Photopic Negative Response Amplitude Research Articles

Slope between positive and negative ERG components in patients with open-angle glaucoma.

To evaluate ERG morphology, in particular the slope between P50 and N95 components of the PERG, as well as between the b-wave and the photopic negative response (PhNR) of the light-adapted (LA) ERG in patients with retinal ganglion cell (RGC) dysfunction due to open-angle glaucoma. The PERG and LA-ERG traces of 16 glaucoma patients and 21 age-similar controls were retrospectively analysed. The ERG signal between the peak of the positive component (P50 and b-wave) towards the negative component (N95 and PhNR) was described by a linear regression y = a + bx, where the parameter b indicated the steepness of the P50-N95 and b-PhNR slope. The P50-N95 slope was less steep in glaucoma patients (-0.079 ± 0.034 vs. -0.166 ± 0.050 in controls, p < 0.001), while the b-PhNR slope was not affected (-4.2 ± 2.1 vs. -4.4 ± 1.2, p = NS). The P50-N95 slope showed strong correlation with PhNR and N95 amplitude (r = -0.68 and -0.92, respectively; p < 0.001), while the b-PhNR slope correlated only with b-wave amplitude (r = -0.66, p < 0.001). The P50-N95 slope is a sensitive indicator of RGC dysfunction in patients with open-angle glaucoma. A similar component of LA-ERG, the b-PhNR slope, is less affected by glaucomatous RGC dysfunction and probably originates from similar retinal mechanisms as the b-wave.

GSK840 Alleviates Retinal Neuronal Injury by Inhibiting RIPK3/MLKL-Mediated RGC Necroptosis After Ischemia/Reperfusion.

This study aimed to explore the impact of GSK840 on retinal neuronal injury after retinal ischemia/reperfusion (IR) and its associated mechanism. We established an in vivo mouse model of IR and an in vitro model of oxygen and glucose deprivation/reoxygenation (OGDR) in primary mouse retinal ganglion cells (RGCs). GSK840, a small-molecule compound, was used to specifically inhibit RIPK3/MLKL-dependent necroptosis. Retinal structure and function evaluation was performed by using hematoxylin and eosin staining, optical coherence tomography, and electroretinography. Propidium Iodide (PI) staining was used for detection of necroptotic cell death, whereas Western blot analysis and immunofluorescence were used to assess necroptosis-related proteins and inner retinal neurons. RIPK3/MLKL-dependent necroptosis was rapidly activated in RGCs following retinal IR or OGDR. GSK840 helped maintain relatively normal inner retinal structure and thickness by preserving inner retinal neurons, particularly RGCs. Meanwhile, GSK840 ameliorated IR-induced visual dysfunction, as evidenced by the improved amplitudes of photopic negative response, a-wave, b-wave, and oscillatory potentials. And GSK840 treatment significantly reduced the population of PI+ RGCs after injury. Mechanistically, GSK840 ameliorated RGC necroptosis by inhibiting the RIPK3/MLKL pathway. GSK840 exerts protective effects against retinal neuronal injury after IR by inhibiting RIPK3/MLKL-mediated RGC necroptosis. GSK840 may represent a protective strategy for RGC degeneration in ischemic retinopathy.

Park7 protects retinal ganglion cells and promotes functional preservation after optic nerve crush via regulation of the Nrf2 signaling pathway.

We aim to investigate the effect of Park7 on mice RGC survival and function following optic nerve crush (ONC), and to explore its potential mechanism. Wild-type male C57BL/6J mice were subjected to optic nerve crush. Six weeks before ONC, mice received rAAV-shRNA (Park7)-EGFP or rAAV-EGFP intravitreally. Western blotting was used to detect Park7 levels. RGC survival was measured using immunofluorescence. Retinal cell apoptosis was detected using terminal deoxynucleotidyl transferase nick-end-labelling. An electroretinogram (ERG) and the optomotor response (OMR) were used to assess RGC function. Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor (Nrf2), and heme oxygenase 1 (HO-1) levels were assessed using western blotting. ONC injury increased the relative expression of Park7 significantly and decreased RGC survival, the amplitude of the photopic negative response (PhNR), and OMR. Intravitreal injection of rAAV-shRNA(Park7)-EGFP downregulated Park7 expression and was clearly demonstrated by the green fluorescence protein in many retinal layers. Moreover, Park7 downregulation aggravated the decrease in RGC survival and amplitude of PhNR as well as the visual acuity after ONC. However, inhibition of Park7 significantly increased Keap1 levels, decreased the total and nuclear Nrf2 levels, and reduced HO-1 levels. Park7 downregulation enhanced RGC injury and decreased retinal electrophysiological response and OMR after ONC in mice via the Keap1-Nrf2-HO-1 signaling pathway. Park7 may have neuroprotective effects and could represent a novel way to treat optic neuropathy.

PhNR and peripapillary RNFL changes in Leber hereditary optic neuropathy with m.G11778A mutation

PurposeTo analyze the functional and structural changes in retinal ganglion cells (RGCs) and their axons that occur during Leber's hereditary optic neuropathy (LHON) using photopic negative response (PhNR) and spectral domain optical coherence tomography (SD-OCT). MethodsIndividuals diagnosed with LHON and their family members were invited to participate in this cross-sectional study. PhNR and OCT were used. The PhNR amplitude and peripapillary retinal nerve fiber layer (pRNFL) thicknesses were compared among the three groups. In addition, affected individuals were divided into subacute, dynamic and chronic phases based on disease duration in order to evaluate the decay in RGCs function and structure. Results73 affected and 30 carriers with a m.11778G > A mutation were included. PhNR amplitude and the thickness of pRNFL significantly decreased in affected individuals and carriers compared to that of the controls (P＜0.001). However, there was no difference between the carriers and the controls (P＞0.05). There was no difference in the PhNR amplitude of different phases (P = 0.464). In the subacute phase, only temporal pRNFL thickness decreased significantly (P＜0.001). PRNFL thickness decreased significantly in dynamic phase (P＜0.001). Temporal pRNFL thickness continued to decrease in the chronic phase (P = 0.042). ConclusionIn the subacute phase, the function of RGCs was severely impaired. Thickness of pRNFL decreased significantly in four quadrants during disease progression. In the chronic phase, pRNFL thickness decreased slightly. Carriers have shown RGCs dysfunction before pathological changes occur, suggesting subclinical abnormalities.

Long-term blue light rearing does not affect in vivo retinal function in young rhesus monkeys.

Exposure to blue light is thought to be harmful to the retina. The purpose of this study was to determine the effects of long-term exposure to narrowband blue light on retinal function in rhesus monkeys. Young rhesus monkeys were reared under short-wavelength "blue" light (n = 7; 465nm, 183 ± 28lx) on a 12-h light/dark cycle starting at 26 ± 2days of age. Age-matched control monkeys were reared under broadband "white" light (n = 8; 504 ± 168lx). Light- and dark-adapted full-field flash electroretinograms (ERGs) were recorded at 330 ± 9days of age. Photopic stimuli were brief red flashes (0.044-5.68cd.s/m2) on a rod-saturating blue background and the International Society for Clinical Electrophysiology of Vision (ISCEV) standard 3.0 white flash on a 30cd/m2 white background. Monkeys were dark adapted for 20min and scotopic stimuli were ISCEV standard white flashes of 0.01, 3.0, and 10cd.s/m2. A-wave, b-wave, and photopic negative response (PhNR) amplitudes were measured. Light-adapted ERGs in young monkeys were compared to ERGs in adult monkeys reared in white light (n = 10; 4.91 ± 0.88years of age). For red flashes on a blue background, there were no significant differences in a-wave (P = 0.46), b-wave (P = 0.75), and PhNR amplitudes (P = 0.94) between white light and blue light reared monkeys for all stimulus energies. ISCEV standard light- and dark-adapted a- and b-wave amplitudes were not significantly different between groups (P > 0.05 for all). There were no significant differences in a- and b-wave implicit times between groups for all ISCEV standard stimuli (P > 0.05 for all). PhNR amplitudes of young monkeys were significantly smaller compared to adult monkeys for all stimulus energies (P < 0.05 for all). There were no significant differences in a-wave (P = 0.19) and b-wave (P = 0.17) amplitudes between young and adult white light reared monkeys. Long-term exposure to narrowband blue light did not affect photopic or scotopic ERG responses in young monkeys. Findings suggest that exposure to 12h of daily blue light for approximately 10months does not result in altered retinal function.

Ocular Morpho-Functional Evaluation in ATTRv Pre-Symptomatic Carriers: A Case Series.

The present study aimed to investigate ocular findings in hereditary transthyretin amyloidosis (ATTRv) pre-symptomatic carriers. Fourteen ATTRv pre-symptomatic carriers, who are patients with positive genetic testing but without signs or symptoms of the disease, were retrospectively evaluated. Retinal morphology was assessed using optical coherence tomography (OCT) and OCT-angiography. Retinal function was evaluated using cone b-wave and photopic negative response (PhNR). Pupillometry and in vivo corneal confocal microscopy (IVCM) were performed. ATTRv pre-symptomatic carriers presented a significantly reduced central macular thickness (CMT) (p = 0.01) and outer nuclear layer (ONL) thickness (p = 0.01) in comparison to normal controls. No differences were found when analyzing sub-foveal choroidal thickness, retinal nerve fiber layer and ganglion cell complex. In comparison to healthy controls, pre-symptomatic carriers presented an attenuated superficial retinal vascular network and a significantly augmented PhNR amplitude (p = 0.01). However, PhNR implicit times, B-wave amplitude and B-wave peak time did not show significant differences in comparison to controls. No differences were found for pupillometric values. All the examined eyes presented alterations in the IVCM. Preclinical ocular structural and functional abnormalities can be found in ATTRv pre-symptomatic carriers. Thus, an extensive ophthalmological evaluation should be included at the baseline visit and during follow-up. Considering the availability of new drugs potentially able to prevent or delay disease progression, the identification of new disease biomarkers appears to be particularly promising.

Correlation between OCT-angiography and photopic negative response in patients with primary open angle glaucoma

PurposeTo evaluate the association between OCT-angiography (OCTA) and photopic negative response (PhNR) in open angle glaucoma (OAG) patients and assess the diagnostic accuracy of these parameters in early detection of glaucoma.MethodsA total of 152 eyes were enrolled in this study, 28 eyes with mild POAG (group I), 44 eyes with moderate-severe POAG (group 2) & 80 eyes of healthy subjects (control group). Full ophthalmological examination, OCTA and PhNR measurements were underwent for all participants. RNFL, GCC thicknesses, PhNR (implicit time and amplitude) were recorded. The superficial and deep capillary plexus vessel density (SCP-VD%, DCP-VD%) were measured by using 6 × 6 mm macula OCTA scans. The peripapillary vessel density (RPC-VD %) were measured by using 4.5 × 4.5 mm optic disk head OCTA scans.ResultsThere were reduction of the median Interquartile range (IQR) thickness of the GCC and RNFL in OAG eyes versus normal (P < 0.001). RPC-VD%, SCP-VD % and DCP-VD% were significantly reduced in OAG eyes versus normal (P < 0.001). Increased OAG severity was associated with more reduction in PhNR amplitude and increased implicit time. Reduced PhNR amplitude and prolonged latency were significantly correlated with reduced vascular parameters. The RCP-VD and PhNR amplitude demonstrated higher diagnostic accuracy (98.7) with the largest AUC and higher sensitivity and specificity (100% & 98.7%, respectively), followed by the PhNR implicit time with (AUC = 0.995) with a diagnostic accuracy 98.7. The SCP-VD, RNFL and GCC thickness had a diagnostic accuracy of (75.0, 81.6 & 84.2), respectively (P < 0.001).ConclusionsOCTA vascular parameters displayed significant positive correlation with PhNR amplitude and significant negative correlation with PhNR implicit time. OCTA and PhNR parameters showed a high diagnostic accuracy for detection of glaucoma, and both may provide promising insight in early detection of glaucoma.This study was retrospectively registered on ClinicalTrials.gov (identifier, NCT05104294).

Intravitreal Fluocinolone Acetonide for Diabetic Macular Edema: Long-Term Effect and Structure/Function Correlation.

The long-term effect of intravitreal Fluocinolone acetonide (FAc) on retinal morphology and function in diabetic macular edema (DME) was investigated. Seventeen eyes of twelve consecutive DME patients, treated by intravitreal FAc, were retrospectively evaluated. Retinal morphology was assessed with central macular thickness (CMT). Retinal function was assessed by best-corrected visual acuity (BCVA) and cone b-wave and photopic negative response (PhNR). The main outcome was a mean change in CMT at month 24. The secondary outcomes were changes in cone b-wave and PhNR at month 24. The incidence of adverse events was also recorded. Mean CMT decreased from 406.52 µm (±138.74) at baseline to 310 µm (±130.39) at 24 months (p = 0.008). No significant changes in the other parameters were found. At baseline, BCVA and PhNR amplitude were negatively correlated (r = −0.55) with CMT. At the end of follow-up, the change in CMT was negatively correlated with baseline CMT (r = −0.53, p = 0.03) and positively correlated with baseline PhNR amplitude (r = 0.58, p < 0.01). A significant, long-term reduction in CMT was observed in DME patients after FAc implant. The anti-edema effect tended to be stronger in patients with the poorest baseline retinal morphology (CMT) and function (PhNR). Structure/function correlations might help to characterize the patients who may benefit from this treatment.

Olaparib, a PARP-1 inhibitor, protects retinal cells from ocular hypertension-associated oxidative damage.

Glaucoma is the most common cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP) and relative hypoxia in the retina stimulate the production of reactive oxygen species (ROS), which, in turn, puts the retina and optic nerve under chronic oxidative stress. Emerging evidence has shown that oxidative stress can trigger PARP-1 overactivation, mitochondrial-associated endoplasmic reticulum membrane (MAM) dysregulation, and NLRP3 activation. Oxidative damage can trigger inflammasome activation, and NLRP3 is the only inflammasome associated with MAM dysregulation. In addition, multiple transcription factors are located on the MAM. This study aimed to investigate the protective effects and underlying mechanisms of a PARP-1 inhibitor (olaparib) against chronic ocular hypertension-associated retinal cell damage. We also mimicked hypoxic stimulation of a retinal precursor cell line by exposing the cells to 0.2% O2 in vitro. We discovered that chronic ocular hypertension (COH) induces oxidative damage and MAM dysregulation in the retinal ganglion cells (RGCs). The protein levels of cleaved-PARP and NLRP3 were upregulated in the retinas of the COH rats. Olaparib, a PARP-1 inhibitor, alleviated COH-induced RGC loss, retinal morphological alterations, and photopic negative response amplitude reduction. Olaparib also relieved hypoxic stimulation-induced loss of cell viability and MAM dysregulation. Additionally, some indicators of mitochondrial performance, such as reactive oxygen species accumulation, mitochondrial Ca2+ influx, and mitochondrial membrane potential collapse, decreased after olaparib treatment. Olaparib attenuated the hypoxia-induced upregulation of NLRP3 protein levels as well as the phosphorylation of ERK1/2 and histone H2A.X. These results suggest that olaparib protects RGCs from chronic intraocular pressure elevation in vivo and alleviates the abnormal MAM dysregulation and mitochondrial dysfunction caused by hypoxia in vitro. This protection may be achieved by inhibiting PARP-1 overactivation, NLRP3 upregulation, and phosphorylation of ERK1/2.

Electroretinography reveals retinal dysfunction in Parkinson's disease despite normal high-resolution optical coherence tomography findings

IntroductionParkinson's disease (PD)-associated inner retinal abnormalities, particularly the retinal ganglion cells (RGC) layer, on optical coherence tomography (OCT) have recently gained importance as a biomarker of non-motor involvement of the disease but functional RGC evaluation using photopic negative response (PhNR) has not yet been determined. This study aims to compare structural and functional findings of the retina and optic nerve in PD with healthy controls (CT) including PhNR and OCT. MethodsForty-one eyes of 21 PD patients and 38 eyes of 19 CT underwent ophthalmic examination including visual contrast sensitivity test (CS), OCT, light-adapted full-field electroretinography (ffERG), and PhNR. OCT was used to measure the peripapillary retinal nerve fiber layer, the segmented macular layers, and the choroid. For functional parameters, CS, ffERG (oscillatory potentials, photopic response, 30 Hz-flicker), and PhNR waves were used. Measurements were compared using generalized estimating equation and significance was set at P ≤ 0.05. ResultsThe PD group presented a significantly lower mono- and binocular CS, oscillatory potentials amplitude, b-wave amplitude on ffERG (152.3[45.4] vs 187.1[32.7]μV; P = 0.002), and PhNR amplitude (135.0[35.0] vs 156.3[34.1]μV; P = 0.025). There was no statistically significant difference in OCT measurements between groups. No correlation was found between statistically significant measurements and clinical data. ConclusionsFunctional abnormalities on CS, ffERG, and PhNR can be detected in PD even when structural damages are not observed on OCT. PhNR represents a new potential biomarker in PD. Our findings indicate dysfunction of bipolar, amacrine, and retinal ganglion cells in PD, probably with a cellular dysfunction overcoming morphological damage.

Early changes in photopic negative response in eyes with glaucoma with and without choroidal detachment after filtration surgery

Background/aimsTo evaluate the electroretinographic (ERG) changes in the early postoperative period following glaucoma filtration surgery, and its relationship with choroidal detachment (CD).MethodsThis retrospective observational single-centre study included 57 consecutive patients...

Correlation Between Optical Coherence Tomography and Photopic Negative Response of Flash Electroretinography in Ganglion Cell Complex Assessment in Glaucoma Patients.

PurposeTo investigate the correlation between the photopic negative response (PhNR) of the light-adapted flash electroretinography (ERG) and measurements of standard automated perimetry (SAP) and optical coherence tomography (OCT) in assessment of retinal ganglion cells’ (RGCs) affection in glaucoma.Patients and MethodsA cross-sectional study included 40 eyes of glaucoma patients and 40 eyes of age- and gender-matched normal subjects. Participants underwent a complete ophthalmologic assessment, SAP, OCT, and light-adapted flash ERG using the extended PhNR protocol of the International Society for Clinical Electrophysiology of Vision (ISCEV). Glaucomatous eyes were divided into 3 subgroups: mild (n = 15), moderate (n = 11) and severe glaucoma (n = 14) according to the mean deviation (MD) of SAP. Measurements of SAP, OCT and ERG parameters were analyzed, and correlations between PhNR measurements and other study measurements were evaluated.ResultsPhNR amplitudes and PhNR/b-wave ratios were significantly reduced in glaucoma cases compared to healthy controls, and they showed a significant and progressive decline across the three glaucoma subgroups (P < 0.05). An exception to this is PT (b-wave peak to PhNR trough) PhNR amplitude where its reduction was statistically non-significant when comparing between controls and mild glaucoma cases (P = 0.178), and between moderate and severe glaucoma cases (P = 0.714). PhNR amplitudes and PhNR/b-wave ratios correlated significantly with SAP and OCT parameters (P < 0.05).ConclusionPhNR correlates well with SAP and OCT parameters in glaucoma assessment. PhNR could be a valuable supplementary tool for objective assessment of the RGCs’ function in glaucoma.

The electroretinography and optical coherence tomography data matching in patients with advanced stages of glaucoma

AbstractPurposeTo determine the specific changes in the parameters of electroretinography (ERG), reflecting various aspects of retinal ganglion cell (GC) function, and optical coherence tomography (OCT), and their correlations in patients with advanced stages of primary open‐angle glaucoma (POAG).MethodsThe study included 35 people (55 eyes) with stages II and III POAG, divided into two subgroups, and 28 healthy age‐matched individuals (32 eyes). Transient and stationary pattern‐electroretinograms (PERG) and photopic negative response (PhNR) were recorded according to the ISCEV Standards (RETIport/scan, Roland Consult). The thickness of the GC complex (GCC) of the macular region was assessed (Heidelberg Spectralis OCT). The correlation analysis of the GCC indicators and the ERG data was performed. Validation for normal data distribution was performed using the Shapiro‐Wilk test. The Student's t‐test was used to compare normally distributed independent samples. Correlation analysis was performed using Pearson's correlation coefficient.ResultsWe found a reduction in the amplitude of N95 and P50 waves of transient PERG, the stationary PERG, PhNR, and PhNR/b index, and an increase in the peak latency of the N95 and P50 in both patient groups (p &lt; 0.05). A statistically significant thinning of all layers of the GCC was noted in all the studied sectors (p &lt; 0.01). The most essential morphological/functional correlations we determined between the amplitude of stationary PERG and the thickness of the GCC (r &gt; 0.8; p &lt; 0.01). The results showed moderate correlation relationships between parameters of the transient PERG and GCC (r &gt; 0.4; p &lt; 0.01) and between the PhNR amplitude and GCC thickness (r &gt; 0.5; p &lt; 0.01).ConclusionsWe documented specific changes in the morphological and functional parameters of the inner retina in patients with advanced stages of POAG. The detected regularities can be used as clinical markers of the disease and monitor the efficiency of a chosen therapeutic strategy.

Influence of pre‐adaptation time to background illumination on photopic negative response of the full‐field electroretinogram

AbstractPurposeThe photopic negative response (PhNR) is a negative wave (latency ~70ms) of the full‐field electroretinogram (ERG) which represents ganglion cell activity. The amplitude is most distinctive for a red stimulus on a blue background. In the literature different pre‐adaptation times (range from few seconds to 10min) to the blue background can be found. The aim of the study presented here was to verify whether the pre‐adaptation time to the blue background has an influence on the PhNR wave.MethodsIn total 12 subjects (25.4±2.0years, 4m, 8f) participated in the study. For visual stimulation, a full‐field stimulator with a red flash (wavelength: 625nm, flash strength: 1.5cds/m², duration: ≤ 5ms, inter‐flash interval: 1s) on blue background (wavelength: 455nm, luminance: 10cd/m²) was used. For ERG recording, Ag/AgCl ring‐shaped skin‐electrodes were placed at the lower eyelid, the ipsilateral earlobe, and the forehead. The subjects were light adapted before all measurements. Each ERG measurement consisted of a pre‐adaptation time (15s/1/2/5/10min, randomized order) followed by an ERG measurement, which includes 20 artifact‐free sweeps. The PhNR wave was defined as the minimum after the b‐wave in the latency range from 60 to 80ms and was measured from the baseline (BT) and from the b‐wave peak (PT). For statistical analysis, the Friedman‐test was applied between the pre‐adaptation times for both measured amplitudes and the latency (α=0.05).ResultsThe PhNR could be measured and analyzed from all subjects. The Friedman‐test showed no significant difference between the pre‐adaption times for both amplitudes and the latency (*p ≤ 0.0167; pBT‐amplitude = 0.281, pPT‐amplitude = 0.797, platency = 0.448).ConclusionsWe found no influence of the pre‐adaption time to the blue background on the PhNR amplitude and latency. Therefore, for future work only a short pre‐adaptation time of a few seconds is sufficient for a stable PhNR wave measurement for light adapted subjects.

Significant correlations between focal photopic negative response and focal visual sensitivity and ganglion cell complex thickness in glaucomatous eyes

To determine whether there are significant correlations between the focal photopic negative response (PhNR), the focal visual sensitivity and the ganglion cell complex (GCC) thickness in glaucomatous eyes. Single-center observational study. Fifty-two eyes of 52 patients (71.4 ± 9.42years) with clinically diagnosed open angle glaucoma were studied. Thirty-six age-matched normal subjects served as controls. The focal PhNR of the focal macular electroretinograms (fmERGs) were elicited by a 15° circular, a superior semicircular or an inferior semicircular stimulus centered on the fovea. The thickness of the GCC was measured in the corresponding retinal areas in the spectral-domain optical coherence tomographic images. The visual sensitivities (dB) were measured by microperimetry at the retinal area where the fmERGs were elicited and were converted to liner values (1/Lambert). The focal PhNR amplitudes were significantly correlated with the visual sensitivities of the full-circle (R = 0.532), the superior (R = 0.530) and inferior (R = 0.526) semicircular responses (P < 0.0001). The GCC thickness was correlated with the visual sensitivities in the same areas with stronger correlations (R = 0.700, 0.759 and 0.650, respectively; P < 0.0001). The focal PhNR amplitudes were proportionally reduced with the thinning of the GCC thickness (R = 0.494, 0.518 and 0.511, respectively; P < 0.0001). The significant correlations between the focal PhNR amplitudes, the focal visual sensitivities and the GCC thickness indicate that these may be good biomarkers to track the changes in the physiology and anatomy of the macular area in glaucomatous eyes.

Empirical mode decomposition denoising of the electroretinogram to enhance measurement of the photopic negative response

Background and objectiveThe photopic negative response (PhNR) of the electroretinogram (ERG) can be useful in the diagnosis and management of glaucoma. Its utility is limited by its large degree of measurement variability, which can be caused by low frequency oscillations and baseline wander. In this work we show a new denoising strategy using the empirical mode decomposition (EMD) which improves repeatability. MethodsERGs were performed on both eyes of 56 patients using red-on-blue stimulus after 2 min of preadaptation, capturing 10 sweeps per recording. Two recordings were obtained to provide intrasession test–retest estimates. Denoising was performed by removing the residue after the decomposition with the EMD, the Ensemble EMD (EEMD) and the Complete ensemble EMD with adaptive noise (CEEMDAN). The PhNR was measured as the amplitude, relative to the prestimulus baseline, of the first negative going trough after the b wave. The coefficient of repeatability (CoR) was calculated to represent 95% of the test–retest differences for the PhNR between sessions. ResultsDenoising with all of the varieties of the EMD improved the test–retest repeatability of the PhNR. The best results were achieved with the CEEMDAN algorithm, which for the PhNR amplitude improved the coefficient of repeatability relative to the effective dynamic range from 20.2% to 8.3%. ConclusionsThe EMD can be used to remove low frequency baseline drift and oscillation from the ERG and improve the test–retest repeatability of PhNR measurements. This technique could be deployed for a range of visual and other electrophysiological tests.

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.

Ocular direct current stimulation affects retinal ganglion cells

Ocular 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*).

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 &lt; 0.01) thinning of all layers of the GCC was revealed in all studied sectors. Significant (p &lt; 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 &lt; 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 &lt; 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 &lt; 0.05), the peak N95 T-PERG latency, and the RNFL thickness in the upper sector of the perifovea (r = –0.43; p &lt; 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 &lt; 0.01), the peak latency of N95, and the thickness of the RNFL in the upper sector of the parafovea (r = –0.31; p &lt; 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 &lt; 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 &lt; 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.

Оценка фотопического негативного ответа у пациентов с наследственной оптической нейропатией Лебера

Purpose. To assess the retinal ganglion cells function in patients with Leber's hereditary optic neuropathy (LHON) by registering the photopic negative response (PhNR) while the photopic electroretinography is performed. Material and methods. 14 patients with different LHON mutations and 9 healthy individuals were examined. A standard ophtalmological examination was performed, including visual fields, spectral optical coherence tomography, photopic electroretinography and PhNR tests. Results. Significant differences in the PhNR latency (68.4±4.01/64.28±5.37, p&lt;0,01) and the PhNR amplitude (21.5±9.34/32.72±12.73, p&lt;0,003) were revealed in patients with LHON and the control group. The study revealed significant differences between the PhNR latency (р&lt;0.01) and the PhNR amplitude (р&lt;0.008) in patients with visual acuity (VA) ≤ 0.1 and the control group, and between the PhNR amplitude in patients with VA≥0.13 and the control group (р&lt;0.05). There were found significant correlations between the PhNR parameters and visual acuity, mean sensitivity, RNFL and GCC thickness. A strong positive correlation was found between the PhNR amplitude and the GCC thickness in patients with VA≥0.3. Conclusion. The PhNR parameters reflect the retinal ganglion cells function in patients with LHON and correlate with RNFL and GCC structural changes. Key words: Leber hereditary optic neuropathy, mitochondrial optical neuropathies, retinal ganglion cell, photopic negative response, PhNR.