Pattern electroretinogram, blue-yellow visual evoked potentials and the risk of developing visual field defects in glaucoma suspects: a longitudinal "survival" analysis with a very long follow-up.

PURPOSE: Estimating glaucoma suspects' risk for visual field defects helps to avoid under- and over-treatment. In this retrospective, longitudinal cohort study with a very long follow-up, we studied whether pattern electroretinograms (PERG) amplitudes and blue-on-yellow visual evoked potential (BY-VEP) latencies can predict visual field defects. METHODS: Participants of the Erlangen Glaucoma Study were examined with PERG and BY-VEP between 9/1991 and 8/2001. Stimuli were created using an optical bench with Maxwellian view and consisted of vertical gratings (0,88 cpd) in a 32° field for both PERG and BY-VEP. Patients were treated according to clinical standards and performed standard automated perimetry (SAP) annually. Retrospectively, patients with normal SAP at baseline were selected. Primary endpoint was conversion to perimetric glaucoma. Predictive value was modeled using Kaplan-Meier analyses and a multivariate cox proportional hazards model with the continuous variables PERG amplitude, BY-VEP peak time and SAP square-root of loss variance (sLV) after stratification for Jonas classification of the optic discs. RESULTS: Of 412 patients (288: Jonas 0, 103: I, and 21: II; baseline age: 20-60 years), 65 converted to perimetric glaucoma during follow-up (0.5-23.3 years; median 5.5 years). Optic disc classification was a strong risk factor for conversion (log rank p < 0.0001), and patients with more advanced changes progressed earlier. In the multivariate analysis (log rank p = 0.005), only PERG amplitude remained an independent risk factor after stratification for optic disc morphology (p = 0.021), with a ~ 30% higher risk per µV amplitude decrease. CONCLUSIONS: PERG helps to estimate glaucoma suspects' risk for visual field defects.

Objective detection of visual field defects with multifrequency VEPs.

PURPOSE: To correlate multifrequency pattern reversal VEPs in quadrants (QmfrVEPs) with perimetric field losses for objective detection of visual field losses. METHODS: QmfrVEP measurements were performed using four LED-based checkerboard stimulators to stimulate the four quadrants of the visual field. QmfrVEPs were measured monocularly in 5 normal subjects and in 5 glaucoma patients who showed losses in conventional Octopus perimetry. The pattern reversal frequency varied slightly between the stimulators: (11.92, 12.00, 12.08 and 12.16 reversals/sec). The responses to the different stimuli were identified by discrete Fourier analysis. VEPs were recorded using different electrode configurations, and the recording with the highest signal-to-noise ratio (SNR) was used for further analysis. RESULTS: QmfrVEP responses from the different quadrants can be reliably measured and separated using the 0.08 reversals/sec interstimulus reversal frequency differences. The signal-to-noise ratio in the four quadrants was significantly correlated with the equivalent visual field losses obtained with perimetry (Spearman rank correlation: P < 0.001). In the five glaucoma patients, the SNR was reduced in 15 out of the 16 quadrants with a perimetric defect, in comparison to the results in quadrants of healthy subjects. This confirms the sensitivity of the procedure. CONCLUSION: QmfrVEP responses can be measured reliably. This pilot study suggests that high SNR values exclude visual field defects and that focal defects can be identified in glaucoma patients. TRIAL REGISTRATION: www. CLINICALTRIALS: gov . NCT00494923.

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 < 0.05; perimetric 153.1 ± 17.8 ms, p < 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 < 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.

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

Purpose: To compare the electroretinographical (ERG) responses elicited by L- and M-cone isolating ON- and OFF-sawtooth stimuli in normal subjects and glaucoma patients. Methods: Twenty-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. Results: The responses to L-ON and to M-OFF stimuli and vice versa resembled each other particularly with 70° stimuli. The PL-add amplitudes were not significantly different between the normal subjects and glaucoma patients, whereas the LNL-add amplitude was significantly (P < 0.01) smaller in the glaucoma patients. Both PM-add and LNM-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° LNL-add amplitude and the 0.8° PERG amplitude were significantly correlated with RNFLT. Conclusions: The 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.

Steady-State Visually Evoked Potentials Elicited by Multifrequency Pattern-Reversal Stimulation.

PURPOSE: It has been shown that multifrequency stimulation with multifocal electroretinography can reduce recording time without a loss in signal-to-noise ratio. Here, we studied the applicability of multifrequency stimulations for steady-state visually evoked potential (VEP) recordings. METHODS: Multifrequency VEPs were recorded monocularly from 10 healthy subjects using pattern-reversal stimuli. The reversal frequency varied between 5 and 30 Hz. Pattern-reversal checkerboard stimuli were generated using four square arrays, each containing 100 light-emitting diodes (LEDs), positioned in four quadrants. Each array had a temporal frequency that differed slightly from the nominal frequency. The long duration of the data acquisition ensured that the slightly different stimulus frequencies in the four LED arrays can be resolved and that the responses to the stimulus in each array can be distinguished (e.g., with a frequency resolution: 0.011 Hz at 12 Hz). The best response from the four recording electrode configuration, defined as the recording with the maximal signal-to-noise ratio, was used for further analysis. Algorithmic latencies were calculated from the ratio of phase data and frequencies in a range of 4 and 20 Hz. RESULTS: Quadrant-VEPs with simultaneous pattern-reversal stimulation yielded a significant dependency on temporal frequency and stimulus location. The frequency range leading to the maximal response amplitude was between 10 and 12 Hz. Response phases decreased approximately linearly, with increasing temporal frequency suggesting a mean algorithmic latency between 112 and 126 ms. CONCLUSIONS: Multifrequency stimulation using LED arrays is an efficient method for recording pattern-reversal VEPs while all stimuli are presented at the same time. TRANSLATIONAL RELEVANCE: Simultaneously recorded VEPs as performed by the multi-frequency method can be used for objective measurements of visual field defects.

Predictive Factors for Visual Field Conversion: Comparison of Scanning Laser Polarimetry and Optical Coherence Tomography.

PURPOSE: The purpose of this study was to compare the ability of scanning laser polarimetry (SLP) and spectral-domain optical coherence tomography (SD-OCT) to predict future visual field conversion of subjects with ocular hypertension and early glaucoma. METHODS: All patients were recruited from the Erlangen glaucoma registry and examined using standard automated perimetry, 24-hour intraocular pressure profile, and optic disc photography. Peripapillary retinal nerve fiber layer thickness (RNFL) measurements were obtained by SLP (GDx-VCC) and SD-OCT (Spectralis OCT). Positive and negative predictive values (PPV, NPV) were calculated for morphologic parameters of SLP and SD-OCT. Kaplan-Meier survival curves were plotted and log-rank tests were performed to compare the survival distributions. Contingency tables and Venn-diagrams were calculated to compare the predictive ability. RESULTS: The study included 207 patients-75 with ocular hypertension, 85 with early glaucoma, and 47 controls. Median follow-up was 4.5 years. A total of 29 patients (14.0%) developed visual field conversion during follow-up. SLP temporal-inferior RNFL [0.667; 95% confidence interval (CI), 0.281-0.935] and SD-OCT temporal-inferior RNFL (0.571; 95% CI, 0.317-0.802) achieved the highest PPV; nerve fiber indicator (0.923; 95% CI, 0.876-0.957) and SD-OCT mean (0.898; 95% CI, 0.847-0.937) achieved the highest NPV of all investigated parameters. The Kaplan-Meier curves confirmed significantly higher survival for subjects within normal limits of measurements of both devices (P<0.001). Venn diagrams tested with McNemar test statistics showed no significant difference for PPV (P=0.219) or NPV (P=0.678). CONCLUSIONS: Both GDx-VCC and SD-OCT demonstrate comparable results in predicting future visual field conversion if taking typical scans for GDx-VCC. In addition, the likelihood ratios suggest that GDx-VCC's nerve fiber indicator<30 may be the most useful parameter to confirm future nonconversion. (http://www.ClinicalTrials.gov number, NTC00494923; Erlangen Glaucoma Registry).

Can Glaucomatous Visual Field Progression be Predicted by Structural and Functional Measures?

PURPOSE: The aim of this study was to compare the predictive value of retinal nerve fiber layer thickness (RNFLT) measurements obtained by optical coherence tomography (OCT), morphometric parameters of confocal scanning laser ophthalmoscopy (CSLO), and frequency-doubling technique perimetry to predict visual field conversion of normal individuals, ocular hypertensive subjects, and early preperimetric glaucoma patients as determined by standard automated perimetry (SAP). PATIENTS AND METHODS: This longitudinal single-center study included 107 eyes of 56 controls, 164 eyes of 98 patients with ocular hypertension, and 169 eyes of 110 patients with preperimetric glaucoma. At baseline, all patients and controls underwent OCT (Spectralis OCT), CSLO (Heidelberg Retina Tomograph) examination, optic disc photography, and frequency-doubling technique perimetry. At baseline SAP was normal in all participants. Univariate and multivariate hazard ratios (HRs) were measured to model the conversion-free survival including morphometric functional and clinical variables. RESULTS: The median follow-up period was 6.9 years. In total, 48 eyes (10.9%) demonstrated visual field conversion in the follow-up. RNFLT temporal-inferior outside normal limits demonstrated the highest HR with 1.2 (95% confidence interval, 1.1-1.4) per 10 µm loss for OCT, and Glaucoma probability score global outside normal limits demonstrated the highest HR with 1.3 (95 % confidence interval, 1.1-1.5) per 0.1 increase for CSLO in a multivariate model adjusted for photograph-based glaucoma staging, central corneal thickness, and SAP pattern SD. CONCLUSIONS: Both measurement of RNFLT by OCT and Glaucoma probability score by CSLO are highly predictive of future visual field conversion and provide independent predictive information beyond optic disc assessment, central corneal thickness, and SAP pattern SD.

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.

Comparison of frequency doubling and flicker defined form perimetry in early glaucoma.

PURPOSE: To compare perimetric data based on the second-generation frequency doubling technology (FDT) and on flicker defined form (FDF) stimulation in early glaucoma patients. METHODS: Seventy-two experienced glaucoma patients and 50 healthy subjects of the Erlangen Glaucoma Registry participated in the study. The definition of glaucoma was solely based on optic disc appearance. All patients underwent FDF perimetry (HEP), FDT perimetry (Matrix), standard automated perimetry (SAP, Octopus), and peripapillar measurements of the RNFL thickness (Spectralis OCT). Exclusion criteria were: mean defect (MD) in SAP > 6 dB, eye diseases other than glaucoma, or non-reliable FDF or FDT measurements. Statistical analyses included comparison of the standard indices and correlations between methods. Venn-diagrams show the number of patients with abnormal results in HEP, Matrix, SAP, and mean RNFL thickness. RESULTS: Mean defect data from FDT and FDF perimetry were strongly correlated (R = -0.85, P <0.001). In this cohort of early glaucoma patients, the MD values were 6.1 ± 5.0 dB (FDF) and 4.5 ± 4.1 dB (FDT). Sensitivity in this patient group was 65 % for FDF-MD, 60 % for FDT-MD, and 60 % for RNFL-thickness, all at a specificity of 95 %. The correlation analysis between local RNFL thickness and corresponding visual defects revealed significant Spearman correlation coefficients for the arcuate bundles of the visual field (FDF-inferior: R = -0.65, FDF-superior: R = -0.74, FDT-inferior: R = -0.55, FDT-superior: R = -0.72). CONCLUSION: FDF and FDT stimulations can be used to detect patients with early glaucoma. Combined consideration of RNFL thickness and results from one of these perimetric tests can increase the total number of detected patients.

Steady-state multifocal visual evoked potential (ssmfVEP) using dartboard stimulation as a possible tool for objective visual field assessment.

PURPOSE: To investigate whether a conventional, monitor-based multifocal visual evoked potential (mfVEP) system can be used to record steady-state mfVEP (ssmfVEP) in healthy subjects and to study the effects of temporal frequency, electrode configuration and alpha waves. METHODS: Multifocal pattern reversal VEP measurements were performed at 58 dartboard fields using VEP recording equipment. The responses were measured using m-sequences with four pattern reversals per m-step. Temporal frequencies were varied between 6 and 15 Hz. Recordings were obtained from nine normal subjects with a cross-shaped, four-electrode device (two additional channels were derived). Spectral analyses were performed on the responses at all locations. The signal to noise ratio (SNR) was computed for each response using the signal amplitude at the reversal frequency and the noise at the neighbouring frequencies. RESULTS: Most responses in the ssmfVEP were significantly above noise. The SNR was largest for an 8.6-Hz reversal frequency. The individual alpha electroencephalogram (EEG) did not strongly influence the results. The percentage of the records in which each of the 6 channels had the largest SNR was between 10.0 and 25.2 %. CONCLUSION: Our results in normal subjects indicate that reliable mfVEP responses can be achieved by steady-state stimulation using a conventional dartboard stimulator and multi-channel electrode device. The ssmfVEP may be useful for objective visual field assessment as spectrum analysis can be used for automated evaluation of responses. The optimal reversal frequency is 8.6 Hz. Alpha waves have only a minor influence on the analysis. Future studies must include comparisons with conventional mfVEP and psychophysical visual field tests.

Confocal Laser Scanning Tomography to Predict Visual Field Conversion in Patients With Ocular Hypertension and Early Glaucoma.

PURPOSE: To compare Moorfields regression analysis (MRA), Glaucoma probability score (GPS), and different discriminant functions to predict future visual field conversion of patients with ocular hypertension and early glaucoma. PATIENTS AND METHODS: The study included 120 eyes of patients with ocular hypertension and 110 eyes of patients with early glaucoma from the Erlangen glaucoma registry. Annually, all patients underwent standard automated perimetry, 24-hour intraocular pressure profile, optic disc photography, and HRT (Heidelberg Retina Tomograph I-III; Heidelberg Engineering) measurements. The cohort was divided into 2 groups based on the development of repeatable glaucomatous visual fields. Positive predictive values and negative predictive values were compared for MRA, GPS, and the classification of Bathija, Iester, Mardin, and Mikelberg at baseline. Kaplan-Meier Survival curves and Logrank tests were used to evaluate equality of survival distributions for different test results. RESULTS: Median follow-up was 9.04 years. 26 eyes (11.3%) demonstrated glaucomatous visual field loss in the follow-up. MRA temporal-superior and temporal-inferior outside normal limits were predictive of future visual field loss with positive predictive values of 33.3% and 28.6%. Normal GPS Temporal Sector demonstrated a negative predictive value of 96.4% and normal results in discriminant functions between 94.7% and 95.5%. CONCLUSIONS: Confocal scanning laser tomography is a useful imaging modality to predict future visual field conversion. Development of visual field defects in 10 years is highly unlikely, if GPS classification and/or classification of discriminant analysis at baseline are normal. MRA temporal-superior and temporal-inferior outside normal limits are associated with future VF conversion (ClinicalTrials.gov number, NCT00494923).

The Effect of Long-term Antiglaucomatous Drug Administration on Central Corneal Thickness.

PURPOSE: To evaluate rates of changes per year of central corneal thickness after antiglaucomatous drug administration with ß-blockers, prostaglandin analogs, and carbonic anhydrase inhibitors monotherapy and combined topical antiglaucomatous therapy, in a cohort of patients with ocular hypertension, glaucoma suspects, and patients with perimetric glaucoma as compared with normal controls. PATIENTS AND METHODS: This retrospective single-center study included 130 eyes as healthy controls, 121 eyes of ocular hypertensive patients, 105 eyes of glaucoma suspects, and 49 eyes of perimetric glaucoma patients. All patients underwent standard automated perimetry, 24-hour intraocular pressure profile, optic disc photography, and optical coherence pachymetry (OCP; Heidelberg Engineering). The cohort was divided into 8 groups on the basis of topical antiglaucomatous medication. Linear regression analysis was conducted to analyze the relationship between central corneal thickness and exposure to antiglaucomatous medication during the follow-up. RESULTS: Central corneal thickness did not change during the follow-up for investigated diagnostic subgroups. There was a statistically significant decrease in central corneal thickness for eyes treated with prostaglandin monotherapy (-3.1 µm/y for left eye), and a combined therapy with prostaglandins, carbonic anhydrase inhibitors, and ß-blockers (-5.8 and -3.8 µm/y for right and left eye, respectively). CONCLUSIONS: We recommend regular measurements before and during therapy with prostaglandin monotherapy and a combined therapy with prostaglandins, carbonic anhydrase inhibitors, and ß-blockers. Follow-up intraocular pressure measurements may be underestimated for eyes treated with the aforementioned treatment regimens if central corneal thickness is not measured on a regular basis.

Predicted and measured retinal nerve fiber layer thickness from time-domain optical coherence tomography compared with spectral-domain optical coherence tomography.

IMPORTANCE: New methods are needed to compare peripapillary retinal nerve fiber layer thickness (pRNFLT) measurements taken from time-domain optical coherence tomography (TD-OCT) and spectral-domain OCT (SD-OCT). OBJECTIVE: To compare the agreement of measured and predicted pRNFLT using different equations based on pRNFLT measurements obtained by TD-OCT and SD-OCT. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional single-center study that took place at the Department of Ophthalmology, University of Erlangen-Nuremberg from November 16, 2005, to June 3, 2015, and included 138 eyes of control participants, 126 eyes of patients with ocular hypertension, 128 eyes of patients with preperimetric glaucoma, and 160 eyes of patients with perimetric glaucoma. All participants had standard clinical examinations to obtain TD-OCT (via Stratus OCT) and SD-OCT (via Spectralis OCT) measurements of pRNFLT. Two groups were matched for diagnostic subgroup, eye side, sex, and age. The TD-OCT measurements of the first group were used to predict the mean SD-OCT and 6-sector vertical-split pRNFLT measurements of the second group and vice versa. The agreement between the predicted pRNFLT calculations of conversion equations and measured pRNFLT of the second group was evaluated by intraclass correlation coefficients and Bland-Altman plots. MAIN OUTCOMES AND MEASURES: Mean and sectoral pRNFLT measurements obtained by TD-OCT and SD-OCT as well as the agreement between measured and predicted pRNFLT. RESULTS: The agreement for all investigated equations to predict mean pRNFLT measurements with intraclass correlation coeffecients ranged from 0.937 to 0.939. Bland-Altman plots demonstrated systemic biases between -0.7 µm and +1.1 µm for measured and predicted mean pRNFLT measurements. The ratio method demonstrated an intraclass correlation coefficient of 0.969 for the temporal-inferior sector. The best color-code agreement between both OCT devices was achieved by the no conversion method, with κ = 0.731 (95% CI, 0.656-0.806) for the mean pRNFLT. CONCLUSIONS AND RELEVANCE: These data suggest that the prediction of mean pRNFLT values by equations derived from TD-OCT and SD-OCT can be conducted with high levels of agreement. In individual cases and singular sectors, high prediction errors may occur. When longitudinal imaging data from both TD-OCT and SD-OCT are available, conversion equations may provide longitudinal comparability.

Flicker-defined form perimetry in glaucoma patients.

PURPOSE: To assess the potential of flicker-defined form (FDF) perimetry to detect functional loss in patient groups with beginning glaucoma, and to evaluate the dynamic range of the FDF stimulus in individual patients and at individual test positions. METHODS: FDF perimetry and standard automated perimetry (SAP) were performed at identical test locations (adapted G1 protocol) in 60 healthy subjects and 111 glaucoma patients. All patients showed glaucomatous optic disc appearance. Grouping within the glaucoma cohort was based on SAP-performance: 33 "preperimetric" open-angle glaucoma (OAG) patients, 28 "borderline" OAG (focal defects and SAP-mean defect (MD) <2 dB), 33 "early" OAG (SAP-MD < 5 dB), 17 "advanced" OAG. All participants were experienced in psychophysical and perimetric tests. Defect values and the areas under receiver operating characteristic curves (ROC) in patient groups were statistically compared. RESULTS: The values of FDF-MD in the preperimetric, borderline, and early OAG group were 2.7 ± 3.4 dB, 5.5 ± 2.6 dB, and 8.5 ± 3.4 dB respectively (all significantly above normal). The percentage of patients exceeding normal FDF-MD was 27.3 %, 60.7 %, and 87.9 % respectively. The age-adjusted FDF-mean defect (MD) of the G1X-protocol was not significantly correlated with refractive error, lens opacity, pupil size, or gender. Occurrence of ceiling effects (inability to detect targets at highest contrast) showed a high correlation with visual field losses (R = 0.72, p < 0.001). Local analysis indicates that SAP losses exceeding 5 dB could not be distinguished with the FDF technique. CONCLUSION: The FDF stimulus was able to detect beginning glaucoma damage. Patients with SAP-MD values exceeding 5 dB should be monitored with conventional perimetry because of its larger dynamic range.

Evidence for two types of lateral interactions in visual perception of temporal signals.

The aim of this work was to investigate the mechanisms of lateral interactions involved in flicker perception. Furthermore, the spatial properties of the monoptic and dichoptic components of these mechanisms were studied. We quantified the perceived flicker strength (PFS) in the center of a test stimulus, which was simultaneously modulated with a surround stimulus of variable size. The modulation depth of a separate stimulus, identical to the center test stimulus but without the surround, was determined using a two-alternative forced choice procedure. Using LCD goggles synchronized to the frame rate of a CRT screen, the center and surround of the test stimulus were presented either monoptically or dichoptically. In the monoptic condition, center-surround interactions have subcortical and cortical origins. In the dichoptic condition, center-surround interactions must have a cortical origin. The difference between the dichoptic and the monoptic data is an estimate of the contribution of the subcortical mechanisms. At each condition (surround stimulus size; monoptic or dichoptic presentation), the PFS was measured for phase differences between center and surround stimuli. The PFS changed systematically with phase difference. It also was observed that the PFS in the center stimulus changed merely be the presence of a surround stimulus independently of the center-surround phase difference. We propose that this is a phase-independent mechanism related to contrast adaptation owing to the presence of surround modulation. Our data suggest that both phase-dependent and -independent mechanisms have cortical and subcortical origins. There were no systematic differences between the spatial properties of subcortical and cortical components involved in PFS modulation.

Pattern electroretinograms during the cold pressor test in normals and glaucoma patients.

PURPOSE: To examine the influence of the cold pressor test (CPT) on steady-state pattern electroretinograms (PERG) in healthy subjects and glaucoma patients. METHODS: Steady-state PERGs to 7.8 Hz pattern reversal stimuli were recorded in 63 subjects. Fifteen healthy control subjects, 14 patients with ocular hypertension (OHT), and 34 patients with open-angle glaucoma (20 normotensive [NTG] and 14 high tension glaucoma [HTG]) were examined. Steady-state PERG amplitudes and latencies were analyzed at baseline, during cold stimulus using a modified CPT, and during the subsequent recovery phase. Blood pressure and heart rate were simultaneously recorded in 10 normals and 11 glaucoma patients. RESULTS: During the three test conditions (baseline, ice water, and warm water) glaucoma patients (NTG and HTG) showed significantly reduced PERG amplitudes in comparison with control subjects (P < 0.001) and with OHT patients (P < 0.004). Patients with OHT displayed lower PERG amplitudes than control subjects (nonsignificant, with consideration of Bonferroni). Only NTG patients showed a significant effect of the CPT on PERG amplitude (significant decrease during warm water P = 0.02). Latencies shortened significantly during warm-water period after cold stimulus in control subjects (P = 0.05) and in NTG patients (P = 0.02) with a nonsignificant trend of shortened latencies in the OHT (P = 0.06) and HTG groups (P = 0.3). Systolic and diastolic blood pressure increased during cold water (P < 0.001) and decreased during warming-up conditions (P < 0.001). CONCLUSIONS: This study shows that a CPT influences the PERG responses particularly in NTG. (ClinicalTrials.gov number, NCT00494923.).

Time course of induced astigmatism after canaloplasty.

PURPOSE: To study the changes in astigmatism after canaloplasty and to analyze its correlation with long-term intraocular pressure (IOP) results. METHODS: Twenty-six eyes of 26 consecutive patients with primary open-angle glaucoma (n=14) and pseudoexfoliative glaucoma (n=12) undergoing canaloplasty were included in this retrospective study. Canaloplasty comprised of 360-degree catheterisation of Schlemm canal by means of a flexible microcatheter with distension of the canal by 2 tensioning 10-0 polypropylene sutures. Primary outcome measures included IOP, glaucoma medication usage, astigmatism, and adverse events at 2, 4, 12, and 24 weeks postoperatively. RESULTS: The mean preoperative IOP was 21.1±5.8 mm Hg. The mean IOP decreased to 14.25 ±4.3 mm Hg at 6 months. Mean astigmatism preoperatively was 0.77±0.5 D, which increased to 3.3±1.7 D at 2 weeks postoperatively (P≤0.05; Wilcoxon-test). Thereafter, the astigmatism underwent a spontaneous decline, reaching 1.9±0.8 D at 4 weeks and 1.2±0.74 D at 12 weeks postoperatively. Best-corrected visual acuity did not change significantly. Six months after canaloplasty, mean astigmatism reached the preoperative range of 0.86±0.52 D. Astigmatism at 2 weeks correlated significantly and inversely with IOP at 6 months (r=0.59, P=0.005; Spearman). CONCLUSIONS: The change of astigmatism after canaloplasty follows a clear time course with a maximum at 2 weeks reaching preoperative values at 6 months. The amount of surgically induced astigmatism might be helpful to predict outcome of canaloplasty in terms of IOP reduction.

Perimetric measurements with flicker-defined form stimulation in comparison with conventional perimetry and retinal nerve fiber measurements.

PURPOSE: We compared the results of flicker-defined form (FDF) perimetry with standard automated perimetry (SAP) and retinal nerve fiber layer (RNFL) thickness measurements using spectral domain optical coherence tomography (OCT). METHODS: A total of 64 healthy subjects, 45 ocular hypertensive patients, and 97 "early" open-angle glaucoma (OAG) patients participated in this study. Definition of glaucoma was based exclusively on glaucomatous optic disc appearance. All subjects underwent FDF perimetry, SAP, and peripapillary measurements of the RNFL thickness. The FDF perimetry and SAP were performed at identical test locations (G1 protocol). Exclusion criteria were subjects younger than 34 years, SAP mean defect (SAP MD) > 5 dB, eye diseases other than glaucoma, or nonreliable FDF measurements. The correlations between the perimetric data on one hand and RNFL thicknesses on the other hand were analyzed statistically. RESULTS: The age-corrected sensitivity values and the local results from the controls were used to determine FDF mean defect (FDF MD). The FDF perimetry and SAP showed high concordance in this cohort of experienced patients (MD values, R = -0.69, P < 0.001). Of a total of 42 OAG patients with abnormal SAP MD, 38 also displayed abnormal FDF MD. However, FDF MD was abnormal in 28 of 55 OAG patients with normal SAP MD. The FDF MD was significantly (R = -0.61, P < 0.001) correlated with RNFL thickness with a (nonsignificantly) larger correlation coefficient than conventional SAP MD (R = -0.48, P < 0.001). CONCLUSIONS: The FDF perimetry is able to uncover functional changes concurrent with the changes in RNFL thickness. The FDF perimetry may be an efficient functional test to detect early glaucomatous nerve atrophy. (ClinicalTrials.gov number, NCT00494923.).

Longitudinal analysis of progression in glaucoma using spectral-domain optical coherence tomography.

PURPOSE: To compare the longitudinal loss of RNFL thickness measurements by SD-OCT in healthy individuals and glaucoma patients with or without progression concerning optic disc morphology. METHODS: A total of 62 eyes, comprising 38 glaucomatous eyes with open angle glaucoma and 24 healthy controls, were included in the study (Erlangen Glaucoma Registry, NTC00494923). All patients were investigated annually over a period of 3 years by Spectralis SD-OCT measuring peripapillary RNFL thickness. By masked comparative analysis of photographs, the eyes were classified into nonprogressive and progressive glaucoma cases. Longitudinal loss of RNFL thickness was compared with morphological changes of optic disc morphology. RESULTS: Mixed model analysis of annual OCT scans revealed an estimated annual decrease of the RNFL thickness by 2.12 µm in glaucoma eyes with progression, whereas glaucoma eyes without progression in optic disc morphology lost 1.18 µm per year in RNFL thickness (P = 0.002). The rate of change in healthy eyes was 0.60 µm and thereby also significantly lower than in glaucoma eyes with progression (P < 0.001). The intrasession variability of three successive measurements without head repositioning was 1.5 ± 0.7 µm. The loss of mean RNFL thickness exceeded the intrasession variability in 60% of nonprogressive eyes, and in 85% of progressive eyes after 3 years. CONCLUSIONS: LONGITUDINAL MEASUREMENTS OF RNFL THICKNESS USING SD-OCT SHOW A MORE PRONOUNCED REDUCTION OF RNFL THICKNESS IN PATIENTS WITH PROGRESSION COMPARED WITH PATIENTS WITHOUT PROGRESSION IN GLAUCOMATOUS OPTIC DISC CHANGES. (www.clinicaltrials.gov number, NTC00494923.).

Glaucoma diagnostic performance of GDxVCC and spectralis OCT on eyes with atypical retardation pattern.

PURPOSE: To investigate the impact of typical scan score (TSS) on discriminating glaucomatous and healthy eyes by scanning laser polarimetry and spectral domain optical coherence tomography (SD-OCT) in 32 peripapillary sectors. PATIENTS AND METHODS: One hundred two glaucoma patients and 32 healthy controls underwent standard automated perimetry, 24-hour intraocular pressure profile, optic disc photography, GDxVCC, and SD-OCT measurements. For controls, only very typical scans (TSS=100) were accepted. Glaucoma patients were divided into 3 subgroups (very typical: TSS=100; typical: 99≥TSS≥80, atypical: TSS<80). Receiver operating characteristic curves were constructed for mean retinal nerve fiber layer values, sector data, and nerve fiber indicator (NFI). Sensitivity was estimated at ≥90% specificity to compare the discriminating ability of each imaging modality. RESULTS: For discrimination between healthy and glaucomatous eyes with very typical scans, the NFI and inferior sector analyses 26 to 27 demonstrated the highest sensitivity at ≥90% specificity in GDxVCC and SD-OCT, respectively. For the typical and atypical groups, sensitivity at ≥90% specificity decreased for all 32 peripapillary sectors on an average by 10.9% and 17.9% for GDxVCC and by 4.9% and 0.8% for SD-OCT. For GDxVCC, diagnostic performance of peripapillary sectors decreased with lower TSS, especially in temporosuperior and inferotemporal sectors (sensitivity at ≥90% specificity decreased by 55.3% and by 37.8% in the atypical group). CONCLUSIONS: Diagnostic accuracy is comparable for SD-OCT and GDxVCC if typical scans (TSS=100) are investigated. Decreasing TSS is associated with a decrease in diagnostic accuracy for discriminating healthy and glaucomatous eyes by scanning laser polarimetry. NFI is less influenced than the global or sector retinal nerve fiber layer thickness. The TSS score should be included in the standard printout. Diagnostic accuracy of SD-OCT is barely influenced by low TSS.