged 43–68 with initial primary open-angle glaucoma (POAG), and a comparison group of 38 relatively healthy subjects (45 eyes) aged 42–70 were tested for pattern-reversed visual evoked potentials (PVEP), transient and stationary pattern-ERGs (PERG) according to ISCEV, and photopic negative response (PhNR).Results. The P100 amplitudes in both clinical groups differed significantly from the norm in PVEP on small and large patterns. The elongation of peak latency (T) of P100 compared with norm was significant for the stimulus 1° in group 2. In both groups of patients, increased variability of the temporal parameters of PERG and PVEP for small patterns was found. In groups 1 and 2, a decrease in the amplitude of P50 and N95 peaks of transient PERG for all stimuli was revealed, which was the most significant for the 0.3° pattern. In group 1, the N95 peak was significantly delayed in PERG for large patterns. A statistically significant reduction in the steady-state PERG's amplitude was found in the groups of suspected glaucoma and initial POAG. The sharpest changes were found for small (0.8° and 0.3°) patterns. The elongation of T compared to the norm was most pronounced for PERG at 0.3°, but due to the high variability of temporary indicators within the group, it had no statistical significance. The amplitude of PhNR was significantly different from the norm in the ERG for a flash of 3.0 cd·sec/m2.Conclusion. In patients with suspected glaucoma, a decrease in the P100 VEP amplitude with the simultaneous elongation of T may be considered as a criteria for the plastic stage at the level of lateral geniculate nucleus. Markers of functional changes in RGCs are the decrease in the amplitude of PhNR in response to bright flash, and P50 and N95 of PERG for pattern size 0.3°. The results indicate a greater vulnerability of the parvocellular system to early events in the development of GON.

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Monitoring for glaucoma progression with SAP, electroretinography (PERG and PhNR) and OCT

Documenta Ophthalmologica ◽

10.1007/s10633-021-09854-8 ◽

2021 ◽

Author(s):

Barbara Cvenkel ◽

Maja Sustar ◽

Darko Perovšek

Keyword(s):

Optic Disc ◽

Repeated Measurements ◽

Photopic Negative Response ◽

Ganglion Cell Complex ◽

Automated Perimetry ◽

Stable Group ◽

Standard Automated Perimetry ◽

Glaucoma Progression ◽

The Mean ◽

Over Time

Abstract Purpose To investigate the value of pattern electroretinography (PERG) and photopic negative response (PhNR) in monitoring glaucoma compared to standard clinical tests (standard automated perimetry (SAP) and clinical optic disc assessment) and structural measurements using spectral-domain OCT. Methods A prospective study included 32 subjects (32 eyes) with ocular hypertension, suspect or early glaucoma monitored for progression with clinical examination, SAP, PERG, PhNR and OCT for at least 4 years. Progression was defined clinically by the documented change of the optic disc and/or significant visual field progression (EyeSuite™ trend analysis). One eye per patient was included in the analysis. Results During the follow-up, 13 eyes (40.6%) showed progression, whereas 19 remained stable. In the progressing group, all parameters showed significant worsening over time, except for the PhNR, whereas in the stable group only the OCT parameters showed a significant decrease at the last visit. The trend of change over time using linear regression was steepest for the OCT parameters. At baseline, only the ganglion cell complex (GCC) and peripapillary retinal nerve fibre (pRNFL) thicknesses significantly discriminated between the stable and progressing eyes with the area under the ROC curve of 0.72 and 0.71, respectively. The inter-session variability for the first two visits in the stable group was lower for OCT (% limits of agreement within ± 17.4% of the mean for pRNFL and ± 3.6% for the GCC thicknesses) than for ERG measures (within ± 35.9% of the mean for PERG N95 and ± 59.9% for PhNR). The coefficient of variation for repeated measurements in the stable group was 11.9% for PERG N95 and 23.6% for the PhNR, while it was considerably lower for all OCT measures (5.6% for pRNFL and 1.7% for GCC thicknesses). Conclusions Although PERG and PhNR are sensitive for early detection of glaucomatous damage, they have limited usefulness in monitoring glaucoma progression in clinical practice, mainly due to high inter-session variability. On the contrary, OCT measures show low inter-session variability and might have a predicting value for early discrimination of progressing cases.

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Can Variability of Pattern ERG Signal Help to Detect Retinal Ganglion Cells Dysfunction in Glaucomatous Eyes?

BioMed Research International ◽

10.1155/2015/571314 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 6

Author(s):

Alberto Mavilio ◽

Francesca Scrimieri ◽

Donato Errico

Keyword(s):

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Second Harmonic ◽

Pattern Electroretinogram ◽

Mean Deviation ◽

Automated Perimetry ◽

Pattern Erg ◽

Retinal Ganglion ◽

Standard Automated Perimetry ◽

Fiber Layer

Objective. To evaluate variability of steady-state pattern electroretinogram (SS-PERG) signal in normal, suspected, and glaucomatous eyes.Methods. Twenty-one subjects with suspected glaucoma due to disc abnormalities (GS), 37 patients with early glaucoma (EG), and 24 normal control (NC) were tested with spectral-domain optical coherence tomography (SD-OCT), standard automated perimetry (SAP), and SS-PERG. Mean deviation (MD), pattern standard deviation (PSD), retinal nerve fiber layer (RNFL), and ganglionar complex cells (GCC) were evaluated. The SS-PERG was recorded five consecutive times and the amplitude and phase of second harmonic were measured. PERG amplitude and coefficient of variation of phase (CVphase) were recorded, and correlation with structural and functional parameters of disease, by means of one-way ANOVA and Pearson’s correlation, was analysed.Results. PERG amplitude was reduced, as expression of retinal ganglion cells (RGCs) dysfunction, in EG patients and GS subjects compared to NC patients (P<0.0001). CVphase was significantly increased in EG patients and GS subjects, compared to healthy (P<0.0001), and it was also correlated with PSD (P=0.0009), GCC (P=0.028), and RNFL (P=0.0078) only in EG patients.Conclusions. Increased intrasession variability of phase in suspected glaucomatous eyes may be a sign of RGCs dysfunction.

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The Assessment of Morphological and Functional Changes in the Detection of the Initial Stage of Primary Glaucoma

Ophthalmology in Russia ◽

10.18008/1816-5095-2021-4-857-865 ◽

2021 ◽

Vol 18 (4) ◽

pp. 857-865

Author(s):

N. I. Kurysheva ◽

L. V. Lepeshkina

Keyword(s):

Open Angle Glaucoma ◽

Angle Closure ◽

Ganglion Cell Complex ◽

Automated Perimetry ◽

Standard Automated Perimetry ◽

Fiber Layer ◽

Glaucoma Progression ◽

Functional Changes ◽

Primary Glaucoma ◽

Sd Oct

Purpose — to study morphological and functional changes in the detection of primary glaucoma progression.Patients and methods. 128 patients (128 eyes, among them — 64 eyes with primary open angle glaucoma (POAG) and 64 with primary angle closure glaucoma (PACG)) with the initial MD of –6.0 dB were examined at the Ophthalmology Center of the FMBA of Russia from May 2016 to November 2019. The values of corneal-compensated IOP were also considered: minimal (IOPmin), peak (IOPmax) and its fluctuations (IOPfluct). The progression was measured using standard automated perimetry (SAP) and spectral-domain OCT (SD-OCT). During the observation period, each patient received the average of 8.42 ± 2.08 SAP and SD-OCT. Progressive thinning of the retinal nerve fiber layer (RNFL) and its ganglion cell complex (GCC) were evaluated using SD-OCT. If RNFL and/or GCC had a trend of significant (p < 0.05) thinning, the eye was classified as having the SD-OCT progression. The correlation between the rate of progression detected by SAP (ROP1) using thinning of RNFL (ROP2) and GCC (ROP3) with other clinical parameters was analyzed.Results and discussion. Glaucoma progression was detected in 73 eyes. While the isolated use of SAP did not allow detecting progression, it was possible to detect it in 39 % cases by SD-OCT. The combination of both methods allowed detecting progression in 57 %. In both forms, ROP1 correlated with IOPmin: in PACG r = 0.41, p = 0.023 and in POAG r = 0.43, p = 0.016. In PACG, ROP2 and ROP3 correlated with the foveal choroid thickness: r = 0.46, p = 0.019 and r = 0.47, p = 0.009, respectively. At the same time, ROP3 was associated with peak IOP (r = –0.402, p = 0.025); the correlation of peak IOP with its fluctuations amounted to 0.7 (p < 0.001).Conclusion. SD-OCT is more informative than SAP in determining the progression of the initial primary glaucoma. The combination of these two methods 1.5 times increases the possibility of detecting progression in comparison with the isolated use of SD-OCT. The choroid thickness, associated with the IOP fluctuations, plays an important role in the progression of PACG.

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Comparison of Two Different OCT Systems: Retina Layer Segmentation and Impact on Structure-Function Analysis in Glaucoma

Journal of Ophthalmology ◽

10.1155/2016/8307639 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 11

Author(s):

Livia M. Brandao ◽

Anna A. Ledolter ◽

Andreas Schötzau ◽

Anja M. Palmowski-Wolfe

Keyword(s):

Structure Function ◽

Linear Models ◽

Function Analysis ◽

Open Angle Glaucoma ◽

Statistical Significance ◽

Plexiform Layer ◽

Inner Plexiform Layer ◽

Automated Perimetry ◽

Standard Automated Perimetry ◽

Layer Segmentation

Purpose. To compare two different spectral-domain optical coherence tomography (OCT) systems in regard to full macular thickness (MT) and ganglion cell layer-inner plexiform layer (GCIPL) measures and in regard to structure-function correlation when compared to standard automated perimetry (SAP).Methods. Seventeen primary open angle glaucoma patients and 16 controls (one eye per subject) were enrolled. MT and GCIPL thicknesses were measured by Cirrus and Spectralis OCTs. Octopus Perimeter 101 (G2 protocol) reports sensitivity in mean defect (dB). Differences between measurements were assessed with Student’st-test and Bland Altman. Diagnostic performance was also compared between each parameter calculating the areas under the operator receiver (ROC). Linear models were used to investigate structure-function association between OCT and SAP.Results. Disagreement between OCTs in both MT and GCIPL values was significant. Spectralis values were thicker than Cirrus. Average difference between OCTs was 21.64 μm (SD 4.5) for MT and 9.8 μm (SD 5.4) for GCIPL (p<0.001). Patients differed significantly from controls in both OCTs, in both measurements. MT and GCIPL were negatively associated with MD (p<0.001).Conclusions. Although OCT values were not interchangeable, both machines differentiated patients from controls with statistical significance. Structure-function analysis results were comparable, when either OCT was compared to SAP.

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Exploratory Study of the Association between the Severity of Idiopathic Intracranial Hypertension and Electroretinogram Photopic Negative Response Amplitude Obtained Using a Handheld Device

Life ◽

10.3390/life11050437 ◽

2021 ◽

Vol 11 (5) ◽

pp. 437

Author(s):

Antony Raharja ◽

Shaun M. Leo ◽

Isabelle Chow ◽

Mathura Indusegaran ◽

Christopher J. Hammond ◽

...

Keyword(s):

Intracranial Hypertension ◽

Disease Severity ◽

Idiopathic Intracranial Hypertension ◽

Retinal Nerve Fibre Layer ◽

Negative Response ◽

Photopic Negative Response ◽

Mean Deviation ◽

Automated Perimetry ◽

Standard Automated Perimetry ◽

Handheld Device

The photopic negative response (PhNR) is a negative component of the photopic flash electroretinogram that follows the b-wave and is thought to arise from the retinal ganglion cells. Reduction in its amplitude in idiopathic intracranial hypertension (IIH) has been previously documented using formal electroretinography. This study explored the use of a handheld device (RETeval, LKC technologies, USA) in 72 IIH patients of varying stages and severity (and seven controls) and investigated associations between PhNR parameters and disease severity. PhNR amplitudes at 72ms (P72) and p-ratio (ratio to b-wave peak value) differed significantly across groups, with a trend towards smaller amplitudes in those with severe IIH, defined as papilloedema with Modified Frisén Scale (MFS) ≥ 3, retinal nerve fibre layer (RNFL) ≥ 150μm or atrophic papilloedema (p = 0.0048 and p = 0.018 for P72 and p-ratio, respectively). PhNR parameters did not correlate with MFS, RNFL thickness, standard automated perimetry mean deviation or macular ganglion cell layer volume. This study suggests that PhNR measurement using a handheld device is feasible and could potentially augment the assessment of disease severity in IIH. The clinical utility of PhNR monitoring in IIH patients requires further investigation.

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Ocular direct current stimulation affects retinal ganglion cells

Scientific Reports ◽

10.1038/s41598-021-96401-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Maren-Christina Blum ◽

Alexander Hunold ◽

Benjamin Solf ◽

Sascha Klee

Keyword(s):

Retinal Ganglion Cells ◽

Repeated Measures ◽

Ganglion Cells ◽

Cell Activity ◽

Photopic Negative Response ◽

Pattern Reversal ◽

Retinal Ganglion ◽

Weak Current ◽

Positive Effects ◽

Significant Difference

AbstractOcular current stimulation (oCS) with weak current intensities (a few mA) has shown positive effects on retinal nerve cells, which indicates that neurodegenerative ocular diseases could be treated with current stimulation of the eye. During oCS, a significant polarity-independent reduction in the characteristic P50 amplitude of a pattern-reversal electroretinogram was found, while no current stimulation effect was found for a full field electroretinogram (ffERG). The ffERG data indicated a trend for a polarity-dependent influence during oCS on the photopic negative response (PhNR) wave, which represents the sum activity of the retinal ganglion cells. Therefore, an ffERG with adjusted parameters for the standardized measurement of the PhNR wave was combined with simultaneous oCS to study the potential effects of direct oCS on cumulative ganglion cell activity. Compared with that measured before oCS, the PhNR amplitude in the cathodal group increased significantly during current stimulation, while in the anodal and sham groups, no effect was visible (α = 0.05, pcathodal = 0.006*). Furthermore, repeated-measures ANOVA revealed a significant difference in PhNR amplitude between the anodal and cathodal groups as well as between the cathodal and sham groups (p* ≤ 0.0167, pcathodal − anodal = 0.002*, pcathodal − sham = 0.011*).

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