Luminance-modulated adaptation of global flash mfERG: fellow eye losses in asymmetric glaucoma

PURPOSE: To use the global flash multifocal electroretinogram (mfERG) in patients with asymmetric glaucoma to determine whether retinal function is affected in fellow eyes that have no glaucomatous visual field defects. METHODS: Forty normal subjects and 12 patients with asymmetric glaucoma were recruited for visual field and mfERG measurement. The mfERG was assessed by using a global-flash stimulation paradigm with four video frames: 103 scaled hexagonal elements followed by a dark frame, a global-flash frame, and a dark frame. The localized luminance difference was set at 96%, 65%, 49%, and 29% display contrast during the four different test conditions, respectively. The first-order kernel response was measured, and the "adaptive index" which has been used previously was calculated. RESULTS: In fellow eyes with normal visual fields, the amplitude of the induced component (IC) was significantly reduced, and the adaptive index was reduced by a factor of almost 10 (P < 0.0001), as it was in the glaucomatous eyes. Although the adaptive index in the better (fellow) eye of the patients with glaucoma was slightly higher than in the eyes with diagnosed glaucoma, these differences were not statistically significant. CONCLUSIONS: The significant reduction of the adaptive index in the better eyes in subjects with asymmetric glaucoma shows that the fast adaptive mechanism(s) were reduced in these eyes. This implies that eyes that have functionally normal visual acuity and visual fields have abnormal fast-adaptive mechanisms.     

The effect of contrast and luminance on mfERG responses in a monkey model of glaucoma

PURPOSE: To evaluate the effect of contrast and luminance attenuation on the multifocal electroretinogram (mfERG) responses of normal and glaucomatous eyes of cynomolgus monkeys. METHODS: Nine adult male cynomolgus monkeys with unilateral experimentally induced glaucoma were used. Hypertension-induced damage was confirmed by tomography of the optic disc. mfERGs were recorded with five different stimulus contrasts and/or luminance settings. The first-order and the first slice of second-order responses were analyzed. RESULTS: Waveforms of normal and glaucomatous eyes differed in shape and amplitude. Second-order responses contributed to first-order responses of the signals in the normal eyes, but made a negligible contribution to the signals in the glaucomatous eyes. Contrast and luminance attenuation affected both first- and second-order responses. The differences between signals in normal and glaucomatous eyes were sufficiently large for an unsupervised clustering algorithm to achieve accurate segregation. CONCLUSIONS: The observations in this study indicate that outer and inner retinal generators participate in first-order mfERG responses and that both inner and outer retinal contributors respond to contrast and luminance changes in stimulus. The hypertension-induced changes in the mfERG furthermore suggest damage to both inner and outer retina.     

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.     

Visual evoked potentials under luminance contrast and color contrast stimulation in glaucoma diagnosis

PURPOSE: To evaluate the diagnostic value of visual evoked potential (VEP) assessment with luminance-contrast and color-contrast stimulation in the detection of glaucoma. PATIENTS AND METHODS: The study included 59 patients (96 eyes) with glaucomatous changes of the optic disc and visual field defects and 58 control eyes of 29 healthy patients. Four types of pattern VEP stimulation (0.9 cycle/degree) were performed in all patients: achromatic, alternating sine-wave stripe pattern: 6 reversals per second, contrast of 10% (activation of predominantly the magnocellular pathway); isoluminant, red-green stripe pattern: 83.3 milliseconds onset, 83.3 milliseconds offset, contrast of 30% and 80% (activation of predominantly the parvocellular pathway); and blue grating with yellow background adaptation: 200 milliseconds onset, 500 milliseconds offset (activation of the blue-sensitive pathway). RESULTS: The glaucoma group and the control group differed significantly (P < 0.01) in the peak times of all chromatic VEP responses and to a lesser degree in the achromatic VEP. Considering the amplitudes, only the low-contrast red-green stimulus showed a statistically significant reduction in glaucoma. At a predefined specificity of 90%, in separating patients with glaucoma from healthy control subjects, the peak time of the blue-yellow VEP had a high sensitivity (90%), whereas the sensitivity of the achromatic VEP was low (31%). The red-green VEP showed a sensitivity of 73% using low contrast and 71% using high contrast. In a paired correlation analysis with visual field defects, all stimulations showed significant (P < 0.05) results. Correlation coefficients were highest (R = 0.79, P < 0.01) for the peak time of the blue-yellow VEP. CONCLUSIONS: VEP measurements with presumable stimulation of single neuronal pathways can detect glaucomatous optic nerve damage in a considerable fraction of patients with visual field loss. Occipital responses to chromatic stimulation seem to be more sensitive to glaucoma damages than do responses to achromatic pattern reversal stimulation.     

Functional involvement of cone photoreceptors in advanced glaucoma: a multifocal electroretinogram study

The purpose of the study is (1) to demonstrate the anatomical variation of cone photoreceptor density across normal retina as a sectoral amplitude asymmetry of photopic multifocal electroretinogram (mfERG) and (2) to study the potential presence of sequential or differential, functional cone photoreceptor damage in glaucoma using this amplitude asymmetry. A 37-Block scaled mfERG was recorded from 22 controls and 27 glaucoma subjects. The N1 and P1 amplitudes of averaged responses from corresponding zones nasal and temporal to fovea were analyzed for asymmetry in controls and glaucoma subjects. Amplitude asymmetry was demonstrable for both N1 (p < 0.001) and P1 (p < 0.001) parameters in control subjects. Although this amplitude asymmetry was preserved in glaucoma subjects with moderate field defects, it was not demonstrable in patients with advanced field defects. The anatomical variation in cone photoreceptor distribution across normal retina is demonstrated as an amplitude asymmetry in first order kernel responses of mfERG. The cone photoreceptors in the region nasal to fovea appear to be affected only in advanced glaucoma possibly suggesting that photoreceptors could follow a sequential damage like the overlying neuroretinal rim in glaucoma.     

Functional damage to inner and outer retinal cells in experimental glaucoma

PURPOSE: To investigate the cellular sources underlying the functional damage observed by multifocal electroretinography (mfERG) responses of glaucomatous eyes of monkeys. METHODS: First- and second-order (K1 and K2, respectively) mfERG responses of three normal and three experimentally induced glaucomatous eyes of cynomolgus monkeys were measured at two different levels of luminance. Retinal contributors to the responses were isolated by intravitreal injections of pharmacological agents that suppress specific retinal cells. gamma-Aminobutyric acid (GABA) and glycine were administered to block inner retinal function, followed by 2-amino-4-phosphonobutyric acid (APB), to block ON-bipolar cells. RESULTS: An inner retinal component removed by GABA and glycine was found in both the normal and glaucomatous eyes. However, it was attenuated in the latter, correlating with changes observed in the baseline K1 responses. Delays in the latency of outer retinal components were found in the responses of the glaucomatous eyes. K2 responses were dominated by an inner retinal contribution and were diminished in the responses of glaucomatous eyes. The outer retina responded to increased luminance with a shorter implicit time. A distinct wave part of the inner retinal component responded to increased luminance with increased amplitudes. CONCLUSIONS: The integration of the retinal sources forming the mfERG response was compared between normal and glaucomatous monkey eyes. Both inner and outer retinal functions were aberrant in the responses of the glaucomatous eyes, with the attenuation of the inner retinal function more conspicuous. Nevertheless, glaucomatous eyes retained certain inner retinal activity, despite the advanced stage of disease. K2 responses were more sensitive to glaucomatous changes than were K1 responses.     

Monitoring glaucoma progression with visual evoked potentials of the blue-sensitive pathway

PURPOSE: To determine the value of visual evoked potentials with blue-on-yellow pattern stimulation in follow-up of glaucoma. METHODS: This prospective longitudinal concurrent study included a heterogeneous cohort of two groups, perimetric (n = 161) and preperimetric (n = 118), of patients with chronic open-angle glaucoma and 113 healthy control subjects. In the preperimetric glaucoma group, patients showed glaucomatous abnormalities of the optic disc, maximum intraocular pressure higher than 21 mm Hg, and unremarkable computerized visual field examination results. Patients underwent up to three VEP measurements with blue-on-yellow pattern stimulation, as well as qualitative and morphometric evaluation of color stereo optic disc photographs. Mean follow-up time between measurements was 24 months. VEP measurements were separately analyzed in preperimetric subjects, with and without progression of optic nerve damage. Progression of glaucoma was defined as increasing loss of neuroretinal rim. RESULTS: A separate analysis of VEP peak times in patients in the preperimetric group, with and without progression of glaucomatous optic nerve damage, showed no significant difference at baseline but a significant prolongation (P = 0.01) in patients with progressive disease, 2 years before morphologic changes were evident. VEPs in patients with nonprogressive disease were statistically unchanged during the observation period. The perimetric group and both preperimetric groups showed significantly prolonged VEP peak times in comparison with the control group (P < 0.001). CONCLUSIONS: In addition to photographic evaluation to detect glaucomatous disc atrophy, the blue-on-yellow VEP may be an objective electrophysiological tool for monitoring patients with glaucoma, because peak times are significantly associated with progression of optic nerve damage.     

Slow-stimulated Multifocal ERG in High- and Normal-tension Glaucoma

Purpose: To study the ability and sensitivity of the slow stimulation multifocal ERG (mfERG) to detect glaucomatous damage. Methods: Right eyes of 20 patients with normal-tension glaucoma (NTG), 15 patients with high-tension glaucoma (HTG) and 15 healthy volunteers underwent testing with the mfERG (VERIS 4.1^TM). The central 50 degrees of the retina were stimulated by 103 hexagons (m-sequence: 2¹³-1, Lmax: 100 cd/m², Lmin: 1 cd/m², background: 50 cd/m²). Each m-sequence step was followed by 3 black frames (Lmax: < 1 cd/m²). Five response averages of the first order response component (KI) were analyzed: the central 7.5 degrees and the 4 adjoining quadrants. The amplitudes from the first minimum, N1, to the first maximum, P1, and from P1 to the second minimum, N2, were analyzed as well as the latencies of N1, P1, N2 and the latencies of 3 multifocal oscillatory potentials (mfOPs) with their maxima at about 73, 80 and 85 ms. Results: For each parameter the percentage of deviation from the mean of the control group was calculated. These values were then added for each individual to form a deviation index (DI). Seventeen patients (85.0%) with NTG and 3 patients (20.0%) with HTG showed a DI outside the normal range. The major changes were observed in the mfOPs of the NTG patients. MfOPs were then selectively filtered at 100–300 Hz and their scalar product was analyzed over an epoch of 68–105 ms. This confirmed that mfOPs differed significantly from the control in the central 7.5° and, for NTG, in the nasal field. With a logistic regression analysis the mfOPs had a sensitivity to differentiate 85% of the NTG patients and 73% of the HTG patients from normal. Conclusions: Under these conditions, the slow-stimulated mfERG can detect glaucomatous dysfunction in NTG (85.0%). The differences observed between NTG and HTG are in support of a different underlying pathomechanism.     

Multifocal pattern electroretinogram: cellular origins and clinical implications.

PURPOSES: The purposes of this article are to gain insight into the cellular origins of the multifocal pattern electroretinogram (mPERG) and evaluate its potential for clinical use. METHODS: mPERGs were recorded from four anesthetized monkeys before and after pharmacologic blockade of light-driven activity of inner-retinal neurons and from 55 normal human subjects (19-91 years) and six patients with glaucoma (43-77 years of age). Stimuli consisted of counterphase-modulated black and white triangles organized in 61-scaled hexagons with mean luminance 100 cd/m2 and 100% contrast. The stimulus array subtended 31 degrees vertically and 37 degrees horizontally at 48 cm. The amplifier cutoff frequencies were 3 and 100 Hz. Responses were grouped as quadrants and the first slice of the second-order kernel was analyzed. RESULTS: The mPERG responses of monkeys and humans were similar. In the monkey responses, there was an early positive potential (P1) around 25 ms and a later positive potential (P2) found selectively in the nasal field quadrants around 31 ms. These responses were seen around 22 and 36 ms in the human responses. After blockade of inner-retinal activity in monkeys, P1 amplitude was greatly reduced at all retinal locations and P2 was eliminated. P1 and P2 amplitudes were significantly reduced in the glaucomatous eyes relative to amplitudes of age-matched controls. Reductions in the amplitudes of P1 and P2 could easily discriminate between glaucomatous visual field quadrants with and without behavioral sensitivity losses. However, these alterations are likely to reflect diffuse losses. CONCLUSIONS: mPERG responses contain prominent contributions from inner-retinal neurons that can be reduced in glaucomatous eyes. These findings raise the possibility that the mPERG could be potentially useful in the objective estimation of neural damage in glaucoma. However, further refinement of recording techniques will be required if the mPERG is to be used to detect focal damage.     

Cone-mediated multifocal electroretinogram in early age-related maculopathy and its relationships with subjective macular function tests

PURPOSE: To investigate the multifocal electroretinogram (mfERG) and subjective function in early age-related maculopathy (ARM). METHODS: Seventeen subjects with early ARM with visual acuity (VA) of 6/12 or better and 20 age-matched control subjects were examined. We assessed mfERGs, high and low contrast distance VA, near VA, low luminance VA, contrast sensitivity, saturated and desaturated Panel D-15 and visual fields (mean sensitivity). The mfERG responses were analysed by comparing central-overall (method 1) and superior-inferior (method 2) ratios. RESULTS: The mfERG did not discriminate between the groups whereas colour vision (tritan deficiency), contrast sensitivity, and high contrast and low contrast VA showed significantly reduced responses for the early ARM group compared with the control group (p < or = 0.01). The mfERG first-order kernel responses correlated significantly with the desaturated D-15 in both methods (r = -0.5, p < or = 0.05). Fundus grading was not correlated with the mfERG measures. CONCLUSIONS: Although the mfERG correlated significantly with the desaturated D-15 in early ARM, suggesting it operates at a sensitive level, it failed to discriminate between the control and ARM groups. In our sample, the subjective function measures were more sensitive than the mfERG measures.     

The contour of the juxtapapillary nerve fiber layer in glaucoma

Reliable structural markers for early glaucomatous optic nerve damage would facilitate the diagnosis of glaucoma at an early stage, possibly before visual field loss occurs. Computerized image analyses were used to develop and analyze new structural parameters for glaucomatous optic nerve damage. Multiple measurements of relative juxtapapillary nerve fiber layer height were made in glaucoma patients (n = 112), patients suspected of having glaucoma (n = 87), and in age-matched normal control subjects (n = 53). The average relative nerve fiber layer (NFL) height differed in glaucoma patients and normal subjects by 70 microns, but differences exceeded 100 microns at the superior and inferior poles of the disc. Mean values for "glaucoma suspects" were intermediate between those for the normal subjects and glaucoma groups. The ability of summary statistics of relative NFL height measurements to discriminate between normal and glaucomatous eyes was superior to that of the standard disc parameters cup-disc ratio, disc rim area, and cup volume. Measurements of relative NFL height correlated with indices of visual field loss; the strongest correlations occurred for measurements at the superior and inferior poles. Measurements of juxtapapillary NFL height may prove useful to detect glaucomatous optic nerve damage at an early stage and to accurately recognize progressive nerve damage over time.     

Objective VEP perimetry in glaucoma: asymmetry analysis to identify early deficits

PURPOSE: The multifocal visual evoked potential (VEP) shows markedly symmetrical responses between the two eyes of control subjects. Patients with glaucoma and patients considered at high risk for glaucoma were examined to determine if VEP asymmetry could be identified and used for diagnosis and detection of early damage. METHODS: Multifocal pattern VEP recordings were performed using a single channel bipolar occipital electrode position and the Visual Evoked Response Imaging System (VERIS). There were 125 subjects: 24 control subjects, 70 patients with glaucoma, and 31 patients considered at high risk for glaucoma. A between-eye relative asymmetry coefficient (RAC) was determined for each of the 60 test points in the VEP field. The RAC for patients with glaucoma and patients considered at risk for glaucoma were compared with values from control subjects. Correlation between Humphrey thresholds and RAC scores was performed. RESULTS: Patients with glaucoma and patients considered at risk for glaucoma both showed significantly larger mean quadrant RAC values. When point by point analysis was performed, 69 out of 70 scotomas were identified with a cluster of at least 3 points of P < 0.05. For those considered at high risk for glaucoma, 10 out of 31 patients had abnormal areas in the VEP field. There was a strong correlation (r = 0.82) between quadrantic RAC mean values and Humphrey quadrant threshold scores in an asymmetric glaucoma subgroup. Abnormal VEP responses were identified in parts of the visual field that were still normal on perimetry. CONCLUSIONS: Asymmetry analysis correctly identifies patients with glaucomatous field loss and shows abnormalities in many patients considered at high risk for glaucoma who still have normal fields. Asymmetry analysis is able to identify objectively the extent of glaucomatous damage and may be able to detect changes before subjective field loss occurs.     

An attempt to detect glaucomatous damage to the inner retina with the multifocal ERG

PURPOSE: To detect glaucomatous damage to the inner retina using the multifocal electroretinogram (mERG). METHODS: The stimulus array consisted of 103 hexagons with a mean luminance of 100 cd/m2 and a contrast of 50%. The mERG was recorded from 13 control subjects, 18 patients with open-angle glaucoma (OAG), 4 glaucoma suspects, and one patient with ischemic optic neuropathy (ION). Individual responses, as well as responses summed within quadrants or across the entire array, were measured in a number of ways. Humphrey visual fields were obtained for all patients, and the mean total deviation (MD) values for the 18 patients with OAG ranged from -2.2 to -18.2 with a mean (SD) of -7.3 (4.5). RESULTS: The mERG measure that best discriminated between the patients and the control subjects was the ratio of the amplitude at 8 msec after the peak response to the amplitude at the peak. Although the value of this ratio fell below the median of the control group for 16 of the 18 OAG patients, only 6 of these patients had ratios that fell below the normal range. Other measures of first- and second-order kernels did not do as well. Both within and across patients, the correlation between local field loss and the mERG ratio measure was poor. Furthermore, although in some patients the mERG waveform is clearly different from normal, in other patients (including the patient with ION) the waveform approximates the normal even in visual field areas with substantial sensitivity loss. CONCLUSIONS: Because glaucomatous damage is known to affect the ganglion cell axon, these data suggest that damage to ganglion cell axons is not a sufficient condition to produce changes in the mERG as measured here and that in patients with clear changes in mERG waveforms, these changes do not appear to be well localized and local waveforms are poorly correlated with local changes in field sensitivity.     

LED刺激器多焦视网膜电图一阶和二阶反应波形研究

目的研究二极管发光器(LED)的多焦视网膜电图(mfERG)的一阶及二阶波形特点。设计前瞻性、非对照干预研究。研究对象18例(18眼)正常人。方法18眼随机分为两组分别作阴极射线管(CRT)及LED的mfERG检查。LED刺激时间分为1/10(1．7ms)、3/10(5ms)、5/10(8．3ms)、7/10(11．7ms)、10/10(16．7ms)5种。主要指标mfERG总和反应波形特点,P1、N1及N2波形态、振幅密度及潜伏期。结果CRT及LED刺激器mfERG一阶反应波形基本相似；CRT及LED刺激器的mfERG二阶反应波形不同,前者的P1波呈尖峰状,后者的P1波较宽,呈方形,且伴有一个较深的N2波。随着刺激时间的延长,LED刺激器的mfERG一阶及二阶反应中的P1波及N1波的振幅密度增加,潜伏期延长。结论CRT及LED刺激器的mfERG一阶反应波形基本相同,但LED的二阶反应波形更丰富,其可能包涵了更多视网膜内层信息。(眼科,2006,15：351-355)     

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.     

Multifocal visual evoked potential responses in glaucoma patients with unilateral hemifield defects

PURPOSE: To determine whether the multifocal visual evoked potential (mfVEP) technique can detect damage to the visual system in the unaffected hemifields of patients with glaucoma and unilateral hemifield defects. DESIGN: Experimental study. METHODS: Monocular mfVEPs and achromatic automated perimetry (AAP) were obtained in both eyes of 16 patients with open-angle glaucoma and unilateral hemifield defects. The mfVEPs were obtained using a pattern-reversal dartboard array with 60 sectors; the entire display was 44.5 degrees in diameter. For each pair of mfVEP responses an interocular ratio of root-mean-square amplitude was calculated. These values were compared with the mean values obtained from 30 control subjects. Probability plots for MfVEP were derived. A cluster analysis was used to determine whether an mfVEP hemifield was normal or abnormal. RESULTS: Three of 60 (5.0%) mfVEP hemifields from control subjects had significant mfVEP deficits based upon a cluster of abnormal points. Significant mfVEP deficits were detected in the affected AAP hemifield in 15 of 16 (93.8%) glaucoma patients and in 6 of 16 patients in hemifields with apparently normal AAP. The percentage of hemifields with abnormal mfVEPs, but normal AAP, was significantly higher for the glaucoma patients than for the controls (37.5% vs 5.0%, P <.001, chi square).In glaucomatous eyes with achromatic visual fields defects limited to one hemifield, the mfVEP technique can detect evidence of glaucomatous damage in the unaffected hemifield.     

Can frequency-doubling technology and short-wavelength automated perimetries detect visual field defects before standard automated perimetry in patients with preperimetric glaucoma?

PURPOSE: To assess the ability of frequency-doubling technology (FDT) perimetry and short-wavelength automated perimetry (SWAP) to detect glaucomatous damage in preperimetric glaucoma subjects. PARTICIPANTS: Two hundred seventy-eight eyes of 278 subjects categorized as normal eyes [n=98; intraocular pressure <20 mm Hg, normal optic disc appearance, and standard automated perimetry (SAP)]; preperimetric glaucoma eyes (n=109; normal SAP and retinal nerve fiber layer defects or localized optic disc notching and thinning); and glaucoma patients (n=71; intraocular pressure >21 mm Hg, optic disc compatible with glaucoma, and abnormal SAP). METHODS: The preperimetric glaucoma group underwent at least 2 reliable full-threshold 24-2 Humphrey SAPs, full-threshold C-20 FDT, full-threshold 24-2 SWAP, optic disc topography using the Heidelberg Retina Tomograph II, laser polarimetry using the GDx VCC, and Optical Coherence Tomography (Zeiss Stratus OCT 3000). Receiver operating characteristic curves were plotted for the main Heidelberg Retina Tomograph, Optical Coherence Tomography, and GDx VCC parameters for the normal and glaucoma patients. The area under the receiver operating characteristic curve was used to determine the parameters indicating glaucomatous damage in the optic disc or retinal nerve fiber layer, which were used to establish additional subgroups of patients with preperimetric glaucoma. FDT and SWAP sensitivities were calculated for the patient subsets with structural damage and normal SAP. RESULTS: At least 20% of the patients with preperimetric glaucoma demonstrated functional losses in FDT and SWAP. The more severe the structural damage, the greater the sensitivity for detecting glaucomatous visual field losses. CONCLUSIONS: FDT and SWAP detect functional losses in cases of suspected glaucoma before glaucomatous losses detected by SAP.     

Inner retinal contributions to the multifocal electroretinogram: patients with Leber's hereditary optic neuropathy (LHON)

In this study we examine the multifocal electroretinogram (mfERG) recorded from patients suffering from Leber's hereditary optic neuropathy (LHON), a degeneration of the ganglion cell and nerve fibre layers of the retina. We compared the mfERGs recorded from 11 patients with LHON, to those from 11 control subjects. The pattern ERG (PERG) was additionally performed with 9 of the patients. MfERGs were recorded and analysed using the VERIS^TM 3.01 system with a stimulus of 103 equal-sized hexagons. For analysis, hexagons were grouped according to distance from the optic nerve head (ONH) and according to distance from the fovea. Two significant differences were found between the waveforms of the two groups: In the first order kernel, the control group showed a component around 34 ms that decreased with distance from the ONH. This component was reduced in the LHON group of subjects. In the second order (first slice) kernel, the patient group was missing features that decrease with distance from the fovea in the control group. PERG amplitudes showed a significant correlation with the amplitude of the second order mfERG kernel. The results show that the damage to ganglion cells and nerve fibres caused by LHON can be detected in mfERG recordings and indicate that activity from the inner retina can contribute significantly to first and second order waveforms.     

Binocular visual impairment in glaucoma

Monocular and binocular vision was assessed in patients with glaucoma (n = 21), in patients with ocular hypertension (n = 20), and in age-matched visual control subjects (n = 20) using three tests: color vision with the Lanthony Desaturated D-15 test, low spatial frequency contrast sensitivity with the Pelli-Robson chart, and stereoacuity with the RANDOT test. No significant differences were found among the groups in the severity or type of color vision loss. Monocular contrast sensitivity testing showed considerable overlap among groups but a significant loss of contrast sensitivity in the glaucoma patients relative to ocular hypertensives and control subjects. Binocular testing also showed a significant loss of contrast sensitivity in the glaucoma patients compared with both the ocular hypertensives and the control subjects. Stereoacuity also was significantly impaired in the glaucoma patients. These results indicate that two tests of binocular function, stereoacuity and binocular contrast sensitivity testing, may have utility in identifying early glaucomatous damage.     

Polarimetric measurement of retinal nerve fiber layer thickness in glaucoma diagnosis

PURPOSE: To evaluate reliability and diagnostic value of polarimetric measurements of the retinal nerve fiber layer (RNFL) thickness in the diagnosis of glaucoma. METHODS: The study included 81 eyes with perimetric glaucoma with glaucomatous changes of the optic disc and visual field defects; 52 eyes with preperimetric glaucoma with glaucomatous optic disc abnormalities and normal achromatic visual fields; and 70 normal eyes. For determination of reliability, four examiners repeated polarimetric measurements five times in ten normal subjects. RESULTS: The polarimetric variables were significantly correlated with increasing mean visual field defect and decreasing neuroretinal rim area. In correlation analyses with visual field defects, correlation coefficients were highest for the variable "superior/nasal ratio" and "the Number," a variable calculated by the neural network of the device. In correlations with neuroretinal rim area, correlation coefficients were highest for measurements of the inferior nerve fiber layer thickness. The preperimetric glaucoma group and the control group differed significantly in the variables "superior/nasal ratio" and "the Number" and, to a smaller degree, in the variables "superior/temporal ratio" and "superior/inferior ratio." The Number variable had a sensitivity of 82% and 58% at a predefined specificity of 80% in separating perimetric glaucoma patients and preperimetric glaucoma patients, respectively, from control subjects. Reproducibility of the polarimetric measurements ranged between 70% and 89%. CONCLUSION: Polarimetric measurements of the RNFL thickness can detect glaucomatous optic nerve damage in patients with visual field loss, and in some patients with preperimetric glaucomatous optic nerve damage. Considering the fast performance, easy handling, and low maintenance costs, RNFL polarimetry may be helpful in glaucoma diagnosis.