Ralf P. Tornow

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.

Retinal Nerve Fiber Layer Segmentation on FD-OCT Scans of Normal Subjects and Glaucoma Patients

Automated measurements of the retinal nerve fiber layer thickness on circular OCT B-Scans provide physicians additional parameters for glaucoma diagnosis. We propose a novel retinal nerve fiber layer segmentation algorithm for frequency domain data that can be applied on scans from both normal healthy subjects, as well as glaucoma patients, using the same set of parameters. In addition, the algorithm remains almost unaffected by image quality. The main part of the segmentation process is based on the minimization of an energy function consisting of gradient and local smoothing terms. A quantitative evaluation comparing the automated segmentation results to manually corrected segmentations from three reviewers is performed. A total of 72 scans from glaucoma patients and 132 scans from normal subjects, all from different persons, composed the database for the evaluation of the segmentation algorithm. A mean absolute error per A-Scan of 2.9 µm was achieved on glaucomatous eyes, and 3.6 µm on healthy eyes. The mean absolute segmentation error over all A-Scans lies below 10 µm on 95.1% of the images. Thus our approach provides a reliable tool for extracting diagnostic relevant parameters from OCT B-Scans for glaucoma diagnosis.

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.).

Wavelet denoising of multiframe optical coherence tomography data

We introduce a novel speckle noise reduction algorithm for OCT images. Contrary to present approaches, the algorithm does not rely on simple averaging of multiple image frames or denoising on the final averaged image. Instead it uses wavelet decompositions of the single frames for a local noise and structure estimation. Based on this analysis, the wavelet detail coefficients are weighted, averaged and reconstructed. At a signal-to-noise gain at about 100% we observe only a minor sharpness decrease, as measured by a full-width-half-maximum reduction of 10.5%. While a similar signal-to-noise gain would require averaging of 29 frames, we achieve this result using only 8 frames as input to the algorithm. A possible application of the proposed algorithm is preprocessing in retinal structure segmentation algorithms, to allow a better differentiation between real tissue information and unwanted speckle noise.

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.).

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).

Influence of atypical retardation pattern on the peripapillary retinal nerve fibre distribution assessed by scanning laser polarimetry and optical coherence tomography

Aim To investigate the influence of atypical retardation pattern (ARP) on the distribution of peripapillary retinal nerve fibre layer (RNFL) thickness measured with scanning laser polarimetry in healthy individuals and to compare these results with RNFL thickness from spectral domain optical coherence tomography (OCT) in the same subjects. Methods 120 healthy subjects were investigated in this study. All volunteers received detailed ophthalmological examination, GDx variable corneal compensation (VCC) and Spectralis-OCT. The subjects were divided into four subgroups according to their typical scan score (TSS): very typical with TSS=100, typical with 99≥TSS ≥91, less typical with 90≥TSS ≥81 and atypical with TSS ≤80. Deviations from very typical normal values were calculated for 32 sectors for each group. Results There was a systematic variation of the RNFL thickness deviation around the optic nerve head in the atypical group for the GDxVCC results. The highest percentage deviation of about 96% appeared temporal with decreasing deviation towards the superior and inferior sectors, and nasal sectors exhibited a deviation of 30%. Percentage deviations from very typical RNFL values decreased with increasing TSS. No systematic variation could be found if the RNFL thickness deviation between different TSS-groups was compared with the OCT results. Conclusions The ARP has a major impact on the peripapillary RNFL distribution assessed by GDx VCC; thus, the TSS should be included in the standard printout.

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.

Non-mydriatic video ophthalmoscope to measure fast temporal changes of the human retina

The analysis of fast temporal changes of the human retina can be used to get insight to normal physiological behavior and to detect pathological deviations. This can be important for the early detection of glaucoma and other eye diseases. We developed a small, lightweight, USB powered video ophthalmoscope that allows taking video sequences of the human retina with at least 25 frames per second without dilating the pupil. Short sequences (about 10 s) of the optic nerve head (20° x 15°) are recorded from subjects and registered offline using two-stage process (phase correlation and Lucas-Kanade approach) to compensate for eye movements. From registered video sequences, different parameters can be calculated. Two applications are described here: measurement of (i) cardiac cycle induced pulsatile reflection changes and (ii) eye movements and fixation pattern. Cardiac cycle induced pulsatile reflection changes are caused by changing blood volume in the retina. Waveform and pulse parameters like amplitude and rise time can be measured in any selected areas within the retinal image. Fixation pattern ΔY(ΔX) can be assessed from eye movements during video acquisition. The eye movements ΔX[t], ΔY[t] are derived from image registration results with high temporal (40 ms) and spatial (1,86 arcmin) resolution. Parameters of pulsatile reflection changes and fixation pattern can be affected in beginning glaucoma and the method described here may support early detection of glaucoma and other eye disease.

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.