Photopic 30 Hz flicker ERG as a predictor for rubeosis in central retinal vein occlusion

AIMS: To investigate the predictive value of the cone b-wave implicit time in the photopic compared with the scotopic 30 Hz flicker ERG for rubeosis in central retinal vein occlusion. METHODS: 44 patients with a central retinal vein occlusion were examined with full field electroretinogram (ERG). RESULTS: The average implicit time in the photopic 30 Hz flicker ERG in patients who developed rubeosis (n=15) was 38.3 ms. In the patients who did not develop rubeosis (n=29) it was 31.3. The difference is statistically significant (p=0.0000000004). CONCLUSION: The photopic cone b-wave implicit time in the 30 Hz flicker ERG is a good predictor for rubeosis.     

Association of electroretinogram and morphological findings in branch retinal vein occlusion with macular edema

The objective of this study is to evaluate the relations among electroretinogram parameters (cone a-wave, cone b-wave, and 30-Hz flicker), retinal thickness, and retinal volume in patients with branch retinal vein occlusion (BRVO) and macular edema. We prospectively examined 33 patients (33 eyes) with BRVO and macular edema. The amplitude and implicit time of the a-wave cone, b-wave cone, and 30-Hz flicker were calculated automatically from the ERG. Retinal thickness and volume were measured by optical coherence tomography (OCT) in nine macular subfields. Then, correlations between the ERG parameters and morphological parameters were analyzed. The 30-Hz flicker amplitude was significantly smaller in the eyes with BRVO and macular edema than in the unaffected contralateral eyes. Thirty-hertz flicker and cone b-wave implicit times were significantly longer in the eyes with macular edema than in the unaffected eyes. The implicit time of the cone b-wave was correlated with both retinal thickness and retinal volume in the temporal subfields. Thirty-hertz flicker amplitude was correlated with both retinal thickness and volume in the temporal and superior outer (site of occlusion) subfields, while 30-Hz flicker implicit time was correlated with retinal thickness and volume in the outer temporal subfield. Multiple regression analysis demonstrated that the retinal thickness and volume of the temporal subfields were significant “determinants” of the implicit time for the cone b-wave and 30-Hz flicker, as well as the 30-Hz flicker amplitude. These findings suggest that OCT parameters of the temporal region may reflect postreceptoral cone pathway function in BRVO patients with macular edema.     

视网膜中央静脉阻塞性黄斑水肿的OCT与ERG的对比分析

目的：观察视网膜中央静脉阻塞性黄斑水肿的黄斑区视网膜厚度与视网膜电图( electroretinogram, ERG )各项参数(Cone-a,Cone-b和30Hz)变化的关系。
　　方法：随机选择视网膜中央静脉阻塞患者25例25眼及25只对侧眼分别行明视闪光视网膜电图及光学相干断层扫描( optical coherence tomography,OCT)检查,明视闪光视网膜电图检查测各项参数的振幅和潜伏期, OCT测量黄斑区九部分的视网膜厚度,分析黄斑区形态参数与明视闪光视网膜电图各参数变化之间的关系。
　　结果：黄斑区除颞侧外七个部位视网膜厚度与 ERG 的Cone-b和30 Hz潜伏期相关。
　　结论：研究发现视网膜中央静脉阻塞患者的黄斑区视网膜厚度与内层视网膜功能密切相关。     

On-response deficit in the electroretinogram of the cone system in X-linked retinoschisis

PURPOSE: The purpose of this study was to evaluate the hypothesis that the reduced b-wave to a-wave ratio of the brief-flash electroretinogram (ERG) of the cone system typically observed in X-linked retinoschisis (XLRS) represents a relatively greater deficit in the ON response (response to light onset) than the OFF response (response to light offset). A second purpose was to investigate the use of sawtooth flicker as a stimulus for eliciting ERG ON and OFF responses. METHODS: Light-adapted, full-field ERGs were recorded in six patients with XLRS and six age-similar control subjects in response to 8-Hz rapid-on and rapid-off sawtooth flicker to emphasize ON and OFF responses, respectively. ERG responses were analyzed in terms of the amplitudes and implicit times of the a-wave, b-wave, and d-wave components. RESULTS: There was no significant difference between the patients with XLRS and the control subjects for either the amplitude of the a-wave of the ON response or the amplitude of the d-wave of the OFF response. However, the amplitude of the b-wave of the ON response was reduced significantly in the patients with XLRS, resulting in a significantly reduced b-wave to d-wave ratio. The patients' implicit times were increased significantly for all waveform components. CONCLUSIONS: The reduced b-wave to d-wave ratio of the ERG of the cone system in these patients with XLRS is consistent with a relative dysfunction of the cone ON bipolar cell pathway in this disorder. The results show further that sawtooth flicker is a promising stimulus for eliciting well-defined ERG waveforms that can provide a quantitative assessment of the properties of ON and OFF responses in retinal disease.     

Dependence of cone b-wave implicit time on rod amplitude in retinitis pigmentosa

Computer-averaged full-field rod and cone electroretinograms (ERGs) were evaluated in 63 patients with retinitis pigmentosa and 116 normal subjects. Cone b-wave implicit times to 30 Hz white flicker and to 1.0 Hz white flashes on a white background were both inversely proportional to the log amplitude of the dark-adapted rod b-wave, even when controlling for the log amplitude of the dark-adapted cone b-wave. Cone ERGs were also obtained from a subset of 12 patients with retinitis pigmentosa in the presence of photopically-matched red and blue backgrounds that allowed direct assessment of the effect of rod function on cone b-wave implicit time in the patients. The effectiveness of the blue background in reducing cone b-wave implicit time relative to that obtained with the red background varied with the amplitude of the rod ERG. The results of both experiments suggest that delays in cone b-wave implicit time obtained with 30 Hz white flicker or with background adaptation in patients with retinitis pigmentosa are due, at least in part, to rod disease.     

Early panretinal photocoagulation for ERG‐verified ischaemic central retinal vein occlusion

Purpose: We have previously shown that photopic cone b‐wave implicit time ≥35.0 ms in 30 Hz flicker electroretinography (ERG) predicts ocular neovascularization (NV) in central retinal vein occlusion (CRVO). Here, we evaluate the effects of early panretinal photocoagulation (PRP) in patients with ERG‐verified ischaemic CRVO. Methods: Patients with CRVO, admitted to our department between 2000 and 2008, were classified as having ischaemic or non‐ischaemic CRVO based on the ERG‐results. In a first group of 71 patients, 18 patients had ischaemic CRVO and were assigned to standard treatment that is regular examinations and PRP as soon as NV was found. In a consecutive group of 65 patients, 18 patients with ischaemic CRVO received early PRP. In this group, ERG was performed on average 6 weeks after the first symptoms of CRVO. The patients underwent PRP as soon as possible after the ERG‐examination, and the treatment was completed within one to three sessions. Results: Twelve patients in the standard treatment group developed neovascular glaucoma during a mean period of 5 months after the CRVO. In the early treatment group, one patient developed subtle iris rubeosis 7 months after PRP. Otherwise, none of the patients showed any signs of ocular NV, and the intraocular pressure remained within normal range, without the necessity of supplementary medication, during a mean follow‐up of 41 months. Conclusions: This study indicates that ocular NV in patients with CRVO can be predicted by photopic 30 Hz flicker ERG and that early PRP in ERG‐verified ischaemic CRVO could be suggested as standard treatment.     

The photopic negative response of the flash electroretinogram in retinal vein occlusion

The photopic negative response (PhNR) has recently been shown to be severely affected in central retinal artery occlusion (CRAO), despite relative preservation of the cone b-wave compared to that in the healthy unaffected fellow eye. The aim of this study was to test how the PhNR of the flash electroretinogram (ERG) is affected in human retinal vein occlusion. PhNR was elicited with red stimuli (1 cd s/m², 5 cd s/m², and 7 cd s/m² with 4 ms duration) and blue background (10 cd/m²). Standard Ganzfeld flash ERG was produced according to the ISCEV standard for the clinical electroretinogram (2004). Sixteen patients with central retinal vein occlusion (CRVO), 14 patients with branch retinal vein occlusion (BRVO), and 16 controls were analyzed. The amplitude of the PhNRs was significantly smaller in the CRVO and BRVO eyes than those in the unaffected fellow or control eyes (p = 0.000). There was a significantly greater reduction of PhNR amplitudes than that of other waves including the OPs, rod b-wave, combined a-wave and b-wave, cone a-wave and b-wave, and 30 Hz flicker ERG. Thus, PhNR amplitude in retinal vein occlusion is severely affected. There is a potential role for PhNR in assessing inner retinal damage and evaluating the effect of treatment.     

Photopic 30 Hz flicker electroretinography predicts ocular neovascularization in central retinal vein occlusion

PURPOSE: To confirm the predictive value of photopic cone b-wave implicit time in 30 Hz flicker electroretinography (ERG) for ocular neovascularization (NV) in central retinal vein occlusion (CRVO), and to compare the ERG results to the presumed healthy fellow eye. METHODS: A retrospective analysis of 71 consecutive patients with CRVO. After ERG examination, all patients were followed for at least 12 months, or until NV was found. Three patients died during the study period; none of the other patients were lost to follow-up. RESULTS: Twenty-four patients (33.8%) developed NV during follow-up. The mean cone b-wave implicit time of all patients was 32.6 ms [standard deviation (SD) 5.21]. All 18 patients with an implicit time of 35.0 ms or higher (> 0.5 SD from mean) developed NV. In patients who developed NV, the average implicit time was 38.5 ms (range 29.7-43.9 ms); in patients without NV (n = 47), the average implicit time was 29.6 ms (range 24.7-34.9 ms) (P < 0.0001). The average implicit time in the presumed healthy fellow eye was 28.7 ms (range 24.4-33.9 ms) in patients with NV, and 26.5 ms (range 23.7-33.2 ms) in patients without NV (P = 0.002). The mean interocular difference in implicit time was 9.9 ms (range 4.1-15.7 ms) in patients with NV and 2.9 ms (range -1.0 to 10.0 ms) in patients without NV (P < 0.0001). CONCLUSION: Patients with CRVO should be examined routinely with photopic 30 Hz flicker ERG, which is a simple and objective clinical test that can identify patients at risk of ocular NV. On the assumption that the presented ERG settings are used, implicit times of 35.0 ms or higher (> 0.5 SD from mean) are clearly associated with the development of ocular NV. To compare the ERG result of the affected eye to the presumed healthy fellow eye is probably of less value.     

Electroretinographic findings in the Standard Wire Haired Dachshund with inherited early onset cone–rod dystrophy

Purpose To describe electroretinographic (ERG) findings in a strain of Standard Wire Haired Dachshund (SWHD)-derived dogs at the ages of approximately 5, 8 and 52 weeks selected for inherited early onset cone–rod dystrophy. Methods Nineteen affected and 13 age-matched control SWHDs were included in the study. All dogs were subjected to standardized bilateral Ganzfeld ERGs and ophthalmoscopic examinations at regular intervals. Results Photopic cone-derived ERG amplitudes were significantly lower and never reached similar levels as those recorded in control dogs. In affected dogs there was no increase with age in amplitudes recorded using 30.1 and 50.1 Hz flicker stimuli. In contrast, in the control groups the photopic b-wave amplitude recorded at 50.1 Hz increased significantly from age 5 to 8 and from 5 to 52 weeks. In affected animals, scotopic rod-derived amplitudes were significantly lower for most recordings compared to those of control dogs, although they increased significantly from age 5 to 8 weeks in both affected and controls. Both a- and b-wave implicit times were significantly longer in the youngest affected group when compared to the age-matched control group at 0.6 log cd s/m² and 5.1 Hz single flash light stimuli. In the control dogs, however, there was a significant shortening in a-wave implicit times from age 5 to 8 weeks, and in a- and b-wave implicit times recorded at 5.1 Hz single flash stimuli from age 5 to 52 weeks. Conclusions The described retinal degeneration in the SWHD is an early onset cone–rod dystrophy, initially affecting the cone system most severely. Early functional changes are seen in the rod system as well. Inner retina also appears affected already at a young age with findings indicating postsynaptic functional changes already at the earliest time point studied, at age 5 weeks. The present study further indicates that the canine retina reaches maturity later than previously reported, or that there exist major breed differences.     

Predominant loss of the photopic negative response in central retinal artery occlusion

PURPOSE: To determine how the photopic negative response (PhNR) is affected in central retinal artery occlusion (CRAO). DESIGN: Observational case series. METHODS: Seven patients with unilateral CRAO were included. Full-field scotopic and photopic electroretinograms (ERGs) including the PhNR were recorded. Each ERG amplitude in the affected eye was expressed as a percentage of amplitude of the corresponding wave in the unaffected eye. RESULTS: Mean of the PhNR amplitude was reduced to 12.3 +/- 11.7% of that of unaffected eyes whereas the cone b-wave amplitude was attenuated to only 73.4 +/- 30.4%. This reduction of the PhNR amplitude was more significant than that of other waves including the rod b-wave, maximum a-wave and b-wave, cone a-wave and b-wave, and 30 Hz flicker ERG (P <.005). CONCLUSIONS: The PhNR was severely affected in CRAO despite relative preservation of the cone b-wave, implicating massive loss of ganglion cells and their axons.     

ON-pathway dysfunction and timing properties of the flicker ERG in carriers of X-linked retinitis pigmentosa

PURPOSE: Carriers of X-linked retinitis pigmentosa (XLRP) frequently show prolonged implicit times of the flicker electroretinogram (ERG). This study tested the hypothesis that a preferential response attenuation within the cone depolarizing (ON) bipolar cell (DBC) pathway is a major contributing factor. METHODS: Light-adapted, full-field ERGs were recorded from 10 XLRP carriers and 12 visually normal control subjects. Fundamental amplitudes and phases of ERG responses to sinusoidally flickering stimuli at temporal frequencies ranging from 8 to 96 Hz were analyzed within the framework of a recent vector summation model of the cone system ERG to test for evidence of a response attenuation within the DBC pathway. In addition, ERG responses to sawtooth flicker were examined for a reduced b- to d-wave amplitude ratio, indicative of ON pathway dysfunction. RESULTS: The carriers' fundamental response phases at 32 Hz correlated significantly with their log ratios of response amplitudes at 32 versus 12 Hz (r = 0.89, P < 0.001) and with their log b- to d-wave amplitude ratios (r = 0.71, P < 0.05), both of which were used as indices of response attenuation within the DBC pathway. A control experiment demonstrated that a reduced sensitivity of cone phototransduction made at most only a minimal contribution to the timing changes in the carriers' flicker ERG responses. CONCLUSIONS: The overall pattern of results indicates that a preferential response attenuation within the DBC pathway is the primary source of timing changes in the flicker ERGs of these carriers of XLRP. These findings illustrate the value of analyzing ERG responses to flickering stimuli at multiple temporal frequencies to evaluate mechanisms of disease action in photoreceptor degenerations.     

Electroretinogram parameters at presentation as predictors of rubeosis in central retinal vein occlusion patients

This report evaluates the prognostic value of parametric electroretinography (ERG) techniques in the development of rubeosis in central retinal vein occlusion (CRVO). An ERG protocol was followed on the initial clinic visit for 21 CRVO patients. None of these patients had neovascular complications or any treatment before the ERG examination. The ERG data were used to define an intensity-response (I-R) function, b-wave to a-wave peak ratio (b/a-wave ratio), and 30-Hz b-wave implicit time. A Naka-Rushton function was fitted to the I-R data to obtain values for maximum saturated response (Rmax) and for the log of the half-saturation intensity (log K). The authors' results show that ERG parameters relating both to the effective number of responding retinal elements and to the sensitivity of responding elements have significant prognostic value. Unexpectedly high predictive values were found for the Rmax and b/a ratio, parameters thought to correlate with the effective number of responding elements, compared with log K and 30-Hz implicit time, parameters thought to relate more closely to retinal ischemia. A multiple discriminant analysis, combining information from these ERG parameters, allowed separation of CRVO patients in whom rubeosis would develop from those in whom it would not, with a false-positive rate of only 14%.     

A late receptor dystrophy in the Labrador retriever

Dark adapted single flash and light adapted 30 Hz photopic flicker ERGs were recorded from a litter of seven Labrador Retrievers bred from parents affected with generalized progressive rod-cone dystrophy. After an initial increase of b-wave amplitudes from 5 weeks to 4 months similar to the controls, the b-wave amplitudes of the litter were significantly decreased (P less than 0.005) at 7 months. At 21 months the b-wave amplitudes were very low, although some response to 30 Hz photopic flicker was still left. The ERG changes indicated a late onset progressive rod-cone dystrophy which developed after maturation of the retina. The development of this photoreceptor dystrophy has not previously been described.     

Detection using the multifocal electroretinogram of mosaic retinal dysfunction in carriers of X-linked retinitis pigmentosa

PURPOSE: To examine whether a mosaic pattern of retinal dysfunction in obligate carriers of X-linked retinitis pigmentosa (XLRP) could be observed in local electroretinographic responses obtained with the multifocal electroretinogram (mfERG). DESIGN: Prospective observational case series. PARTICIPANTS: Five obligate carriers of XLRP (mean age, 53.2 years) were recruited into the study. METHODS: Examination of each subject included a complete ocular examination, Humphrey visual field, standard full-field electroretinogram (ERG), and mfERG testing. For the mfERG, we used a 103-scaled hexagonal stimulus array that subtended a retinal area of approximately 40 in diameter. The amplitudes and implicit times in each location for the mfERG was compared with the corresponding value determined for a group of normally sighted, age-corrected control subjects. MAIN OUTCOME MEASURES: Mapping of 103 local electroretinographic response amplitudes and implicit times within the central 40 with the multifocal electroretinogram. RESULTS: Localized regions of reduced mfERG amplitudes and/or delayed implicit times were found in four of five carriers. In one of these four carriers, a mosaic pattern of mfERG dysfunction was present even in the absence of any clinically apparent retinal changes, retinal sensitivity losses on Humphrey field testing, or abnormal full-field cone ERG responses. However, one carrier with a typical tapetal-like reflex demonstrated no deficit on any functional tests. CONCLUSIONS: The mfERG demonstrated patchy areas of retinal dysfunction in some carriers of XLRP. This mosaic pattern of dysfunction may be observed in some patients with a normal-appearing fundus, normal psychophysical thresholds, and normal amplitude and implicit time full-field ERG cone responses.     

Retinal function and PKC alpha expression after focal laser photocoagulation

Purpose

To examine the effects of focal laser photocoagulation on general and local retinal function and to relate electrophysiological findings with changes in protein kinase C (PKC) alpha expression.

Methods

Twelve rabbits were treated with 70 spots of laser photocoagulation in the central cone-rich retina. The operated eyes were investigated with electroretinography (full-field ERG and multifocal electroretinography, mfERG) preoperatively and at 1, 3, and 5 weeks after surgery. The expression of PKC alpha was examined at all three time points using immunohistochemistry, and PKC alpha mRNA levels were quantified using real-time polymerase chain reaction (PCR). Immunohistochemistry for glial fibrillary acidic protein (GFAP) and hematoxylin and eosin staining was employed to monitor the extent and dynamics of the morphological response.

Results

The full-field ERG revealed a significant increase in b-wave amplitudes derived from the isolated rod response (blue light) at all three time points after surgery (p?Conclusions Focal laser treatment in the rabbit eye induces local and wide-spread alterations in both rod- and cone-mediated retinal function in the form of supernormal b-wave amplitudes in the full-field ERG and increased latency in the mfERG. The electrophysiological abnormalities are accompanied by a progressive down-regulation of the PKC alpha isoenzyme in rod bipolar cells, reaching far beyond the treated area. PKC alpha is down-regulated directly by impaired protein synthesis, and also possibly indirectly by protein consumption related to GFAP up-regulation. The results indicate that focal laser photocoagulation interferes with PKC-alpha-mediated inhibitory regulation of inner retinal signal transmission.     

Retinal and neurologic findings in the Laurence-Moon-Bardet-Biedl phenotype

The nosology of the Laurence-Moon and Bardet-Biedl syndromes has been controversial. Presented is a patient with polydactyly, retinopathy, ataxia, low-average intellectual function, and obesity. These features constitute a composite of both syndromes and reflect the clinical heterogeneity that may be seen. Accordingly, the authors suggest the use of the term "Laurence-Moon-Bardet-Biedl phenotype" until these syndromes can be defined in some other manner. The neuroradiologic studies document atrophy of the cerebellum that accounts for the ataxia. Electroretinograms (ERG) demonstrate the decline in retinal function over a 16-year interval and the delayed cone ERG b-wave implicit time with normal cone amplitudes to 30 Hz white flicker that can exist in the early stage of this disorder.     

Electroretinograms in carriers of blue cone monochromatism

We recorded full-field electroretinograms from seven female obligate carriers of X-linked blue cone monochromatism and eight daughters of obligate carriers. We observed that all obligate carriers had one or more of the following abnormalities: delayed cone b-wave implicit times to 30-Hz white flicker, loss of the a1 oscillation in responses to single flashes of white light under dark-adapted conditions, subnormal b-wave amplitudes to single flashes of white light under dark-adapted conditions, and subnormal cone responses to 30-Hz white flicker. All had normal rod responses to blue light. Three of eight daughters of obligate carriers had abnormal electroretinograms comparable to those recorded from obligate carriers. These obligate carriers have a partial but comparable deficiency of red and green cone function.     

Visual Electrophysiologic Findings in Patients From an Extensive Brazilian Family with Leber's Hereditary Optic Neuropathy Visual electrophysiology in LHON

Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease, associated with mitochondrial DNA (mtDNA) point mutations and characterized by bilateral, usually sequential, rapid loss of central vision. The purpose of this study was to investigate electrophysiologically a small cohort of members from an extensive Brazilian family affected by LHON. Pattern-reversal visual evoked potentials (PVEP), and full-field electroretinograms (ERG) were performed on the four index members, all carrying the 11778 homoplasmic mtDNA mutation. They were a 14-year-old recently affected male, his unaffected mother, and her two affected brothers. The three affected members all had bilateral profound visual loss with visual acuities that ranged from 20/250 to CF, cecocentral defects, and severe dyschromatopsia (by FM-100). The unaffected (carrier) female had normal visual acuities, visual fields and color discrimination. Severely prolonged P100 latencies and decreased N75-P100 peak amplitudes were found in pattern-reversal VEPs for three affected members. Normal PVEP responses were found in the carrier female. Rod and cone ERG responses were normal in two affected members, but both the carrier mother and her affected son showed reduced peak-to-peak amplitude for single-flash cone response and 30 Hz flicker, with normal b-wave implicit times. Thus, optic nerve function, evaluated by PVEP, was severely reduced in LHON affected members and normal in the carrier female. However, reduced ERG cone responses suggest that LHON can also affect retinal elements, even in the absence of fundus and other clinical changes that constitute the full and classical expression of LHON.     

Electrophysiological studies in newly onset type 2 diabetes without visible vascular retinopathy

The purpose of this study was to investigate the early alterations of retinal function, assessed with electrophysiology, in newly onset type 2 diabetes patients without vascular retinopathy. Seventeen patients with newly diagnosed type 2 diabetes (duration 7±3 months), without any vascular retinopathy in fundus photographs, were examined with full-field electroretinogram (ERG) and multifocal ERG (mfERG). The results were compared with those of age-matched subjects without diabetes. In the dark-adapted full-field ERG, the a-wave and the 30-Hz flicker implicit times were delayed in diabetes patients compared to controls, P=0.001 and P=0.020. In the first-order kernel of the mfERG, the first positive wave, P1, was delayed in all areas measured. The electrophysiological examinations demonstrate early alterations of retinal function characterised by a delayed a-wave implicit time in the dark-adapted full-field ERG, representing the rod signalling, and alterations in the multifocal ERG reflecting cone and/or postreceptoral function.     

Intrasession variability of the full-field ERG

Objectives: (1) To document variability of the full-field ERG within single recording sessions under ISCEV standards. (2) To identify clinical factors contributing to the observed variability. Methods: Nine volunteer subjects were studied, aged 19–32 with no history of retinal disease. ISCEV standard ERGs were recorded. Dark-adapted “standard combined” and light-adapted “cone” b-wave amplitudes and implicit times were measured. Multiple flashes were presented at different interflash intervals and after different periods of dark and light adaptation. The stability of the stimulus flash was measured with a photometer. Results: The statistical coefficient of variability was roughly 2.5% for the standard combined b-wave amplitude and 4.5% for the cone b-wave. B-wave implicit times showed a coefficient of variability of 2% for standard combined responses and 1.25% for cone responses. Variation in interflash interval, dark and light adaptation times, and sporadic unusual waveforms influenced measured b-wave amplitudes. Conclusion: Intrasession variability is much lower than previously reported values for intersession variability. Nonetheless, it represents a baseline of variability that will affect results and that may be minimized by recognition and control of contributing factors.