Steady-state Pattern Electroretinogram Research Articles

Correlations between Steady-State Pattern Electroretinogram and Humphrey Visual Field Analyzer Global Indices and Their Associations with Retinal Ganglion Cell Layer-Inner Plexiform Layer Thickness in Glaucoma Suspects.

The purpose of this study was to investigate the utility of steady state pattern electroretinogram (ss-PERG) in detecting retinal ganglion cell (RGC) dysfunction in glaucoma suspects (GS) who had normal 24-2 Humphrey Visual Fields (HFA). This was a prospective cohort study of GS patients who were identified based on optic disc appearance with normal HFAs. Patients received a complete eye examination, standard automated perimetry (SAP), optical coherence tomography (OCT), and ss-PERG measurements. The ss-PERG parameters, Magnitude (Mag), Magnitude D (MagD), and MagD/Mag ratio, were examined, along with their relationships between HFA and OCT measurements. Twenty-five patients were included in this study, with a total of 49 eyes. Fifteen eyes had abnormal ss-PERG parameters and when compared to GS eyes with normal ss-PERG parameters, there were significant differences in HFA 24-2, retinal nerve fiber layer (RNFL) thickness, and ganglion cell layer and inner plexiform layer (GCL + IPL) thickness. All ss-PERG parameters were significantly correlated with 24-2 VF mean deviation (MD) and visual field index (VFI), as well as 10-2 VF MD after controlling for age, sex, intraocular pressure, central corneal thickness, and spherical equivalent. When controlled for age, spherical equivalent, and IOP, MagD/Mag ratio significantly contributed to the variance in average GCL + IPL thicknesses, whereas 24-2 VF MD and 10-2 VF MD did not. MagD/Mag ratio also significantly accounted for variance in all macular GCL + IPL sectors, while 10-2 VF MD did not. ss-PERG has significant correlations with HFA global indices and was predictive of GCL + IPL thickness in GS patients. Clinical Significance. ss-PERG may serve as a useful functional tool for detecting and measuring RGC dysfunction in GS. It appears to be more sensitive than HFA in the detection of early changes in GCL + IPL thicknesses and may be helpful to use in conjunction with current diagnostic studies to improve the ability of monitoring GS progression.

Effect of eccentric fixation on the steady-state pattern electroretinogram

PurposeThe steady-state pattern electroretinogram (ssPERG) is used to assess retinal ganglion cell function in a variety of research contexts and diagnostic applications. In certain groups of patients or study participants, stable central fixation of the stimulus is not guaranteed. The present study aimed at assessing the effects of misfixation on the ssPERG response to checkerboard reversal stimuli.MethodsUsing two check sizes (0.8° and 15°), we compared ssPERG responses for several amounts of fixation deviation, ranging from 0° to 19° horizontally and from 0° to 14° diagonally. The stimulus area extended to 15° eccentricity, stimulus reversal rate was 15/s.ResultsUp to around 7° eccentricity, there was no sizable effect of fixation deviation under most conditions. Effects were somewhat larger for nasal than for temporal deviation, in particular for small checks. Diagonal deviation was associated with a response to luminance onset/offset at 7.5 Hz (subharmonic of the reversal rate), most prominently when the interior of a large check was fixated.ConclusionGenerally, moderate inaccuracies of fixation do not have a sizable effect on ssPERG amplitude. However, with large checks, the luminance response has to be considered.

Leber Hereditary Optic Neuropathy Gene Therapy: Longitudinal Relationships Among Visual Function and Anatomical Measures

To assess longitudinal relationships among visual function and anatomical measures of gene therapy in G11778A Leber hereditary optic neuropathy (LHON). Phase 1 clinical trial. This was a single-institution study of patients with G11778A LHON. Patients with chronic bilateral visual loss >12 months (group 1, n=11), acute bilateral visual loss <12 months (group 2, n=9), or unilateral visual loss (group 3, n=8) were administered unilateral intravitreal AAV2(Y444,500,730F)-P1ND4v2 injection with low, medium, high, and higher doses to worse eye for groups 1 and 2 and better eye for group 3. Oucome measures were best-corrected visual acuity (BCVA), visual field mean deviation (VF MD), steady-state pattern electroretinogram (SS-PERG), optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness and ganglion cell+inner plexiform layer (GCIPL) thickness, and National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) scores. Mean follow-up was 33.6 months (range=18-36 months). Baseline SS-PERG amplitude was much reduced in both eyes of all groups including asymptomatic eyes of group 3, and showed no appreciable changes irrespective of disease stage and treatment. Significant and progressive GCIPL and RNFL thinning occurred in all eyes; BCVA and VF MD fluctuated in treated and fellow eyes, with some eyes having modest improvement that may be related to natural history or to gene therapy. Mean NEI-VFQ-25 scores declined in group 3 subjects (P=.023), CONCLUSION: Asymptomatic eyes in LHON patients with unilateral visual loss may be beyond the window of effective neuroprotection given reduced GCIPL and SS-PERG. Randomization of patients to an untreated control group would help to assess treatment effect by accounting for variable natural history. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Posterior Pole Asymmetry Analysis as a Diagnostic Tool in Glaucoma Suspects: An Electrophysiological Approach.

Spectral domain optical coherence tomography (SD-OCT) with posterior pole asymmetry analysis (PPAA) provides a mapping of posterior pole retinal thickness with asymmetry analysis between hemispheres of each eye. We investigated whether these structural abnormalities were correlated with functional retinal ganglion cell (RGC) loss, quantified by steady state pattern electroretinogram (ssPERG), in glaucoma suspects (GS). Twenty GS (34 eyes) were enrolled in a prospective study at the Manhattan Eye, Ear, and Throat Hospital. All subjects underwent ophthalmological examination, including Humphrey visual field, Spectralis Glaucoma Module Premium Edition (GMPE) SD-OCT PPAA, and ssPERG testing. The ability of ssPERG parameters (Magnitude [Mag, µv], MagnitudeD [MagD, µv], and MagD/Mag ratio) to predict PPAA thickness (total, superior, and inferior thickness, [µm]) was tested via adjusted multivariate linear regression analysis. Mag explained 8% of variance in total PPAA change (F(1,29)=6.33, B=6.86, 95% CI: 1.29-12.44, p=0.018), 8% in superior PPAA change (F(1,29)=5.57, B=6.92, 95% CI: 0.92-12.92, p=0.025), and 7.1% in inferior PPAA change (F(1,29)=5.83, B=6.80, 95% CI: 1.04-12.56, p=0.022). Similarly, MagD explained 9.7% of variance in total PPAA change (F(1,29)=8.09, B=6.47, 95% CI: 1.82-11.13, p=0.008), 10% in superior PPAA change (F(1,29)=7.33, B=6.63, 95% CI: 1.62-11.63, p=0.011), and 8.5% in inferior PPAA change (F(1,29)=7.25, B=6.36, 95% CI: 1.53-11.18, p=0.012). MagD/Mag ratio and PPAA were not significantly associated. To the best of our knowledge, this is the first study demonstrating a positive relationship between RGC dysfunction and retinal thickness changes between the superior and inferior hemispheres. The detection of asymmetrical structural loss, combined with functional RGC assessment using ssPERG, may be an informative tool for early glaucoma diagnosis.

Pattern Electroretinogram in Ocular Hypertension, Glaucoma Suspect and Early Manifest Glaucoma Eyes: A Systematic Review and Meta-analysis

To provide standardized confidence limits of the transient pattern electroretinogram (tPERG) P50 and N95 and steady state pattern electroretinogram (ssPERG) amplitudes in normal controls as compared to ocular hypertension (OHT), glaucoma suspect (GS), or early manifest glaucoma (EMG) eyes. The identification of standardized confidence limits in the context of pattern electroretinogram (PERG) might overcome the high intrinsic variability of the measure, and it might lead to a more intuitive understanding of the results as well as to an easier comparison of data from multiple tests, sites, and operators. The study protocol was prospectively registered on the International Prospective Register of Systematic Reviews (ID: CRD42022370032). A literature search was conducted on PubMed, Web of Science, and Scopus. Studies comparing PERG raw data in normal control eyes as compared to OHT, GS, or EMG were included. The risk of bias was assessed using the National Institute for Health and Clinical Excellence quality assessment tool. The main outcome was the P50, N95, and ssPERG amplitude difference between the control and the study groups' eyes. The standardized mean difference was calculated as a measure of the effect size for the primary outcome. A subanalysis was conducted based on the type of electrodes adopted for the PERG measurements (invasive vs. noninvasive). Of the 4580 eligible papers, only 23 were included (1754 eyes). Statistically significant amplitude differences were found in the P50, N95, and ssPERG amplitudes between normal controls and OHT, GS, and EMG eyes. The highest standardized mean difference values were observed in the ssPERG amplitude in all 3 sets of comparison. The subanalysis did not reveal any statistically significant differences between invasive and noninvasive recording strategies. The use of standardized values as the main outcome measures in the context of the PERG data analysis is a valid approach, normalizing several confounding factors which have affected the clinical utility of PERG both for individual patients and in clinical trials. Steady state PERG apparently better discriminates diseased eyes compared to tPERG. The adoption of skin-active electrodes is able to adequately discriminate between healthy and diseased statuses. Proprietary or commercial disclosure may be found after the references.

Structure-Function Relationship between Steady-State Pattern Electroretinogram, Optical Coherence Tomography, and Visual Field Test

Structure-Function Relationship between Steady-State Pattern Electroretinogram, Optical Coherence Tomography, and Visual Field Test

Retrograde Optic Nerve Degeneration in Pituitary Adenoma: A Study with RE-PERG.

RE-PERG is altered in presence of primary neuronal degeneration of retinal ganglion cells, both in glaucoma and other diseases. A previous study showed that in a model of retrograde degeneration (vascular dementia) RE-PERG was normal. In this study, we enrolled patients with pituitary adenoma (PA) to evaluate RE-PERG findings in another model of retrograde degeneration compared with healthy controls (HC). Based on the outcome of the present and our previous studies with RE-PERG, and reviewing the literature, we discuss the physiopathology of glaucoma. Twelve PA patients and 14 age-matched HC were recruited. All participants performed visual field (VF) test, retinal nerve fiber layer (RNFL) and ganglion cells complex (GCC) thickness measurement by means of optical coherence tomography (OCT), visual evoked potentials (VEPs) and RE-PERG, a non-invasive, fast steady-state pattern electroretinogram (SS-PERG) sampled in five consecutive blocks of 130 events. VEPs amplitude was significantly lower in PA with respect to HC (6.8±0.6 vs 7.4±0.6 µV; p=0.045). VEPs latency was higher in PA (123.2±5.8 vs 103.6±4.1 msec; p<0.01). As for VF, mean defect (MD) and pattern standard deviation (PSD) were higher in PA (-6.6±2.6 vs -0.01±1.02 dB; p<0.01 and 8.5±3.1 vs 1.5±0.3; p<0.01, respectively). RNFL thickness was lower in PA (88±8.1 vs 97±9.3 µ; p=0.01). There was no statistically significant difference between PA and HC for RE-PERG. There was a significant correlation among MD, PSD, VEPs amplitude, PERG amplitude and RNFL thickness in the PA group, whereas no correlation was found with SDPh, which remains as normal as in the HC group. Our findings confirm that RE-PERG is not altered in retrograde degeneration. Based on the outcome of the present and our previous studies about RE-PERG and glaucoma, we assume that in glaucoma a double mechanism of retinal ganglion cells degeneration, both retrograde and primary, can coexist.

Pattern Electroretinogram Parameters and their Associations with Optical Coherence Tomography in Glaucoma Suspects.

AimTo investigate whether steady state pattern electroretinogram (ssPERG) could identify retinal ganglion cell (RGC) dysfunction, and to assess the relationship between ssPERG with optical coherence tomography (OCT) measurements in glaucoma suspects (GS).Materials and methodsThis was a prospective cohort study of GS, identified based on suspicious optic disk appearance and glaucoma risk factors. Complete eye exam, Standard automated perimetry, OCT, and ssPERG were performed. Magnitude (Mag), Magnitude D (MagD), and MagD/Mag ratio were subsequently used in the correlation and linear regression analyses between ssPERG parameters and the RNFL, GCL/IPL, and macular thicknesses measurements.ResultsForty-nine eyes of 26 patients were included. Mag and MagD were significantly correlated with the superior, inferior, and average RNFL thicknesses (avRNFLT). All ssPERG parameters were significantly correlated with the average and minimum GCL/IPL thicknesses and the inner macular sector thicknesses. Mag and MagD significantly predicted the superior, inferior, and avRNFLT in the regression analysis. All ssPERG parameters were predictive of GCL/IPL thickness in all sectors as well as the average and minimum GCL/IPL thicknesses. All ssPERG parameters were predictive of all inner macular sector thicknesses and MagD was also predictive of some outer macular sector thicknesses as well.ConclusionssPERG has significant correlations with and is predictive of RNFL, GCL/IPL, and macular thicknesses in glaucoma suspects.Clinical significancessPERG may serve as a useful objective functional tool for identifying and following the progression of disease in glaucoma suspects.How to cite this articleTirsi A, Wong A, Zhu D, et al. Pattern Electroretinogram Parameters and their Associations with Optical Coherence Tomography in Glaucoma Suspects. J Curr Glaucoma Pract 2022;16(2):96-104.

The Relationship Between Stage of Leber's Hereditary Optic Neuropathy and Pattern Electroretinogram Latency.

PurposeThe purpose of this study was to compare the baseline steady-state pattern electroretinogram (SS-PERG) of patients with G11778A Leber hereditary optic neuropathy (LHON) with different stages of visual acuity (VA) loss before allotopic gene therapy (GT).MethodsPatients (n = 28) were enrolled into groups (GT I: chronic bilateral VA ≤35 Early Treatment Diabetic Retinopathy Study [ETDRS]; GT II: acute bilateral VA ≤35 ETDRS; GT III: acute unilateral, VA ≤35 ETDRS, and better eye VA ≥70 ETDRS) and tested with SS-PERG together with 210 age-matched normal controls (NCs). SS-PERG amplitude (nV) and latency (ms) of each eye were averaged for groups GT I, GT II, and NC. Symptomatic eyes (GT III-S) and asymptomatic eyes (GT III-A) of group GT III were included separately and accounted for by using generalized estimating equation (GEE) methods.ResultsCompared to NC, SS-PERG amplitudes were reduced similarly by approximately 50% (P < 0.001) among all GT groups (NC > GT I, GT II, GT III-S, and GT III-A). SS-PERG latencies were shorter by ≥3.5 ms in all LHON groups and differed by disease stage (G III-A < NC, P = 0.002; GT III-S < GT III-A, P = 0.01; GT II < GT III-S, P = 0.03; GT I < NC, P < 0.001, but not different from other GT groups, all P > 0.1).ConclusionsAlthough SS-PERG amplitude reduction did not distinguish between disease stages, SS-PERG latency shortening occurred in asymptomatic eyes and symptomatic eyes and distinguished between disease stages.Translational RelevanceSS-PERG latency shortening is consistent with primary damage of smaller/slower axons and sparing of larger/faster axons and may provide an objective staging of LHON, which may be helpful to determine efficacy in LHON trials.

PERG adaptation for detection of retinal ganglion cell dysfunction in glaucoma: a pilot diagnostic accuracy study

It has been previously demonstrated that the adaptive phase changes of steady-state pattern electroretinogram (SS-PERG), recorded during 4-min presentation of patterned stimuli, are reduced in glaucoma suspects and patients compared to normal subjects. Our study aims at testing the hypothesis that adaptive changes of SS-PERG, recorded using the novel optimized Next Generation PERG (PERGx) protocol, differ between glaucoma patients and controls. In this pilot cross-sectional study, we included 28 glaucoma patients and 17 age-matched normal subjects. Both patients and controls underwent a full ophthalmologic examination, visual field testing, OCT and PERGx. The PERGx signal was sampled over 2 min (providing 1 noise and 9 signal packets) in response to alternating gratings generated on an OLED display. PERGx amplitude and phase were analyzed to quantify adaptive changes over recording time. Receiver operating characteristic (ROC) curves were used to study the diagnostic accuracy of PERGx parameters in distinguishing glaucoma patients from normal subjects. PERGx amplitude and phase data showed declining trends in both groups. PERGx amplitude slope and grand-average vector amplitude and phase were significantly different in patients compared to controls (p < 0.01), whereas phase angular dispersion was greater in patients but not significantly different between the two groups. The area under the ROC curves were 0.87 and 0.76 for PERGx amplitude slope and grand-average vector amplitude, and 0.62 and 0.87 for PERGx angular dispersion and grand-average vector phase, respectively. The PERGx paradigm resulted highly accurate in detecting the reduction of amplitude adaptive changes in glaucoma patients, presumably due to the loss of functional retinal ganglion cell autoregulation. Thus, PERG adaptation, recorded by this new protocol, might be helpful in the identification and diagnosis of early glaucomatous dysfunction.

Steady-State Pattern Electroretinography in Eyes with Glaucoma and High Myopia.

PurposeTo investigate features of the steady-state pattern electroretinogram (ssPERG) in subjects with glaucoma (G), high myopia (HM; spherical equivalent ≤-6D) and glaucoma with high myopia (GHM).Patients and MethodsOur study included 48 participants divided into 3 groups (G, HM, and GHM) who each underwent monocular ssPERG testing with Diopsys NOVA PERG protocols. The ConStim protocol detects distinct topographic patterns of dysfunction 16° and 24° around the central macula. MagD is the amplitude of the average signal and MagD/Mag ratio indicates the consistency of the response. ssPERG indices were compared between groups and correlated with functional (ie, visual field mean deviation (VFMD)) and structural (ie, average retinal nerve fibre layer (RNFL) thickness; Cirrus optical coherence tomography) features.ResultsParticipants had an average age of 59.4±7.6 years. Mean Humphrey VFMD was −14.22 ± 2.88dB, −2.62 ± 1.18dB and −12.80 ± 2.60dB for G, HM and GHM groups, respectively. Mean RNFL thickness was 63.0 ± 8.20μm, 69.5 ± 15.7μm and 60.6 ± 5.0μm for G, HM and GHM groups, respectively. For the 24° setting, no significant differences were noted for any of the parameters. For the 16° setting, MagD was lower in the GHM group compared to the HM group (0.29µV vs 0.52µV; p = 0.02). Significant differences were noted for the MagD/Mag ratio between HM and G groups (0.58 vs 0.40; p = 0.02) and between HM and GHM groups (0.58 vs 0.35; p = 0.002). There were positive correlations between both MagD 16° and MagD/Mag ratio 16° with VFMD (correlation coefficient [r]=0.37, p = 0.009; and r = 0.44, p = 0.002, respectively) and RNFL (r = 0.43, p = 0.002; and r = 0.48, p = 0.001, respectively).ConclusionMagD/Mag ratio at 16° was significantly lower in glaucomatous eyes (with or without high myopia) compared to those with high myopia without glaucoma, suggesting that glaucoma has a distinct impact on MagD/Mag ratio at 16° irrespective of the presence of myopia.

Longitudinal Study of Retinal Structure, Vascular, and Neuronal Function in Patients With Relapsing-Remitting Multiple Sclerosis: 1-Year Follow-Up.

ObjectiveThe purpose of this study was to quantify retinal structural, vascular, and functional changes in patients with relapsing-remitting multiple sclerosis (RRMS) over 1 year.MethodsEighty-eight eyes of 44 patients with RRMS underwent assessments of low contrast letter acuity (LCLA), retinal ganglion cell function detected by the steady-state pattern electroretinogram (PERG), axonal microstructural integrity measured as birefringence, intraretinal layer thicknesses by ultra-high-resolution optical coherence tomography (OCT), volumetric vessel density (VVD) by OCT angiography, and retinal tissue perfusion (RTP) by the Retinal Function Imager (RFI). All measurements were performed at baseline and 1-year follow-up. The impacts of disease activities and a history of optic neuritis (ON) were analyzed.ResultsCompared to baseline, there were no significant differences in all variables (P > 0.05), except for the axonal birefringence and RTP. The birefringence's of the retinal fiber layer at the temporal and superior quadrants was significantly decreased (P < 0.05), whereas RTP was significantly increased (P < 0.05). In the subgroup with ON, significantly longer PERG latency and decreased VVD were observed at follow-up (P < 0.05). In patients with improved LCLA, significantly increased RTP and decreased VVD (P < 0.05) were also observed.ConclusionsThis is the first longitudinal study that assessed the RTP and VVD, along with other retinal structural and functional parameters in MS. The recovery of retinal vascular function occurred with the improved LCLA, suggesting that these measurements may be associated with disease progression.Translational RelevanceThe retinal microvascular changes could be potential biomarkers for monitoring therapeutic efficacy in MS.

Compartmental Differences in Macular Retinal Ganglion Cell Function.

PurposeThe purpose of this study was to investigate local differences of macular retinal ganglion cell (RGC) function by means of the steady-state pattern electroretinogram (SS-PERG).MethodsSS-PERGs were recorded in healthy subjects (n = 43) in response to gratings (1.6 c/deg, 15.63 reversals/s, and 98% contrast) presented on an LED display (800 cd/m2, 12.5 degrees eccentricity at 30 cm viewing distance) partitioned in triangular sectors (inferior [I]; nasal [N]; superior [S]; and temporal [T]) or concentric regions (central [C] and annulus [A]). For each partition, response amplitude (nV), amplitude adaptation (% change over recording time), phase/latency (deg/ms), and oscillatory potentials (OPs) amplitude (root mean square [RMS] nV) were measured. Data were analyzed with Generalized Estimating Equation (GEE) statistics.ResultsAmplitude differed (P < 0.001) between sectors (I: 254 nV; N: 328 nV; S: 275 nV; T: 264 nV; and N>T, I) as well as concentrically (C: 684 nV; A: 323 nV; and C>A). Latency did not differ between sectors (range = 53–54 ms, P = 0.45) or concentrically (range = 51–51 ms, P = 0.7). Adaptation did not differ (P = 0.66) concentrically (C: −19% and A: −22%) but differed (P = 0.004) between sectors (I: +25% and S: −29%). The OP amplitude did not differ (P = 0.5) between sectors (range = 63–73 nV) as well as concentrically (range = 82–90 nV, P = 0.3).ConclusionsAmplitude profiles paralleled RGC densities from histological studies. Adaptation profile suggested greater autoregulatory challenge in the inferior retina. Latency profile may reflect axonal conduction time to the optic nerve head assuming a direct relationship between axon length and its size/velocity. Location-independent OPs may reflect preganglionic activity.Translational RelevanceNormal macular RGC function displays local differences that may be related to local vulnerability in optic nerve disorders.

Use of a novel telemetric sensor to study interactions of intraocular pressure and ganglion-cell function in glaucoma

Aims(1) To test the feasibility of simultaneous steady-state pattern electroretinogram (ssPERG) and intraocular pressure (IOP) measurements with an implanted IOP sensor. (2) To explore the scope of this approach for...

Long-term PERG monitoring of untreated and treated glaucoma suspects.

To investigate long-term structural and functional progression of untreated and treated glaucoma suspects (UGS and TGS). Retrospective analysis of serial steady-state pattern electroretinogram (PERG), mean retinal nerve fiber layer thickness (RNFLT), and standard automated perimetry mean deviation (SAP-MD) in UGS (N = 20) and TGS (N = 18). Outcome measures were the rates of change (linear regression slopes) of PERG amplitude, PERG phase, mean RNFLT, and SAP-MD over 9.8 ± 1.3years (15.6 ± 4.2 visits). The number of patients with significant (P < 0.05) progression slopes for PERG amplitude, PERG phase, RNFLT, and SAP-MD was, respectively, UGS: 5, 0, 4, 2; TGS: 8, 2, 6, 5. In UGS, outcome measures were not correlated with each other. In TGS, both PERG amplitude and RNFLT were significantly (P < 0.05) correlated with SAP-MD (R ≥ 0.58), while PERG amplitude and RNFLT were not correlated with each other (R = 0.43, P = 0.064). The rate of change of SAP-MD was predicted (P < 0.05) by a linear combination of RNFLT slope and PERG amplitude slope. Results substantiate and extend previous results showing that steady-state PERG amplitude progressively decreased over time in a proportion of glaucoma suspects, with relatively steeper slope in TGS compared to UGS. RNFLT progression also had a steeper slope in TGS compared to UGS; however, progressions of PERG amplitude and RNFLT were not significantly correlated. Both PERG progression and RNFLT progression independently contribute to prediction of visual field progression.

Shortened Pattern Electroretinogram Latency and Impaired Autoregulatory Dynamics to Steady-State Stimuli in Patients With Multiple Sclerosis.

The steady-state pattern electroretinogram (PERG) is a sensitive measure of retinal ganglion cell (RGC) function that includes within-test progressive changes-adaptation-reflecting RGC autoregulatory dynamics. Comprehensive PERG assessment in patients with multiple sclerosis (MS) (with or without optic neuritis [ON]) may provide unique information about RGC dysfunction and its progression, as well as a comparison between functional loss and structural loss as measured by optical coherence tomography (OCT). The goal of this project was to measure steady-state PERG components and their associations with intraretinal layer thicknesses in MS. One hundred forty eyes of 70 patients with relapsing-remitting MS and 126 eyes of 63 age- and sex-matched healthy control subjects (HC) were investigated using a new-generation PERG method and ultrahigh-resolution OCT. Of MS eyes, there were 30 eyes with ON (MSON), 22 non-ON fellow eyes (MSFE), and 88 non-ON MS eyes (MSNON). PERG amplitude, phase (latency), and adaptation of amplitude and phase were measured and correlated with OCT-determined thicknesses of intraretinal layers. The average PERG amplitude in MSON eyes was significantly lower than MSFE (P = 0.007), MSNON (P = 0.002), and HC (P < 0.001). The PERG amplitude in MSFE eyes was also significantly lower than HC (P = 0.039). The PERG latency in MSON eyes was significantly shorter than in MSFE (P = 0.001), MSNON (P = 0.002), and HC (P < 0.001). The PERG latency in MSFE (P = 0.007) and MSNON (P = 0.002) was significantly shorter than in HC. However, no significant differences were found between MSFE and MSNON (P > 0.05). PERG adaptation of amplitude in MSON was significantly lower than that in MSNON (P = 0.039) and HC (P = 0.037). Both the amplitude and latency in the MS eyes were significantly correlated with the thicknesses of the macular retinal nerve fiber layer (mRNFL) and ganglion cell-inner plexiform layer (GCIPL). Shortened PERG latency and impaired autoregulatory dynamics occurred in MS, suggesting preferential dysfunction of small, slower RGC axons and decreased ability of RGC to autoregulate their gain in response to PERG stimulus. The established relations of PERG measurements with intraretinal thickness measurements suggested that PERG losses were primarily associated with GCIPL and mRNFL thinning.

Steady-State Pattern Electroretinogram and Frequency Doubling Technology in Adult Dyslexic Readers.

PurposeDyslexia is a reading disorder with neurological deficit of the magnocellular pathway. The aim of our study was to evaluate the functionality of the magnocellular–Y (M–Y) retinal ganglion cells in adult dyslexic subjects using steady-state pattern electroretinogram and frequency doubling perimetry.MethodsTen patients with dyslexia (7 females and 3 males), mean age 28.7 ± 5.9 years, and 10 subjects without dyslexia (6 females and 4 males), mean age 27.8 ± 4.1 years, were enrolled in the study and underwent both steady-state pattern-electroretinogram examination and frequency doubling perimetry.ResultsThere was a significant difference in the amplitude of the steady-state pattern electroretinogram of the dyslexic group and the healthy controls (0.610±0.110 μV vs 1.250±0.296 μV; p=0.0001). Furthermore, in the dyslexic group we found a significant difference between the right eye and the left eye (0.671±0.11 μV vs 0.559±0.15 μV; p=0.001). With frequency doubling perimetry, the pattern standard deviation index increased in dyslexic eyes compared to healthy controls (4.40±0.81 dB vs 2.99±0.35 dB; p=0.0001) and in the left eye versus the right eye of the dyslexic group (4.43±1.10 dB vs 3.66±0.96 dB; p=0.031). There was a correlation between the reduction in the wave amplitude of the pattern electroretinogram and the simultaneous increase in the pattern standard deviation values (r=0.80; p=0.001). This correlation was also found to be present in the left eye (r=0.93; p<0.001) and the right eye (r=0.81; p=0.005) of dyslexic subjects.ConclusionOur study shows that there was an alteration of the activity of M–Y retinal ganglion cells, especially in the left eye. It confirms that in dyslexia there is a deficit of visual attention with damage not only of the magnocellular-dorsal pathway but also of the M-Y retinal ganglion cells.

Test-retest repeatability of the pattern electroretinogram and flicker electroretinogram.

To evaluate the repeatability of the steady-state pattern electroretinogram (PERG) and full-field flicker electroretinogram (Flicker ERG) protocols, delivered by the office-based Neuro Optic Vision Assessment (NOVA)™ testing platform, in healthy subjects. Healthy individuals underwent PERG (16° and 24°) and Flicker ERG [fixed luminance (FL) and multi-luminance (ML)] testing protocols. Test-retest repeatability of protocols was calculated using intra-class correlation coefficients (ICC). Reference values of the parameters of the aforementioned tests were also calculated. The ICCs for the PERG parameters ranged from 0.793 to 0.911 (p < 0.001). The ICCs for the Flicker ERG parameters ranged from 0.968 to 0.994 (p < 0.001). A linear regression analysis was applied to assess the impact of age on ERG responses. Age had a significant impact on all PERG parameters (16° or 24°). The phase response of the FL Flicker ERG significantly decreased with age (β = - 0.837, p ≤ 0.001). The FL Flicker ERG Magnitude was also impacted with a significant quadratic effect of age (β = - 0.0047, p = 0.0004). Similarly, the Phase Area Under the Curve (Phase AUC) of the ML Flicker ERG significantly declined with age (β = - 0.007, p = 0.009), and the impact on the Magnitude AUC was significant as well, with a negative quadratic age effect. The PERG and Flicker ERG protocols, delivered by an office-based testing platform, were shown to have good-to-excellent test-retest repeatability when tests were performed in the same order and in immediate succession.

RE-PERG, a new paradigm for glaucoma diagnosis, in myopic eyes.

PurposeTo evaluate reliability of steady-state pattern electroretinogram (ssPERG) phase variability in re-test (procedure called RE-PERG) in the presence of myopia, which is known to affect ssPERG amplitude, in glaucomatous patients (GP), normal controls (NC), and myopic patients (MY).MethodsThe procedure was performed on 50 GP, 35 NC, and 19 MY. All subjects were examined with RE-PERG, spectral-domain coherence tomography (SD-OCT), and standard automated perimetry (SAP). Standard deviation of phase (ssPERG SDph) and mean amplitude value (ssPERG Amp) of second harmonic (2ndH) were correlated, by means of one-way ANOVA and Pearson correlation, with mean deviation (MD) and pattern standard deviation (PSD) assessed by SAP and retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness assessed by SD-OCT. Receiving operating characteristics were calculated in cohort populations with and without myopia.ResultsGP showed significant differences from the control group for MD, PSD, RNFL, GCC, ssPERG Amp, and ssPERG SDph; GP also showed significant differences from the MY group for all the parameters except for ssPERG Amp, which is reduced in both groups. In GP group, ssPERG Amp showed a specificity of 82.1% (95% confidence interval [CI]I: 66.5–92.5). In MY group, ssPERG Amp was reduced in 58% of the patients. As a consequence of this, in GP and MY groups, considered as a whole, total specificity dropped to 70.69% (95% CI: 57.3–81.9). In the GP group, ssPERG SDph showed a specificity of 84.6% (95% CI: 69.5–91.1). In both GP and MY groups, considered as a whole, ssPERG SDph total specificity increased from 84.6% to 93.1% (95% CI: 83.3–98.1).ConclusionIntrinsic phase variability of ssPERG is not influenced by myopia, even in the presence of fundus alterations.

Decoding PERG: A neuro-ophthalmic retinal ganglion cell function review.

Currently, the clinical evaluation of neuro-ophthalmologic diseases are mainly focused on identifying stages where structural or functional damage occur. Recognition of retinal ganglion cell (RGC) functional patterns as well as monitoring RGC dysfunction can be performed using steady-state pattern electroretinogram (PERG). The analysis of the amplitude and latency shift aid on providing information on early damage or monitoring of the RGC, allowing for prompt clinical intervention and management modification, potentially changing the natural history of the disease. The purpose of this article is to review the latest findings in PERG, in early manifest glaucoma, non arteritic ischemic optic neuropathy, multiple sclerosis with unilateral recovered optic neuritis and its fellow eyes. The steady-state PERG responses provide new and early specific information in neuro-ophthalmic diseases affecting the inner retina. Steady state PERG presents specific amplitude and latency outcomes based on the neuro-ophthalmic disease affecting the inner retina, allowing early recognition of changes at the level of RGC and the degree of RGC dysfunction. In addition, PERG alterations may be induced in healthy subjects as well as susceptible eyes using different stress tests such as head down tilting or water drinking tests.