Steady-state Pattern Electroretinogram Research Articles

Little effect of 0.01% atropine eye drops as used in myopia prevention on the pattern electroretinogram.

Daily administration of 0.01% atropine eye drops is a promising approach for myopia control. The mechanism of action is believed to involve the dopaminergic system of the retina, triggering an increased release of dopamine. Previous studies in psychiatric condition such as major depression suggest that pattern electroretinogram (PERG) amplitudes are modulated by changes in retinal dopamine. It is thus plausible that atropine eye drops could have an effect on PERG amplitudes. The present study was designed to test this, assessing the difference in amplitude between contrast levels and the ratio of amplitudes between check sizes as primary endpoints. We included 14 participants with no more than ± 2 diopters of ametropia and visual acuity of at least 1.0. One eye was chosen randomly in each participant for atropine application (14days, one drop of 0.01% atropine solution once daily before bedtime). We recorded two sets of steady-state PERG recordings: one with different contrasts (25% and 98%) and one with different check sizes (0.8° and 17°). Near-point distance, near visual acuity, and pupil diameter were measured additionally. The recordings to different contrasts did not show atropine-related changes of PERG amplitude. A small increase by 6% of the amplitude difference between contrast levels with atropine application was not significant (p = 0.08). Raw amplitudes in the check size condition increased with atropine by 17% (p < 0.01) and 10% (p < 0.03) for small and large checks, respectively, without a significant concomitant effect on the amplitude ratio. Pupil size was significantly affected (median increase 0.5mm, p < 0.002). However, neither of the experimental conditions was associated with a significant correlation between pupil size and PERG effects. The effects on PERG primary endpoints after the 14-day period of atropine administration were small, especially compared to effect sizes in major depression, and statistically insignificant. Effects on raw amplitude were inconsistent. The present results suggest that retinal processing as reflected by PERG does not sizably change following a treatment regimen with atropine that is typical for myopia control.

A Prospective Evaluation of the Repeatability and Reliability of New Steady-state Pattern Electroretinogram Parameters.

The purpose of this study was to determine the repeatability and reproducibility of a new Pattern Electroretinography (PERG) device in healthy subjects. A total of 40 eyes of 20 healthy subjects (45.6±6.8 y, 70% female) were enrolled in this prospective study. Steady-state PERG were recorded using the Diopsys NOVA (Diopsys Inc., NJ) to obtain the Magnitude, MagnitudeD, MagnitudeD/Magnitude Ratio, and Signal to Noise Ratio. Subjects underwent 2 "contrast sensitivity" protocols with the same electrodes and 2 after changing electrodes, by a single examiner. Eyes were stimulated separately using high and low contrast patterns. The same examination was repeated by a different operator following the same protocol 6 months after the baseline measures. Repeatability and reproducibility of the readings were calculated using intraclass correlation coefficient (ICC). A Bland-Altman plot was used to analyze the agreement between measures. ICC of Magnitude, MagnitudeD, MagnitudeD/Magnitude ratio, and SNR were 0.87, 0.81, 0.36, and 0.81, respectively between measures taken with the same electrodes (repeatability). After changing electrodes, ICC of the Magnitude, MagD, MagD/Mag ratio, and SNR were 0.79, 0.85, 0.51, and 0.83, respectively during the same session as baseline measures, and 0.87, 0.85, 0.40, and 0.76 when repeated after 6 months (reproducibility). The variability of MagD/Mag ratio increased with successive test repetitions. Mag, MagD, and SNR were repeatable and reproducible, whereas the MagD/Mag ratio was less repeatable and reproducible. These results suggest that the former parameters are sufficiently reliable to be used in clinical practice.

Pattern Electroretinogram Detects Localized Glaucoma Defects.

PurposeWe evaluated the clinical ability of pattern electroretinogram (PERG) to detect functional losses in the affected hemifield of open-angle glaucoma patients with localized perimetric defects.MethodsHemifield (horizontally-defined) steady-state PERGs (h-PERGs) were recorded in response to 1.7 c/deg alternating gratings from 32 eyes of 29 glaucomatous patients with a perimetric, focal one-hemifield defect, 10 eyes of 10 glaucomatous patients with a diffuse perimetric defect, and 18 eyes of 18 age-matched normal subjects. Standard automated perimetry (SAP) and spectral-domain optical coherence tomography (SD-OCT) for retinal nerve fiber layer (RNFL) thickness also were performed. h-PERG amplitudes and ratios, calculated corresponding hemifield perimetric deviations, as well as hemiretina RNFL thicknesses were analyzed.Resultsh-PERG amplitudes, perimetric deviations, and RNFL thicknesses showed losses (P < 0.001) when comparing affected with unaffected hemifields of localized glaucomatous eyes. No differences were found in h-PERG amplitudes between hemifields of normal or diffuse glaucomatous eyes. h-PERG amplitude ratios (affected/unaffected hemifield) in localized glaucoma were lower (P < 0.001) than the ratios from normal or diffuse glaucomatous eyes. The areas under the receiver operating characteristic curves for h-PERG amplitude ratios, comparing localized-defect glaucomatous eyes with normal or diffuse glaucomatous eyes, were 0.93 and 0.91, respectively.Conclusionsh-PERG assessment showed good diagnostic accuracy to confirm localized glaucomatous defects detected perimetrically. This test may be particularly useful in cognitively impaired patients or young/nonverbal patients unable to provide reliable visual fields.Translational Relevanceh-PERG provides a sensitive objective measure to confirm focal losses detected with SAP and/or RNFL thickness analysis.

Retinal ganglion cell function in recovered optic neuritis: Faster is not better

ObjectiveTo assess residual retinal ganglion cell (RGC) function in patients with recovered optic neuritis (ON) and multiple sclerosis (MS). MethodsAge-matched controls (C, n = 32) and MS patients (n = 17) with history of ON in one eye but normal visual acuity and color vision were tested with steady-state Pattern Electroretinogram (PERG). Light Emitting Diodes (LED)-generated bar gratings, robust signal averaging and Fourier analysis were used to assess response amplitude and latency. ResultsPERG amplitude was similar for C, ON and fellow eyes (FE) (P = 0.4), but PERG latency was shortened in ON by 3.2 ms (P = 0.002) and in FE by 2.0 ms (P = 0.02) and was correlated (P < 0.01) with both Retinal Nerve Fiber Layer (RNFL) and Ganglion Cell Inner Plexiform Layer (GCIPL) thicknesses. PERG latency shortening could be simulated in control subjects (n = 8) by dioptrically blurring the edges of gratings (high spatial frequencies), which reduced activity of parvocellular RGCs with smaller/slower axons. The blurred PERG latency was shorter than baseline by 2.9 ms (P = 0.01). ConclusionsPERG latency is shortened in both eyes of MS patients with recovered unilateral ON, suggesting relative dysfunction of RGCs with slower axons and sparing of RGCs with faster axons. SignificanceAssessment of PERG latency in MS and ON may help identifying and monitoring RGC dysfunction. PERG latency shortening in FE suggests primary retinopathy in MS.

Macular and Multifocal PERG and FD-OCT in Preperimetric and Hemifield Loss Glaucoma.

To evaluate the ability of macular and multifocal (mf) pattern electroretinogram (PERG) to differentiate preperimetric glaucoma (PG) and glaucoma with hemifield loss (GHL) from controls, to compare the discrimination ability of PERG and fourier-domain optical coherence tomography (FD-OCT), and to assess the relationship between measurements. Standard automated perimetry, steady-state and transient PERG and mfPERG measurements were obtained from PG (n=14, 24 eyes), GHL (n=5, 7 eyes), and controls (n=19, 22 eyes). Circumpapillary retinal nerve fiber layer (cpRNFL), full-thickness macula, and segmented macular layer thicknesses on FD-OCT were investigated. Measurements were compared using mixed effects linear models. The relationships between measurements and the diagnostic performance of each technology were assessed. Compared with controls, average P50 peak time transient PERG responses were reduced in PG and GHL, whereas average latency and amplitude steady-state and mfPERG responses were abnormal only in GHL. cpRNFL and macular thickness measurements in PG and GHL differed significantly from controls. A significant relationship was found between PERG and most FD-OCT or SAP parameters. Partial least squares discriminant analysis revealed that OCT parameters, along with mfPERG and transient PERG parameters had similar ability to discriminate PG and GHL from healthy controls. PERG and OCT parameters may be abnormal, with significant correlations between measurements, in PG eyes. Both technologies may be useful for detection of early glaucoma.

Steady-state pattern electroretinogram and short-duration transient visual evoked potentials in glaucomatous and healthy eyes.

This study evaluates two rapid electrophysiological glaucoma diagnostic tests that may add a functional perspective to glaucoma diagnosis. This study aimed to determine the ability of two office-based electrophysiological diagnostic tests, steady-state pattern electroretinogram and short-duration transient visual evoked potentials, to discern between glaucomatous and healthy eyes. This is a cross-sectional study in a hospital setting. Forty-one patients with glaucoma and 41 healthy volunteers participated in the study. Steady-state pattern electroretinogram and short-duration transient visual evoked potential testing was conducted in glaucomatous and healthy eyes. A 64-bar-size stimulus with both a low-contrast and high-contrast setting was used to compare steady-state pattern electroretinogram parameters in both groups. A low-contrast and high-contrast checkerboard stimulus was used to measure short-duration transient visual evoked potential parameters in both groups. Steady-state pattern electroretinogram parameters compared were MagnitudeD, MagnitudeD/Magnitude ratio, and the signal-to-noise ratio. Short-duration transient visual evoked potential parameters compared were amplitude and latency. MagnitudeD was significantly lower in glaucoma patients when using a low-contrast (P=0.001) and high-contrast (P<0.001) 64-bar-size steady-state pattern electroretinogram stimulus. MagnitudeD/Magnitude ratio and SNR were significantly lower in the glaucoma group when using a high-contrast 64-bar-size stimulus (P<0.001 and P=0.010, respectively). Short-duration transient visual evoked potential amplitude and latency were not significantly different between the two groups. Steady-state pattern electroretinogram was effectively able to discern between glaucomatous and healthy eyes. Steady-state pattern electroretinogram may thus have a role as a clinically useful electrophysiological diagnostic tool.

Next Generation PERG Method: Expanding the Response Dynamic Range and Capturing Response Adaptation.

PurposeTo compare a new method for steady-state pattern electroretinogram (PERGx) with a validated method (PERGLA) in normal controls and in patients with optic neuropathy.MethodsPERGx and PERGLA were recorded in a mixed population (n = 33, 66 eyes) of younger controls (C1; n = 10, age 38 ± 8.3 years), older controls (C2; n = 11, 57.9 ± 8.09 years), patients with early manifest glaucoma (G; n = 7, 65.7 ±11.6 years), and patients with nonarteritic ischemic optic neuropathy (N; n = 5, mean age 59.4 ± 8.6 years). The PERGx stimulus was a black-white horizontal grating generated on a 14 × 14 cm LED display (1.6 cycles/deg, 15.63 reversals/s, 98% contrast, 800 cd/m2 mean luminance, 25° field). PERGx signal and noise were averaged over 1024 epochs (∼2 minutes) and Fourier analyzed to retrieve amplitude and phase. Partial averages (16 successive samples of 64 epochs each) were also analyzed to quantify progressive changes over recording time (adaptation).ResultsPERGLA and PERGx amplitudes and latencies were correlated (Amplitude R2 = 0.59, Latency R2 = 0.39, both P < 0.0001) and were similarly altered in disease. Compared to PERGLA, however, PERGx had shorter (16 ms) latency, higher (1.39×) amplitude, lower (0.37×) noise, and higher (4.2×) signal-to-noise ratio. PERGx displayed marked amplitude adaptation in C1 and C2 groups and no significant adaptation in G and N groups.ConclusionsThe PERGx high signal-to-noise ratio may allow meaningful recording in advanced stages of optic nerve disorders. In addition, it quantifies response adaptation, which may be selectively altered in glaucoma and optic neuropathy.Translational RelevanceA new PERG method with increased dynamic range allows recording of retinal ganglion cell function in advanced stages of optic nerve disorders. It also quantifies the response decline during the test, an autoregulatory adaptation to metabolic challenge that decreases with age and presence of disease.

RE-PERG, a new procedure for electrophysiologic diagnosis of glaucoma that may improve PERG specificity.

PurposeA significant variability of the second harmonic (2ndH) phase of steady-state pattern electroretinogram (SS-PERG) in intrasession retest has been recently described in glaucoma patients (GP), which has not been found in healthy subjects. To evaluate the reliability of phase variability in retest (a procedure called RE-PERG or REPERG) in the presence of cataract, which is known to affect standard PERG, we tested this procedure in GP, normal controls (NC), and cataract patients (CP).MethodsThe procedure was performed on 50 GP, 35 NC, and 27 CP. All subjects were examined with RE-PERG and SS-PERG and also with spectral domain optical coherence tomography and standard automated perimetry. Standard deviation of phase and amplitude value of 2ndH were correlated by means of one-way analysis of variance and Pearson correlation, with the mean deviation and pattern standard deviation assessed by standard automated perimetry and retinal nerve fiber layer and the ganglion cell complex thickness assessed by spectral domain optical coherence tomography. Receiver operating characteristics were calculated in cohort populations with and without cataract.ResultsStandard deviation of phase of 2ndH was significantly higher in GP with respect to NC (P<0.001) and CP (P<0.001), and it correlated with retinal nerve fiber layer (r=−0.5, P<0.001) and ganglion cell complex (r=−0.6, P<0.001) defects in GP. Receiver operating characteristic evaluation showed higher specificity of RE-PERG (86.4%; area under the curve 0.93) with respect to SS-PERG (54.5%; area under the curve 0.68) in CP.ConclusionRE-PERG may improve the specificity of SS-PERG in clinical practice in the discrimination of GP.

Steady-state pattern electroretinogram and frequency doubling technology in anisometropic amblyopia.

BackgroundSteady-state pattern electroretinogram (PERG) and frequency doubling technology (FDT) perimetry can be used to selectively investigate the activity of the M-Y ganglion cells in adult anisometropic amblyopes.MethodsFifteen normal subjects (mean 27.8±4.1 years) and 15 adults with anisometropic amblyopia (mean 28.7±5.9 years) were analyzed using steady-state PERG and FDT.ResultsThe amplitude of steady-state PERG was significantly different not only among the control group and both the amblyopic eye (P=0.0001) and the sound eye group (P=0.0001), but also between the latter two groups (P=0.006). The difference in FDT mean deviation was statistically significant not only between the control group and amblyopic eye group (P=0.0002), but also between the control group and the sound eye group (P=0.0009). The FDT pattern standard deviation was significantly higher in the control group rather than in the amblyopic eye (P=0.0001) or the sound eye group (P=0.0001). A correlation was found between the reduction in PERG amplitude and the increase in FDT-pattern standard deviation index not only in amblyopic (P=0.0025) and sound (P=0.0023) eyes, but also in the healthy control group (P=0.0001).ConclusionThese data demonstrate that in anisometropic amblyopia, there is an abnormal functionality of a subgroup of the magnocellular ganglion cells (M-Y), and the involvement of these cells, together with the parvocellular pathway, may play a key role in the clinical expression of the disease.

Distinctive morphological and functional changes in retinal ganglion cells associated with normal aging and early stage of glaucoma

Early diagnosis of primary open-angle glaucoma (POAG) is closely connected with detection of normal age-related changes in the retina. It is also essential to develop reliable methods for quantitative evaluation of retinal nerve fiber layer (RNFL) thickness and retinal ganglion cells (RGCs) structure and function as well as to extend opportunities for inter-instrumental comparisons. to assess the function of RGCs from parvo- and magnocellular pathways by means of pattern electroretinography and to evaluate the degree of retinal sensitivity loss and RNFL thickness using new methods of analysis in normal aging and the early stage of POAG. Four groups were formed: group 1 - young healthy participants, group 2 - aged controls, group 3 - glaucoma suspects, and group 4 - early-stage POAG patients. In all groups we investigated the MD and PSD indices of static computer perimetry (HEP, Heidelberg Edge Perimeter, SAP and FDF tests) and RNFL thickness provided by HRT III (Heidelberg Engineering). Pattern electroretinograms (PERGs) were recorded with the RETImap system (Roland Consult) at the check sizes of 0.8° and 16°. For steady-state and transient PERGs the 0.8°/16° and N95/P50 ratios were calculated, respectively. There was a statistically significant difference in PERG amplitudes to 0.8° checks (p=0.0001) and in 0.8°/16° ratios (p=0.0001) between the groups 1 and 2. Differences between the groups 2 and 3 as well as 3 and 4 were statistically significant only as to 0.8° checks (p=0.03 and p=0.001, respectively). Responses to 16° checks were alike in all groups. We have also applied original formulas to determine the relative loss of RGCs and their axons and the congruence coefficient for morphological and functional parameters in normal aging and the early stage of POAG. The discovered age-related PERG changes convincingly indicate a greater parvocellular RGC loss as compared to magnocellular. Thus, the PERG ratio (0.8°/16°) should be corrected for the subject's age. The proposed indices of relative decline in retinal light sensitivity and RNFL thinning have been shown to be useful for quantifying the loss of RGC bodies and axons in normal aging and early-stage glaucoma.

A portable device for recording evoked potentials, optimized for pattern ERG

Recording evoked potentials in un-anesthetized animals and people is a powerful technique to non-invasively measure the function of neurons. As such, the primary output neurons of the eye can be assessed by the pattern electroretinogram (PERG). Currently, electro-physiologic setups to perform PERG or related recordings are costly, complicated, and non-portable. Here, we design a simple steady-state PERG system, based off an Arduino board. The amplifier is built on a shield that fits over a microcontroller board, an Arduino, which digitizes the signal and sends it to a computer that presents stimuli then records and analyzes the evoked potentials. We used the device to record PERG accurately with a sensitivity as low as half a microvolt. The device has also been designed to implement other evoked potential recordings. This simple device can be quickly constructed and used for experiments in moving systems. Additionally, this device can be used to expose students in underserved areas to research technology that they would otherwise not have access to.

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

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.

Rescue of retinal function by BDNF in a mouse model of glaucoma.

Vision loss in glaucoma is caused by progressive dysfunction of retinal ganglion cells (RGCs) and optic nerve atrophy. Here, we investigated the effectiveness of BDNF treatment to preserve vision in a glaucoma experimental model. As an established experimental model, we used the DBA/2J mouse, which develops chronic intraocular pressure (IOP) elevation that mimics primary open-angle glaucoma (POAG). IOP was measured at different ages in DBA/2J mice. Visual function was monitored using the steady-state Pattern Electroretinogram (P-ERG) and visual cortical evoked potentials (VEP). RGC alterations were assessed using Brn3 immunolabeling, and confocal microscope analysis. Human recombinant BDNF was dissolved in physiological solution (0.9% NaCl); the effects of repeated intravitreal injections and topical eye BDNF applications were independently evaluated in DBA/2J mice with ocular hypertension. BDNF level was measured in retinal homogenate by ELISA and western blot. We found a progressive decline of P-ERG and VEP responses in DBA/2J mice between 4 and 7 months of age, in relationship with the development of ocular hypertension and the reduction of Brn3 immunopositive RGCs. Conversely, repeated intravitreal injections (BDNF concentration = 2 µg/µl, volume = 1 µl, for each injection; 1 injection every four days, three injections over two weeks) and topical eye application of BDNF eye-drops (12 µg/µl, 5 µl eye-drop every 48 h for two weeks) were able to rescue visual responses in 7 month DBA/2J mice. In particular, BDNF topical eye treatment recovered P-ERG and VEP impairment increasing the number of Brn3 immunopositive RGCs. We showed that BDNF effects were independent of IOP reduction. Thus, topical eye treatment with BDNF represents a promisingly safe and feasible strategy to preserve visual function and diminish RGC vulnerability to ocular hypertension.

Provocative intraocular pressure challenge preferentially decreases venous oxygen saturation despite no reduction in blood flow.

Ocular disease can both alter the retina's oxygen requirements, and decrease its ability to cope with changes in metabolic demand. We examined the influence of a moderate intraocular pressure (IOP) elevation on three outcome measures: arterial and venous oxygen saturation, blood flow, and the pattern electroretinogram (PERG). We increased IOP to ˜30mmHg in 23 healthy participants (22-39years) using a mechanical probe applied to the eyelid, thereby lowering ocular perfusion pressure (OPP) by ~30%. The Oxymap retinal oximeter was used to measure oxygen saturation for arteries and veins. Blood flow, volume and velocity were measured using the Heidelberg retinal flowmeter and steady-state PERG waveforms (8.34Hz) were recorded bilaterally (200 sweeps). For each outcome measure, data was obtained three times: at baseline, 1min into sustained IOP elevation, and 1min after the probe was removed. During IOP elevation, changes in oxygen saturation of retinal arteries failed to reach statistical significance [F(1,30)=3.69, p=0.05], whereas venous oxygen saturation was significantly reduced [F(1,21)=27.43, p<0.01]. Blood flow increased slightly [F(2,40)=6.28, p<0.0001], PERG amplitude significantly reduced [F(2,44)=24.24, p<0.0001] and PERG phase was significantly delayed [F(2,44)=17.00, p<0.0001]. Contralateral eyes were unchanged. OPP reduction correlated little with PERG amplitude, PERG phase or venous oxygen saturation. Mild, acute IOP elevation increases arterio-venous oxygen saturation differences primarily through lowering venous oxygen saturation, suggesting increased oxygen consumption by healthy neurons when physiologically stressed.

Relationship between transient and steady-state pattern electroretinograms: theoretical and experimental assessment.

We determined if the overlap of transient (tr) pattern electroretinograms (PERG(tr)) can explain the generation of the steady-state (SS) pattern electroretinogram (PERG(SS)), and investigated the relationship between the two types of responses. Slightly jittered pattern reversals were used to generate quasi SS (QSS) PERG(SS) responses from eight normal subjects, recorded using lower eyelid skin electrodes, at rates between 6.9 and 26.5 reversals per second (rps). Jittered quasi PERG(SS) were deconvolved using the frequency domain continuous loop averaging deconvolution method. Additionally, conventional PERG(tr) at 2.2 rps and PERG(SS) at each of the QSS stimulation rates were obtained from all subjects. Two synthetic PERG(SS) responses were constructed at each stimulation rate, one using the PERG(tr) obtained at that rate, and the other using the conventional 2.2 rps PERG(tr). Synthetic responses then were compared to the recorded PERG(SS) using amplitude, latency, and spectral measurements. Findings indicate that the PERG(SS) obtained at SS rates can be predicted using the superposition of deconvolved tr PERGs at each particular rate. Although conventional PERG(tr) can explain PERG(SS) obtained at rates below 15.4 rps (≥ 97% correlation), for higher reversal rates only deconvolved responses obtained at that rate can produce the recorded SS responses (96% vs. 65% correlation at 26.5 rps). The study shows that PERG(SS) results from the overlapping of tr PERG(tr) waveforms generated at that reversal rate. The first two peaks (N(SS) and P(SS)) of the PERG(SS) reflect N35 and P50 waves of the tr PERG(tr). The N95 amplitude is reduced at conventional (16 rps) SS rates, but contributes to the overall PERG(SS) amplitude.

Pattern Electroretinograms During the Cold Pressor Test in Normals and Glaucoma Patients

To examine the influence of the cold pressor test (CPT) on steady-state pattern electroretinograms (PERG) in healthy subjects and glaucoma patients. Steady-state PERGs to 7.8 Hz pattern reversal stimuli were recorded in 63 subjects. Fifteen healthy control subjects, 14 patients with ocular hypertension (OHT), and 34 patients with open-angle glaucoma (20 normotensive [NTG] and 14 high tension glaucoma [HTG]) were examined. Steady-state PERG amplitudes and latencies were analyzed at baseline, during cold stimulus using a modified CPT, and during the subsequent recovery phase. Blood pressure and heart rate were simultaneously recorded in 10 normals and 11 glaucoma patients. During the three test conditions (baseline, ice water, and warm water) glaucoma patients (NTG and HTG) showed significantly reduced PERG amplitudes in comparison with control subjects (P < 0.001) and with OHT patients (P < 0.004). Patients with OHT displayed lower PERG amplitudes than control subjects (nonsignificant, with consideration of Bonferroni). Only NTG patients showed a significant effect of the CPT on PERG amplitude (significant decrease during warm water P = 0.02). Latencies shortened significantly during warm-water period after cold stimulus in control subjects (P = 0.05) and in NTG patients (P = 0.02) with a nonsignificant trend of shortened latencies in the OHT (P = 0.06) and HTG groups (P = 0.3). Systolic and diastolic blood pressure increased during cold water (P < 0.001) and decreased during warming-up conditions (P < 0.001). This study shows that a CPT influences the PERG responses particularly in NTG. (ClinicalTrials.gov number, NCT00494923.).

Unwrapping of transient responses from high rate overlapping pattern electroretinograms by deconvolution

ObjectiveDue to overlapping, temporal information is mostly lost in high rate steady-state pattern electroretinograms (PERGSS). This study develops a deconvolution method and a display/recording system to “unwrap” PERGSS and obtain a transient, “per stimulus” response (PERGtr) regardless of reversal rate. MethodsProcessing and instrumentation, including high temporal resolution display and acquisition were developed for deconvolving PERGs acquired at high rates by slight jittering of reversal onsets at a given mean rate. ResultsThe system was successfully tested at eight rates from 2.2 to 78.1rps. At medium rates (17.4–41.2rps) recordings with conventional morphology (N35–P50–N95) but earlier peaks and higher amplitudes were extracted up to 40rps. At higher rates, smaller triphasic responses were obtained, exhibiting similar peak latencies, but reversed polarity. Oscillating potentials (OPs) were also recorded at all rates after deconvolution. ConclusionsTransient PERGs and OPs can be extracted from quasi steady-state PERG recordings obtained at high rates with a deconvolution algorithm using high temporal resolution display and acquisition systems. SignificanceThe methodology to extract transient and oscillatory responses from steady-state PERGs could be useful in understanding high rate responses and diagnosis of various retinal diseases by revealing temporal information on waveform components which cannot be normally observed.

Adaptation of the Steady-state PERG in Early Glaucoma

Previous studies have shown that the onset of high-contrast, fast reversing patterned stimuli induces rapid blood flow increase in retinal vessels in association with slow changes of the steady-state pattern electroretinogram (PERG) signal. We tested the hypothesis that adaptive PERG changes of normal controls differed from those of glaucoma suspects and patients with early manifest glaucoma. Subjects were 42 glaucoma suspects (Standard Automated Perimetry-MD -0.89±1.8 dB), 22 early manifest glaucoma (MD -2.12±2.4 dB) with visual acuity of ≥20/20 and 16 age-matched normal controls from a previous study. The PERG signal was sampled every ~15 seconds over 4 minutes in response to gratings (1.6 cyc/degree, 100% contrast) reversing 16.28 times/s. Amplitude/phase values of successive PERG samples were fitted with a nonparametric locally weighted polynomial regression smoothing function to retrieve the initial and final values and calculate their difference (δ) and the residual SD around the fitted function. The magnitude of PERG adaptive change compared to random variability was calculated as log10 of percentage coefficient of variation (CoV)=100×residual SDr÷δ. Grand-average PERGs were also obtained by averaging all samples of the same series. The grand-average PERG amplitude [analysis of variance (ANOVA), P=0.02], but not phase (ANOVA, P=0.63), decreased with increasing severity of disease. Adaptive changes [log10 (CoV)] of PERG amplitude were not significantly associated with disease severity (ANOVA, P=0.27) but adaptive changes [log10 (CoV)] of PERG phase were (ANOVA, P=0.037; linear trend, P=0.011). The steady-state PERG signal displayed slow adaptive changes over time that could be isolated from random variability. PERG adaptive changes differed from those of grand-average PERGs (corresponding the standard steady-state PERG), thus representing a new source of biological information about retinal ganglion cell function that may have potential in the study of glaucoma and optic nerve diseases.

Photopic Negative Response versus Pattern Electroretinogram in Early Glaucoma

Photopic negative response (PhNR) and pattern electroretinogram (PERG) are electrophysiological markers of retinal ganglion cell function; both are reduced in glaucoma. We compared PhNR and PERG in different stages of the disease. Eleven eyes with preperimetric glaucoma (glaucomatous optic disc with normal field); 18 with manifest glaucoma; and 26 normals were included. We obtained PhNR (flash strength from 0.1-4 cd·s/m(2)) and steady-state PERG and analyzed PhNR amplitude (baseline to 72 ms trough); PhNR/b-wave ratio; PERG amplitude; and PERG ratio (0.8°/16°). Identification of PhNR structure was only reliable ≥1 cd·s/m(2) flash strength; amplitude and receiver operating characteristics (ROC) area under curve (AUC) changed little from 1 to 4 cd·s/m(2). Both PhNR and PERG (amplitude and ratio) were reduced in preperimetric and more so in manifest glaucoma. AUCs based on PhNR/PERG amplitudes were not significantly different from chance in preperimetric glaucoma (AUCs 0.61/0.59), but were significant in manifest glaucoma (0.78/0.76); ratios were significant in both glaucoma groups (0.80/0.73 and 0.80/0.79). In spite of that, PhNR ratio and PERG ratio were not significantly correlated (r = 0.22 across all groups); an ROC based on a combination of both reached AUCs of 0.85/0.90 for preperimetric/manifest glaucoma. Both PhNR and PERG performed similarly to detect glaucoma; for both, ratios performed better than amplitudes. The PhNR has the advantage of not requiring clear optics and refractive correction; the PERG has the advantage of being recorded with natural pupils.

ISCEV standard for clinical pattern electroretinography (PERG): 2012 update

The pattern electroretinogram (PERG) is a retinal response evoked by a contrast-reversing pattern, usually a black and white checkerboard, which provides information about macular and retinal ganglion cell function. This document from the International Society for Clinical Electrophysiology of Vision (www.iscev.org) is a scheduled revision of the ISCEV PERG Standard, which updates and replaces the 2007 update and all earlier versions. The standard defines a single minimum stimulus and recording protocol for clinical PERG testing to assist practitioners in obtaining good quality responses and to facilitate inter-laboratory comparison. The present revision tightens stimulus specifications, expands on steady-state PERG recording, addresses visual stimulus display distinctions (CRT vs. LCD), and provides a more explicit definition of response components.