The multifocal pattern electroretinogram in glaucoma

BACKGROUND: The pattern ERG can be used to detect early glaucomatous change, because the response of cells in the inner retina from (typically) 20 degrees -40 degrees of area is reduced before perimetric abnormality is certain. The multifocal pattern electroretinogram (mfPERG) allows analysis of many local regions within this area. The aim of this study was to investigate whether in patients with presumed glaucoma the mfPERG permits diagnosis and discrimination from normals. METHODS: Measurements on 25 age-related normal eyes were compared to those on 23 eyes with different stages of glaucoma. A RETIScan system was used to generate a stimulus pattern of 19 hexagons, each consisting of six triangles. The triangles pattern-reversed black to white at 75 Hz. Those 19 hexagons were grouped into three stimulus regions: a central field, a middle, and a peripheral ring. The complete array subtended 48 degrees at the eye. The hexagons alternated between black and white, in a temporal pattern that followed a corrected binary m-sequence (length 512, 10 cycles with 39 s each). The amplitudes and latencies of positive responses at approximately 50 ms (P-50) and negative responses at approximately 95 ms (N-95) were analyzed. RESULTS: In patients with glaucoma the P-50 and N-95 components of the mfPERG were significantly reduced for the central area and both outer rings compared to normal volunteers (p<0.001, Mann-Whitney-U). The most distinct reduction was observed for N-95 and the central ring. Changes in latencies were not conclusive. The reduction of the components increased with the stage of glaucoma. A predictive model for detecting early glaucomatous changes was designed based on P-50-N-95 with 88% sensitivity and 76% specificity. CONCLUSION: In glaucoma a marked reduction of components, especially centrally is observed in the mfPERG. This hints to an early involvement of central ganglion cells and may be useful for future functional tests.     

Little correlation of the pattern electroretinogram (PERG) and visual field measures in early glaucoma

Pattern-electroretinograms (PERG) to checkerboard reversal at 16/s. 0.8° and 15° check size and visual fields (Octopus G1) were retrospectively analyzed in 40 eyes of 30 patients with early glaucoma. The mean visual field defect was calculated separately for the central 26°×34° covered by the PERG stimulus (MDc) and the more peripheral area (MDp) surrounding the stimulus. Deeper field loss was correlated with a reduced pattern electroretinogram amplitude (p<0.01 for both MDp and MDc), indicating that the pattern electroretinogram deteriorates as glaucoma advances. If the analysis was confined to those 18 eyes (16 patients) that had no field defect within the area covered by the PERG stimulus (normal MDc but abnormal MDp), 13 of these had an abnormal PERG amplitude (p<0.001). The results suggest that the PERG can reveal impairment of ganglion cell function that is not detected by conventional perimetry.     

The pattern electroretinogram and visual-evoked potential in glaucoma

The pattern electroretinogram (PERG) may reflect ganglion cell or inner retinal layer activity. The most sensitive spatial and temporal variables for testing patients with glaucoma have not yet been identified. Fifty-two glaucoma suspects, 51 glaucoma patients, and 28 normal subjects were studied with the PERG and VEP, using three repetition rates and three spatial frequencies. Fast Fourier transforms were calculated at each spatial frequency and reversal rate. An analysis of variance revealed that normals could be differentiated from ocular hypertension and glaucoma patients using the amplitude of the PERG (second and fourth harmonic). Abnormalities in phase of the PERG between groups were also detected. A discriminant analysis of all amplitude and phase data revealed that the phase shift of the response of the second harmonic at 11 alternations/s (15-min checks) and at 5.5 alternations/s (15-min checks) correctly identified 81% of the normal and 75% of the glaucoma patients. The phase shift determinations of the VEP revealed significant abnormalities using 2 and 1/2 standard deviation confidence limits. There was significant overlap in the pattern ERG amplitude and phase shift in all three groups.     

The relationship between visual disability and visual field in patients with glaucoma

PURPOSE: To evaluate the relationship between visual disability and the remaining visual field in glaucoma patients. DESIGN: Prospective noncomparative survey. PARTICIPANTS: One hundred forty-seven Japanese patients with glaucoma were examined. METHODS: Using a previously developed questionnaire, we assessed the relationship between visual disability indices and both the visual field examined using program 30-2 of the Humphrey Field Analyzer and visual acuity. MAIN OUTCOME MEASURES: Pearson's correlation coefficients between visual disability indices and the 22 visual field and 2 visual acuity measurements were calculated. Multiple regression analysis with stepwise variable selection identified factors significantly contributing to visual disability. RESULTS: We identified a significant correlation between visual disability and both the visual field and visual acuity measurements collected. Of the factors examined, retinal sensitivity in the lower hemifield within 5 degrees of the fixation and visual acuity in the better eye significantly contributed to all the item and total disability indices (DIs), measurements of the degree of visual disability as evaluated by the questionnaire; visual acuity in the worse eye contributed to two of the seven item DIs, as well as the total DI. The R value for total DI (R = 0.87, P < 0.0001) indicated that approximately 76% of the visual disability could be explained by these factors. CONCLUSIONS: The Japanese glaucoma patients' visual disability is explained primarily by retinal sensitivity in the lower hemifield within 5 degrees of the fixation and visual acuity in the better eye and secondarily by visual acuity in the worse eye.     

Check-size specific changes of pattern electroretinogram in patients with early open-angle glaucoma

The pattern electroretinogram was recorded in patients with initial stages of visual field defects due to open-angle glaucoma and in age-matched normal subjects. Both normal subjects and glaucoma patients had a visual acuity above 0.8. Counterphasing checkerboard patterns were used as visual stimuli with a range of check sizes from 0.8° to 15° at 7.8 reversals/s. Whereas the amplitude in glaucoma patients was nearly normal for large check sizes, it was significantly reduced for small check sizes (p = 0.003). Possibly two separate mechanisms that generate the pattern electroretinogram for small and large checks are differentially affected; they may be related to the magnocellular and parvocellular systems. The difference between normals and glaucoma patients was even more significant when the ratios of the amplitudes at small and large check sizes were compared (p < 0.0002). When this ratio is used, the amplitude variability can be partly overcome and the pattern electroretinogram can be a sensitive indicator of ganglion cell function.     

The pattern electroretinogram in glaucoma and ocular hypertension.

Thirty one eyes with established glaucoma, 61 high risk ocular hypertensive (OHTs) eyes, 66 medium risk OHT eyes, 58 low risk OHT eyes, and 47 control eyes have been followed for up to 2 years by clinical examination and pattern electroretinography (PERG). The study was 'masked' so electrophysiological and clinical data were kept separate. Criteria have been devised which enable PERG measurements to distinguish all established glaucomatous eyes from all normal controls; these criteria demonstrate abnormalities in some OHT eyes, particularly those at high risk. The PERG abnormality is greatest in eyes with established glaucoma in which the intraocular pressure has been lowered by treatment. The PERG becomes smaller as the degree of clinical abnormality increases. Test-retest variability of the PERG is sufficiently low to ensure that most of those first described as abnormal continue to be so.     

Correlation between optical coherence tomography, pattern electroretinogram, and visual evoked potentials in open-angle glaucoma patients

OBJECTVE: To correlate the nerve fiber layer (NFL) thickness and the visual function evaluated by electrophysiologic retinal and cortical responses assessed in open-angle glaucoma (OAG) eyes. DESIGN: Prospective case-control study. PARTICIPANTS: Thirty glaucoma patients (mean age, 47.1 +/- 7.15 years; refractive error range, +/- 2 spherical equivalent) with a mean deviation of computerized static perimetry (24/2 Humphrey, Dublin, CA) from -5 to -28 dB and intraocular pressure less than 21 mmHg on pharmacologic treatment and 14 age-matched control participants. METHODS: Nerve fiber layer thickness was measured by optical coherence tomography. Retinal and visual pathway function was assessed by simultaneously recording pattern electroretinograms (PERGs) and visual evoked potentials (VEPs) using high-contrast (80%) checkerboard stimuli (the single check edges subtend 15 minutes of the visual arc) reversed at the rate of two reversals per second. Linear regression analyses were adopted to establish the correlation between NFL thickness and PERG and VEP parameters. MAIN OUTCOME MEASURES: Nerve fiber layer thickness measurements in each quadrant (superior, inferior, nasal, and temporal) were taken and then averaged (12 values averaged) and identified as NFL overall, whereas the data obtained in the temporal quadrant only (three values averaged) were identified as NFL temporal. PERG P50 implicit time and P50-N95 amplitude and VEP P100 implicit time and N75-P100 amplitude were also measured. RESULTS: In OAG eyes, we found a significant (P < 0.01) reduction in NFL thickness in both NFL overall and NFL temporal evaluations with respect to the values observed in control eyes. PERG and VEP parameters showed a significant (P < 0.01) delay in implicit time and a reduction in peak-to-peak amplitude. In OAG eyes, the NFL overall and NFL temporal values were significantly correlated (P < 0.01) with the PERG P50 implicit time and P50-95 peak-to-peak amplitude. No correlations (P > 0.01) between NFL values and VEP parameters were found. CONCLUSIONS: There is a correlation between PERG changes and NFL thickness, but there is no correlation between VEP changes and NFL thickness in patients affected by OAG.     

单眼视野损伤程度对青光眼患者双眼视野的影响

目的：探讨单眼视野丢失严重程度对原发性闭角型青光眼、原发性开角型青光眼和正常眼压性青光眼患者双眼视野缺损的影响。

方法：根据双眼单眼视野缺损的阶段,将120例青光眼患者和30例健康参与者分为正常、早期、中度或重度四个阶段。通过整合视野和Esterman双眼视野评估确定双眼视野。在组内和组间比较单眼和双眼视野参数。

结果：对于一只眼睛处于正常或早期阶段而另一只眼睛处于严重阶段的患者,双眼综合视野平均偏差分别为-2.8±1.1、-5.5±1.9dB,以及Esterman的平均得分分别为99.1%±1.7%和95.6%±4.7%。当双眼发展为中度或重度损伤(中度/中度,中度/重度或重度/重度)时,双眼综合视野平均偏差低于-6dB,中度/中度和中度/严重损伤组Esterman的平均得分分别为94.2%±6.0%、94.3%±4.9%,但当双眼处于重度损伤阶段时,Esterman的平均得分迅速从大于90%下降到68.4%±26.3%。

结论：如果一只眼睛处于正常或早期阶段,双眼视野可以保持相对完整。当双眼进展到中度或重度阶段时,通过双眼综合视野平均偏差测量的双眼视野缺损是显著的,并且仅当双眼进入严重阶段时才检测到显著的Esterman双眼视野缺损。     

Comparison of visual field tests in glaucoma patients with a central visual field defect

ObjectiveTo compare the 24-2 and 10-2 visual fields (VFs) and investigate the degree of differences between the 2 tests in glaucomatous eyes with central VF defects.DesignRetrospective study.ParticipantsIn all, 99 eyes of 99 glaucoma patients who underwent both the 24-2 VF and 10-2 VF tests within 6 months were enrolled.MethodsGlaucomatous eyes with damage involving a central VF defect were divided into 3 groups based on the average total deviation (TD) of 12 central points in the 24-2 VF test. The TD difference was calculated by subtracting the average TD of the 10-2 VF test from the average TD of 12 central points in the 24-2 VF test. The absolute central TD difference in each quadrant was defined as the absolute value of the TD value obtained by subtracting the average TD of 4 central points in the 10-2 VF test from the innermost TD in the 24-2 VF test in each quadrant.ResultsThe TD differences differed significantly between the severe group and the early and moderate groups ( p < 0.001). In the superonasal quadrant, the absolute central TD difference was significantly greater in the moderate group than in the early group ( p < 0.05). In the superotemporal quadrant, the absolute central TD difference was significantly greater in the severe group than in the other 2 groups ( p < 0.001).ConclusionsOur results indicate that the results of VF tests for different VFs can be inconsistent, depending on the degree of central defects and the VF quadrant.     

The pattern of visual deficits in amblyopia

Amblyopia is usually defined as a deficit in optotype (Snellen) acuity with no detectable organic cause. We asked whether this visual abnormality is completely characterized by the deficit in optotype acuity, or whether it has distinct forms that are determined by the conditions associated with the acuity loss, such as strabismus or anisometropia. To decide this issue, we measured optotype acuity, Vernier acuity, grating acuity, contrast sensitivity, and binocular function in 427 adults with amblyopia or with risk factors for amblyopia and in a comparison group of 68 normal observers. Optotype acuity accounts for much of the variance in Vernier and grating acuity, and somewhat less of the variance in contrast sensitivity. Nevertheless, there are differences in the patterns of visual loss among the clinically defined categories, particularly between strabismic and anisometropic categories. We used factor analysis to create a succinct representation of our measurement space. This analysis revealed two main dimensions of variation in the visual performance of our abnormal sample, one related to the visual acuity measures (optotype, Vernier, and grating acuity) and the other related to the contrast sensitivity measures (Pelli-Robson and edge contrast sensitivity). Representing our data in this space reveals distinctive distributions of visual loss for different patient categories, and suggests that two consequences of the associated conditions--reduced resolution and loss of binocularity--determine the pattern of visual deficit. Non-binocular observers with mild-to-moderate acuity deficits have, on average, better monocular contrast sensitivity than do binocular observers with the same acuity loss. Despite their superior contrast sensitivity, non-binocular observers typically have poorer optotype acuity and Vernier acuity, at a given level of grating acuity, than those with residual binocular function.     

Update on the pattern electroretinogram in glaucoma.

PURPOSE: To review the efficacy of the pattern electroretinogram (PERG) in early diagnosis of glaucoma. METHODS: Stimulation parameters of check size and temporal frequency are considered. Analyses of various peaks (P50, N95, the N95/P50) and Fourier steady-state are considered. The relation to visual field defects is explored. RESULTS: The PERG is markedly alterated in glaucoma. It shows amplitude reductions in (still) normal areas of the visual field. Optical imaging on the retina needs to be optimal. Higher temporal frequency (>10 reversals/s) improves the sensitivity to detect glaucoma compared with transient stimulation. The ratio between the amplitudes to 0.8 degrees checks and to 16 degrees checks, "PERG ratio," exploits a check size-specific reduction in early glaucoma and reduces variability. Longitudinal studies suggest that the PERG can indicate incipient glaucoma damage before evidence from the visual field. CONCLUSIONS: The PERG is a demanding electrophysiological technique that can serve as a sensitive biomarker for retinal ganglion cell function. With appropriate paradigms, PERG assists in identifying those patients with elevated interocular pressure in whom glaucoma damage is incipient before visual field changes occur.     

The visual field in advanced glaucoma

Summary For analysis of the morphology of the visual field in advanced glaucoma, we tested 62 eyes of 54 late stage glaucoma patients using program 10–2 on the Humphrey Field Analyzer. The fields, which were already reduced to a small central isle, had mostly typical, asymmetric borders with their largest extend to the temporal lower quadrant and their smallest extend to the upper nasal quadrant. An upper nasal step was very frequent. The boundaries are equivalent to the retinal nerve fiber lines. Actually, the glaucomatous isle is a centro-coecal isle, representing a remnant of intact maculo-papillary nerve fiber bundles. A test with a 2° spacing like the Humphrey program 10–2 proved to be useful for routine perimetry in these cases.     

The pattern electroretinogram in patients with optic nerve disease

We analyzed the electroretinogram elicited by pattern stimuli (PERG) in 29 patients with unilateral optic nerve disease. The normal fellow eyes served as a control. When the normal fellow eye was covered and the patient was asked to watch the center of the pattern stimuli with the affected eye, the poor fixation often caused irregular eye movements which resulted in a poor reproducibility of the response. In such instance we opened the normal fellow eye for fixation, which helped to stabilize the affected eye being examined even when visual acuity was extremely poor. The cross-talk phenomenon of the ERG and the reflection of the VER from the normal fellow eye were proved negligible in this recording condition.We analyzed PERGs in comparison with the visual acuity and the degree of optic atrophy. Unlike the results of many previous authors, little correlation was observed between PERG and these two factors. Most patient showed normal or only slightly abnormal PERG, even when the visual acuity was extremely poor and the optic disc was completely atrophic.Our results suggest that, at least with our method, PERG has extremely limited value in detection of optic nerve disease.     

Hemianopic offsets in the visual field of patients with glaucoma

In 359 glaucoma patients (600 eyes), we measured the peripheral field with kinetic targets and the central 30° field of vision with static testing, using the Field-master-5000 automated perimeter to evaluate the prevalence and significance of step-like visual-field defects along the vertical midline (a hemianopic offset). In all, 129 eyes of 121 patients had a hemianopic offset. In 108 eyes the offsets (involving either the peripheral or the central field or both) were associated with other glaucomatous field changes, whereas 21 eyes showed a peripheral offset as an isolated finding. Of the 8 cases of offsets found in both eyes, 7 were binasal and 1 occurred bitemporally but in separate hemifields. This study suggests that hemianopic offsets occur commonly in glaucoma patients but have limited diagnostic value because most are associated with other glaucomatous field changes. However, these findings help in distinguishing glaucomatous offsets from those caused by neurological lesions.     

Contrast sensitivity and pattern visual evoked potential in patients with glaucoma

Contrast sensitivity and pattern visual evoked potential (VEP) were measured in cases of ocular hypertension and primary open-angle glaucoma at various stages. The visual field of each eye was examined quantitatively and the retinal nerve fiber layer and optic disc were precisely assessed with magnified stereoscope fundus photography.This study revealed that contrast sensitivity of the eyes with glaucoma was within the normal range in the very early stage of the disease. As optic nerve damage advanced, high-or low-frequency loss developed. Further optic nerve damage produced a level type of loss.Pattern VEPs also showed increasing abnormalities as glaucomatous optic nerve damage progressed. Measurements of contrast sensitivity and pattern VEP were found not to be as sensitive as quantified precise visual field measurment or color stereosopic fundus photography for detection of minor optic nerve damage in cases of early glaucoma. These methods may be useful, however, as an objective and subjective monitor of progression of optic nerve damage in glaucoma.     

Rate and pattern of visual field decline in primary open-angle glaucoma

PURPOSE: To study the rate and pattern of visual field decline in primary open-angle glaucoma. DESIGN: Retrospective observational case series. PARTICIPANTS: Forty eyes of 40 patients with primary open-angle glaucoma that were followed longitudinally with serial Goldmann visual fields for a minimum period of 8 years in an academic institution. Eyes with any other ocular disease except for mild cataract were excluded. METHODS: Visual fields obtained with worse than 20/50 Snellen visual acuity from cataract were excluded from analysis. In the remainder (671 Goldmann visual fields), the I4e isopter was quantified manually using a grid template previously described by Esterman. The visual field was divided into central and peripheral, superior and inferior, and nasal and temporal regions, all centered at the blind spot. The rate of visual field decline was estimated for each visual field region (including the four quadrants: superonasal [SN], superotemporal [ST], inferotemporal [IT], and inferonasal [IN]) using linear regression. Asymmetry of visual field progression was determined by comparing the rates of progression among the four quadrants. Pertinent clinical factors were evaluated for association with the asymmetry of visual field progression. MAIN OUTCOME MEASURES: Rates of visual field decline for the entire visual field and each region. Long-term clinical outcome measures, including visual acuity, cataract and cup-to-disc ratio progression, intraocular pressures, and medical and surgical interventions were also studied. RESULTS: The rate of visual field change was -1.3% per year for the entire visual field. The rates of visual field section change (in % per year) were -1.3 (central), -1.4 (peripheral), -1.5 (superior), -1.2 (inferior), -1.4 (nasal), -1.2 (temporal), -1.8 (SN), -1.3 (IT), -1.2 (IN), and -1.1 (ST). About half the patients showed symmetric visual field decline, whereas others showed a more asymmetric pattern. Asymmetric visual field progression was associated with the presence of disc hemorrhage, overall rate of visual field progression, and surgical intervention for glaucoma. CONCLUSIONS: In this group of selected patients with primary open-angle glaucoma with a long-term follow-up, all sections of the visual field declined over time. Disc hemorrhage was associated with more asymmetric visual field progression, implicating focal damage to the optic disc.