A comparison of oscillatory potential and pattern electroretinogram measures in diabetic retinopathy

Both basic and clinical electrophysiological investigations have established that the oscillatory potentials (OP) and pattern electroretinogram (PERG) appear to originate from retinal sites that are in proximity. The OPs, subcomponents of the flash ERG, have been shown to reflect disturbances in retinal circulation, and OP amplitude attenuation or loss may be a distinctive feature of diabetic retinopathy. The PERG has been shown to be abnormal in diseases of the optic nerve and ganglion cell body. Thus its relative sensitivity for detection of electroretinal abnormalities in diabetic retinopathy is in question. This study assessed the sensitivity of ERG and OP measures in their detection of abnormalities of electroretinal function in diabetic patients referred to our laboratory. Thirty-five adult Type I patients were studied: 21 with background retinopathy (BR group), 14 with no evidence of background retinopathy (No BR group), and 25 normal control subjects.Monocular OPs were recorded to full-field ganzfeld stimulation at four stimulus intensities. PERGs were obtained from checkerboard pattern reversal stimulation (checksize = 30 arc). Peak-to-peak amplitude and peak implicit time measures of PERGs and OPs were obtained. Subsequent multivariate analysis demonstrated significant differences between normals and diabetic patients, including diabetics with no clinical evidence of retinopathy. In addition, the OP and PERG implicit times appear to be unaffected while OP and PERG amplitudes were diminished in patients with background retinopathy. Only OP amplitudes were found to be significantly diminished in diabetic patients with no photographic evidence of background retinopathy. The PERGs were normal in these patients. Overall, the OP amplitude measures were more sensitive than PERG measures in detecting abnormalities in patients with no retinal photographic evidence of background retinopathy.     

Evaluation of retinal ganglion cell function after intraocular pressure reduction measured by pattern electroretinogram in patients with primary open-angle glaucoma

Background

To evaluate retinal ganglion cell (RGC) function after intraocular pressure (IOP) reduction measured by pattern electroretinogram (PERG) in patients with newly diagnosed, non-treated preperimetric and early stages of primary open-angle glaucoma (POAG).

Methods

Twenty-four eyes from 24 patients with POAG: 11 eyes with preperimetric glaucoma and 13 eyes with early glaucoma received Ganfort ^® (bimatoprost + timolol) once a day for a period of 1 month. Before and after the treatment, following measurements were analyzed: IOP, mean ocular perfusion pressure (MOPP), peak time of P50 and amplitude of P50 and N95 waves in PERG (ISCEV standard 2012). Correlations between PERG P50 and N95 waves, IOP and MOPP were calculated.

Results

After therapy, IOP significantly decreased in all eyes, on average 31%. Significant increase in MOPP in all eyes on average 14% was detected. PERG amplitude of P50 and N95 waves increased in 75 and 79% eyes, respectively, on average P50 by 28% and N95 by 38%. There were no significant interactions between the change of PERG parameters in time and stage of glaucoma.

Conclusions

Significant IOP-lowering therapy can improve RGC function measured by PERG, in patients with preperimetric and early stages of POAG.

     

Electrophysiological evidence that early glaucoma affects foveal vision

The pattern electroretinogram (PERG) and visual evoked potential (PVEP) were recorded simultaneously using a 1.1 cpd pattern which was counterphase modulated at 1 Hz. The responses of ocular hypertensive (OHT) eyes (with normal visual fields) and eyes with early glaucoma (with early visual field defects and/or early cupping of the optic nervehead) were compared to age-matched normal observers. All patients (26 eyes) and normal observers (14 eyes) had normal transient flash electroretinograms. Delays were seen in mean PERG latency in both OHT and early glaucoma eyes, while mean PERG amplitude was significantly reduced only in the early glaucoma eyes. The PVEP responses were unmeasurable in 11/26 patient eyes because the waveforms were grossly abnormal in shape, making it impossible to identify the N- and P-components. The data were categorized in this manner: a patient response was considered abnormal if latency or amplitude exceeded normal limits (PERG or PVEP) or if the waveform was unmeasurable due to its shape (PVEP only). Of the 26 patient eyes, we found that 8 eyes had normal PERG and PVEP, 11 eyes had abnormal PERG and PVEP, one eye had an abnormal PERG and a normal PVEP, and 6 eyes (3 patients) had a normal PERG and an abnormal PVEP. These data support the proposition that foveal vision (as assessed by the PVEP) may be affected by early glaucomatous damage. The relationship between the PERG and PVEP also was evaluated using a new measurement which we call the latency window. Using this measurement, 15/26 patient eyes were abnormal - 9 of these had unmeasurable PVEPs. This measurement could be useful in classifying W-shaped PVEPs as normal or abnormal.This study was supported in part by Grants EY01708 and EY01867 from the National Eye Institute, Bethesda, MD, by Fight For Sight Grant-in-Aid G-274, and by an unrestricted grant from Research to Prevent Blindness, Inc., New York, NY.     

Pattern electroretinogram (PERG) and pattern visual evoked potential (PVEP) in the early stages of Alzheimer’s disease

Alzheimer’s disease (AD) is one of the most common causes of dementia in the world. Patients with AD frequently complain of vision disturbances that do not manifest as changes in routine ophthalmological examination findings. The main causes of these disturbances are neuropathological changes in the visual cortex, although abnormalities in the retina and optic nerve cannot be excluded. Pattern electroretinogram (PERG) and pattern visual evoked potential (PVEP) tests are commonly used in ophthalmology to estimate bioelectrical function of the retina and optic nerve. The aim of this study was to determine whether retinal and optic nerve function, measured by PERG and PVEP tests, is changed in individuals in the early stages of AD with normal routine ophthalmological examination results. Standard PERG and PVEP tests were performed in 30 eyes of 30 patients with the early stages of AD. The results were compared to 30 eyes of 30 normal healthy controls. PERG and PVEP tests were recorded in accordance with the International Society for Clinical Electrophysiology of Vision (ISCEV) standards. Additionally, neural conduction was measured using retinocortical time (RCT)—the difference between P100-wave latency in PVEP and P50-wave implicit time in PERG. In PERG test, PVEP test, and RCT, statistically significant changes were detected. In PERG examination, increased implicit time of P50-wave (P < 0.03) and amplitudes reductions in P50- and N95-waves (P < 0.0001) were observed. In PVEP examination, increased latency of P100-wave (P < 0.0001) was found. A significant increase in RCT (P < 0.0001) was observed. The most prevalent features were amplitude reduction in N95-wave and increased latency of P100-wave which were seen in 56.7% (17/30) of the AD eyes. In patients with the early stages of AD and normal routine ophthalmological examination results, dysfunction of the retinal ganglion cells as well as of the optic nerve is present, as detected by PERG and PVEP tests. These dysfunctions, at least partially, explain the cause of visual disturbances observed in patients with the early stages of AD.     

Detection of optic neuropathy in glaucomatous eyes with normal standard visual fields using a test battery of short-wavelength automated perimetry and pattern electroretinography

PURPOSE: To evaluate the clinical use of a test battery of short-wavelength automated perimetry (SWAP), frequency-doubling technology (FDT) perimetry, and pattern-electroretinography (PERG) in patients with definite primary open-angle glaucoma (POAG) but normal results on standard automated perimetry (SAP). STUDY DESIGN: Prospective, comparative, observational case series. PARTICIPANTS: Thirty-six patients with POAG with standard visual field defects in one eye and normal standard visual fields in the contralateral eye and 36 normal controls were enrolled. MAIN OUTCOME MEASURES: SWAP, PERG, FDT, and SAP were performed in all eyes, and global indices and amplitudes were used for statistical analysis. RESULTS: When contralateral POAG eyes with asymmetric glaucomatous damage was compared, a paired t test showed significant differences in SAP mean deviation (MD) (P < 0.0001), SWAP-MD (P = 0.0003), FDT-MD (P = 0.0008), and PERG amplitudes (P < 0.0001). When comparing between POAG eyes with normal results on SAP and normal controls, Student's t test showed significant differences for SWAP-MD (P < 0.0001), FDT-MD (P = 0.0006), PERG N1P1-amplitude (P = 0.0486) and P1N2-amplitude (P < 0.0001); receiver operating characteristic analysis revealed promising accuracy for SWAP-MD of 73.6% (P < 0.0001). SWAP-MD (P < 0.0001) and FDT-MD (P < 0.0001) correlated significantly with SAP-MD and with each other (range, P < 0.0001 to P = 0.0020). Regression analysis revealed that PERG P1N2-amplitude could improve the power of SWAP-MD from 73.6% to detect early POAG in eyes with normal results on SAP to an accuracy of 81.9%. CONCLUSIONS: A test battery of SWAP-MD and PERG P1N2-amplitude could detect glaucomatous optic neuropathy in POAG eyes with normal standard visual fields, whereas FDT-MD and SWAP-MD significantly correlated with each other and with SAP-MD. All tests were able to detect the eye with the more severe glaucomatous optic neuropathy in patients with asymmetric POAG.     

Quantitative assessment of aqueous flare intensity in diabetes

Aqueous flare intensity was measured with the laser flare-cell meter in 231 eyes of diabetic patients and 31 eyes of normal age-matched controls. Diabetic patients were divided into four groups based on the degree of retinopathy: (1) non-retinopathy, 42 eyes; (2) background retinopathy, 72; (3) preproliferative retinopathy, 23; and (4) proliferative retinopathy, 94. There was no significant difference between the normal controls and the non-retinopathy group, whereas the rest of the diabetic groups showed significantly higher flare values than did normal controls (P < 0.001). Flare intensity increased with the progression of retinopathy. Our results demonstrate that clinical use of the flare-cell meter enables the quantitative assessment of blood-aqueous barrier function in diabetics and suggest that diabetic iridopathy, as one of the manifestations of diabetes in the anterior part of the eye, exists even in the early stages of this disease and progresses in parallel with retinopathy.Supported in part by research grant 62870070 from the Ministry of Education and Culture of Japan     

Comparing three different modes of electroretinography in experimental glaucoma: diagnostic performance and correlation to structure

Purpose

To compare diagnostic performance and structure–function correlations of multifocal electroretinogram (mfERG), full-field flash ERG (ff-ERG) photopic negative response (PhNR) and transient pattern-reversal ERG (PERG) in a non-human primate (NHP) model of experimental glaucoma (EG).

Methods

At baseline and after induction of chronic unilateral IOP elevation, 43 NHP had alternating weekly recordings of retinal nerve fiber layer thickness (RNFLT) by spectral domain OCT (Spectralis) and retinal function by mfERG (7F slow-sequence stimulus, VERIS), ff-ERG (red 0.42 log cd-s/m² flashes on blue 30 scotopic cd/m² background, LKC UTAS-E3000), and PERG (0.8° checks, 99% contrast, 100 cd/m² mean, 5 reversals/s, VERIS). All NHP were followed at least until HRT-confirmed optic nerve head posterior deformation, most to later stages. mfERG responses were filtered into low- and high-frequency components (LFC, HFC, >75 Hz). Peak-to-trough amplitudes of LFC features (N1, P1, N2) and HFC RMS amplitudes were measured and ratios calculated for HFC:P1 and N2:P1. ff-ERG parameters included A-wave (at 10 ms), B-wave (trough-to-peak) and PhNR (baseline-to-trough) amplitudes as well as PhNR:B-wave ratio. PERG parameters included P50 and N95 amplitudes as well as N95:P50 ratio and N95 slope. Diagnostic performance of retinal function parameters was compared using the area under the receiver operating characteristic curve (A-ROC) to discriminate between EG and control eyes. Correlations to RNFLT were compared using Steiger’s test.

Results

Study duration was 15 ± 8 months. At final follow-up, structural damage in EG eyes measured by RNFLT ranged from 9% above baseline (BL) to 58% below BL; 29/43 EG eyes (67%) and 0/43 of the fellow control eyes exhibited significant (>7%) loss of RNFLT from BL. Using raw parameter values, the largest A-ROC findings for mfERG were: HFC (0.82) and HFC:P1 (0.90); for ff-ERG: PhNR (0.90) and PhNR:B-wave (0.88) and for PERG: P50 (0.64) and N95 (0.61). A-ROC increased when data were expressed as % change from BL, but the pattern of results persisted. At 95% specificity, the diagnostic sensitivity of mfERG HFC:P1 ratio was best, followed by PhNR and PERG. The correlation to RNFLT was stronger for mfERG HFC (R = 0.65) than for PhNR (R = 0.59) or PERG N95 (R = 0.36), (p = 0.20, p = 0.0006, respectively). The PhNR flagged a few EG eyes at the final time point that had not been flagged by mfERG HFC or PERG.

Conclusions

Diagnostic performance and structure–function correlation were strongest for mfERG HFC as compared with ff-ERG PhNR or PERG in NHP EG.

     

Pattern electroretinograms for the detection of neural loss in patients with permanent temporal visual field defect from chiasmal compression

Purpose To evaluate the ability of full-field and hemifield pattern electroretinogram (PERG) parameters to differentiate between healthy eyes and eyes with band atrophy (BA) of the optic nerve. Methods Twenty-six eyes from 26 consecutive patients with permanent temporal hemianopic visual field defects and BA of the optic nerve from previous chiasmal compression and 26 healthy subjects were studied prospectively. All patients were submitted to an ophthalmic examination including Humphrey 24-2 SITA Standard automated perimetry. Full-field and hemifield (nasal and temporal) stimulation transient pattern electroretinograms (PERG) were recorded using checkerboard screens. Amplitudes and peak times for the P50 and N95 as well as the overall P50+N95 amplitude were measured. The intraocular N95:P50 amplitude ratio was calculated. Comparisons were made using Student’s t-test. Receiver operating characteristic (ROC) curves were used to describe the ability of PERG parameters to discriminate the groups. Results Full-field P50, N95, and P50+N95 amplitude values were significantly smaller in eyes with BA than in control eyes (P < 0.001). Nasal and temporal hemifield PERG studies revealed significant differences in N95 and P50+N95 amplitudes measurements. No significant difference was observed regarding peak times or N95:P50 amplitude ratios. Nasal and temporal hemifield PERG values did not differ significantly in eyes with BA or in controls. Using the 10th percentile of normals as the lower limit of normal, 16 of 26 eyes were considered abnormal according to the best discriminating parameters. Conclusions Transient PERG amplitude measurements were efficient at differentiating eyes with BA and permanent visual field defects from normal controls. Hemifield stimulation PERG parameters were unable to detect asymmetric hemifield neural loss, but further studies are required to clarify this issue. Study registered on ClinicalTrial.gov number: NCT00553761     

Detection of diabetic retinopathy: a comparison between red-free digital images and colour transparencies

Background The aim of this study was to compare how diabetic retinopathy was detected from red-free digital images and colour transparencies.Methods Two ophthalmologists graded two-field, nonstereoscopic, 60° red-free digital images and colour transparencies utilizing an ETDRS-based grading scale, from 107 mainly type 2 diabetic patients. The discordantly scored eyes were graded by the graders together to obtain a consensus level of retinopathy for each method. The eyes with discordant consensus grading results were further graded using all available photographic material to reach a final consensus level of diabetic retinopathy. Intermethod variations were presented as percentages and using kappa (k) and weighted kappa (wk) statistics. The errors of the two consensus gradings with respect to the final consensus grading were compared using McNemars test.Results For the colour transparencies there was an agreement between the individual and the consensus grading results in 93% (k=0.90, wk=0.97) and 86% (k=0.79, wk 0.88) for grader 1 and grader 2. Corresponding figures for red-free digital images were 88% (k=0.83, wk=0.96) and 84% (k=0.78, wk 0.91). Agreement between methods was obtained in 76/107 eyes (71%; k=0.58 and wk=0.79). In the 31 discordantly graded eyes the level of retinopathy was underestimated in 20/31 (64%) vs 7/31 eyes (23%) and overestimated in 1/31 (3%) vs 3/31 eyes (10%) from colour transparencies and red-free digital images, respectively. The error tendencies were significantly lower when using red-free digital images (p<0.008).Conclusions Red-free digital images are comparable with two-field colour transparencies in the identification of mild to moderate nonproliferative diabetic retinopathy.     

Pattern electroretinogram for monitoring the efficacy of intravitreal triamcinolone injection in diabetic macular edema

Purpose: To investigate the efficacy of intravitreal triamcinolone (IVT) by evaluation of pattern electroretinogram (PERG) in diabetic patients with clinically significant macular edema (CSME). Methods: Forty eyes of 40 diabetic patients were treated with 8 mg of IVT injection as primary therapy for CSME. The main outcome measures included best-corrected visual acuity, fundus fluorescein angiography, P₅₀ amplitudes of pattern electroretinogram (PERG) and intraocular pressures before and after injection. Results: The mean follow-up time was 6.1 months. Mean visual acuity improved significantly from a mean LogMAR value of 1.14 ± 0.16 at baseline to a maximum of 0.73 ± 0.30. The mean baseline P₅₀ amplitude of PERG before intravitreal injection was 1.5 ± 0.9 V. After the treatment, it was 2.l ± 1.1 V at 1-month, 2.4 ± 1.0 V at 3-month and 2.1 ± 0.9 V at last visit and the differences were significant when compared with baseline values (for each, p < 0.001). Temporary increases in intraocular pressures were controlled with topical antiglaucomatous medications, if required. Conclusion: IVT injection provides rapid improvement in visual acuity of diabetic patients with CSME that has been supported by P₅₀ amplitudes of PERG. P₅₀ amplitudes of PERG may be used as novel predictive value in the evaluation of the effectiveness of IVT injection.