Robert Lämmer

Automated segmentation of the optic nerve head for diagnosis of glaucoma

Glaucoma is the second most common cause of blindness worldwide. Low awareness and high costs connected to glaucoma are reasons to improve methods of screening and therapy. A well-established method for diagnosis of glaucoma is the examination of the optic nerve head using scanning-laser-tomography. This system acquires and analyzes the surface topography of the optic nerve head. The analysis that leads to a diagnosis of the disease depends on prior manual outlining of the optic nerve head by an experienced ophthalmologist. Our contribution presents a method for optic nerve head segmentation and its validation. The method is based on morphological operations, Hough transform, and an anchored active contour model. The results were validated by comparing the performance of different classifiers on data from a case-control study with contours of the optic nerve head manually outlined by an experienced ophthalmologist. We achieved the following results with respect to glaucoma diagnosis: linear discriminant analysis with 27.7% estimated error rate for automated segmentation (aut) and 26.8% estimated error rate for manual segmentation (man), classification trees with 25.2% (aut) and 22.0% (man) and bootstrap aggregation with 22.2% (aut) and 13.4% (man). It could thus be shown that our approach is suitable for automated diagnosis and screening of glaucoma.

Association of LOXL1 Common Sequence Variants in German and Italian Patients with Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma

PURPOSE Three common sequence variants in the lysyl oxidase-like 1 (LOXL1) gene were recently associated with both pseudoexfoliation (PEX) and pseudoexfoliation glaucoma (PEXG) in populations from Iceland and Sweden. In this study, the genetic association of these variants was investigated in patients with PEX or PEXG of German and Italian descent. METHODS The three LOXL1 single-nucleotide polymorphisms (SNPs), one intronic (rs2165241) and two nonsynonymous coding SNPs (rs1048661: R141L and rs3825942: G153D) were genotyped in a total of 726 unrelated patients with PEX or PEXG (517 Germans and 209 Italians) and 418 healthy subjects who had normal findings in repeated ophthalmic examinations, and a genetic association study was performed. RESULTS Strong association with the three LOXL1 common sequence variants was seen in both the PEX and PEXG patient groups independent of their geographic origin (rs2165241, combined OR = 3.42, P = 1.28 x 10(-40); rs1048661, OR = 2.43, P = 2.90 x 10(-19); and rs3825942, OR = 4.87, P = 8.22 x 10(-23)). Similarly, the common frequent haplotype (G-G) composed of the two coding SNPs (rs1048661 and rs3825942) was strongly associated in PEX and PEXG cohorts of both populations with the disease (combined OR = 3.58, P = 5.21x 10(-43)). CONCLUSIONS Genetic variants in LOXL1 confer risk to PEX in German and Italian populations, independent of the presence of secondary glaucoma, confirming findings in patients from Northern Europe.

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.

Baseline Magnetic Resonance Imaging of the Optic Nerve Provides Limited Predictive Information on Short-Term Recovery after Acute Optic Neuritis

Background In acute optic neuritis, magnetic resonance imaging (MRI) may help to confirm the diagnosis as well as to exclude alternative diagnoses. Yet, little is known on the value of optic nerve imaging for predicting clinical symptoms or therapeutic outcome. Purpose To evaluate the benefit of optic nerve MRI for predicting response to appropriate therapy and recovery of visual acuity. Methods Clinical data as well as visual evoked potentials (VEP) and MRI results of 104 patients, who were treated at the Department of Neurology with clinically definite optic neuritis between December 2010 and September 2012 were retrospectively reviewed including a follow up within 14 days. Results Both length of the Gd enhancing lesion (r = -0.38; p = 0.001) and the T2 lesion (r = -0.25; p = 0.03) of the optic nerve in acute optic neuritis showed a medium correlation with visual acuity after treatment. Although visual acuity pre-treatment was little but nonsignificantly lower if Gd enhancement of the optic nerve was detected via orbital MRI, improvement of visual acuity after adequate therapy was significantly better (0.40 vs. 0.24; p = 0.04). Intraorbitally located Gd enhancing lesions were associated with worse visual improvement compared to canalicular, intracranial and chiasmal lesions (0.35 vs. 0.54; p = 0.02). Conclusion Orbital MRI is a broadly available, valuable tool for predicting the improvement of visual function. While the accurate individual prediction of long-term outcomes after appropriate therapy still remains difficult, lesion length of Gd enhancement and T2 lesion contribute to its prediction and a better short-term visual outcome may be associated with detection and localization of Gd enhancement along the optic nerve.

Optical coherence tomography in patients with a history of juvenile multiple sclerosis reveals early retinal damage

Some 3%−10% of patients with multiple sclerosis (MS) experience disease onset before the age of 18 years (‘early’ onset MS, EOMS). Optical coherence tomography is a non‐invasive method to measure retinal nerve fibre layer thickness (RNFLT) and total macular volume (TMV) and may be useful to differentiate axonal and neuronal damage in the retina of patients with a history of EOMS. Here RNFLT and TMV in EOMS patients after a mean disease duration of 11.6 years were compared with patients with age‐ or disease‐duration‐matched later onset MS (LOMS) and healthy controls (HCs).

ICE-Syndrome: A Case Report of Implantation of a Microbypass Xen Gel Stent After DMEK Transplantation

Purpose: Treatment of glaucoma eyes with iridocorneal endothelial syndrome is complex. Minimally invasive glaucoma surgery, such as one that implements a novel, microinvasive device, known as Xen gel stents, has shown promise in surgical glaucoma treatment and offers a new therapeutic option. Methods: This is a case report. Results: A successful implantation of Xen45 gel stent in a woman with secondary glaucoma due to unilateral iridocorneal endothelial syndrome after descement membrane endothelial keratoplasty operation, and the follow-up are presented. Conclusions: Implantation of Xen gel stents may be a promising option for minimally invasive glaucoma surgery in difficult situations, as low adverse effects, good postsurgery visual acuity and sufficient regulation of intraocular pressure can be seen.

Short-term fluctuation of intraocular pressure is higher in patients with pseudoexfoliation syndrome despite similar mean intraocular pressure: a retrospective case–control study

PurposeHigher levels of short-term fluctuation of intraocular pressure (IOP) are characteristic of pseudoexfoliation syndrome (PEX). However, it is not known whether they are just a side effect of the higher mean intraocular pressure (IOP) or an independent feature. The purpose of this study was to compare short-term fluctuation of IOP between eyes with PEX and control eyes that were matched as closely as possible for mean IOP.MethodsIn this retrospective case–control study, all patients with confirmed PEX were identified from the database of the Erlangen Glaucoma Registry. From the same database, matched control eyes with similar treatment, age, glaucoma stage, and mean IOP were identified. For each patient, data from multiple extended diurnal IOP profiles were available.ResultsSeventy-eight eyes were included in the study (39 with PEX and 39 matched control eyes). Although a very close match was achieved, a small but statistically significant difference in mean IOP was still present, but this did not seem to explain the differences in IOP fluctuation levels. Eyes with PEX had significantly higher short-term IOP fluctuations (SD of IOP and range of IOP).ConclusionsThe higher levels of short-term fluctuation in IOP appear to be an independent feature of PEX and not merely a secondary effect of the higher mean IOP. We suggest that this may have practical implications, even if IOP fluctuation levels should not prove to be an independent risk factor for development/progression of glaucoma, because more frequent measurements are needed in these patients to obtain good estimates of mean IOP and changes in IOP under treatment.

Atypical retardation patterns in scanning laser polarimetry are associated with low peripapillary choroidal thickness.

PURPOSE Scanning laser polarimetry (SLP) results can be affected by an atypical retardation pattern (ARP). One reason for an ARP is the birefringence of the sclera. The purpose of this study was to investigate the influence of the peripapillary choroidal thickness (pChTh) on the occurrence of ARP. METHODS One hundred ten healthy subjects were investigated with SLP and spectral domain OCT. pChTh was measured in B-scan images at 768 positions using semiautomatic software. Values were averaged to 32 sectors and the total peripapillary mean. Subjects were divided into four groups according to the typical scan score (TSS) provided by the GDxVCC: group 1 TSS, 100; group 2 TSS, 90-99; group 3 TSS, 80-89; group 4 TSS, <80. RESULTS Mean pChTh (± SD) in 110 healthy subjects was 141 μm (±49 μm). There was a significant correlation between pChTh and TSS (r = 0.608; P < 0.001). In TSS groups 1 to 4, mean pChTh was 168 μm (±38 μm), 148 μm (± 48 μm), 119 μm (±35 μm), and 92 (±42 μm). Mean pChTh of TSS groups 3 and 4 was significantly lower than that of TSS group 1 (P < 0.001). CONCLUSIONS Low values of TSS resulting from the appearance of ARP in SLP are associated with low peripapillary choroidal thickness. Reduced choroidal thickness may result in an increased amount of confounding light getting to the SLP light detectors.

Automated Segmentation of the Optic Nerve Head for Glaucoma Diagnosis

The diagnosis of glaucoma is closely associated with a morphological change in the optic nerve head (ONH), which can be examined with a scanning laser ophthalmoskop (Heidelberg Retina Tomograph). In this contribution a method for automated segmentation of the external margin of the ONH is presented. The method is based on morphological operations, Hough transform and Active Contours. The method was compared with a manually outlined margin on a subset of 159 subjects from the Erlangen Glaucoma Register. The correct classification rate was estimated to be 77.8% when using a tree-based classificator. This result is comparable with the estimated rate based on a manual outlining of the ONH.

Überschwellige periphere Stimulation bei präperimetrischen Glaukomen

BACKGROUND AND PURPOSE Early glaucomatous visual field defects can occur outside the central 30 degrees , which is usually examined in perimetric tests used for glaucoma diagnosis and screening. This study aimed to evaluate the diagnostic value of peripheral suprathreshold stimulation in open angle glaucoma before the development of reproducible visual field damage in standard 30 degrees automatic white-on-white perimetry. METHODS A total of 352 eyes of 352 patients (ages 35-69 years; visual acuity 0.8 or better) from the Erlanger Glaucoma Registry were included in this study. They were divided into two groups: normal eyes and preperimetric glaucoma. All patients underwent a standardized glaucoma examination including Octopus 500EZ static perimetry (G1 program, all three phases); 95 eyes of 95 patients also received a 135-point suprathreshold test pattern of the Humphrey Field Analyzer (model 750i) for detecting peripheral visual field defects. Sensitivity and specificity were calculated for any single test point in phase 3 of the G1 test pattern and the Humphrey 135-point pattern. A score was calculated, and cluster analysis was performed. RESULTS In 33 of 176 (18.8%) eyes with preperimetric glaucoma, the score was 3 or higher in phase 3 of the G1 program (normal eyes: 19 of 196; 9.7%). For both examination modalities, the highest sensitivity was found in test locations in the superior nasal midperiphery, corresponding to neuroretinal rim loss predominantly in the inferotemporal sector in early glaucomatous optic disc atrophy. CONCLUSION Positive test results using suprathreshold stimulation in the midperiphery can be found in patients with preperimetric glaucoma at a significantly higher frequency than in normal subjects. Longitudinal studies will show whether such tests can be useful for predicting perimetric manifestation of the disease.