Electrophysiological markers of advanced stages of glaucomatous optic neuropathy

Purpose: to determine the changes in electrophysiological parameters reflecting specific dysfunctions of retinal ganglion cells (RGCs) at advanced stages of glaucomatous optic neuropathy (GON).Material and methods. The study involved 35 patients (55 eyes) aged 51–76 (63.1 ± 7.7 years) with primary open-angle glaucoma (POAG), divided into two subgroups depending on POAG stages: developed (24 patients, 27 eyes) and advanced stages (24 patients, 28 eyes). The age-matched control group (aged 51–72, 59.8 ± 5.9) included 28 relatively healthy individuals (32 eyes). Transient and steady-state pattern ERG (PERG) and photopic negative response (PhNR) were recorded according to ISCEV standards.Results. A decrease in the amplitude of the transient PERG's N95 and P50-waves and steady-state PERG was found, the degree of which showed an inverse dependence on the angular size of the stimulus, which clearly distinguished the developed and advanced POAG stages from the initial GON. The developed stages are characterized by a decrease in the PhNR amplitude, calculated from the baseline, and the PhNR/b index, the reduction of which was the more significant the greater the intensity of the flash. A significant delay of the N95 peak for patterns of all angular sizes and a less pronounced lengthening of the latency of the P50 wave (significant only for small stimuli 0.8° and 0.3°) in comparison with the age norm were found. The latencies of the steady-state PERG and PhNR practically did not differ from the age norm values.Conclusion. The revealed reduction in the amplitudes of N95 and P50 waves of transient and steady-state PERG, PhNR, and the PhNR/b index, as well as an increase in the peak latency of N95 and P50 waves of transient PERG, may be markers of functional changes in the retina associated with non-adaptive plasticity or reflecting a combination of the processes of adaptive plasticity and degeneration of RGCs. Further research in this area will help give a more accurate characterization of the found regularities and apply the obtained results in clinical practice.

Structural and Functional Correlations in Patients with Advanced Stages of Primary Open-Angle Glaucoma

Purpose: To study the correlations in the diagnosis of patients with advanced stages of primary open-angle glaucoma (POAG) using data from electroretinography and optical coherence tomography (OCT) of the retina.Methods. The study was performed in two clinical subgroups of patients (35 people, 55 eyes) with stages II and III POAG and the age-matched control group (28 healthy people, 32 eyes). The thickness of the ganglion cell complex (GCC), including the retinal nerve fiber layer (RNFL), the retinal ganglion cell layer (RGC), and the inner plexiform layer (INL) in the macular region, was assessed in nine segments. Correlation analysis of morphometric parameters of GCC in advanced POAG was performed with data from previously performed electroretinography: the transient pattern-ERG (T-PERG), stationary pattern-ERG (S-PERG), and photopic negative response (PhNR).Results. Statistically significant (p < 0.01) thinning of all layers of the GCC was revealed in all studied sectors. Significant (p < 0.05) differences in all morphometric characteristics were recorded between the two subgroups. In patients of the 1st subgroup, the greatest differences in morphological parameters from the control group’s values were noted in the lower, upper parafoveal sectors of the RGC layer, as well as in the temporal perifoveolar quadrant. In the 2nd subgroup, significant changes in the thickness of the inner retina layers were recorded for the upper and lower peripheral sectors of the RNFL and the temporal para- and peripheral quadrants of the RGC layer. In the study of morphological-functional relationships, the most significant correlations were revealed for the parameters of S-PERG. The amplitude of S-PERG directly correlated with the thickness of RNFL in the nasal sector of the perifovea (r = 0.86; p < 0.01) in the 1st subgroup of patients and the thickness of the RGC in the nasal sector of the perifovea in the 2nd subgroup (r = 0.84; p < 0.01). Moderate relationships were revealed between the N95/P50 T-PERG index and the RNFL thickness in the upper sector of the perifovea (r = 0.46; p < 0.05), the peak N95 T-PERG latency, and the RNFL thickness in the upper sector of the perifovea (r = –0.43; p < 0.05) in patients of the 1st subgroup. In patients of the 2nd subgroup, there was a correlation between the amplitude of N95 T-PERG and the thickness of the RGC in the lower sector of the perifovea (r = –0.42; p < 0.01), the peak latency of N95, and the thickness of the RNFL in the upper sector of the parafovea (r = –0.31; p < 0.05). A direct correlation was established between the PhNR amplitude from the baseline and the thickness of the RGC layer in the perifovea’s temporal sector (r = 0.72; p < 0.01) in patients with stage II POAG. The PhNR amplitude from the b-wave peak in patients with stage III POAG correlated with the RNFL thickness in the perifovea’s nasal sector (r = 0.51; p < 0.01).Conclusion. Specific patterns of morphological-functional changes in the parameters of the retina’s inner layers in patients with advanced POAG are presented, which can be used as clinical markers in determining an individual therapeutic strategy.

Structural and functional correlations in the pre-perimetric and the initial stages of glaucomatous optic neuropathy

Purpose:to study morphological and functional relationships in the early and preclinical diagnosis of glaucomatous optical neuropathy based on optical coherence tomography (OCT) of the retina and the data of electrophysiological research. Material and methods. Two clinical groups: (I) 35 patients (60 eyes) aged 49–70 (ave. 58.0 ± 5.3 yrs) with suspected glaucoma and (II) 21 patients (30 eyes) aged 46-68 (ave. 61.0 ± 4.8 yrs) with initial primary open-angle glaucoma (POAG), and a comparison group consisting of 36 relativelyhealthy subjects (41 eyes) aged 54–70 (ave. 62.0 ± 4.5 yrs), were subjected to spectral OCT by OСT Spectralis (Heidelberg Engineering, Germany). The thickness of the peripapillary layer of retinal nerve fibers (pRNFL), the minimum rim width (MRW), and the thickness of theretinal layers in the macular region that make up the ganglion cell complex (GCC) were evaluated. Spearman correlation analysis was used to identify correlations between OCT and electroretinography (ERG) data. Results.In patients with suspected glaucoma, changes in the parameters of transient pattern-ERG correlated with RNFL thinning in the macular region, inner plexiform layer (IPL), and ganglion cell layer(GCL) in the parafoveal area. In patients with initial glaucoma, changes in the retinal GCL were detected for the upper, lower, and temporal quadrants, while the nasal and central quadrants remained intact in all three GCC layers (RNFL, GCL, and IPL). In patients with suspected glaucoma, no statistically significant changes in the thickness of the pRNFL as compared with the norm were detected. Yet the MRW differed significantly from the comparison group. The highest number of correlations was found between the parameters of the ERGs and the thickness of the pRNFL. In patients with the initial stage of POAG, there was a significant increase in the thickness of RNFL in the temporal quadrant of the paramacular region. In our opinion, this phenomenon may be associated with the development of reactive gliosis being thereaction of neuroglia in response to changes in vascular and/or dystrophic homeostasis. Conclusion.Specific combinations of changes in the structural parameters of the retina and optic nerve head and the temporal and amplitude indices of the PERG and phototopic negative response have been found, justifying their use as combined markers of early and preclinical diagnosis of POAG.

Blue light blind-spot stimulation upregulates b-wave and pattern ERG activity in myopes

Upregulation of retinal dopaminergic activity may be a target treatment for myopia progression. This study aimed to explore the viability of inducing changes in retinal electrical activity with short-wavelength light targeting melanopsin-expressing retinal ganglion cells (ipRGCs) passing through the optic nerve head. Fifteen healthy non-myopic or myopic young adults were recruited and underwent stimulation with blue light using a virtual reality headset device. Amplitudes and implicit times from photopic 3.0 b-wave and pattern electroretinogram (PERG) were measured at baseline and 10 and 20 min after stimulation. Relative changes were compared between non-myopes and myopes. The ERG b-wave amplitude was significantly larger 20 min after blind-spot stimulation compared to baseline (p < 0.001) and 10 min (p < 0.001) post-stimulation. PERG amplitude P50-N95 also showed a significant main effect for ‘Time after stimulation’ (p < 0.050). Implicit times showed no differences following blind-spot stimulation. PERG and b-wave changes after blind-spot stimulation were stronger in myopes than non-myopes. It is possible to induce significant changes in retinal electrical activity by stimulating ipRGCs axons at the optic nerve head with blue light. The results suggest that the changes in retinal electrical activity are located at the inner plexiform layer and are likely to involve the dopaminergic system.

The photopic negative response (PhNR): measurement approaches and utility in glaucoma

Purpose Visual electrophysiological testing continues to generate interest among glaucoma experts because of its potential help in clarifying disease pathophysiology and promoting early detection of glaucomatous damage. The photopic negative response (PhNR) is a slow negative component of the full-field electroretinogram that has been shown to provide specific information about retinal ganglion cells (RGCs) activity. The purpose of this article is to review the literature to explore the currently available measurement methods and the utility of PhNR in glaucoma diagnostic process. Methods We gathered publications related to the origins, types of stimuli used, measurements methods and applications of the PhNR of ERG in animal models and humans through a search of the literature cited in PubMed. Search terms were: “PhNR”, “photopic negative response”, “glaucoma”, “glaucomatous optic neuropathy”, “ERG”, “electroretinogram”. Results The most reliable PhNR measurements are obtained using a red stimulus on a blue background, without requiring refractive correction, fixation monitoring, or ocular media transparency. Given its direct correlation with RGCs response, the PhNR measured as baseline-to-trough (BT) represents the most reliable parameter of evaluation. Glaucoma patients with evident perimetric defects show pathologic PhNR values. Even though the PhNR is promising in detecting early RGCs impairment, distinguishing between healthy subjects and suspect patients at risk of developing glaucomatous damage still remains challenging. Conclusion The PhNR is a useful additional tool to explore disorders that affect the innermost retina, including glaucoma and other forms of optic neuropathy. In particular, comparing reports of the standard examinations (optic disc assessment, OCT RNFL measurement, standard automated perimetry) with the results of electrophysiological tests may be helpful in solving clinical diagnostic and management dilemmas. On the one hand, the PhNR of the ERG can examine the parvocellular pathways; on the other hand, the steady-state pattern ERG optimized for glaucoma screening (PERGLA) can explore the magnocellular pathways. This could give ophthalmologists a useful feedback to identify early RGCs alterations suggestive of glaucoma, stratify the risk and potentially monitor disease progression.

Electroretinography in psychiatry: A systematic literature review

This review aims to consolidate the available information on use of electroretinography as a diagnostic tool in psychiatry. The electroretinogram (ERG) has been found to have diagnostic utility in cocaine withdrawal (reduced light-adapted b-wave response), major depressive disorder (reduced contrast gain in pattern ERG), and schizophrenia (reduced a- and b-wave amplitudes). This review examines these findings as well as the applicability of ERG to substance use disorder, Alzheimer’s disease, autism spectrum disorder, panic disorder, eating disorders, attention deficit hyperactivity disorder, and medication use. While there have been promising results, current research suffers from a lack of specificity. Further research that quantifies anomalies in ERG present in psychiatric illness is needed.

Functional Evaluation of the Visual Pathway in Patients with Multiple Sclerosis Using a Multifunction Stimulator Monitor

Objectives. To assess the capability of the vision monitor unit Monpack One of detecting visual function alterations in patients with multiple sclerosis (MS) and to evaluate the correlation between structural retinal parameters and functional measurements obtained with this device. Methods. Forty-eight patients with MS and 46 healthy controls were included in a cross-sectional study. All participants underwent a complete functional evaluation of the visual pathway, which included low-contrast visual acuity (LCVA), contrast sensitivity vision (CSV), automated perimetry, multifocal visual evoked potentials (mfVEPs), and pattern electroretinogram (ERG). All tests were performed using the vision monitor unit Monpack One (Metrovision, France), a multifunction stimulator device. Retinal structural measurements were obtained in all subjects using Triton swept source optical coherence tomography (Topcon, Japan). Results. Patients with MS presented reduced low-contrast VA (p<0.001) and reduced CSV at medium (p=0.001, p=0.013) and low (p=0.001, p=0.002) spatial frequencies. All visual field parameters were found to be altered in MS patients compared with controls (≤0.001). Patients with MS presented lower amplitude of the P100 waveform of the mfVEP in areas corresponding to central (p<0.001), inferonasal (p=0.001), and inferotemporal (p=0.003) retina. The pattern ERG did not show significant differences. Significant correlations were observed between structural retinal measurements and functional parameters, especially between the inner macular areas and measurements corresponding to contrast sensitivity and perimetry indexes. Conclusions. Patients with MS present visual dysfunction detectable with the vision monitor unit Monpack One. This device may be a fast and useful tool to provide a full evaluation of axonal damage in patients with multiple sclerosis.

The neuro-ophthalmological effects related to long-term occupational exposure to organic solvents in painters

Purpose: Organic solvents are widely used in many industries, and usually, exposure occurs with mixtures of solvents. Organic solvent mixtures are known for their ability to affect tissues of high lipid content including the myelin sheath in the nervous system. The purpose of this work was to study the evidence that long-term (more than 10 years) exposure to organic solvent mixtures among painters can induce neuro-ophthalmological effects on the function of retinal ganglion cells and the optic tract. Methods: Twenty workers with long-term occupational exposure to mixed organic solvents were compared to 40 control subjects. The controls were matched for age, gender, and demographic characteristics but were not occupationally exposed to any known organic solvents, using the following comparators: visual evoked potential (VEP), electroretinogram (ERG), color vision (CV), and contrast sensitivity (CS) testing. Environmental monitoring was done in the work environment with consideration to the American Conference of Governmental Industrial Hygienists Threshold Limit Values (ACGIH-TLVs). Results: The exposed group had significantly longer latency and higher amplitude of VEP waves especially P100, higher Color Confusion Index (CCI), especially affecting the blue–yellow spectrum, and lower Log CS. There was no significant difference between exposed and nonexposed groups in full-field flash ERG response; however, in the pattern ERG, the exposed group had significantly longer latency of P50, which reflects changes in the retinal ganglion cell. Conclusion: Long-term occupational exposure to mixed organic solvents appeared to affect the optic tract functions in the form of increasing latency of VEP response, affecting the quality of CV and decreasing CS. It also affects the retinal ganglion cell layer with increased latency of P50 of the pattern ERG response.

Visual Evoked Potentials and Electroretinograms

Electrophysiological testing of vision permits the objective assessment of the function of the retina, visual pathways, and cortices. This chapter covers visual evoked potentials (VEPs) and electroretinography (ERG). Flash ERG is useful in evaluating the outer retinal function and specifically helping in the diagnosis of retinal degeneration, monitoring the progress of retinal diseases, monitoring the retinal toxicity of drugs, and understanding the pathophysiology of retinal disorders. VEPs to various stimuli are useful in evaluating macular disorders, diagnosing optic neuropathies, detecting silent pathologies in the absence of other clinical signs of visual impairment, and evaluating disturbances of visual processing in degenerative diseases of the central nervous system. Simultaneous recording of pattern ERG and pattern VEP permits the differentiation between maculopathies and optic neuropathy.