RESUMEN
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.
Asunto(s)
Electrorretinografía , Glaucoma de Ángulo Abierto/fisiopatología , Enfermedades del Nervio Óptico/fisiopatología , Retina/fisiopatología , Trastornos de la Visión/fisiopatología , Campos Visuales , Humanos , Persona de Mediana Edad , Estimulación LuminosaRESUMEN
PURPOSE: This study was undertaken to characterize the influence of contrast, luminance, and spatial frequency of a pattern stimulus on the pupil reaction of healthy subjects. First measurements with this technique in patients with glaucoma were compared with those in a control group. METHOD: Grating patterns were presented using a Maxwellian-view system to study series of contrast, luminance, and spatial frequency in three healthy subjects. The best two stimulus conditions were determined and were then used to examine 19 patients with open-angle glaucoma and 16 control subjects. RESULTS: In healthy subjects, an increasing contrast led to an increase in amplitude and a decrease in latency of the pupil reflex. Increasing luminance also resulted in an increase in the amplitude. The offset component of the pupil reflex was most pronounced at low spatial frequencies and the onset component at high spatial frequencies. When healthy subjects were compared with patients with glaucoma, control subjects generally had higher amplitudes, velocity, and acceleration of pupil constriction than did the patients with glaucoma. These differences were significant when the test was performed with a spatial frequency of 6.25 cyc/deg. CONCLUSIONS: Best stimulus conditions to elicit a pupil response to a pattern grating stimulus are 100% contrast and 55 cd/m(2) mean luminance. The choice of the spatial frequency determines which component of the pupil reflex is more pronounced. Differences between patients with glaucoma and healthy control subjects are demonstrable.
Asunto(s)
Glaucoma de Ángulo Abierto/fisiopatología , Pupila/fisiología , Reflejo Pupilar/efectos de la radiación , Sensibilidad de Contraste/fisiología , Humanos , Luz , Persona de Mediana Edad , Hipertensión Ocular/fisiopatología , Estimulación LuminosaRESUMEN
BACKGROUND: Vascular dysregulation in open-angle glaucomas can be identified by measuring the blood circulation during exposure to cold water. Aim of this study was to find out whether the same cold stimulus would lead to functional changes in the visual evoked potentials (VEP) of the short-sensitive pathway in normals and glaucoma patients. PATIENTS AND METHODS: Blue-on-yellow pattern-visual evoked potentials were studied in 22 healthy control persons and 47 patients with primary open-angle glaucoma (25 high-pressure glaucomas, 22 normal pressure glaucomas with clinical signs of vasospastic hyperreactivity). A blue stripe pattern, presented in onset-offset mode on a yellow adaptation light served as the stimulus. Cold provocation was initiated by dipping one hand of the patient into cold water of 3 degrees C to 5 degrees C. The onset amplitudes and peak times were measured without cold exposition as well as two and four minutes after the cold exposition began. RESULTS: In the group of vasospastic glaucoma patients a significant reduction of visual evoked potential-amplitudes was observed during cold provocation (amplitude before ice exposition: 4.17 microV, amplitude following two minutes of ice exposition: 3.52 microV; paired test: P < 0.01). Other subject groups showed no significant amplitude reductions after cold provocation. Peak times of both open-angle glaucoma groups (132.3 +/- 18.7 milliseconds in high pressure, 132.7 +/- 14.5 milliseconds in normal pressure) were significantly increased in comparison to normals (117.4 +/- 8.0 milliseconds). However, no significant influence of the cold provocation on peak times could be found in all groups. CONCLUSION: Peak times of the blue-on-yellow visual evoked potentials are significantly prolonged in patients with primary open-angle glaucomas. Cold provocation causes a significant amplitude reduction of the blue-on-yellow visual evoked potential in the present normal-pressure glaucoma patients and reflects vascular dysregulation in patients with vasospastic hyperreactivity.
Asunto(s)
Frío , Potenciales Evocados Visuales/fisiología , Ojo/irrigación sanguínea , Glaucoma de Ángulo Abierto/fisiopatología , Vías Visuales/fisiopatología , Presión Sanguínea/fisiología , Temperatura Corporal , Femenino , Dedos/irrigación sanguínea , Humanos , Presión Intraocular/fisiología , Masculino , Persona de Mediana Edad , Pruebas del Campo Visual , Campos VisualesRESUMEN
PURPOSE: To evaluate whether various types of chronic open-angle glaucoma differ in predictive factors for progression of glaucomatous optic nerve damage. DESIGN: Observational cohort study. SETTING: Prospective observational clinical study. PATIENTS: 517 eyes of 300 Caucasian patients with chronic open-angle glaucoma with elevated intraocular pressure (primary open-angle glaucoma, n = 289; secondary open-angle glaucoma, n = 50) and with normal intraocular pressure (n = 178). OBSERVATION PROCEDURE: During follow-up (median: 49 months, 6 months-130 months), all patients underwent repeated evaluation of color stereo optic disk photographs and white-on-white visual field examination. MAIN OUTCOME MEASURES: Progression of glaucoma was defined as neuroretinal rim loss during the study period. RESULTS: For patients with elevated intraocular pressure, significantly predictive factors for eventual progression were older age, advanced perimetric damage, smaller neuroretinal rim, and larger area of beta zone of parapapillary atrophy. In contrast, in the normal intraocular pressure group, a significant predictive factor was presence of disk hemorrhages at baseline. Within the patients with elevated intraocular pressure, the primary open-angle glaucoma group and the secondary open-angle glaucoma group did not differ in predictive factors for progression of glaucoma. CONCLUSIONS: Open-angle glaucoma patients with normal intraocular pressure and open-angle glaucoma patients with elevated intraocular pressure differ in predictive factors for eventual progression of glaucomatous optic nerve damage. It may have clinical importance and may be helpful in the discussion of the pathogenesis of the glaucomas.
Asunto(s)
Glaucoma de Ángulo Abierto/diagnóstico , Enfermedades del Nervio Óptico/diagnóstico , Adolescente , Adulto , Anciano , Enfermedad Crónica , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Glaucoma de Ángulo Abierto/fisiopatología , Humanos , Presión Intraocular , Masculino , Persona de Mediana Edad , Disco Óptico/patología , Enfermedades del Nervio Óptico/fisiopatología , Estudios Prospectivos , Factores de Riesgo , Agudeza Visual , Campos VisualesRESUMEN
BACKGROUND: The diagnostic value of multifocal visual evoked potentials (mf VEP) in glaucoma research is still under debate. Several previous studies proclaim it to be a useful tool for clinical applications, but according to other studies, different problems (low specificity, poor records, and interindividual variation) still retard its clinical use. The aim of the present study was to examine whether the mf VEP data obtained with the RETIscan system are appropriate for formulating a classification rule for glaucoma. METHOD: We examined and evaluated 65 eyes in 38 advanced glaucoma patients and 27 normal subjects, using four occipital gold cup electrodes (cross layout) for bipolar recording and a CRT monitor (display diameter 60 degrees, chequerboard pattern reversal, 60 segments in dartboard layout) for stimulation. In each case, eight cumulative measurements (77 s each) were made. The data of the 60 segments were cross-correlated with a RETIscan-internal VEP norm ("VEP finder"), combined in 16 sectors, and evaluated via the classification technique "double-bagging" and the Wilcoxon U-test. RESULTS: In three out of the 16 sectors, the VEP amplitudes of the patients were significantly reduced (Wilcoxon U-test). Applying double-bagging on the cross-correlated data (with VEP finder) resulted in a sensitivity of 75% and a specificity of 71%, and the estimated misclassification rate was 27%. For uncorrelated data (without VEP finder), the same analysis achieved a sensitivity of about 60% and a specificity of 40%. CONCLUSIONS: Estimated sensitivity and specificity suggest that by using the RETIscan system for recording, a classification of the VEP data--i.e. a separation between normal and glaucoma subjects--is possible.
Asunto(s)
Técnicas de Diagnóstico Oftalmológico , Potenciales Evocados Visuales , Glaucoma de Ángulo Abierto/diagnóstico , Investigación Biomédica , Femenino , Humanos , Presión Intraocular , Masculino , Persona de Mediana Edad , Reconocimiento Visual de Modelos , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Trastornos de la Visión/diagnóstico , Campos VisualesRESUMEN
The evaluation of a new medical diagnostic test may focus on two different scientific questions: (1). The new test may replace an existing one because of lower cost or higher validity. A related question would be the selection of the 'best' test(s) from a bundle of new or established measurements. (2). The new test may be used supplementary to other new or established procedures. In a recent publication, Leisenring and co-workers (Stat Med 1997; 16:1263-1281) developed a general marginal regression model for comparisons of diagnostic tests focussing on question (1). i.e. on the selection of the 'best' procedure. They applied the GEE approach of Liang and Zeger (Biometrika 1987; 73:13-22) to adjust for the correlation of data as a nuisance parameter. Using the general framework provided by Leisenring et al., we extend their approach and apply the GEE methodology to question (2). i.e. to the investigation of which of several diagnostic tests should be used supplementary to each other. We analyse data from a longitudinal study concerning pathogenesis, diagnosis and long-term course of the eye disease glaucoma. We find a dependence of the correlation structure of several diagnostic measurements on the severity of the disease. This result may be useful in clinical applications as regards the selection of subsets of diagnostic measurements in individual diagnostic processes but also in investigations concerning the relationship of the pathogenic process and the rationales of the different diagnostic procedures.
Asunto(s)
Biometría/métodos , Técnicas de Laboratorio Clínico/estadística & datos numéricos , Técnicas de Apoyo para la Decisión , Análisis de Regresión , Estudios de Casos y Controles , Técnicas de Diagnóstico Oftalmológico , Glaucoma/diagnóstico , Humanos , Modelos Logísticos , Sensibilidad y EspecificidadRESUMEN
PURPOSE: To evaluate stereoscopic visual evoked potentials (S-VEP) in normal controls and in patients with glaucomatous optic nerve damage. METHODS: Computer-generated dynamic random-dot stereograms were used to elicit cortical visual evoked potentials using wireless electric liquid crystal shutter glasses. Normal subjects (n=22) and patients with glaucoma (n=22) were investigated using five different disparities from 9 to 40 arc min. Statistical dependency of measurements with different stimulus at identical patients was adjusted for. RESULTS: Peak times of onset and offset response of S-VEP can be significantly delayed in glaucomas. A general linear regression model confirmed that differences between patients and normals depend on disparity. S-VEP onset shows no significant difference between controls and glaucomas at 9 arc min disparity. At high disparities, however, peak time of the onset response was significantly (p<0.01) delayed in glaucomas when compared with normals (normals: 125.8+/-13 ms, glaucomas: 148.2+/-25.6 ms at 40 arc min). CONCLUSIONS: Visual evoked potential elicited by the onset of a random-dot stereogram can be used for objective measurement of stereoacuity in a clinical setting. Differences between controls and glaucomas in high and low disparities could indicate a stereo-specific deficit in glaucoma.
Asunto(s)
Percepción de Profundidad/fisiología , Potenciales Evocados Visuales/fisiología , Glaucoma de Ángulo Abierto/fisiopatología , Femenino , Humanos , Presión Intraocular , Modelos Lineales , Masculino , Persona de Mediana Edad , Fibras Nerviosas/patología , Enfermedades del Nervio Óptico/fisiopatología , Células Ganglionares de la Retina/patología , Disparidad Visual/fisiología , Agudeza VisualRESUMEN
PURPOSE: To analyze the sensitivity of various sensory tests adjusted for glaucomatous optic disc damage. METHODS: In a cross-sectional study, the results of testing of 196 control subjects (age range, 18-69 years) and 308 patients with chronic open-angle glaucoma (age range, 18-70 years) were included. The perimetric mean defect (MD), a temporal contrast sensitivity test (TCS), a spatiotemporal contrast sensitivity test (STCS), the peak time of a blue-on-yellow visual evoked potential (BYVEP), and the amplitude of a pattern-reversal electroretinogram (PERG) were evaluated by a specific logistic regression model. This model included glaucomatous damage, quantified by neuroretinal rim area corrected for disc size, as a covariate of sensitivity. RESULTS: Sensitivity of diagnostic tests increased for all procedures with increasing loss of neuroretinal rim area. With progressing optic disc damage, MD and STCS showed higher sensitivity than did TCS. BYVEP showed a higher sensitivity than PERG in all disease stages. In general, the psychophysical tests were more sensitive than the electrophysiological ones. CONCLUSIONS: The specific model used in this study was an appropriate tool to analyze the sensitivity of several sensory glaucoma tests in relation to disease stage. Moreover, tests that were more sensitive in early disease stages (TCS) and others that were more sensitive in more advanced stages (MD, STCS) were identified.
Asunto(s)
Técnicas de Diagnóstico Oftalmológico , Glaucoma de Ángulo Abierto/diagnóstico , Modelos Estadísticos , Disco Óptico/patología , Enfermedades del Nervio Óptico/diagnóstico , Adolescente , Adulto , Anciano , Enfermedad Crónica , Sensibilidad de Contraste , Estudios Transversales , Progresión de la Enfermedad , Electrorretinografía , Potenciales Evocados Visuales , Femenino , Glaucoma de Ángulo Abierto/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Enfermedades del Nervio Óptico/fisiopatología , Sensibilidad y Especificidad , Pruebas del Campo VisualRESUMEN
BACKGROUND: The m-sequence technique is a typical tool for the multifocal ERG. The use of LEDs instead of a computer monitor enables a new technique that merits closer investigation: The cyclic summation technique. The aim of this study was to compare the two methods. METHODS: Six normal right eyes were examined with the RETIscan system using DTL electrodes. With an LED array (display diameter 52 degrees, 103 segments, 1 foveal + 102 arranged in six concentric rings) we studied: (1). first order kernels (m-sequence); (2). 30-Hz flicker responses (m-sequence); (3). 30-Hz flicker responses (cyclic summation). The three methods were tested with a pattern of concentric rings generated by selective deactivation of LEDs (the central LED and rings 2, 4 and 6; rings 1, 3 and 5 remained active). In each case six cumulative measurements (40 s each) were made and stored separately. To determine the signal-to-noise ratio, the average mf ERG response to all active LEDs was divided by the average response to the inactive ones. RESULTS: 1. Using cyclic summation the signal-to-noise ratio exceeds the signal-to-noise ratio of both m-sequence-controlled stimuli about twofold. This implies also better spatial resolution with the cyclic summation technique 2. Since the signal-to-noise ratio increases faster with the cyclic summation technique than with the m-sequence technique, the gain of time in mf ERG can reach 80%. CONCLUSION: As far as the signal-to-noise ratio and measuring time is concerned, the cyclic summation technique outmatches the m-sequence technique in mf ERG.
Asunto(s)
Electrorretinografía/métodos , Fenómenos Fisiológicos Oculares , Adulto , Electrorretinografía/instrumentación , Humanos , Persona de Mediana Edad , Estimulación Luminosa/métodos , Valores de Referencia , Factores de TiempoRESUMEN
BACKGROUND: Large-scale screening in glaucoma diagnosis is expensive and time consuming. Sequential classification strategies can provide an effective combination of time-efficiency and diagnostic accuracy for glaucoma screening. METHODS: In a cross-sectional clinical study, a sequential diagnostic strategy, based on several psychophysical and electrophysiological tests, was evaluated on measurements from 595 eyes from 310 patients with primary open-angle glaucoma, and 419 eyes from 213 control subjects (age range 18-70 years in each group). Patients and controls successively underwent up to five psychophysical and electrophysiological diagnostic tests. Optic disc morphometry was taken as gold standard. Adapting group sequential techniques, sensitivity and specificity for the whole diagnostic program were controlled, allotting overall error rates of 10%. The criteria for the diagnostic process were developed in a learning sample (677 eyes) and verified in a validation sample (337 eyes). RESULTS: In the validation sample, 62.0% of the examined eyes could be classified, using a sequential 15-min two-step program. An overall 13.6% "gain" of saved time, compared to non-sequential discriminant analysis, was achieved without loss of diagnostic accuracy. A sequential 45-min five-step program classified 68.8% of the whole sample before morphometry, saving approximately 39% of examination time, compared to taking the complete discriminant score. CONCLUSION: Especially in screening, where the use of time-consuming and complicated diagnostic procedures is restricted, the implementation of testing programs based on group sequential strategies might be a promising means of saving personnel resources and reducing inconvenience for patients.
Asunto(s)
Técnicas de Diagnóstico Oftalmológico , Glaucoma de Ángulo Abierto/clasificación , Glaucoma de Ángulo Abierto/diagnóstico , Disco Óptico/patología , Enfermedades del Nervio Óptico/diagnóstico , Trastornos de la Visión/diagnóstico , Campos Visuales , Adolescente , Adulto , Anciano , Estudios Transversales , Electrofisiología , Potenciales Evocados Visuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psicofísica , Sensibilidad y Especificidad , Pruebas del Campo VisualRESUMEN
BACKGROUND: The aim of this study was to evaluate the diagnostic usefulness of the FDT perimeter protocol (C-20-5) in combination with a database system for analysis of single test locations. METHODS: One hundred seventy-three ocular hypertensive eyes, 116 "preperimetric" open-angle glaucoma eyes (glaucomatous optic disc atrophy, elevated intraocular pressure, no visual field defects in standard white-on-white perimetry), 199 "perimetric" open-angle glaucoma eyes (glaucomatous optic disc atrophy and visual field defects), and 151 control eyes underwent FDT screening and conventional white-on-white perimetry. Four repeated measurements were carried out in 15 glaucoma patients at 2-h intervals to judge reproducibility of all test locations. The present screening strategy begins testing at the normal 5% probability level. If a stimulus is not detected, further targets are presented. FDT-Viewfinder and statistics software were used for case-wise recalculation of all missed localized probability levels and correlation with corresponding test locations using conventional perimetry. RESULTS: Analysis of repeated measurements in patients reveals that variation of single test points can be considerable. However, the numbers of missed test-stimuli calculated globally or in quadrants are significantly correlated with corresponding Octopus visual field defects (Spearman rank correlation P<0.001). Using a predefined specificity of 96% in control eyes, 11% of ocular hypertensive eyes, 28.5% of "preperimetric" glaucoma eyes and 86.9% of "perimetric" glaucoma eyes have been classified glaucomatous using an overall score and with consideration of different cut-off points in right and left eyes. CONCLUSION: Point-wise analysis of FDT screening results can be helpful for classification of patient groups and consideration of the individual learning curve in repeated measurements. The C-20-5 protocol of the FDT perimeter is able to detect a considerable proportion of glaucomatous patients.
Asunto(s)
Glaucoma de Ángulo Abierto/diagnóstico , Hipertensión Ocular/diagnóstico , Trastornos de la Visión/diagnóstico , Pruebas del Campo Visual/métodos , Campos Visuales , Adulto , Reacciones Falso Positivas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
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.