Reduced contrast sensitivity, pattern electroretinogram ratio, and diminished a-wave amplitude in patients with major depressive disorder.

The electroretinogram (ERG), a non-invasive electrophysiological tool used in ophthalmology, is increasingly applied to investigate neural correlates of depression. The present study aimed to reconsider previous findings in major depressive disorder (MDD) reporting (1) a diminished contrast sensitivity and (2) a reduced patten ERG (PERG) amplitude ratio, and additionally, to assess (3) the photopic negative response (PhNR) from the flash ERG (fERG), with the RETeval® device, a more practical option for clinical routine use. We examined 30 patients with a MDD and 42 healthy controls (HC), assessing individual contrast sensitivity thresholds with an optotype-based contrast test. Moreover, we compared the PERG ratio, an established method for early glaucoma detection, between both groups. The handheld ERG device was used to measure amplitudes and peak times of the fERG components including a-wave, b-wave and PhNR in both MDD patients and HCs. MDD patients exhibited diminished contrast sensitivity together with a reduced PERG ratio, compared to HC. With the handheld ERG device, we found reduced a-wave amplitudes in MDD, whereas no significant differences were observed in the fERG b-wave or PhNR between patients and controls. The reduced contrast sensitivity and PERG ratio in MDD patients supports the hypothesis that depression is associated with altered visual processing. The findings underscore the PERG's potential as a possible objective marker for depression. The reduced a-wave amplitude recorded with the RETeval® system in MDD patients might open new avenues for using handheld ERG devices as simplified approaches for advancing depression research compared to the PERG.

Effect of eccentric fixation on the steady-state pattern electroretinogram.

PURPOSE: The 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. METHODS: Using 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. RESULTS: Up 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. CONCLUSION: Generally, moderate inaccuracies of fixation do not have a sizable effect on ssPERG amplitude. However, with large checks, the luminance response has to be considered.

Ambient lighting alters pattern electroretinogram P50 peak time and spatial sensitivity.

PURPOSE: Our aim was to explore the effect of ambient lighting on the pattern ERG (PERG). METHODS: We compared PERGs recorded in two conditions; room lights on and room lights off. PERGs from 21 adult participants were recorded from each eye to high contrast checks of 50' side width, reversing 3rps in a large (30°) and then standard (15°) field. This was performed first in lights-ON conditions, then 2 min after the room lights were switched off. A minimum of 2 averages of 300 trials were acquired for each condition. A subset of 10 participants had PERGs recorded to a 50' check width with a range of stimulus contrasts (96-18%), also to a range of different check widths (100'-12') at high contrast in both ambient lighting conditions in a 30° field. RESULTS: The lights-ON P50 median peak time (PT) was 3 ms earlier than the lights-OFF P50 from the 30° field (range 0-5 ms) and 15° field (range 0-6 ms). The earlier lights-ON P50 PT was evident at different stimulus contrasts, even after accounting for stimulus contrast reductions associated with stray ambient lighting in lights-ON conditions. Lights-OFF and lights-ON P50 PT were similar to different check widths; the lights-OFF P50 PT to a 50' check width matched the lights-ON P50 PT to a 25' check width. CONCLUSION: PERG P50 PT in lights-ON ambient light conditions can be earlier than in lights-OFF ambient light conditions. The difference in P50 PT with ambient light may reflect alterations in spatial sensitivity associated with retinal adaptation. These results emphasise the clinical importance of consistent ambient lighting for PERG recording and calibration.

Sensitivity and specificity of the uniform field electroretinogram in glaucoma detection in comparison to the pattern electroretinogram.

PURPOSE: To determine the ability of the photopic negative response (PhNR) of the uniform field electroretinogram (UF-ERG) to identify early glaucomatous changes in comparison to the checkerboard and bar stimuli of the pattern electroretinogram (PERG). METHODS: Forty-nine glaucoma patients were classified into two groups: glaucoma-suspect (23 eyes) and early to moderate glaucoma (30 eyes), based on their clinical examination and the results of standard automated perimetry. Thirty patients (30 eyes) with intraocular pressures (IOP) of 21 mmHg or less, with no history of reported high IOP, were included as controls. PERG and UF-ERG recordings were obtained on a Diagnosys D-341 Attaché-Envoy System. Visual field testing was done only for glaucoma-suspect and glaucoma patients. RESULTS: All three tests (PERG bar stimulus, PERG checkerboard stimulus and PhNR) displayed significantly prolonged peak times for glaucoma and glaucoma-suspect patients, with delays ranging from 7.8 to 14.8%, depending on the test. The PERG bar stimulus also showed a significantly lower N95 amplitude for both glaucoma groups (with reductions of 26.0% and 33.0% for glaucoma-suspect and glaucoma groups, respectively). The PERG checkerboard N95 amplitude component had high sensitivity for detecting glaucoma patients but a low specificity (97% and 37%, respectively; AUC = 0.61). Overall, the PhNR peak time showed the highest sensitivity and specificity (77% and 90%, respectively; AUC = 0.87). CONCLUSIONS: PERG bar stimuli and the PhNR of the UF-ERG can be used in the clinical setting to detect glaucoma-related changes in glaucoma-suspect and glaucoma patients. However, our data confirm that the PhNR peak time has the best combined sensitivity and specificity.

ISCEV standard for clinical pattern electroretinography (2024 update).

The pattern electroretinogram (PERG) is a localized 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 (ISCEV; www.iscev.org ) presents an updated and revised Standard for clinical PERG testing. This replaces the 2013 and all earlier versions. Minimum protocols for basic PERG stimuli, recording methods and reporting are specified, to promote consistency of methods for diagnosis and monitoring purposes, while responding to evolving clinical practices and technology. The main changes in the updated ISCEV Standard for clinical PERG include expanded guidance about large stimulus fields, stimulus parameters for simultaneous PERG and pattern visual evoked potential recording, baseline drift correction, and use of consistent ambient room lighting. These changes aim to provide a clinically relevant document about current practice which will facilitate good quality recordings and inter-laboratory comparisons.

Macular function in patients with medium myopia.

PURPOSE: This work aims at assessing whether electrophysiological functional changes in the macular region appear in medium myopia, even in the presence of a normal macular OCT scan and how axial length correlates with macular OCT parameters in medium myopia. METHODS: The study included right eyes of 17 patients with myopia of medium degree (SE < - 6D to > - 3D). Control group consisted of 20 eyes of patients of age and sex that matched healthy controls with normal macular and optic nerve OCT results and normal axial length. Full ophthalmic examination (the distance best-corrected visual acuity, intraocular pressure, refractive error, the anterior and posterior segment of the eye in a slit lamp, the axial length of the eyeball) with OCT of the macular and optic disk and the PERG test were performed in the study and control groups. Only the patients with normal ophthalmic and OCT examination results were qualified. The interview covering questions on risk factors of myopia onset and progression such as prematurity, family history of myopia was carried out in both groups. In myopic group, the question relating to time of near work was also asked. Study and control groups were tested with the use of Shapiro-Wilk, Mann-Whitney, Student's t test, Pearson and Spearman's rank correlation tests. RESULTS: AL was significantly longer in myopia group (p < 0.01), and SE value was lower (p < 0.01). Longer implicit time of P50 was found in the study group, but amplitudes of P50 and N95 waves were not significantly reduced (p < 0.05). AL showed correlations with P50 implicit time (p < 0.05) and with reduction in retinal fiber nerve layer and ganglion cells and inner plexus layer (p < 0.05). CONCLUSION: Patients with myopia of medium degree have a dysfunction of retinal cone system of the macular region even when OCT scans show no abnormalities. Elongation of AL correlates with reduction in retinal fiber nerve layer and ganglion cells and inner plexus layer. Longitudinal follow-up studies may answer the question whether this increase in implicit time may be indicative of a faster myopia progression or of myopic retinal pathology, i.e., whether it may help to determine which patient would benefit from earlier or more intensive management of myopia progression.

Analysis of the slope between P50 and N95 waves of the large field pattern electroretinogram as an additional indicator of ganglion cell dysfunction.

AIM: Dysfunction of the retinal ganglion cells (RGC) can be detected by the pattern electroretinogram (PERG) as a reduction of the N95 amplitude, a decrease of the ratio between N95 and P50 amplitude and/or a shortening of P50 peak time. Additionally, the slope from the top of the P50 towards the N95 (P50-N95 slope) is less steep than in control subjects. The aim of the study was to quantitatively evaluate this slope in large field PERGs in controls and patients with RGC dysfunction due to optic neuropathy. SUBJECTS AND METHODS: Large field (21.6°X27.8°) PERGs and optical coherence tomography (OCT) data from 30 eyes of the 30 patients with different types of clinically confirmed optic neuropathies, and with P50 amplitudes within normal limits and abnormal PERG N95 were retrospectively analysed and compared to 30 healthy eyes of 30 control subjects. The P50-N95 slope was analysed with a linear regression from 50 to 80 ms after the stimulus reversal. RESULTS: The patients with optic neuropathy exhibited a significant reduction of the N95 amplitude (p < 0.001) and N95/P50 ratio (p < 0.001), the P50 peak time was mildly shorter (p = 0.03). The P50-N95 slope was significantly less steep in eyes with optic neuropathies (- 0.089 ± 0.029 vs. - 0.220 ± 0.041, p < 0.001). Thickness of temporal RNFL and the P50-N95 slope appeared to be the most sensitive and specific parameters for detecting RGC dysfunction (AUC = 1.0). CONCLUSIONS: The slope between the P50 and N95 waves of a large field PERG is considerably less steep in patients with RGC dysfunction and could thus be an efficient biomarker, particularly in the diagnosis of early or borderline cases.

Associations between steady-state pattern electroretinography and estimated retinal ganglion cell count in glaucoma suspects.

PURPOSE: To estimate retinal ganglion cell (RGC) count in glaucoma suspects (GS) and ascertain its relationships with steady-state pattern electroretinography (ssPERG) parameters. METHODS: In this prospective cross-sectional study, 22 subjects (44 eyes) were recruited at the Manhattan Eye, Ear, and Throat Hospital. Subjects underwent complete eye examinations, optical coherence tomography, standard automated perimetry, and ssPERG testing. Eyes were divided into two groups based upon clinical data: healthy subjects and GS. RGC count was estimated using the combined structure-function index. RESULTS: Estimated RGC count, average retinal nerve fiber layer thickness (ARNFLT), and average ganglion cell layer and inner plexiform layer thickness (GCIPLT) were reduced in GS eyes (p ≤ 0.001 for all parameters). Pearson correlations revealed that ssPERG magnitude and magnitudeD correlated with ARNFLT (r ≥ 0.53, p < 0.001), GCIPLT (r > 0.38, p < 0.011), and estimated RGC count (r > 0.46, p < 0.002). Six mediation analyses revealed that estimated RGC count mediated the relationships among ssPERG parameters, ARNFLT, and GCIPLT. CONCLUSION: Steady-state PERG parameters demonstrated linear correlations with estimated RGC count. The associations among ssPERG parameters and structural measures were mediated by estimated RGC count.

Structure-function models for estimating retinal ganglion cell count using steady-state pattern electroretinography and optical coherence tomography in glaucoma suspects and preperimetric glaucoma: an electrophysiological pilot study.

PURPOSE: To derive and validate structure-function models for estimating retinal ganglion cell (RGC) count using optical coherence tomography (OCT) and steady-state pattern electroretinography (ssPERG) parameters in glaucoma suspects (GS) and preperimetric glaucoma (PPG). METHODS: In this prospective cross-sectional study, 25 subjects (50 eyes) were recruited at the Manhattan Eye, Ear, and Throat Hospital. Subjects underwent comprehensive eye examinations, OCT, standard automated perimetry (SAP), and ssPERG testing. Eyes were divided into three groups based on the Global Glaucoma Staging System: healthy (N = 30), GS (N = 10), and PPG (N = 10) eyes. The combined structure-function index (CSFI), which estimates retinal ganglion cell count (eRGCCSFI) from SAP and OCT parameters, was calculated in each study subject. Two prediction formulas were derived using a generalized linear mixed model (GLMM) to predict eRGCCSFI from ssPERG parameters, age, and average retinal nerve fiber layer thickness (ARNFLT) in 30 eyes selected at random (training group). GLMM predicted values were cross-validated with the remaining 20 eyes (validation group). RESULTS: The ARNFLT, ssPERG parameters magnitude (Mag) and magnitudeD (MagD), and eRGCCSFI were significantly different among study groups (ANOVA p ≤ 0.001). Pearson correlations demonstrated significant associations among ARNFLT, ssPERG parameters, and eRGCCSFI (r2 ≥ 0.31, p < 0.001). Two GLMMs predicted eRGCCSFI from Mag (eRGCMag) and MagD (eRGCMagD), respectively, with significant equations (F(3,18), F(3,19) ≥ 58.37, R2 = 0.90, p < 0.001). eRGCMag and eRGCMagD in the validation group (R2 = 0.89) correlated with eRGCCSFI similarly to the training group. Multivariate pairwise comparisons revealed that eRGCMag and eRGCMagD distinguished between healthy, GS, and PPG eyes (p ≤ 0.035), whereas independent Mag, MagD, and ARNFLT measures did not distinguish between GS and PPG eyes. CONCLUSION: This pilot study offers the first combined structure-function models for estimating RGC count using ssPERG parameters. RGC counts estimated with these models were generalizable, strongly associated with CSFI estimates, and performed better than individual ssPERG and OCT measures in distinguishing healthy, GS, and PPG eyes.

Pattern ERGs suggest a possible retinal contribution to the visual acuity loss in acute optic neuritis.

PURPOSE: Macular involvement in optic neuritis (ON) is well-recognised but poorly understood and may be of clinical relevance. This study explores macular structure-function correlates in acute ON. METHODS: This cross-sectional cohort study recruited ON patients within 14 days of symptom onset. Subjects underwent pattern electroretinography (PERG), pattern visual evoked potentials (PVEP) and optical coherence tomography (OCT) imaging. PERG P50 and N95 components were correlated with OCT data. RESULTS: Twenty-six individuals with ON were recruited, comprising eleven multiple sclerosis (MS-ON), six myelin oligodendrocyte glycoprotein associated (MOG-ON) and nine with isolated ON. These were compared with 28 healthy controls. PVEPs were undetectable in 11 (42%) of individuals with ON. When detectable, PVEP P100 was delayed (median 136 ms range 110-173 ms) and amplitude reduced (median 6 µV, range 3-14 µV) in ON compared with controls (both p < 0.001). PERG P50 component amplitudes, largely reflecting macular function, were reduced in affected eyes (median 2.3 µV; range 0.8-5.0 µV) compared with controls (3.3 µV; range 2.8-5.7 µV) and compared with fellow eyes (p < 0.001). The N95:P50 ratio was below the reference range in the affected eyes of five patients. Eight cases (32%) had subnormal P50 amplitudes (< 2.0 µV), and these patients had poorer visual acuity (p = 0.020). P50 amplitudes were positively correlated with an increase in inner nuclear layer thickness (rs = 0.36; p = 0.009) and macular ganglion cell and inner plexiform layer (mGCIPL) thickness (rs = 0.44, p = 0.022). CONCLUSION: PERG P50 component reduction reveals dysfunction of inner macular layers in acute ON and correlates with structural alterations on OCT. These early macular pathologic processes are likely to contribute to the visual loss.

The electrophysiological tests in the early detection of the visual pathway dysfunction in patients with microadenoma.

PURPOSE: To evaluate the validity of electrophysiological tests in the early diagnosis of a ganglion cells and/or optic nerve dysfunction in patients with pituitary microadenoma. METHODS: 66 eyes, from 33 patients with microadenoma with no evidence of the optic chiasm compression in magnetic resonance imaging (MRI) and the visual impairment in the routine ophthalmological examination, standard static perimetry (24-2 white on white) and optical coherence tomography (HD-OCT), were analysed. The pattern electroretinogram (PERG), standard pattern visual evoked potentials (PVEPs) and multichannel visual evoked potentials (mVEPs) (ISCEV standards) were performed. The results obtained from the electrophysiological tests were compared to the same number of age-matched healthy controls. RESULTS: Statistically significant differences between the patients with microadenoma and healthy controls were detected in all electrophysiological tests (p < 0.001). The most frequent abnormalities were observed in mVEPs (25/33 patients, 75.8%; 43/66 eyes, 65.2%). The most frequent features registered in this test were: (1°4')-an increase in the P100wave latency from uncrossed fibres (13/33 patients, 39.39%; 21/66 eyes, 31.8%) and (0°16')-an amplitude reduction of this wave from the crossed fibres (11/33 patients, 33.33%; 19/66 eyes, 28.8%). The changes in PVEPs (15/33 patients, 45.5%; 25/66 eyes, 37.9%) and PERG (10/33 patients, 30.3%; 15/66 eyes, 22.7%) were also registered. Of all the tests and parameters analysed in the study, the greatest diagnostic value in detecting the visual pathway dysfunction in this group of patients was the amplitude of P100 wave from the crossed fibres of the mVEPs (1°4') with a sensitivity of 60.6% and a specificity of 93.8%. These parameters suggest that this type of dysfunction is downstream to the chiasm and can also indicate the visual pathway dysfunction severity. CONCLUSIONS: In patients with microadenoma, the abnormalities in the electrophysiological tests are registered even without clinical evidence of visual impairment from the routine ophthalmological examination, SAP, OCT and chiasmal compression in MRI. The mVEPs have the most significant role in the diagnosis of the visual pathway dysfunction in patients with microadenoma.

Repeated measurements of ERGs and VEPs using chloral hydrate sedation and propofol anesthesia in young children.

PURPOSE: Sedation with chloral hydrate or anesthesia using propofol allow ocular examination and testing in young children, but these drugs may affect electrophysiologic recordings. We compared the flash and pattern ERGs and VEPs recorded with each drug in a cohort of young children enrolled in a prospective study of optic nerve hypoplasia (ONH) syndrome. METHODS: ERGs and VEPs to light-adapted, standard, full-field flashes, to standard and steady-state pattern-reversal (PR) were recorded with cycloplegia in 9 participants. Age range at the first session, with chloral hydrate was 8-23 mo; at the second session with propofol it was 20-29 mo. Examiners masked to the drug and clinical conditions measured the waveforms for longitudinal, paired comparisons between the sessions. RESULTS: Flash ERG amplitudes did not differ between sessions; peak times were longer at the second session (propofol) by clinically insignificant amounts (< 2 ms, p = 0.002). Standard PERGs had larger amplitudes and later peaks in the second session (propofol) than with chloral hydrate (P50 2.9 vs 4.7 µV, p = 0.016 and 43 vs 52 ms, p < 0.001; N95 4.0 vs 6.1 µV, p = 0.003 and 91 vs 98.5 ms p = 0.034.). These differences were present for those with an interval of  > 10 mo between sessions (n = 5, 10 eyes) but not for those with a shorter inter-test interval (< 8 mo, p > 0.05, n = 4). Magnitudes of the steady-state PERGs did not differ between tests but the waveforms had earlier peaks at the second test with propofol. Flash VEP waveforms were present in 10/18 eyes and showed 72% agreement for recordability between sessions. Standard pattern VEPs were recordable in only a few eyes in this cohort with ONH. CONCLUSIONS: Light-adapted flash ERG waveforms were generally similar with chloral hydrate and with propofol. Larger PERGs with later peaks, found in the second session (propofol) could reflect maturation of the PERG generators, as the differences found were associated with a greater age difference between the sessions, but we do not rule out that small differences in the waveforms may be drug-related. There are insufficient VEP data from these children with ONH to identify drug-related or maturational effects on VEPs.

Correlations between visual morphological, electrophysiological, and acuity changes in chronic non-arteritic ischemic optic neuropathy.

PURPOSE: To study whether there is a correlation between the macular and optic nerve morphological condition and the retinal ganglion cells (RGCs) and visual pathways' function, and to investigate whether visual acuity (VA) changes might be related to the morpho-functional findings in chronic non-arteritic ischemic optic neuropathy (NAION). METHODS: In this retrospective study, 22 patients (mean age 62.12 ± 6.87) with chronic unilateral NAION providing 22 affected and 22 fellow eyes without NAION (NAION-FE), and 20 (mean age 61.20 ± 7.32) healthy control subjects were studied by spectral domain optical coherence tomography (Sd-OCT) for investigating macular thickness (MT) and volume (MV) of the whole (WR), inner (IR) and outer retina (OR), and the peripapillary retinal nerve fiber layer thickness (RNFL-T) measured overall and for all quadrants. Also, simultaneous 60' and 15' pattern electroretinogram (PERG) and visual evoked potentials (VEP) and VA were assessed. Differences of MT and MV of WR, IR, OR, and RNFL-T overall and for all quadrants, PERG amplitude (A), VEP implicit time (IT), and A and VA values between NAION eyes and controls were assessed by one-way analysis of variance. Pearson's test was used for regression analysis. A p value < 0.01 was considered as significant. RESULTS: In NAION eyes as compared to NAION-FE eyes and controls, significant (p < 0.01) changes of MT, MV of WR and IR, RNFL-T, 60' and 15' PERG A, VEP IT and A, and VA were found. No significant (p > 0.01) OR changes were observed between groups. In NAION eyes, significant (p < 0.01) correlations between MV of WR and IR and 15' PERG A were found. Overall, RNFL-T values were significantly correlated (p < 0.01) with those of 60' PERG A and VEP IT and A; temporal RNFL-T values were correlated (p < 0.01) with 15' PERG A and VEP IT and A ones. Temporal RNFL-T, MV-IR, and 15' PERG A as well as VEP IT were significantly (p < 0.01) correlated with VA. Significant (p < 0.01) linear correlations between 60' and 15' PERG A findings and the corresponding values of 60' and 15' VEP A were also found. CONCLUSION: Our findings suggest that in chronic NAION, there is a morpho-functional impairment of the IR, with OR structural sparing. VA changes are related to the impaired morphology and function of IR, to the temporal RNFL-T reduction and to the dysfunction of both large and small axons forming the visual pathway.

Visual Disfunction due to the Selective Effect of Glutamate Agonists on Retinal Cells.

One of the causes of nervous system degeneration is an excess of glutamate released upon several diseases. Glutamate analogs, like N-methyl-DL-aspartate (NMDA) and kainic acid (KA), have been shown to induce experimental retinal neurotoxicity. Previous results have shown that NMDA/KA neurotoxicity induces significant changes in the full field electroretinogram response, a thinning on the inner retinal layers, and retinal ganglion cell death. However, not all types of retinal neurons experience the same degree of injury in response to the excitotoxic stimulus. The goal of the present work is to address the effect of intraocular injection of different doses of NMDA/KA on the structure and function of several types of retinal cells and their functionality. To globally analyze the effect of glutamate receptor activation in the retina after the intraocular injection of excitotoxic agents, a combination of histological, electrophysiological, and functional tools has been employed to assess the changes in the retinal structure and function. Retinal excitotoxicity caused by the intraocular injection of a mixture of NMDA/KA causes a harmful effect characterized by a great loss of bipolar, amacrine, and retinal ganglion cells, as well as the degeneration of the inner retina. This process leads to a loss of retinal cell functionality characterized by an impairment of light sensitivity and visual acuity, with a strong effect on the retinal OFF pathway. The structural and functional injury suffered by the retina suggests the importance of the glutamate receptors expressed by different types of retinal cells. The effect of glutamate agonists on the OFF pathway represents one of the main findings of the study, as the evaluation of the retinal lesions caused by excitotoxicity could be specifically explored using tests that evaluate the OFF pathway.

In vivo evaluation of retinal ganglion cells and optic nerve's integrity in large animals by multi-modality analysis.

Large animal models of optic nerve injury are essential for translating novel findings into effective therapies due to their similarity to humans in many respects. However, most current tests evaluating the integrity of retinal ganglion cells (RGCs) and optic nerve (ON) are based on rodent animal models. We aimed to evaluate and optimize the in vivo methods to assess RGCs and ON's function and structure in large animals in terms of reproducibility, simplicity and sensitivity. Both goats and rhesus macaques were employed in this study. By using goats, we found anesthesia with isoflurane or xylazine resulted in different effects on reproducibility of flash visual evoked potential (FVEP) and pattern electroretinogram (PERG). FVEP with the large-Ganzfeld stimulator was significantly more stable than that with mini-Ganzfeld stimulator. PERG with simultaneous binocular stimulation, with superior simplicity over separate monocular stimulation, was appliable in goats due to undetectable interocular crosstalk of PERG signals. After ON crush in goats, some FVEP components, PERG, OCT and PLR demonstrated significant changes, in line with the histological study. By using rhesus macaque, we found the implicit time of PVEP, FVEP and PERG were significantly more reproducible than amplitudes, and OCT and PLR demonstrated small intersession variation. In summary, we established an optimized system to evaluate integrity of RGCs and ON in large animals in vivo, facilitating usage of large animal models of optic nerve diseases.

XEN Gel Stent in the management of primary open-angle glaucoma.

PURPOSE: To assess the efficacy and safety of the XEN Gel Stent in patients with primary open-angle glaucoma. MATERIALS AND METHODS: Twenty eyes of 17 patients (6 males, 11 females) with primary open-angle glaucoma were implanted with XEN Gel Stent. The following data were ascertained in each participant at baseline and at 1, 3, 6, 9 and 12 months following implanting procedure: intraocular pressure, number of anti-glaucoma medications, retinal sensitivity (PS 24/2 w/w), pattern electroretinogram (ISCEV standard), as well as the number of complications. RESULTS: The mean intraocular pressure reduction in a 1-year follow-up was 18% (21.56 vs. 17.69 mmHg, p < 0.001). The mean number of anti-glaucoma medications was reduced from 3.2 to 1.6 (p = 0.001). The PERG parameters at baseline and at 12 months postoperatively included a stable amplitude of P50 (2.55 µV vs. 2.65 µV, p = 0.024) and N95 (3.45 µV vs. 3.38 µV, p = ns) waves. The delta N95 and delta P50 amplitudes remained stable over the follow-up period (p = ns). The mean deviation (MD) of PS 24/2 was - 6.54 dB vs. - 8.43 dB, p = ns, whereas the pattern standard deviation (PSD) was 6.18 dB vs. 6.91 dB, p = ns. Transient hypotony within the first postoperative week occurred in 18 eyes (90%), whereas hyphema occurred in two eyes (10%). Needle revision of a filtration bleb was performed in five eyes (25%). CONCLUSIONS: The XEN Gel Stent enables significant reduction in intraocular pressure with very low complication rates. It ensures a stabilization of the retinal function as established with the PERG.

The importance of the electrophysiological tests in the early diagnosis of ganglion cells and/or optic nerve dysfunction coexisting with pituitary adenoma: an overview.

BACKGROUND AND METHODS: Based on the available literature, it is suggested, in the clinical evaluation of the chiasmal tumors, that the following electrophysiological tests: visual evoked potentials to pattern-reversal stimulation, multifocal visual evoked potentials (mfVEPs), and pattern electroretinogram (PERG) play an important role in the diagnosis of the optic nerve and retinal dysfunction in the course of pituitary tumors. RESULTS: Macroadenomas and also microadenomas may cause dysfunction of retinal ganglion cells (RGCs) and their axons, even in the absence of changes in the routine ophthalmological examination, retinal sensitivity in standard automated perimetry, and retinal nerve fiber layer thickness in optical coherent tomography. The most frequently observed changes in electrophysiological tests were as follows: in PVEPs-the crossed/uncrossed asymmetry distribution, altered waveform, increase in P100-wave peak time, and/or reduction in amplitude; in mfVEPs-the peak time prolongation and/or amplitude reduction in C1-wave; in PERG-the reduction in N95-wave amplitude and decreased N95:P50 amplitude ratio. Hemifield PVEPs were more often abnormal than full-field PVEPs. Multi-channel recording is recommended for the assessment of the anterior visual pathway. The use of mfVEP offers the possibility to register localized disturbances of the optic nerve and ganglion cells. Additionally, an amplitude of N95-wave reduction in PERG correlated with a lack of postoperative visual acuity recovery. The postoperative improvement in the visual field was found to be associated with a normal N95:P50 amplitude ratio. The RGCs dysfunction manifested by decrease in PhNR/b-wave amplitude ratio was associated with the worse visual fields outcome. A review of the literature summarizing the electrophysiological testing in the pituitary adenoma is discussed. CONCLUSION: In patients with pituitary tumor, detection of the early dysfunction of the visual pathway may lead to modification of the medical treatment regimen and reduce the incidence of irreversible optic nerve damage.

The clinical value of the multi-channel PVEP and PERG in the diagnosis and management of the patient with pituitary adenoma: a case report.

PURPOSE: To present a patient with a diagnosis of pituitary adenoma and progressive visual pathway dysfunction detected in the electrophysiological tests in one-year follow-up. Patient is a 59-year-old male with a non-secreting pituitary macroadenoma. METHODS: Routine ophthalmological evaluation, standard automatic perimetry (SAP), retinal nerve fibers layer and the ganglion cell complex thickness in optical coherent tomography (OCT), as well as electrophysiological examinations (pattern electroretinogram-PERG, multi-channel pattern visual evoked potentials-multi-channel PVEPs record according to ISCEV standards) were performed. The examination and additional tests were conducted 3 times (in 0, 6 and 12 months) and 6 months after neurosurgery. RESULTS: Visual acuity, funduscopic examinations, SAP, OCT and electrophysiological test results at the first visit were all normal. In both eyes, the abnormalities were observed only in the multi-channel PVEP and PERG despite the absence of the changes in the routine ophthalmological examination and additional tests after 6- and 12-month follow-up. The tumor growth but without chiasmal compression was confirmed by magnetic resonance imaging. The progression of the optic pathway dysfunction in the electrophysiological tests was a cause of surgical removal of the pituitary tumor. CONCLUSION: This case highlights novel observations that in patients with pituitary tumor, detection of the early dysfunction of the visual pathway may lead to modification of the medical treatment regimen and reduce the incidence of irreversible optic nerve damage.

VEP and PERG in patients with multiple sclerosis, with and without a history of optic neuritis.

PURPOSE: Visual electrophysiology is routinely used to detect the visual complications of multiple sclerosis, but the analysis mostly focuses on visual evoked potential (VEP) and especially the P100 component. Our goal was to analyze the components and waveform alterations of VEPs and pattern electroretinograms (PERGs) in patients with multiple sclerosis (MS) with good vision. METHODS: The main VEP and PERG components of 85 patients with MS were analyzed in two groups: 38 patients who had optic neuritis in their history (ON group) and 47 patients who had never had optic neuritis (MS group). The results were compared against a control group of 47 healthy subjects. RESULTS: Both VEP and PERG alterations occurred in a greater number of patients than expected, and these alterations were not necessarily linked to ON in the history or a deterioration of visual acuity. CONCLUSIONS: Both VEP and PERG can detect dysfunction in the visual system in MS, even if the patient has no subjective symptoms. Even if PERG is not routinely used in neuro-ophthalmology, the results suggest that PERG assessment may provide useful information describing the retinal defect in MS.

Predictive value of N95 waveforms of pattern electroretinograms (PERGs) in children with optic nerve hypoplasia (ONH).

PURPOSE: As part of a long-term, prospective study of prenatal and clinical risk factors for optic nerve hypoplasia (ONH) at Children's Hospital Los Angeles, pattern ERGs (PERGs) were evaluated for prognostic value using an automated objective and robust analytical method. METHODS: Participants were 33 children with ophthalmoscopically diagnosed ONH [disc diameter-to-disc macula ratio (DD/DM) less than 0.35 in one or both eyes on fundus photographs]. Using cycloplegia and chloral hydrate sedation in one session before 26 months of age, we recorded PERGs to checkerboard reversal using five check sizes. Participants were followed with clinical and psychometric testing until 5 years of age. PERGs were analysed using automated robust statistics based on magnitude-squared coherence and bootstrapping optimized to objectively quantify PERG recovery in the challenging recordings encountered in young patients. PERG measures in the fixating or better-seeing eyes were compared with visual outcome data. RESULTS: PERG recording was complete to at least three check sizes in all eyes and to all five sizes in 79%. Probability of recording a PERG that is significantly different from noise varied with check size from 73% for the largest checks to 30% for the smallest checks (p = 0.002); smaller waveforms were associated with earlier implicit times. The presence of significant PERGs in infancy is associated with better visual outcomes; the strongest association with visual outcome was for the threshold check size with a significant N95 component (ρ = 0.398, p = 0.02). CONCLUSIONS: Automated statistically robust signal-processing techniques reliably and objectively detect PERGs in young children with ONH and show that congenital deficits of retinal ganglion cells are associated with diminished or non-detectable PERGs. The later negativity, N95, was the best indicator of visual prognosis and was most useful to identify those with good visual outcomes (≤0.4 LogMAR). Although PERGs reflect function of the inner layers of the central retina, they lack the specificity required to determine prognosis reliably in individual cases.