Robert Laemmer

Retinal nerve fiber layer thickness in normals measured by spectral domain OCT.

PurposeTo determine normal values for peripapillary retinal nerve fiber layer thickness (RNFL) measured by spectral domain Optical Coherence Tomography (SOCT) in healthy white adults and to examine the relationship of RNFL with age, gender, and clinical variables. Patients and MethodsThe peripapillary RNFL of 170 healthy patients (96 males and 74 females, age 20 to 78 y) was imaged with a high-resolution SOCT (Spectralis HRA+OCT, Heidelberg Engineering) in an observational cross-sectional study. RNFL thickness was measured around the optic nerve head using 16 automatically averaged, consecutive circular B-scans with 3.4-mm diameter. The automatically segmented RNFL thickness was divided into 32 segments (11.25 degrees each). One randomly selected eye per subject entered the study. ResultsMean RNFL thickness in the study population was 97.2±9.7 &mgr;m. Mean RNFL thickness was significantly negatively correlated with age (r=−0.214, P=0.005), mean RNFL decrease per decade was 1.90 &mgr;m. As age dependency was different in different segments, age-correction of RNFL values was made for all segments separately. Age-adjusted RNFL thickness showed a significant correlation with axial length (r=−0.391, P=0.001) and with refractive error (r=0.396, P<0.001), but not with disc size (r=0.124). ConclusionsNormal RNFL results with SOCT are comparable to those reported with time-domain OCT. In accordance with the literature on other devices, RNFL thickness measured with SOCT was significantly correlated with age and axial length. For creating a normative database of SOCT RNFL values have to be age adjusted.

Correlation between Local Glaucomatous Visual Field Defects and Loss of Nerve Fiber Layer Thickness Measured with Polarimetry and Spectral Domain OCT

PURPOSE To study the correlation between local perimetric field defects and glaucoma-induced thickness reduction of the nerve layer measured in the peripapillary area with scanning laser polarimetry (SLP) and spectral domain optical coherence tomography (SOCT) and to compare the results with those of a theoretical model. METHODS The thickness of the retinal nerve fiber layer was determined in 32 sectors (11.25 degrees each) by using SLP with variable cornea compensation (GDxVCC; Laser Diagnostics, San Diego, CA) and the newly introduced high-resolution SOCT (Spectralis; Heidelberg Engineering, Heidelberg, Germany). Eighty-eight healthy subjects served as control subjects, to determine the thickness deviation in patients with glaucoma. The relationship between glaucomatous nerve fiber reduction and visual field losses was calculated in six nerve fiber bundle-related areas. Sixty-four patients at different stages of open-angle glaucoma and 26 patients with ocular hypertension underwent perimetry (Octopus G1; Haag-Streit, Köniz, Switzerland) and measurements with the two morphometric techniques. RESULTS Sector-shaped analyses between local perimetric losses and reduction of the retinal nerve fiber layer thickness showed a significant association for corresponding areas except for the central visual field in SLP. Correlation coefficients were highest in the area of the nasal inferior visual field (SOCT, -0.81; SLP, -0.57). A linear model describes the association between structural and functional damage. CONCLUSIONS Localized perimetric defects can be explained by reduced nerve fiber layer thickness. The data indicate that the present SOCT is useful for determining the functional-structural relationship in peripapillary areas and that association between perimetric defects and corresponding nerve fiber losses is stronger for SOCT than for the present SLP. (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.).

Comparison of scanning laser polarimetry and optical coherence tomography in quantitative retinal nerve fiber assessment.

PurposeTo investigate the relationship between retinal nerve fiber layer (RNFL) measurements in corresponding areas obtained with scanning laser polarimetry and optical coherence tomography and to compare their discriminating ability in the diagnosis of preperimetric and perimetric glaucoma. Patients and MethodsThree hundred eighty-six subjects—57 healthy controls, 145 ocular hypertensive patients, 89 with preperimetric glaucoma, and 95 with perimetric glaucoma—were recruited from the Erlangen Glaucoma Registry. Perimetry, 24-hours intraocular pressure profile, stereographic optic disc slides, optical coherence tomography StratusOCT, and scanning laser polarimetry GDx VCC (Carl Zeiss Meditec, Inc, Dublin, CA) were performed in all patients. Receiver operating characteristic (ROC) curves were constructed for mean RNFL values, sector data, and indices. Sensitivity was estimated at ≥90% and ≥80% of specificity to compare the discriminating ability of each imaging modality. ResultsFor discrimination between glaucomatous and healthy eyes in GDx VCC the nerve fiber index demonstrated the largest area under the ROC curve (AUROC) (0.962±0.013), whereas in StratusOCT the largest AUROC (0.986±0.006) was found in the inferior quadrant. For preperimetric glaucoma detection the nerve fiber index achieved the largest AUROC (0.783±0.037). In contrast, the total RNFL average obtained using StratusOCT showed the largest AUROC (0.904±0.025). Bland-Altman plots showed good agreement between both instruments. ConclusionsBoth the GDx VCC and StratusOCT demonstrate increasing RNFL loss with advanced glaucomatous damage and were comparable in the diagnosis of perimetric glaucoma. Preperimetric glaucomatous damage may be better assessed by StratusOCT.

Quantification of neuroretinal rim loss using digital planimetry in long-term follow-up of normals and patients with ocular hypertension.

PurposeThe purpose of this study was to investigate if digital planimetry is appropriate for quantification of neuroretinal rim loss in patients with ocular hypertension (OHT) and if there is an age-related neuroretinal rim loss in normals. Patients and MethodsFifty-six patients with OHT without optic disc change, 13 patients with OHT and conversion to early glaucoma during follow-up and 42 age-matched controls were recruited from the Erlangen Glaucoma Registry. Annually, all patients underwent complete ophthalmologic examination including detailed diagnostic testing concerning glaucoma. Gold standard for morphologic evaluation of the optic nerve head was the semiquantitative 2-dimensional-method described by Jonas. Optic disc images from baseline and after 5 or 10 years follow-up were used for digital planimetry. Optic disc area and cup area were measured using commercial software: Soft Imaging System analysis. The investigator was masked for diagnosis and time point of examination. ResultsMean neuroretinal rim loss was 0.36% per year in controls, 0.54% per year in patients with OHT without progressive disease, and 0.95% per year in OHT and conversion. ConclusionsNeuroretinal rim loss was highest in the group of OHT with conversion to early glaucoma during follow-up. In the control group we detected a very low mean neuroretinal rim loss during 10-year follow-up. In ocular hypertensive patients without progressive disease mean neuroretinal rim loss was approximately twice compared with normals.

Comparison of Bruch's Membrane Opening Minimum Rim Width and Peripapillary Retinal Nerve Fiber Layer Thickness in Early Glaucoma Assessment

PURPOSE To compare the diagnostic value of Bruchs membrane opening minimum rim width (BMO-MRW) and retinal nerve fiber layer thickness (RNFLT) in patients with ocular hypertension, preperimetric, and perimetric glaucoma. METHODS One hundred eighty-one eyes consisting of 40 healthy controls, 41 ocular hypertensive subjects, 50 subjects with preperimetric glaucoma and 50 with perimetric glaucoma were included. One randomly selected eye was included. All patients underwent slit-lamp examination, funduscopy, achromatic perimetry, and 24-hour IOP profile. Bruchs membrane opening-MRW and RNFLT (3 peripapillary circle scans, 12°/14°/16°) data were obtained using spectral domain optical coherence tomography. Areas under the receiver operating characteristics curves (AUROC) as well as sensitivity at fixed specificity were computed globally and for six vertical split sectors. Venn diagrams were plotted to identify patients that were diagnosed by one of the two parameters only. RESULTS For RNFLT the smallest circle diameter showed highest diagnostic accuracy and was used for comparison with BMO-MRW. Distinguishing perimetric glaucoma, RNFLT and BMO-MRW showed comparable AUROCs in global (AUROC, 95% confidence interval: 0.954, 0.911-0.996 and 0.929, 0.872-0.986) and sectoral (0.929, 0.877-0.981 and 0.946, 0.904-0.996) analysis. For preperimetric glaucoma BMO-MRW and RNFLT also demonstrated comparable performance in global (0.839, 0.757-0.921 and 0.821, 0.731-0.912) and sectoral (0.860, 0.782-0.938 and 0.835, 0.750-0.920) analysis. When identifying ocular hypertensive eyes AUROCs were lower for global RNFLT and BMO-MRW (0.493, 0.365-0.621 and 0.562, 0.433-0.691). A combined parameter showed an AUROC of 0.959, 0.921 to 0.996 for perimetric and 0.849, 0.770 to 0.929 for preperimetric glaucoma. CONCLUSIONS Bruchs membrane opening-MRW and RNFLT are comparably useful parameters for discrimination of preperimetric and perimetric glaucomatous eyes and show potential to assist each other in glaucoma diagnosis. (www.ClinicalTrials.gov number, NTC00494923; Erlangen Glaucoma Registry.).

Visualization of changes of the iris configuration after peripheral laser iridotomy in primary melanin dispersion syndrome using optical coherence tomography.

Pigment or melanin dispersion syndrome is characterized by radial iris transillumination defects, retrocorneal Krukenberg spindle, and dense trabecular pigmentation. Reverse pupillary block has been presumed as one possible pathogenetic mechanism for backward bowing of the iris leading to iris-zonular rubbing and distribution of melanin granules in the anterior chamber. Laser iridotomy is recommended as a treatment to prevent further melanin dispersion and development of pigmentary glaucoma. The effect of Nd:YAG laser iridotomy as a prophylactic and potentially causal treatment in melanin dispersion syndrome can be easily visualized by optical coherence tomography as a fast and noncontact procedure.

Influence of glaucomatous damage and optic disc size on glaucoma detection by scanning laser tomography.

PurposeTo investigate the impact of glaucomatous damage and optic disc size on different automated Heidelberg Retina Tomograph classifications for discriminating glaucoma and healthy controls. Patients and MethodsTwo hundred seventy-three glaucoma patients and 276 healthy controls were recruited from the Erlangen Glaucoma Registry. Standard static white on white perimetry, 24-hour intraocular pressure profile, stereographic optic disc slides, and scanning laser tomography were performed in all patients and controls. The effect of glaucoma stage and disc size on the diagnostic accuracy was evaluated using receiver operating characteristic curves. Results of the Glaucoma Probability Score were compared with other recently described multivariate classifications. ResultsAreas under the receiver operating characteristic curves for discrimination between glaucoma and healthy eyes of the overall classification by Glaucoma Probability Score, Moorfields regression analysis, Bathija, Iester, Mikelberg, and Mardin increased from 0.71, 0.65, 0.70, 0.67, 0.65, and 0.63 for early glaucoma (Jonas: stage I) to 0.96, 0.95, 0.94, 0.94, 0.92, and 0.88 for advanced glaucomatous damage (Jonas: stage IV). Best performance of discrimination between glaucoma and healthy eyes using area under the receiver operating characteristic curves were observed for medium-sized discs (2.1 to 2.49 mm2) and worst performance for large optic discs (>3.1 mm2). Glaucoma Probability Score classification was superior to other investigated classifications in most of the investigated subgroups. ConclusionsThe diagnostic accuracy of all classifications depends on the optic disc size and the glaucoma stage. Glaucoma Probability Score showed a better diagnostic performance than Moorfields regression analysis and was similar to that of Bathija.

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, NTC00494923).

Analysis of Visual Appearance of Retinal Nerve Fibers in High Resolution Fundus Images: A Study on Normal Subjects

The retinal ganglion axons are an important part of the visual system, which can be directly observed by fundus camera. The layer they form together inside the retina is the retinal nerve fiber layer (RNFL). This paper describes results of a texture RNFL analysis in color fundus photographs and compares these results with quantitative measurement of RNFL thickness obtained from optical coherence tomography on normal subjects. It is shown that local mean value, standard deviation, and Shannon entropy extracted from the green and blue channel of fundus images are correlated with corresponding RNFL thickness. The linear correlation coefficients achieved values 0.694, 0.547, and 0.512 for respective features measured on 439 retinal positions in the peripapillary area from 23 eyes of 15 different normal subjects.