Anselm G. Jünemann

Improving glaucoma diagnosis by the combination of perimetry and HRT measurements

PurposeThe aim of this study was to determine, whether the combination of morphologic data of the optic nerve head and visual field (VF) data would improve diagnosis of glaucoma, on the basis of the measurements alone. Patients and MethodsEighty-eight perimetric glaucomatous and 88 normal optic discs from the Erlangen Glaucoma Registry were matched for age. All normals and patients were examined in a standardized manner (Slitlamp biomicroscopy, gonioscopy, 24 h-applanation tonometry, automated VF testing, 15-degree optic disc stereographs, and Heidelberg Retina Tomograph (HRT)-scanning of the optic disc). The HRT variables were calculated in 4 optic disc sectors. All variables were calculated with the softwares standard reference plane. To gain the same allocation of sectors as provided by the HRT software, the VF responses were averaged within 4 sectors. Classification results of these VF responses were compared with the summarized results within 4 sectors. Six different combinations of morphologic and VF data were used to assess their suitability to diagnose the disease. HRT measurements, and the standard output of the Octopus (HRT/PERI1), HRT measurements and the summarized sectors and their standard deviations (HRT/PERI2), HRT measurements, standard output of the octopus and the summarized sectors and their standard deviations (HRT/PERI1/PERI2), standard output of the Octopus (PERI1), summarized sectors of the Octopus and their standard deviations (PERI2) and HRT measurements. To assess the diagnostic value of the different data sets machine learning classifiers, stabilized linear discriminant analysis, classification trees, bagging, and double-bagging were applied. ResultsCombination of morphologic and VF data improved the automated classification rules. The accuracy to diagnose glaucoma just by VF and HRT indices was maximized for double-bagging using both diagnostic tools. An estimated misclassification probability of less than 0.07 could be achieved for the primary open angle glaucoma patients combining HRT and VF sectors by double bagging. So highest sensitivity was 95% and specificity 91%, achieved by double-bagging and combination of HRT, PERI1, and PERI2. ConclusionsThe combination of optic disc measurements and VF data could not only improve glaucoma diagnosis in future, but could also help to find an objective way to diagnose glaucomatous optic atrophy. The limitation of the topographic relationship between structure and function is the individual variability of the optic disc morphology and the subjective variability of VF testing.

New Glaucoma Classification Method based on Standard Heidelberg Retina Tomograph Parameters by Bagging Classification Trees

PURPOSE In this article we propose and evaluate nonparametric tree classifiers that can handle non-normal data and a large number of possible predictors using the full set of standard Heidelberg Retina Tomograph measurements for classifying glaucoma. METHODS The classifiers were trained and tested using standard Heidelberg Retina Tomograph parameters from examinations of 98 subjects with glaucoma and 98 normal subjects of the Erlangen Glaucoma Registry. All patients and control subjects were evaluated by 15 degrees -optic disc stereographs, Heidelberg Retina Tomograph measurements, standard computerized white-in-white perimetry, and 24-hour-intraocular pressure profiles. The subjects were matched by age and sex. Standard classification trees as well as bagged classification trees were used. The classification outcome of the trees was compared with the classification by two published linear discriminant functions based on Heidelberg Retina Tomograph variables with respect to their cross-validated misclassification error. RESULTS The bagged classification tree had the lowest misclassification error estimate of 14.8% with a sensitivity of 81.6% at a specificity of 88.8%. The cross-validated error rates of the two linear discriminant function procedures were 20.4% (sensitivity 82.6%, specificity 76.7%) and 20.6% (sensitivity 81.4%, specificity 77.3%) for our set of observations. Bagged classification trees were able to reduce the misclassification error of glaucoma classification. CONCLUSIONS Bagged classification trees promise to be a new and efficient approach for glaucoma classification using morphometric 2- and 3-dimensional data derived from the Heidelberg Retina Tomograph, taking into account all given variables.

Glaucoma detection with frequency doubling perimetry and short-wavelength perimetry

PurposeThe aim of this analysis was to evaluate the diagnostic usefulness of frequency doubling technology (FDT) perimetry and short-wavelength perimetry (SWAP). Moreover, to study a combination of both methods using the machine-learning technique double-bagging, which was recently established in glaucoma research. MethodsForty-three patients with “preperimetric” open-angle glaucoma (glaucomatous optic disc atrophy and no visual field defect in standard perimetry), 26 patients with “perimetric” open angle glaucoma (glaucomatous optic disc atrophy and visual field defect in standard perimetry), and 40 control subjects had FDT screening (protocol: C-20-5) and SWAP (Octopus 101, G2). Criteria for exclusion were color vision abnormalities, media opacities, and an age below 31 years or above 63 years. Data of 1 eye of each patient and control subject entered the statistical evaluation. A point wise evaluation of the diagnostic power of SWAP values was performed to derive spatial patterns of visual field loss. A double-bagging machine-learning algorithm was used to train classification rules on the basis of a combination of FDT scores and nerve fiber related visual field losses in SWAP. The diagnostic power of the classifiers was compared regarding their misclassification error rates and area under the receiver-operating characteristic curve. ResultsThe combination of FDT perimetry and SWAP yielded better diagnostic results compared with FDT or SWAP separately. The overall estimated misclassification error rate of the combined classifier was 24% compared with 28% for both SWAP and FDT perimetry. Regarding the estimated performance of classifier at high specificities (>80%) in control eyes as measured by the partial area under the receiver-operating characteristic curve, the combination of both instruments is also superior to the individual instruments. ConclusionsA combination of SWAP and FDT perimetry, each targeting different neuronal pathways, may improve early glaucoma detection.

Association between localized visual field losses and thickness deviation of the nerve fiber layer in glaucoma.

Purpose:To perform a correlation between morphology and function by studying local perimetric field losses and thickness reduction of the nerve layer in corresponding areas. Method:Forty-seven patients with “preperimetric” open-angle glaucoma, 95 patients with “perimetric” open-angle glaucoma, and 75 control subjects had perimetric (Octopus) and polarimetric measurements. Criteria for exclusion: optic discs larger than 4 mm2, media opacities, polarimetric hourglass pattern in the macular image. Thickness values of the retinal nerve fiber layer were determined in 14 upper and 14 lower sectors (10° each) as well as nasally and temporally (40° each) as provided from the GDx (software version 4000). The healthy control subjects served to determine age-corrected thickness deviation in all sectors. Analyses were calculated in eight nerve fiber bundle related areas. Due to non-linear relationships between perimetric defects and corresponding thickness deviation non-parametric tests were used. Results:Localized visual field defects in the present perimetric patients were highest in upper and lower visual field areas abutting the nasal meridian. Thickness loss of nerve fiber layer however was highest in more circumferential upper and lower nerve fiber bundles. Correlations between local mean defects and deviation of the retinal nerve fiber layer thickness from normals showed a clear association for corresponding areas. The correlation coefficients were significant (P < 0.01) for all arcuate superior and inferior visual field zones except horizontally and not for the area of the lower nasal step. Conclusion:The present correspondence map indicates that focal perimetric defects can be identified best polarimetrically if they occur in the arcuate bundles of the visual field. A lack of correspondence was observed in the area of the papillo-macular bundle.

Combined evaluation of frequency doubling technology perimetry and scanning laser ophthalmoscopy for glaucoma detection using automated classification.

PurposeTo develop a diagnostic setup with classification rules for combined analysis of morphology [Heidelberg Retina Tomograph (HRT)] and function [frequency doubling technology (FDT) perimetry] measurements. MethodsWe used 2 independent case-control studies from the Erlangen eye department as learning and test data for automated classification using random forests. One eye of 334 open angle glaucoma patients and 254 controls entered the study. All individuals underwent HRT scanning tomography of the optic disc, FDT screening, conventional perimetry, and evaluation of fundus photographs. Random forests were learned on individuals of the Erlangen glaucoma registry (102 preperimetric patients, 130 perimetric patients, 161 controls). The classification performances of random forests and built-in classifiers were examined by receiver operator characteristic analysis on an independent second cohort of individuals (47 preperimetric patients, 55 perimetric patients, 93 controls). ResultsHRT measurements had a higher diagnostic power for early glaucomas and FDT perimetry for glaucoma patients with visual field loss. A combination of all parameters using automated classification was superior to single tests in comparison to the diagnostic instrument with the higher diagnostic power in the respective group. Highest sensitivities at a fixed specificity (95%) in the patients of the present test population were: HRT=32%, FDT=19%, combined analysis=47% in preperimetric patients and HRT=76%, FDT=89%, combined analysis=96% in perimetric patients. ConclusionsThe feasibility of machine learning for medical diagnostic assistance could be demonstrated in patients from 2 independent study populations. A predictive model using automated classification is able to combine the advantages of morphology and function, resulting in a higher diagnostic power for glaucoma detection.

Prospective case control study on genetic assocation of apolipoprotein epsilon2 with intraocular pressure.

Glaucomas are a leading cause of blindness throughout the world. This group of diseases has a common characteristic: degeneration of the optic nerve that is usually associated with increased intraocular pressure (IOP). Increased IOP is one of the major risk factors for developing glaucomatous damage, whereby the loss of retinal ganglion cells is the typical pathological finding. However, the pathophysiology of pressure induced glaucomatous optic neuropathy remains unclear and is still a matter for debate. Genome scans have been performed to identify the genomic locations of glaucoma susceptibility genes.1 Apolipoprotein E (APOE), a lipid transporting protein produced in the liver and brain, is unique among apolipoproteins in that it has particular relevance to nervous tissue. It is involved in the mobilisation and redistribution of cholesterol in repair, growth, and maintenance of myelin and neuronal membranes during development or after injury. Recently it has been shown that the APOE e4 allele is associated with elevated risk of normal tension glaucoma.2 The APOE e2 allele was shown to be significantly associated with an elevated risk of age related macular degeneration (AMD).3 This prospective case control study included 32 controls (IOP 21 mm Hg, …

Visual evoked potentials of the blue-sensitive pathway under cold provocation in normals and glaucomas.

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°C to 5°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 μV, amplitude following two minutes of ice exposition: 3.52 μV; 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.

Objective perimetry using a four-channel multifocal VEP system: correlation with conventional perimetry and thickness of the retinal nerve fibre layer

Purpose There is evidence that multifocal visual evoked potentials (VEPs) can be used as an objective tool to detect visual field loss. The aim of this study was to correlate multifocal VEP amplitudes with standard perimetry data and retinal nerve fibre layer (RNFL) thickness. Method Multifocal VEP recordings were performed with a four-channel electrode array using 58 stimulus fields (pattern reversal dartboard). For each field, the recording from the channel with maximal signal-to-noise ratio (SNR) was retained, resulting in an SNR optimised virtual recording. Correlation with RNFL thickness, measured with spectral domain optical coherence tomography and with standard perimetry, was performed for nerve fibre bundle related areas. Results The mean amplitudes in nerve fibre related areas were smaller in glaucoma patients than in normal subjects. The differences between both groups were most significant in mid-peripheral areas. Amplitudes in these areas were significantly correlated with corresponding RNFL thickness (Spearman R=0.76) and with standard perimetry (R=0.71). Conclusion The multifocal VEP amplitude was correlated with perimetric visual field data and the RNFL thickness of the corresponding regions. This method of SNR optimisation is useful for extracting data from recordings and may be appropriate for objective assessment of visual function at different locations. Trial registration number This study has been registered at http://www.clinicaltrials.gov (NCT00494923).

Surgical Management of Traumatic Retinal Detachment with Primary Vitrectomy in Adult Patients

Purpose. To evaluate functional and anatomical results of pars plana vitrectomy (PPV) in the retinal detachment (RD) followed by severe eye trauma. Methods. Retrospective analysis of medical records of forty-one consecutive patients treated with 23-gauge PPV due to traumatic RD. Age, gender, timing of PPV, visual acuity, and presence of intraocular foreign body (IOFB) and proliferative vitreoretinopathy (PVR) were included in the analysis. Results. Mean age of patients was 47 years; the majority of patients were men (88%). Closed globe injury was present in 21 eyes and open globe injury in 20 eyes (IOFB in 13 eyes, penetration injury in 4 eyes, and eye rupture in 3 eyes). Mean follow-up period was 14 months; mean timing of PPV was 67 days. Twenty-seven (66%) eyes had a functional success; 32 eyes (78%) had anatomical success. As a tamponade silicone oil was used in 33 cases and SF6 gas in 8 cases. Conclusions. Severe eye injuries are potentially devastating for vision, but vitreoretinal surgery can improve anatomical and functional outcomes. Among analysed pre- and intra- and postoperative factors, absence of PVR, postoperative retinal attachment, and silicone oil as a tamponade were related to significantly improved visual acuity.

Fettstoffwechselstörungen und Glaukom

Endothelial dysfunction and vascular dysregulation play a role in the multifactorial pathogenesis of glaucomatous optic nerve atrophy. Dyslipidaemia as a risk factor for endothelial dysfunction is associated with glaucoma and cardiovascular morbidity and mortality. In additional to a genetic disposition, a potential mechanism for the pathogenesis of endothelial dysfunction could be an additive effect of several risk factors, like dyslipidaemia, smoking, arterial hypertension, diabetes and hyperhomocysteinaemia. This paper reviews the literature concerning the association between dyslipidaemia and glaucomatous disease and explains the possible role of dyslipidaemia for the pathogenesis and progression of glaucoma. The role of exogeneous modifiable risk factors for prevention and therapy of glaucoma and their neutralisation by changing life style like weight reduction, modifications of nutrition and physical activity, are discussed.