Multifocal VEP and OCT findings in patients with primary open angle glaucoma: A cross-sectional study

ABSTRACT: Bakground To evaluate objectively the anatomical and functional changes of optic nerve in eyes with primary open angle glaucoma (POAG) by the joint use of optical coherence tomography (OCT) and multifocal visual evoked potentials (mfVEP). METHODS: 29 eyes with open angle glaucoma and visual field defects, as well as 20 eyes of 10 age-matched control normal subjects were tested. All participants underwent a complete ophthalmological examination. Moreover, Humphrey visual field test, OCT examination and recording of mfVEP were performed. Amplitude and implicit time of mfVEP, as well as RNFL thickness were measured. Differences in density components of mfVEP and in RNFL thickness among POAG eyes and control eyes were examined using Student's t-test. RESULTS: In glaucomatous eyes the mean Retinal Response Density (RRD) was lower than normal in ring 1, 2 and 3 of mfVEP (p < 0.0001). Specifically the mean amplitude of mfVEP in POAG eyes was estimated at 34.2 +/- 17.6 nV/deg2, 6.9 +/- 4.8 nV/deg2 and 2.6 +/- 1.6 nV/deg2 in rings 1, 2 and 3 respectively. In contrast the mean implicit time was similar to control eyes. In addition, the mean RNFL thickness in POAG eyes was estimated at 76.8 +/- 26.6 mum in the superior area, 52.1 +/- 16.3 mum in the temporal area, 75.9 +/- 32.5 mum in the inferior area and 58.6 +/- 19.4 mum in the nasal area. There was a statistically significant difference in RNFL thickness in all peripapillary areas (p < 0.0001) between POAG eyes and controls, with superior and inferior area to present the highest decrease. CONCLUSIONS: Our study shows that, although Standard Automatic Perimetry is the gold standard to evaluate glaucomatous neuropathy, the joint use of mfVEP and OCT could be useful in better monitoring glaucoma progression.     

Temporal contrast sensitivity using full-field flicker test (Erlangen flicker test) in patients after penetrating keratoplasty

BACKGROUND: The purpose of this study was to evaluate the feasibility of temporal contrast sensitivity testing using full-field flicker stimulation in patients after penetrating keratoplasty (PK) and to assess whether this method is influenced by postoperative corneal topographic changes. METHODS: Forty-five patients (age 46.5+/-14.2, median 47 years) who had undergone PK and 194 age-matched controls were included in this study. The postoperative interval was 11.8+/-10.2 months (median 9 months). Patients with pre-existing glaucoma or any postoperative intraocular pressure elevation were excluded. The indications for PK were keratoconus in 54% of cases, Fuchs' dystrophy in 38% and stromal dystrophies in 8%. Temporal contrast sensitivity was determined with sinusoidal flickering light (37.1 Hz) of constant mean photopic luminance (10 cd/m(2)) presented in a full-field bowl with an increasing threshold strategy. RESULTS: Mean temporal contrast sensitivity did not differ between patients after PK (1.49+/-0.13, range 1.26-1.78, confidence interval 1.45-1.53) and controls (1.55+/-0.17, range 1.16-1.98, confidence interval 1.47-1.51). No significant correlation between temporal contrast sensitivity and visual acuity could be found in patients after PK or in normals ( r<0.2, P=0.3). In patients after PK, temporal contrast sensitivity was statistically independent of keratometric astigmatism ( r=0.3, P=0.7), topographic astigmatism ( r=0.3, P=0.4), spherical equivalent ( r=0.07, P=0.7), central corneal thickness ( r=-0.06, P=0.7) and time since operation ( r=-0.07, P=0.6). CONCLUSIONS: Temporal contrast sensitivity using full-field flicker stimulation seems to be feasible in patients after PK and does not depend on topographic changes of the cornea. The results indicate that the full-field flicker test may be helpful as a supplementary means of detecting early glaucoma caused by ocular hypertension in patients after PK.     

Regional variations in local contributions to the primate photopic flash ERG: revealed using the slow-sequence mfERG

PURPOSE: To determine the variations with eccentricity of the primate photopic ERG and to separate contributions by different retinal cells by using intravitreal pharmacologic agents. METHODS: Slow-sequence multifocal (mf)ERGs were obtained from 19 anesthetized adult rhesus monkeys and 5 normal human subjects. Recordings in monkeys were obtained before and after injections of tetrodotoxin citrate (TTX) to block sodium-dependent spiking; TTX+N-methyl-D-aspartic acid (NMDA)+picrotoxin (PTX) or gamma-aminobutyric acid (GABA) to block all inner retinal activity; L-2 amino-4-phosphonobutyric acid (APB) to block the On-pathway; and cis-2, 3 piperidine dicarboxylic acid (PDA) to block the Off-pathway and the otherwise unblocked inner retinal activity. The stimulus consisted of 103 equal-sized hexagons within 17 degrees of the fovea; every 200 ms (15 frames), each hexagon had a 50% chance of remaining at 20 cd/m(2) or increasing briefly to 4.7 cd-s/m(2). Oscillatory potentials (OPs; 90-300 Hz) were extracted. RESULTS: The slow-sequence mfERG summed over the stimulated area looked similar to a standard photopic, full-field ERG, with a- and b-waves and OPs. OPs in the foveal and temporal retina were larger than in the nasal retina. This nasotemporal asymmetry was removed by TTX, and the OPs were eliminated, either by blocking inner retina activity or by blocking the On-pathway. The summed mfERG waveform, including OPs, was shaped mainly by the more peripheral retinal regions. The foveal b-wave peak occurred about 5 to 6 ms later than in the periphery, with the depolarizing peak of the On-pathway/bipolar contribution occurring earlier than the depolarizing peak of the Off contribution at all eccentricities. The a-wave was composed of a small photoreceptor contribution and postreceptoral portion originating from hyperpolarizing neurons. CONCLUSIONS: The variations in the primate photopic ERG with eccentricity are due to spike-driven oscillatory activity that is more prominent in central and temporal retina than in nasal retina and to the slower timing of all responses in the central, compared with the peripheral, retina. The full-field, photopic ERG most closely resembles the mfERG responses to stimulation of peripheral regions.     

Distribution of oscillatory components in the central retina

This study examines the characteristics and the naso-temporal asymmetries of the higher-order oscillatory components of the multifocal electroretinogram (mERG). The magnitude of the mERG asymmetry and the mechanisms which produce it have not been studied previously. We recorded the mERG from seven normal observers using slow multifocal flicker and response filtering of 10–300 Hz. This permitted, without additional filtering, examination of the dominant first order component and the oscillation-rich components in the first and second order kernels. The oscillatory components in the two kernels had multiple peaks separated by about 6.8 ms, similar to those of conventional oscillatory potentials. Naso-temporal asymmetry of the three response components was analyzed in three groups (concentric rings around the fovea) spanning 1.5–10 deg of retinal eccentricity. The oscillation-rich components were, on average, approximately 14% larger in amplitude in the temporal retina than in corresponding nasal locations (p < 0.05) while the dominant first order component was not asymmetrically distributed. We tested the hypothesis that the asymmetry could be modeled as a combination of a retinal component (RC) and an optic nerve head component (ONHC) which varies in latency as a function of distance from the optic disc. We found that both oscillatory components and the dominant first order response could be decomposed into RCs and ONHCs that are symmetrically distributed. Thus, it appears that the naso-temporal asymmetries of the oscillation-rich components are produced primarily by the relative alignment and enhancement of RC and ONHC wavelets in the temporal retina, and misalignment and partial cancellation in the nasal retina. This revised version was published online in July 2006 with corrections to the Cover Date.     

On and off responses of the photopic fullfield ERG in normal subjects and glaucoma patients

Recent studies suggest a diagnostic value of the photopic negative response (PhNR) with a long-duration stimulus. The aim of this study was to record the on and off responses of the photopic fullfield electroretinogram (ERG) in normal subjects and glaucoma patients. We focused on different waves of the responses after onset and offset of the long-duration stimulus ERG. Photopic fullfield ERGs were recorded in response to a white bright LED flash on a white 20 cd/m² background. Stimulus luminances were 40, 60 and 80 cd/m². Responses were averaged using a flash duration of 240 ms and an offset period of 500 ms. We examined 19 healthy subjects, 27 patients with glaucomatous optic disc atrophy and 7 ocular hypertensive patients. The amplitudes and implicit times of the on and off responses of the human ERG depended on flash luminance. Comparing patients with glaucoma and healthy subjects for the 60 cd/m2 flash, there was a significant change in the PhNRs (at onset: P < 0.01, at offset: P < 0.001) of the d-wave and of the i-wave at offset (P < 0.01). No significant difference was found for peak times of the fullfield ERG and for a- and b-wave amplitudes. PhNR amplitudes were significantly correlated with mean thickness of retinal nerve fibre layer as measured with OCT. In comparison with the normal photopic long-flash ERG, glaucoma patients showed changes in the PhNR amplitude following stimulus onset and in waves following stimulus offset.     

Glaucoma detection is facilitated by luminance modulation of the global flash multifocal electroretinogram

PURPOSE: To investigate the variation of retinal electrophysiological function in glaucoma by using the global flash multifocal electroretinogram (mfERG) stimulation with altered differences in the stimulus luminance of the multifocal flashes, in an attempt to alter the levels of inner retinal contributions. METHODS: The mfERG was assessed with a visual stimulus in steps of four video frames, which consisted of 103 scaled hexagonal elements followed by a dark frame, global flash, and dark frame. The localized luminance difference was set at 96%, 65%, 49%, or 29% stimulus contrast. Thirty subjects with glaucoma and 30 age-matched normal subjects were recruited for visual field and mfERG measurements. RESULTS: This stimulus induces complex local first-order responses with an early direct component (DC) and a later induced component (IC). The luminance-modulated response functions of the DC and IC responses showed markedly different behavior. The peripheral IC showed a linear dependence on luminance difference, whereas the peripheral DC was saturated for higher luminance differences. This saturation became less obvious in subjects with glaucoma, mostly because of greater reduction of the response amplitude in the mid luminance-difference level. An "adaptive index" was calculated from the luminance-difference dependence of the peripheral DC, and it showed a sensitivity of 93%, with a specificity of 95% for differentiating normal from glaucomatous eyes, and also had a significant correlation (r = 0.58) with the glaucomatous visual field defect. CONCLUSIONS: The peripheral DC luminance-modulated response function is altered by the adaptive mechanism that is induced by the global flash; the reduction of the adaptive index may thus relate to an abnormal adaptive mechanism, presumably due to inner retinal damage. Glaucoma appears to produce large reductions of the adaptive index which correlate with field defects.     

Multifocal electroretinogram with a multiflash stimulation technique in open-angle glaucoma

PURPOSE: To analyze a multiflash multifocal electroretinogram in 20 patients with open-angle glaucoma (OAG). METHODS: The stimulation sequence consisted of a binary m-sequence (L(max) 200 cd/m(2), L(min) <1 cd/m(2)). Each m-sequence stimulus was followed by three global flashes (luminance: 400 cd/m(2)) at an interval of 26 ms. RESULTS: The presence of a response to the three global flashes indicated an adaptive effect of the response to the preceding m-sequence stimulus. In the nasal retinal response average the relative amplitude contribution of the response to the second global flash in relation to the other two global flash responses was outside the range of normal (10th-90th percentile) in 10 of 20 OAG patients. CONCLUSIONS: The changes in the relative contribution of the response to the second global flash seem indicative of impaired adaptive effects presumably due to inner retinal damage.     

Dual-directional optokinetic nystagmus elicited by the intermittent display of gratings in primary open-angle glaucoma and normal eyes

PURPOSE: To compare optokinetic nystagmus (OKN) responses to the intermittent display of stimuli between normal subjects and patients with primary open-angle glaucoma (POAG). METHODS: Optokinetic nystagmus (OKN) was recorded in 9 glaucomatous patients and 7 normal subjects. The computer-generated stimuli displayed sinusoidal luminance gratings (16 cd/m(2) mean luminance, 0.5 cyc/deg) with a pi/2 phase shift between successive stimulus gratings. These stimulus gratings were separated by an interstimulus interval (ISI), during which a homogeneous luminance field of 16 cd/m(2) was presented. The ISI duration and the luminance contrast were set at different values. RESULTS: For normal subjects, dual-directional alternating OKN could be evoked in the ISI range from 33 to 100 ms. The dual-directional alternating OKN was defined as that OKN slow phase alternatively tracked in the direction of pi/2 shift (forward OKN) and against the pi/2 shift (reverse OKN). By contrast, for most glaucomatous eyes, nearly no reverse OKN could be evoked at any ISI value. CONCLUSIONS: The lack of reverse OKN in POAG patients in the present experiments is a meaningful finding. The occurrence of reverse OKN during a certain range of ISI duration could be related to the biphasic characteristics of the temporal impulse response in normal subjects, whereas, the lack of reverse OKN might suggest the plausible damage of magnocellular cells in POAG.     

Detection of glaucomatous damage using multifocal ERG

The first‐order kernel analysis in multifocal electroretinogram (mfERG) using low contrast stimulation is suggested as a way to detect the inner retinal responses in animal studies. In this case report, this protocol is applied to human patients with glaucoma to demonstrate the possibility of using mfERG as a tool to detect glaucomatous damage. Two patients with glaucoma were recruited and had mfERG measurements with the 103‐scaled hexagonal stimulus pattern at low (50 per cent) contrast. Their responses were analysed and compared with those from normal subjects with the mfERG measured under the same condition. In the normal subjects, there were obvious oscillatory components on the ascending and descending limbs of the first‐order kernel response to 50 per cent contrast. In the glaucomatous patients, the oscillatory component on the descending limb was obviously diminished. In addition, this component was significantly diminished in the quadrant with a glaucomatous visual field defect. This suggests that the low‐contrast stimulation condition in mERG measurement may provide a good way to detect glaucomatous damage and this may help in clinical diagnosis of glaucoma.     

Selective ganglion cell functional loss in rats with experimental glaucoma

PURPOSE: To characterize retinal functional consequences of elevated intraocular pressure (IOP) in a rat model of experimental glaucoma. METHODS: Unilateral elevation of IOP was produced by hypertonic saline injection into an episcleral vein in 20 adult male Brown-Norway rats. IOP was measured in both eyes of awake animals four to five times per week. After 5 weeks, animals were dark adapted overnight (>12 hours) and full-field electroretinograms (ERGs) were obtained simultaneously from both eyes. Scotopic ERG stimuli were brief white flashes (-6.64-2.72 log cd-s/m(2)). Photopic responses were also obtained (0.97-2.72 log cd-s/m(2)) after 15 minutes of light adaptation (150 cd/m(2)). Eyes were processed the following day for histologic evaluation by light microscopy, including masked determination of optic nerve injury grade (ONIG; 1, normal; 5, severe, diffuse damage). RESULTS: Among experimental eyes, the group average IOP (+/-SD) was 34.5 +/- 4.1 mm Hg, whereas the average for control eyes was 28.1 +/- 0.5 mm Hg (t = 7.1, P < 0.0001). The average ONIG for experimental and control eye groups, respectively, was 3.4 +/- 1.7 and 1.0 +/- 0.02 (t = 6.3, P < 0.0001). The ONIG increased with mean IOP in experimental eyes (r(2) = 0.78, P < 0.0001) and was unrelated to mean IOP in control eyes (r(2) = 0.09, P = 0.18). In experimental eyes with relatively mild IOP elevation (mean IOP < 31 mm Hg) and no structural (histologic) damage to the optic nerve evident by light microscopy (ONIG = 1.1 +/- 0.2, n = 5), there was a selective reduction of the positive scotopic threshold response (pSTR; P < 0.001), whereas other ERG components remained unaltered. In four of the five eyes, pSTR amplitude was reduced by more than 50%, whereas all five had normal scotopic a-wave, b-wave, and OP amplitudes. Eyes with mean IOP of more than 35 mm Hg had reduced a-wave, b-wave, and oscillatory potential (OP) amplitudes. CONCLUSIONS: As demonstrated by prior studies, selective loss of the pSTR is indicative of selective retinal ganglion cell (RGC) injury. In this rat model of experimental glaucoma, selective RGC functional injury occurred before the onset of structural damage, as assessed by light microscopy of optic nerve tissue. The highest IOP levels resulted in nonselective functional loss. Thus, in rodent models of experimental glaucoma, lower levels of chronically elevated IOP may be more relevant to human primary chronic glaucoma.     

Effects of Spectral Characteristics of Ganzfeld Stimuli on the Photopic Negative Response (PhNR) of the ERG

PURPOSE: To determine flash and background colors that best isolate the photopic negative response (PhNR) and maximize its amplitude in the primate ERG. METHODS: Photopic full-field flash ERGs were recorded from anesthetized macaque monkeys before and after pharmacologic blockade of Na(+)-dependent spiking activity with tetrodotoxin (TTX, 1 to 2 muM, n = 3), blockade of ionotropic glutamatergic transmission with cis-2,3 piperidine dicarboxylic acid (PDA, 3.3-3.8 mM, n = 3) or laser-induced monocular experimental glaucoma (n = 6), and from six normal human subjects. Photopically matched colored flashes of increasing stimulus strengths were presented on scotopically matched blue, white, or yellow backgrounds of 100 scot cd/m(2) using an LED-based stimulator. RESULTS: PhNRs that could be eliminated by TTX or severe experimental glaucoma were present in responses to brief (<5 ms) and long-duration (200 ms) stimuli of all color combinations. In normal monkey and human eyes for brief low-energy flashes, PhNR amplitudes were highest for red flashes on blue backgrounds and blue flashes on yellow backgrounds. For high-energy flashes, amplitudes were more similar for all color combinations. For long-duration stimuli, the PhNR(on) at light onset in monkeys was larger for red and blue stimuli, regardless of background color, than for spectrally broader flashes, except for stimuli >17.7 cd/m(2) when PhNR(on)s were all of similar amplitude. For red flashes, eliminating the PhNR(on) pharmacologically or by glaucoma removed the slowly recovering negative wave that normally followed the transient b-wave and elevated the whole ON response close to the level of the b-wave peak. However, for white, blue, and green flashes, a lower-amplitude plateau that could be removed by PDA remained. CONCLUSIONS: For weak to moderate flash strengths, the best stimulus for maximizing PhNR amplitude is one that primarily stimulates one cone type, on a background with minimal adaptive effect on cones. For stronger stimuli, differences in amplitude are smaller. For long-duration stimuli, red best isolates the PhNR(on) because it minimizes the overlapping lower-level plateau that originates from the activity of second-order hyperpolarizing retinal neurons.     

The a-wave of the dark adapted electroretinogram in glaucomas: are photoreceptors affected?

AIMS: To evaluate whether the a-wave of the dark adapted flash electroretinogram (ERG) is affected by glaucomatous damage. METHODS: ERGs were recorded in 20 patients (age 33-65 years) with advanced glaucomas (primary and secondary open angle and low tension glaucomas) and 20 normals using a ganzfeld stimulus. After 30 minutes of dark adaptation and pupil dilatation to at least 7.5 mm in diameter, luminance response functions were obtained presenting white flashes of increasing scotopic luminance (the highest flash intensity being 9.4 cd/s/m2, the lowest being 5.75 log units below it) with an interflash interval of 5 seconds. For each scotopic luminance, the responses of four flashes were averaged. The a-wave's amplitude was measured at 10, 11, and 12 ms. Within the glaucoma group, correlations between the interocular differences of the a-wave's amplitude and the mean deviation of a static perimetry (Octopus 500 perimeter, program G1) were computed for all flash intensities. Between normals and glaucomas, the a-wave's amplitude was compared for all flash intensities (paired t test). RESULTS: Within the glaucoma group, the interocular differences of the a-wave's amplitudes correlated significantly with the differences of the MD for flash intensities of 9.4, 5.3, 1.7, and 0.5 cd/s/m2. The a-wave's amplitude was significantly lower in the glaucoma compared with the normal group (p <0.005) for flash intensities of 9.4 and 5.3 cd/s/m2. CONCLUSION: These electrophysiological results imply that also the outer retinal structures, especially the photoreceptors, may be affected by glaucomatous damage.     

Rod-driven focal macular electroretinogram

PURPOSE: To determine the stimulus conditions required to elicit rod-driven, focal macular electroretinograms (rod FMERGs). METHODS: A blue (lambda(max)=470 nm) stimulus, 5 degrees in size, was imaged at a luminance of 1.5 cd/m(2) on different regions of the human retina. Electroretinograms (ERGs) elicited by this stimulus were recorded from the light- and dark-adapted retina of four subjects without any ophthalmological abnormalities. A subject with cone dystrophy was also tested by this method. RESULTS: Stimulus luminance <==1.5 cd/m(2) did not elicit a response when it was imaged on the optic disc, but higher intensities elicited a small b-wave from stray light. When this stimulus was imaged on the macular area or the 15 degrees temporal retina, an ERG was elicited that had the shape of the full-field scotopic ERG. This stimulus with a luminance of 1.5 cd/m(2) did not elicit a response from stimulation of the macular area of a light-adapted retina but elicited a slow-rising positive b-wave after 30 minutes of dark adaptation. In a subject with cone dystrophy, focal rod response was elicited from the macula, despite no response under photopic conditions. CONCLUSION: We conclude that this stimulus will elicit a response that is derived exclusively from rods and is a focal response with no contribution from stray light.     

Multifocal electroretinogram: age-related changes for different luminance levels

BACKGROUND: Age-related changes in the first-order multifocal electroretinogram (mfERG) responses were measured for two different luminance levels (200 and 700 cd.m(-2)). The relative contribution of optical and neural factors to senescent change in response was evaluated. METHODS: Data were obtained from one eye of each of 71 normal phakic subjects, age 9-80 years. The mfERG responses were recorded with the 7" stimulus-refractor unit (EDI) and VERIS 4.3 using the following protocol: bipolar contact lens, 103 hexagons, consecutive stimulation with 200 and 700 cd.m(-2), pupils > or =6 mm, amplification of 10(5), filter cut-offs at 10 and 300 Hz. RESULTS: Age-correlated decreases in amplitude and response density and increases in P1 implicit time were found for both luminance levels. The mean response density (nV.deg(-2)) was higher for the 700 cd.m(-2) stimulus, but the rate of change with age was not significantly different from that obtained with the 200 cd.m(-2) stimulus. Implicit time was not significantly different for the two light levels, nor was the rate of change with age. The decrease in response density and the increase in implicit time with age were significant across all retinal regions, dividing the 50 deg stimulus into six concentric rings. Age-related change in response density was greatest for the central retina and decreased with increasing retinal eccentricity. CONCLUSION: Log mfERG response changes linearly as a function of age. Analyses of the effects of reduced ocular media transmission and increased stray light, along with ancillary data obtained from pseudophakes, imply that age-related changes in the mfERG are due to both optical and neural factors.     

Visual acuity and multifocal electroretinographic changes after arteriovenous crossing sheathotomy for macular edema associated with branch retinal vein occlusion

PURPOSE: To evaluate the influence of arteriovenous (AV) sheathotomy on retinal function with central multifocal electroretinography (mfERG) in eyes with macular edema secondary to branch retinal vein occlusion (BRVO). METHODS: Fifteen patients (15 eyes) who underwent AV sheathotomy for macular edema secondary to BRVO were included in the study. Best-corrected visual acuity and mfERG responses from the most central seven hexagons were analyzed before and 6 months after the operation. RESULTS: The mean preoperative Early Treatment Diabetic Retinopathy Study (ETDRS) score +/- SD was 34.1 +/- 12.7 letters (Snellen equivalent, 20/50) and significantly improved up to 40.5 +/- 10.9 letters (Snellen equivalent, 20/40) at 6 months after AV sheathotomy (P = 0.027, Wilcoxon signed rank test). The mean preoperative P1 amplitude +/- SD of the most central 7 hexagons was 39.30 +/- 10.86 nV/deg(2) for the affected eye versus 47.72 +/- 6.67 nV/deg(2) for the normal fellow (control) eye (P = 0.013, Mann-Whitney U test) and significantly increased up to 50.71 +/- 15.58 nV/deg at 6 months after the operation (P = 0.014, Wilcoxon signed rank test). Significant correlations between preoperative and postoperative ETDRS score and preoperative P1 amplitude were present (r = 0.929, P < 0.001; r = 0.768, P = 0.001; respectively [Spearman correlation]). CONCLUSIONS: AV sheathotomy improved macular function and anatomical outcome as measured by ETDRS score and mfERG responses in patients with macular edema due to BRVO.     

Reduced recovery of temporal contrast sensitivity after flicker stress in patients with glaucoma

PURPOSE: To compare recovery of temporal contrast sensitivity after flicker stress between control subjects and patients with glaucoma. METHODS: Forty-three patients with primary open-angle glaucoma and secondary open-angle or normal-tension glaucoma of the Erlangen Glaucoma Registry and 30 healthy control subjects had their temporal contrast sensitivity measured at 37 Hz and their recovery time determined after monocular exposure to 30 seconds of 58% contrast full-field flicker. Recovery time of temporal contrast sensitivity was measured as the time interval from cessation of flicker until twice the threshold value was reached. RESULTS: Patients with glaucoma had a significant reduction in temporal contrast sensitivity (P < 0.001). Recovery time was also significantly longer in patients with glaucoma (23.8 +/- 24.1 seconds) than in control subjects (7.6 +/- 2.6 seconds; P < 0.001). There was a significant positive correlation between recovery time and mean visual field defect (0.5; P < 0.001) and a significant negative correlation between recovery time and neuroretinal rim area of the optic disc (0.32; P = 0.04). CONCLUSIONS: Recovery of temporal contrast sensitivity after flicker stress is impaired in some patients with glaucoma. This might be the result of functional impairment of the inner retina, outer retina, or both in glaucoma.     

多焦视皮质诱发电位检查对白内障患者术后视力的预测(英文)

目的:评价术前多焦视皮质诱发电位(multifocal visual evoked potential,mVEP)检查对白内障术后视力的预测价值。方法:随机选取白内障患者共52例60眼,其中老年性白内障27例30眼,合并青光眼的白内障25例30眼(青光眼均为慢性闭角型缓解期或慢性进行期),术前对其行mVEP检查,另取正常对照组30眼。所有患者均行超声乳化联合折叠人工晶状体植入术。患者于术后1wk;1,3mo复查最佳矫正视力(best corrected visual acuity,BCVA)。结果:正常对照组mVEP检测平均主波振幅和潜伏期分别是183±11nV、95±8ms,老年性白内障组平均主波振幅和潜伏期分别是177±10nV、96±8ms,2组在统计学上无显著性差异(P>0.05);合并青光眼的白内障组平均主波振幅和潜伏期分别是138±7nV、99±6ms,与正常对照组及老年性白内障组均存在显著性差异(P<0.05);白内障超声乳化联合人工晶状体植入术后BCVA≥0.8者,无明显眼底视功能改变,其mVEP中心位点主波振幅276±11nV和潜伏期93±8ms与正常对照组无显著性差异(P>0.05);而术后BCVA<0.3者,眼底视功能检查有明显改变(术后检查证实),其mVEP中心位点主波振幅221±6nV,潜伏期105±7ms,与正常对照组差异显著(P<0.05)。结论:白内障术前mVEP振幅和潜伏期的改变可用来客观判断眼底视功能损害及预测术后视力。术前mVEP正常者高度提示术后视力预后良好,而mVEP检查结果变化显著,提示伴有眼底视功能损害,术后BCVA差。因此术前mVEP检查可作为预测白内障术后视力的一种有效、客观的检查方法。     

Responses of Postreceptoral Pathways Elicited by L- and M-Cone Isolating ON- and OFF-Electroretinograms in Glaucoma Patients

PurposeTo compare the electroretinographical (ERG) responses elicited by L- and M-cone isolating ON- and OFF-sawtooth stimuli in normal subjects and glaucoma patients.MethodsTwenty-one normal subjects and 44 primary open-angle glaucoma patients participated in the study. L- and M-cone isolating (18% cone contrast; 284 cd/m²) rapid ON- and rapid OFF-sawtooth (4 Hz) stimuli with two stimulus sizes (full-field (FF) and central 70° diameter) were generated using the triple silent substitution technique. ON- and OFF-response asymmetries were studied by adding the two (to obtain L-add and M-add responses). The initial positive (P) and subsequent late negative (LN) components of the L-add and M-add ERGs were compared between the subject groups and correlated with retinal nerve fiber layer thickness (RNFLT) and pattern ERG responses.ResultsThe responses to L-ON and to M-OFF stimuli and vice versa resembled each other particularly with 70° stimuli. The P_L-add amplitudes were not significantly different between the normal subjects and glaucoma patients, whereas the LN_L-add amplitude was significantly (P < 0.01) smaller in the glaucoma patients. Both P_M-add and LN_M-add were not significantly different between the subject groups. The PERG amplitude with 0.8° check sizes and the 0.8°/16° amplitude ratio (PERG ratio) were significantly (P < 0.05) different between the subject groups. The 70° LN_L-add amplitude and the 0.8° PERG amplitude were significantly correlated with RNFLT.ConclusionsThe ERGs to 70° cone isolating sawtooth stimuli reflect cone opponency. The cone opponent ERG responses were not significantly different between glaucoma patients and normal subjects. Luminance driven L-add responses were significantly different, indicating that central luminance signals are mainly affected in glaucoma.     

The photopic negative response of the blue-on-yellow flash-electroretinogram in glaucomas and normal subjects

The photopic negative response of the flash-electroretinogram driven by the middle- and long-wavelength cones has been shown to be reduced in non-human primates with experimental glaucoma and in human patients with glaucoma. The photopic negative response for the blue-sensitive response has been studied using a blue-green silent-substitution-technique on a red background. The aim of this study was to re-evaluate the value of the photopic negative response of the blue-sensitive pathway in glaucoma using a conventional flash-electroretinogram. In 37 eyes of 37 controls (age: 53 +/- 13.6 years) and 37 eyes of 37 patients with open-angle glaucoma of different perimetric visual field defects (age: 58.3 +/- 10 years; MD: 11.7 +/- 6.7 dB) of the Erlangen glaucoma registry Ganzfeld flash-electroretinograms (LKC, UTAS 3000) were recorded using blue Xenon-flashes of increasing photopic luminance (0.013, 0.018, 0.030, and 0.052 cd s/m(2); 440 nm) on a bright yellow background (238 cd/m(2); 550 nm) after 2 min of light adaptation. Amplitudes and implicit times of the photopic negative response and of L&M-cone- and S-cone-driven b-waves were compared between glaucomas and controls for all flash energies (unpaired t-test). The amplitudes of the photopic negative response were significantly reduced in glaucoma patients for all flash energies (P < 0.001). The implicit times of L&M-cone-driven b-wave (0.013, 0.018, 0.030, and 0.052 cd s/m(2)) and S-cone-driven b-wave (0.030 and 0.052 cd s/m(2)) were significantly prolonged in glaucoma patients (P < 0.05). The changes in these implicit times, however, are very small (1.5 ms or less). The other measures did not differ significantly. The amplitude of the photopic negative response and the implicit times of the L&M-cone and S-cone b-wave in the same responses of the blue-on-yellow flash-electroretinogram are potentially useful in the evaluation of inner-retinal function in glaucoma.     

Porcine global flash multifocal electroretinogram: possible mechanisms for the glaucomatous changes in contrast response function

PURPOSE: The aim of this study was to obtain a better understanding of the cellular contributions to the porcine global flash mfERG by using a pharmacologic dissection method, together with the method using variation of stimulus contrast which has been used to demonstrate mfERG changes in human glaucoma. METHODS: Global flash mfERGs with different stimulus-contrast settings (99%, 65%, 49% or 29%) were recorded from 14 eyes of ten 6-week-old Yorkshire pigs in control conditions and after suppression of inner retinal responses with inhalation of isoflurance (ISO), and injections of tetrodotoxin (TTX) and N-methyl-d-aspartic acid (NMDA). ON- and OFF-pathway responses were isolated by injection of 2-amino-4-phosphonobutyric acid (APB) and cis-2,3-piperidinedicarboylic acid (PDA). RESULTS: The porcine global flash mfERG consisted of an early direct component (DC) and a late induced component (IC). ISO and TTX removed inner retinal contributions to the IC; NMDA application further abolished the oscillatory wavelets in the DC and removed the residual IC waveform. The inner retina contributed regular oscillation-like wavelets (W1, W2 and W3) to the DC and shaped the IC. After removing the inner retinal contributions, the porcine global flash mfERG waveform becomes comparable to that obtained with conventional mfERG stimulation. The remaining waveform (smoothed DC) was mainly contributed by the ON- and OFF-bipolar cells as revealed after APB or PDA injection. Photoreceptors contributed a small signal to the leading edge of N1. The characteristic of contrast response function of DC was demonstrated to be contributed by the inner retinal oscillation-like wavelets. CONCLUSION: We believe that the DC of the porcine global flash mfERG is mainly composed of contributions from photoreceptors, and ON- and OFF-bipolar cells, where inner retinal activity partially shaped the DC with superimposed regular wavelets. However, the IC is dominated by inner retinal activity. The contrast response functions of DC consisted of both outer retinal response and oscillation-like wavelets of the inner retinal response. Both contain different characteristics during contrast modulation of the stimulus, where the changes of W2 of the inner retinal response seem independent of contrast modulation. The DC contrast response feature depends mainly on the relative contribution of inner retinal activities; the loss of inner retinal cells may alter the DC contrast response function, making it tend toward linearity.