Pattern Electroretinogram Latency Research Articles

Fluoxetine Protects Retinal Ischemic Damage in Mice.

To evaluate the neuroprotective effect of the topical ocular administration of fluoxetine (FLX) in a mouse model of acute retinal damage. Ocular ischemia/reperfusion (I/R) injury in C57BL/6J mice was used to elicit retinal damage. Mice were divided into three groups: control group, I/R group, and I/R group treated with topical FLX. A pattern electroretinogram (PERG) was used as a sensitive measure of retinal ganglion cell (RGC) function. Finally, we analyzed the retinal mRNA expression of inflammatory markers (IL-6, TNF-α, Iba-1, IL-1β, and S100β) through Digital Droplet PCR. PERG amplitude values were significantly (p < 0.05) higher in the I/R-FLX group compared to the I/R group, whereas PERG latency values were significantly (p < 0.05) reduced in I/R-FLX-treated mice compared to the I/R group. Retinal inflammatory markers increased significantly (p < 0.05) after I/R injury. FLX treatment was able to significantly (p < 0.05) attenuate the expression of inflammatory markers after I/R damage. Topical treatment with FLX was effective in counteracting the damage of RGCs and preserving retinal function. Moreover, FLX treatment attenuates the production of pro-inflammatory molecules elicited by retinal I/R damage. Further studies need to be performed to support the use of FLX as neuroprotective agent in retinal degenerative diseases.

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.

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.

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.

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.

Neurovascular Changes Associated With the Water Drinking Test.

The water drinking test (WDT) is currently used to temporarily elevate intraocular pressure (IOP) and predict peak IOP in glaucoma. This study investigates neurovascular changes associated with WDT in normal subjects. The effect of WDT (1 L in 5 min) on IOP, mean brachial blood pressure, heart rate, and pattern electroretinogram was assessed within the next hour in 16 healthy subjects (mean age: 33.5±7.9 y). As a control, testing was repeated in the same subjects without WDT 1 week later. Compared with control, WDT resulted in significant peak changes of the following parameters compared with baseline: IOP: +1.7±1.8 mm Hg after 30', mean brachial blood pressure: +3.9±6.3 mm Hg after 15'; heart rate: -9.2±9.8 bpm after 15', pattern electroretinogram latency: +2.1±0.9 ms after 15'. In addition to IOP elevation, WDT was associated with significant changes of hemodynamic parameters and retinal ganglion cell function in young healthy subjects. As these represent risk factors for glaucoma, their assessment upon WDT might increase its predictive power for glaucoma development.

Integrated electrophysiological evaluation in early normal-tension glaucoma

Purpose: To evaluate the variations of intraocular pressure (IOP), morphometric optic nerve head characteristic, perimetric indices and electrophysiological parameters (pattern electroretinogram and visual evoked potentials) before and after topical IOP lowering in patients with early normal-tension glaucoma.Methods: we evaluated 38 eyes of 20 patients with IOP &lt; 21 mmHg, initial glaucomatous optic neuropathy (valued with HRT: retinal nerve fiber layer thickness (RNFL) and linear cup/disk ratio (linear C/D ratio)), minimal visual field defects (Octopus 101: G2 program), best correct visual acuity more than 15/20 and pathological electrophysiological parameters (valued with pattern electroretinogram (PERG) and visual evoked potentials (VEPs)), free of systemic or other ocular diseases. All parameters were evaluated at the beginning of the study (T0) and after 12 months of therapy (T12). A randomized normal control group (27 eyes of 14 subjects) with apparent larger disc cupping underwent all exams at initial of study (T0) and after 12 months (T12).Results: Among electrophysiological parameters, at the beginning of the study NTG P100 VEPs latency is slightly increased and P100 amplitude is reduced compared to normal subjects. There are not significant variations after 12 months. P50 PERG latency in NTG is quite similar respect normal and do not modify after therapy. P50N95 complex PERG amplitude in NTG is reduced compared to normal subjects and slightly increases after 12 months (1.8 vs 1.5 ; 2.4 vs 1.9 micronvolts, with different checkboard spatial frequency). Cortical retinal time (CRT) is slightly delayed in NTG and does not modify. Among visual field indices, MD and CLV is slightly higher in NTG and do not significantly modify after therapy. Among morphometric optic nerve head characteristics, linear C/D and RNFL thickness are quite similar in NTG and do not modify. IOP is quite similar between NTG and control group and modifies in NTG after therapy.Conclusion: In a viewpoint of an integrated diagnostic, electrophysiological tests (VEPs and PERG) could provide a more sensitive measure of retinal ganglion cell integrity and help to distinguish between early normal-pressure glaucoma patients with no or minimal visual field alterations and normal subjects with apparent larger disc cupping.

Integrative properties of retinal ganglion cell electrical responsiveness depend on neurotrophic support and genotype in the mouse

Early stages of glaucoma and optic neuropathies are thought to show inner retina remodeling and functional changes of retinal ganglion cells (RGCs) before they die. To assess RGC functional plasticity, we investigated the contrast-gain control properties of the pattern electroretinogram (PERG), a sensitive measure of RGC function, as an index of spatio-temporal integration occurring in the inner retina circuitry subserving PERG generators. We studied the integrative properties of the PERG in mice exposed to different conditions of neurotrophic support. We also investigated the effect of genotypic differences among mouse strains with different susceptibility to glaucoma (C57BL/6J, DBA/2J, DBA/2.Gpnmb+). Results show that the integrative properties of the PERG recorded in the standard C57BL/6J inbred mouse strain are impaired after deficit of neurotrophic support and partially restored after exogenous neurotrophic administration. Changes in PERG amplitude, latency, and contrast-dependent responses differ between mouse strains with different susceptibility to glaucoma. Results represent a proof of concept that the PERG could be used as a tool for in-vivo monitoring of RGC functional plasticity before RGC death, the effect of neuroactive treatments, as well as for high-throughput tool for phenotypic screening of different mouse genotypes.

Head-down Posture Induces PERG Alterations in Early Glaucoma

To probe susceptibility of retinal ganglion cells (RGC) to physiological stressors associated with moderate head-down body tilt in patients with suspicion of glaucoma or early manifest glaucoma (EMG). One hundred nine subjects with best corrected visual acuity (BCVA) ≥ 20/20 and no disease other than glaucoma [glaucoma suspects (GS)=79, EMG=14, normal controls (NC)=16 and comparable age range were tested. Noncontact intraocular pressure (IOP), pattern electroretinogram (PERG), and brachial blood pressure/heart rate measurements were performed in 3 consecutive conditions (∼0038 min apart): seated (baseline), -10-degree whole body head-down tilt (HDT), and seated again (recovery). PERG amplitude and latency, IOP, and systolic/diastolic blood pressures, heart rate, calculated mean central retinal artery pressure, ocular perfusion pressure, and systolic/diastolic perfusion pressures were evaluated. During HDT, IOP significantly (P<0.001) increased in all groups approximately to the same extent (approximately 20%). PERG amplitude did not change in NC but decreased significantly (P<0.001) in patients (GS, -25%, EMG -23%). PERG phase become delayed in NC (-1.6%, P=0.04) but more so in patients (GS, -2.7%, P<0.001; EMG, -6.0%, P<0.001). The proportion of patients with PERG alterations significantly (P<0.05) exceeding those occurring in age-adjusted and baseline-adjusted NC were, GS: amplitude 20%, phase 15%; EMG: amplitude 14%, phase 50%. All measures recovered baseline values after HDT. Moderate HDT induces temporary worsening of RGC function in a subpopulation of GS and EMG patients. This noninvasive protocol may help disclose abnormal susceptibility of RGCs in a subset of the patients at risk of glaucoma.

Retrograde signaling in the optic nerve is necessary for electrical responsiveness of retinal ganglion cells.

We investigated the role of retrograde signaling in the optic nerve on retinal ganglion cell (RGC) electrical responsiveness in the mouse model. Electrical response of RGC was measured by pattern electroretinogram (PERG) in 43 C57BL/6J mice 4 to 6 months old under ketamine/xylazine anesthesia. PERGs were recorded before and at different times after blockade of axon transport with lidocaine at either the retrobulbar level (2 μL, 40 μg/μL) or at level of the superior colliculus (SC, 1 μL, 40 μg/μL). PERGs also were recorded before and at different times after optic nerve crush 1.5 mm behind the eye, followed by TUJ1-positive RGC counts of excised retinas. As controls, PERGs also were recorded after either saline injections or sham optic nerve surgery. The photopic flash electroretinogram (FERG) and visual evoked potential (FVEP) also were recorded before lidocaine and at relevant times afterwards. Lidocaine injection caused rapid (retrobulbar ~10 minutes, SC 1 hour), reversible reduction of PERG amplitude (≥50%). Optic nerve crush caused rapid (10-20 minutes), irreversible reduction of PERG amplitude (70-75%), increase of PERG latency (>25%), as well as RGC loss (88%) 1 month after crush. FVEP was unaltered by lidocaine. For all procedures, the FERG was unaltered. As experimental interventions were made at postretinal level(s), PERG changes were likely associated with altered supply of retrogradely-delivered material from the SC. This implies that retrograde transport of target-derived molecules is necessary for normal RGC electrical responsiveness. The time course of early PERG changes is consistent with the speed of fast retrograde axon transport.

The Pattern Electroretinogram as a Tool to Monitor Progressive Retinal Ganglion Cell Dysfunction in the DBA/2J Mouse Model of Glaucoma

To determine the baseline characteristics, reliability, and dynamic range of the pattern electroretinogram (PERG) as a tool to monitor progressive RGC dysfunction in the DBA/2J mouse model of glaucoma with spontaneously elevated intraocular pressure (IOP). PERGs were recorded from 56 undilated eyes of 28 anesthetized (ketamine-xylazine-acepromazine) DBA/2J mice of different ages (2-4 months, n = 44 eyes; 12-14 months, n = 12 eyes) in response to contrast reversal of gratings that maximize PERG amplitude (95% contrast, 1-Hz reversal, 0.05 cyc/deg spatial frequency, 50 degrees x 56 degrees field size). Robust averaging (1800 sweeps) was used to isolate PERG from background noise. Cone-driven ERGs in response to diffuse light flashes superimposed on a rod-adapting background (FERG) were also recorded. PERGs had consistent waveforms and were reproducible across batches of mice and operators. In 2- to 4-month-old mice (prehypertensive stage), the PERG amplitude (mean, 8.15 +/- 0.4 microV [SEM]) was considerably larger than the noise (mean 1.18 +/- 0.1 microV). The test-retest variability (two different sessions 1 week apart) and interocular asymmetry of PERG amplitude was approximately 30%, and that of PERG latency was approximately 17%. In 12- to 14-month-old mice (advanced hypertensive stage) the PERG amplitude (mean, 1.29 +/- 0.12 microV) was close to that of noise. In 12- to 14-month-old mice the FERG was reduced to a lesser extent compared with the PERG. The PERG has an adequate signal-to-noise ratio, reproducibility, and dynamic range to monitor the progression of functional changes in the inner retina in DBA/2J mice.

Acute effects of cigarette smoking on pattern electroretinogram

In this study, acute effects of cigarette smoking on the pattern electroretinogram (PERG) were investigated. First, variability of the PERG was studied in a group of young male smokers (26 right eyes of 26 subjects). Then PERGs were investigated in a group of habitual smokers (17 right eyes of 17 subjects) in separate real smoking and sham smoking sessions. On each session PERGs were recorded pre-smoking (PS), immediately after smoking (IAS) and 5 min after smoking (5th) conditions. Real smoking significantly increased P50 amplitudes and decreased N95 latencies. Regarding P50 amplitudes in the real smoking sessions, the differences were significant between PS and IAS (PS: 3.3 +/- 0.5 muV, IAS: 3.7 +/- 0.7microV, P = 0.015) and between PS-5th (PS: 3.3 +/- 0.5microV, 5th: 4.1 +/- 0.9microV, P = 0.039). There was significant difference (P = 0.024) between N95 latencies of PS (98.5 +/- 6.9 ms) and IAS (94.7 +/- 5.1 ms) in the real smoking sessions. No statistically significant difference was observed in sham smoking sessions. Our results indicated, for the first time, that cigarette smoking may influence PERG amplitude and latency significantly in habitual smokers.

Contrast adaptation in retinal and cortical evoked potentials: no adaptation to low spatial frequencies.

Contrast adaptation occurs in both the retina and the cortex. Defining its spatial dependence is crucial for understanding its potential roles. We thus asked to what degree contrast adaptation depends on spatial frequency, including cross-adaptation. Measuring the pattern electroretinogram (PERG) and the visual evoked potential (VEP) allowed separating retinal and cortical contributions. In ten subjects we recorded simultaneous PERGs and VEPs. Test stimuli were sinusoidal gratings of 98% contrast with spatial frequencies of 0.5 or 5.0 cpd, phase reversing at 17 reversals/s. Adaptation was controlled by prolonged presentation of these test stimuli or homogenous gray fields of the same luminance. When adaptation and test frequency were identical, we observed significant contrast adaptation only at 5 cpd: an amplitude reduction in the PERG (-22%) and VEP (-58%), and an effective reduction of latency in the PERG (-0.95 ms). When adapting at 5 cpd and testing at 0.5 cpd, the opposite effect was observed: enhancement of VEP amplitude by +26% and increase in effective PERG latency by + 1.35 ms. When adapting at 0.5 cpd and testing at 5 cpd, there was no significant amplitude change in PERG and VEP, but a small effective PERG latency increase of +0.65 ms. The 0.5-cpd channel was not adapted by spatial frequencies of 0.5 cpd. The adaptability of the 5-cpd channel may mediate improved detail recognition after prolonged blur. The existence of both adaptable and nonadaptable mechanisms in the retina allows for the possibility that by comparing the adaptational state of spatial-frequency channels the retina can discern between overall low contrast and defocus in emmetropization control.