Pattern Electroretinogram Phase Research Articles

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.

Head-down Posture in Glaucoma Suspects Induces Changes in IOP, Systemic Pressure, and PERG That Predict Future Loss of Optic Nerve Tissue.

To obtain pilot data on posture-induced changes of intraocular pressure (IOP), systemic pressure, and pattern electroretinogram (PERG) predictive of future optic nerve tissue loss glaucoma suspects (GSs). Mean peripapillary retinal fiber layer thickness (RNFLT) was measured with optical coherence tomography 2 times/year in 28 GS aged 58±8.9 years over 5.0±0.73 years. All patients had a baseline PERG, IOP, and brachial blood pressure measurements in the seated and -10 degrees head-down-body-tilt (HDT) position. Outcome measures were seated/HDT PERG amplitude and phase, IOP, mean arterial blood pressure, and estimated ocular perfusion pressure. An additional group of 11 similarly aged controls aged 56.9±13 years was tested for comparison. Although all GS had initial RNFLT in the normal range, 9/28 of them developed significant (P<0.05) loss of mean RNFLT [thinners (T)] over the follow-up period as opposed to 19/28 who did not [nonthinners (NT)]. Significant (P<0.05) differences between similarly aged controls, NT, and T were found in PERG amplitude, PERG phase, mean arterial blood pressure, IOP, and ocular perfusion pressure. A nominal logistic regression using baseline PERG and hemodynamic variables was able to distinguish T from NT with an area under receiving operator characteristic of 0.89 (SE, 0.07). Baseline PERG, IOP, and systemic blood pressure, together with their changes upon HDT, may have predictive value for future loss of optic nerve tissue in GS. This study supports the rationale for a full-scale clinical trial to identify patients at high risk of development of glaucoma.

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

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

Adaptation of the Steady-state PERG in Early Glaucoma

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

Pattern electroretinogram progression in glaucoma suspects.

To prospectively monitor progressive changes of retinal ganglion cell function in early glaucoma using the pattern electroretinogram (PERG). Fifty-nine patients enrolled as glaucoma suspects were observed untreated over an average of 5.7±1.4 years, during which they were tested with PERG (PERGLA paradigm) and standard automated perimetry (SAP) 2 times per year. PERG amplitude and phase were normalized for physiological age-related changes, and linear regressions fitted to the data to calculate progression slopes (signal), slope SE (noise), and corresponding signal-to-noise ratios (SNR=slope÷SE). Linear regressions were also used to fit SAP global indices mean deviation (MD) and pattern standard deviation (PSD). On average, progression slopes of PERG amplitude/phase were skewed toward negative values, their mean being significantly (P<0.01) different from zero. In contrast, mean slopes of SAP-MD and PSD were not significantly different from zero. SNRs were higher for PERG than SAP (P<0.01). A substantial number of eyes displayed significant (P<0.05) progression of PERG amplitude (15% to 20%) or PERG phase (16% to 25%). Fewer eyes displayed significant progression of SAP-MD (0% to 2%) or SAP-PSD (4% to 8%). The PERG displayed clear longitudinal loss of signal (diminished amplitude, phase delay, or both) in a substantial number of eyes of patients, indicating progressive deterioration of retinal ganglion cell function. Progression of SAP global indices MD and PSD was found in a relatively smaller number of eyes. It remains to be established whether PERG progression has predictive value for developing visual dysfunction.

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.

Pattern electroretinogram as a function of spatial frequency after retrobulbar optic neuritis.

Steady-state (8-Hz) pattern electroretinograms in response to counterphased sinusoidal gratings of variable spatial frequency (0.6-4.8 c/deg) were recorded in 17 patients who had had retrobulbar optic neuritis in one or both eyes (23 eyes with a clinical history of optic neuritis) and in 21 age-matched normal subjects. Amplitude and phase of the Fourier-analyzed pattern electroretinogram second harmonic were measured. The mean pattern electroretinogram amplitude of patients was significantly reduced compared with that of controls. Amplitude reductions were more marked at intermediate (1-1.4 c/deg) than at lower or higher spatial frequencies. Therefore, the average amplitude versus spatial frequency response function differed significantly in patients compared with controls, displaying a lowpass instead of a band-pass shape. No significant differences in the mean pattern electroretinogram phase were observed between groups at any spatial frequency. These results indicate spatial frequency-dependent abnormalities in the pattern electroretinogram amplitude after optic neuritis, suggesting a specific loss of retinal neurons sensitive to stimuli of intermediate spatial frequencies.