Frequency dependency of temporal contrast adaptation in normal subjects

AbstractThe aim of this study was to determine the influence of temporal frequency of temporal contrast adaptation on contrast sensitivity in healthy subjects. Temporal contrast sensitivities (TCS) were measured monocularly in seven healthy subjects with a modified ERG full-field bowl stimulator at eight different test temporal frequencies (9, 15, 20, 25, 31, 37, 44, 51Hz) using a two-alternative-forced-choice strategy. Before each presentation of the test stimulus, a 100% contrast adapting flicker stimulus was presented (frequencies: 9, 15, 20, 25, 31, 37, 44, 51, 100Hz). At each adapting frequency, a complete set of TCSs was measured. All temporal contrast sensitivities decreased with increasing temporal frequencies. Adaptation led to a general temporal contrast sensitivity decrease. Largest adaptation effects were seen at an adaptation frequency of 25Hz. Reduction of contrast sensitivity was significantly larger at 25Hz adaptation than at 9Hz adaptation (t-test of paired samples, Bonferroni corrected). The results of this study showed a general TCS decrease with the largest effect at an adaptation frequency of 25Hz. This finding indicates that the contrast adaptation probably occurred in the magnocellular-pathway. In future clinical studies adaptation effects could be investigated in patients with reduced temporal contrast sensitivity

Ensemble Pruning for Glaucoma Detection in an Unbalanced Data Set

Background: Random forests are successful classifier ensemble methods consisting of typically 100 to 1000 classification trees. Ensemble pruning techniques reduce the computational cost, especially the memory demand, of random forests by reducing the number of trees without relevant loss of performance or even with increased performance of the sub-ensemble. The application to the problem of an early detection of glaucoma, a severe eye disease with low prevalence, based on topographical measurements of the eye background faces specific challenges. Objectives: We examine the performance of ensemble pruning strategies for glaucoma detection in an unbalanced data situation. Methods: The data set consists of 102 topographical features of the eye background of 254 healthy controls and 55 glaucoma patients. We compare the area under the receiver operating characteristic curve (AUC), and the Brier score on the total data set, in the majority class, and in the minority class of pruned random forest ensembles obtained with strategies based on the prediction accuracy of greedily grown sub-ensembles, the uncertainty weighted accuracy, and the similarity between single trees. To validate the findings and to examine the influence of the prevalence of glaucoma in the data set, we additionally perform a simulation study with lower prevalences of glaucoma. Results: In glaucoma classification all three pruning strategies lead to improved AUC and smaller Brier scores on the total data set with sub-ensembles as small as 30 to 80 trees compared to the classification results obtained with the full ensemble consisting of 1000 trees. In the simulation study, we were able to show that the prevalence of glaucoma is a critical factor and lower prevalence decreases the performance of our pruning strategies. Conclusions: The memory demand for glaucoma classification in an unbalanced data situation based on random forests could effectively be reduced by the application of pruning strategies without loss of performance in a population with increased risk of glaucoma

25 Hz adaptation: Influence on recovery time in glaucoma

INTRODUCTION. Normal temporal contrast sensitivity is maximally influenced by pre-adaptation with 25-Hz temporal contrast flicker. The aim of this study was to investigate the effects of 25-Hz contrast adaptation on recovery of contrast sensitivity in normals, patients with ocular hypertension, preperimetric, perimetric and advanced perimetric open-angle glaucoma. MATERIALS AND METHODS. Temporal contrast sensitivity was examined after pre-adaptation with 25 Hz in the following: 43 normals, 14 ocular hypertension, 10 preperimetric primary open-angle glaucoma, and 33 perimetric open-an­gle glaucoma patients. After pre-adaptation (the time after which a test stimulus could be detected again), recovery time (RT) was measured at 3% and 5% test contrast. Additionally, 25 patients with advanced perimetric open-angle glaucoma were measured at 12%, 25%, and 35% contrast and compared to a normal group consisting of 15 subjects. RESULTS. 1. Measurements of RT are reliable (Cronbach’s a > 0.8). 2. RT was age-dependent requiring an age-correction in further analyses. 3. RT3% and RT5% were significantly prolonged in perimetric primary open-angle glau­coma compared to normals (3% test contrast: p = 0.007; 5% test contrast: p = 0.035). 4. Within each group, RT3% and RT5% were significantly different at both test contrasts (normals, perimetric open-angle glaucoma: p < 0.001; ocular hypertension: p = 0.007; preperimetric open-angle glaucoma: p = 0.035). 5. RT3% and RT5% were significantly correlated with mean defect (p < 0.001) and retinal nerve fibre layer thickness (p = 0.018). RT5% was correlated with loss variance (p = 0.048). 6. RT12%, RT25% and RT35% were significantly prolonged in advanced perimetric glaucoma (p < 0.001), and correlated with mean defect (p < 0.001, p = 0.002, p = 0.013) and retinal nerve fibre layer thickness (p < 0.001, p = 0.003, p = 0.013). RT12% was also correlated with loss variance (p = 0.016). CONCLUSIONS. Measurements of RT after 25-Hz pre-adaptation can be used in glaucoma diagnosis and follow-up examination, especially in monitoring glaucoma progress in advanced perimetric primary open-angle glaucoma

Temporal contrast sensitivity: A potential parameter for glaucoma progression, especially in advanced stages

INTRODUCTION. Previously it could be shown that temporal contrast sensitivity is affected by glaucoma and maximally influenced after 25-Hz adaptation in normals. This study investigated different kinds of 25-Hz temporal contrast adaptation on TCS in patients with ocular hypertension, preperimetric primary open-angle glaucoma, and perimetric open-angle glaucoma. Additionally, correlations of measured data with parameters of glaucoma diagnostic were done and assessed for the potential use of TCS as a parameter for glaucoma progression. MATERIALS AND METHODS. One hundred and four subjects were included: 44 normals, 14 ocular hypertensions, 11 preperimetric primary open-angle glaucomas, and 35 perimetric open-angle glaucomas. Using the Erlangen Flicker Test, temporal contrast sensitivity was measured without adaptation, after pre-adaptation and after pre- and re-adaptations at 25 Hz. Reliability analyses were done. RESULTS. All test strategies showed high reliability (a-Cronbach’s > 0.86). In normals, age-dependency of temporal contrast sensitivity without adaptation (p = 0.052) and after pre- and re-adaptation (p = 0.008) was observed. Temporal contrast sensitivity is significantly reduced after pre-adaptation for all subjects (p < 0.001). Reduction of temporal contrast sensitivity after pre- and re-adaptations was significant in all groups (p < 0.001), but it was smaller than after single pre-adaptation (p < 0.001). Temporal contrast sensitivity without adaptation was significantly reduced in patients with perimetric glaucoma (p = 0.040) but not in patients with ocular hypertension and preperimetric glaucoma. Correlation analyses yielded a significant correlation between temporal contrast sensitivity without adaptation and mean defect (p = 0.003, r = –0.329), loss variance (p = 0.027, r = –0.256), and retinal nerve fibre layer thickness (p < 0.001, r = 0.413) for all subjects and between temporal contrast sensitivity after pre-adaptation and mean defect (p = 0.045, r = –0.239). CONCLUSIONS. Temporal contrast sensitivity seems to be affected in perimetric glaucoma with an overall reduction after adaptation. Significant correlations of temporal contrast sensitivity with perimetric and morphologic parameters offer new aspects of its potential use as a glaucoma progressions marker, especially in advanced stages when perimetric diagnosis is limited

Autoantibodies Activating the β2-Adrenergic Receptor Characterize Patients With Primary and Secondary Glaucoma

Recently, agonistic autoantibodies (agAAb) activating the β2-adrenergic receptor were detected in primary open-angle glaucoma (POAG) or ocular hypertension (OHT) patients and were linked to intraocular pressure (IOP) (1). The aim of the present study was to quantify β2-agAAb in the sera of glaucoma suspects and patients with primary and secondary glaucoma. Patients with OHT (n = 33), pre-perimetric POAG (pre-POAG; n = 11), POAG (n = 28), and 11 secondary OAG (SOAG) underwent ophthalmological examinations including examinations with Octopus G1 perimetry and morphometry. Twenty-five healthy individuals served as controls. Serum-derived IgG samples were analyzed for β2-agAAb using a functional bioassay. The beat-rate-increase of spontaneously beating cultured neonatal rat cardiomyocytes was monitored with 1.6 beats/15 s as cut-off. None of the sera of normal subjects showed β2-agAAb. In POAG or OHT patients increased beating rates of 4.1 ± 2.2 beats/15 s, and 3.7 ± 2.8 beats/15 s were detected (p > 0.05). Glaucoma patients with (POAG) and without perimetric (pre-POAG) defects did not differ (pre-POAG 4.4 ± 2.6 beats/15 s, POAG 4.1 ± 2.0 beats/15 s, p > 0.05). Patients with SOAG yielded mean beating rates of 4.7 ± 1.7 beats/15 s (p > 0.05). β2-agAAb were seen in 73% of OHT, 82% of pre-POAG, 82% of POAG, and 91% SOAG patients (p 0.05). The robust β2-agAAb seropositivity in patients with OHT, pre-POAG, POAG, and SOAG suggest a primary common role for β2-agAAb starting early in glaucoma pathophysiology and turned out to be a novel marker identifying all patients with increased IOP independent of glaucoma stage and entity

Comparative analysis of retinal photoplethysmographic spatial maps and thickness of retinal nerve fiber layer.

The paper presents a comparative study of the pulsatile attenuation amplitude (PAA) within the optic nerve head (ONH) at four different areas calculated from retinal video sequences and its relevance to the retinal nerve fiber layer thickness (RNFL) changes in normal subjects and patients with different stages of glaucoma. The proposed methodology utilizes processing of retinal video sequences acquired by a novel video ophthalmoscope. The PAA parameter measures the amplitude of heartbeat-modulated light attenuation in retinal tissue. Correlation analysis between PAA and RNFL is performed in vessel-free locations of the peripapillary region with the proposed evaluating patterns: 360° circular area, temporal semi-circle, nasal semi-circle. For comparison, the full ONH area is also included. Various positions and sizes of evaluating patterns in peripapillary region were tested which resulted in different outputs of correlation analysis. The results show significant correlation between PAA and RNFL thickness calculated in proposed areas. The highest correlation coefficient Rtemp = 0.557 (p<0.001) reflects the highest PAA-RNFL correspondence in the temporal semi-circular area, compared to the lowest value in the nasal semi-circular area (Rnasal = 0.332, p<0.001). Furthermore, the results indicate the most relevant approach to calculate PAA from the acquired video sequences is using a thin annulus near the ONH center. Finally, the paper shows the proposed photoplethysmographic principle based on innovative video ophthalmoscope can be used to analyze changes in retinal perfusion in peripapillary area and can be potentially used to assess progression of the RNFL deterioration

Blue–Yellow VEP with Projector-Stimulation in Glaucoma

Background and aim!#!In the past, increased latencies of the blue-on-yellow pattern visually evoked potentials (BY-VEP), which predominantly originate in the koniocellular pathway, have proven to be a sensitive biomarker for early glaucoma. However, a complex experimental setup based on an optical bench was necessary to obtain these measurements because computer screens lack sufficient temporal, spatial, spectral, and luminance resolution. Here, we evaluated the diagnostic value of a novel setup based on a commercially available video projector.!##!Methods!#!BY-VEPs were recorded in 126 participants (42 healthy control participants, 12 patients with ocular hypertension, 17 with 'preperimetric' glaucoma, and 55 with perimetric glaucoma). Stimuli were created with a video projector (DLP technology) by rear projection of a blue checkerboard pattern (460 nm) for 200 ms (onset) superimposed on a bright yellow background (574 nm), followed by an offset interval where only the background was active. Thus, predominantly S-cones were stimulated while L- and M-cone responses were suppressed by light adaptation. Times of stimulus onset to VEP onset-trough (N-peak time) and offset-peak (P-peak time) were analyzed after age-correction based on linear regression in the normal participants.!##!Results!#!The resulting BY-VEPs were quite similar to those obtained in the past with the optical bench: pattern-onset generated a negative deflection of the VEP, whereas the offset-response was dominated by a positive component. N-peak times were significantly increased in glaucoma patients (preperimetric 136.1 ± 10 ms, p &amp;lt; 0.05; perimetric 153.1 ± 17.8 ms, p &amp;lt; 0.001) compared with normal participants (123.6 ± 7.7 ms). Furthermore, they were significantly correlated with disease severity as determined by visual field losses retinal nerve fiber thinning (Spearman R = -0.7, p &amp;lt; 0.001).!##!Conclusions!#!Video projectors can be used to create optical stimuli with high temporal and spatial resolution, thus potentially enabling sophisticated electrophysiological measurements in clinical practice. BY-VEPs based on such a projector had a high diagnostic value for detection of early glaucoma. Registration of study Registration site: www.!##!Clinicaltrials!#!gov Trial registration number: NCT00494923

Imaging video plethysmography shows reduced signal amplitude in glaucoma patients in the area of the microvascular tissue of the optic nerve head

Purpose To measure parameters of the cardiac cycle-induced pulsatile light absorption signal (plethysmography signal) of the optic nerve head (ONH) and to compare parameters between normal subjects and patients with different stages of glaucoma. Patients and methods A recently developed video ophthalmoscope was used to acquire short video sequences (10 s) of the ONH. After image registration and trend correction, the pulsatile changing light absorption at the ONH tissue (excluding large vessels) was calculated. The changing light absorption depends on the pulsatile changing blood volume. Various parameters, including peak amplitude, steepness, time-to-peak, full width at half maximum (FWHM), and pulse duration, were calculated for averaged individual pulses (heartbeats) of the plethysmography signal. This method was applied to 19 healthy control subjects and 91 subjects with ocular hypertension, as well as different stages of primary open-angle glaucoma (17 subjects with ocular hypertension, 24 with preperimetric glaucoma, and 50 with perimetric glaucoma). Results Compared to the normal subjects, significant reductions (p < 0.001) in peak amplitude and steepness were observed in the group of perimetric glaucoma patients, but no significant difference was found for time-to-peak, FWHM, and pulse duration. Peak amplitude and steepness showed high correlations with RNFL thickness (p < 0.001). Conclusions The presented low-cost video-ophthalmoscope permits measurement of the plethysmographic signal of the ONH tissue and calculation of different blood flow-related parameters. The reduced values of the amplitude and steepness parameters in perimetric glaucoma patients suggest decreased ONH perfusion and blood volume. This outcome is in agreement with results from other studies using OCT angiography and laser speckle flowgraphy, which confirm reduced capillary density in these patients