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IMAGE Meeting 2013 Vienna PROGRAMME AND ABSTRACTS

Venue and Hotel for the meeting

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WEDNESDAY: get-together-dinner

Meet at 19.40 in hotel lobby (we will have a 15 min walk to the restaurant) For those who missed to meet in the lobby Dinner venue: Restaurant Schnattl

Address: 1080 Wien, Lange Gasse 40 (+43 1 4053400)

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THURSDAY: 9.00 – 13.00: meeting 13.00 – 14.00: lunch 14.00 – 17.30: meeting 19.30: dinner (meet at 19.00 in hotel lobby)

We will have a 25 min walk to the restaurant

For those who missed to meet in the lobby Dinner venue: Restaurant Le Ciel, Grand Hotel Wien

Address: 1010 Wien, Kärntner Ring 9 (+43 1 515 80 9100)

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…or by public transport: Take the tramway Nr. 1 or 71 at Schottenring, exit at the opera,

then 5 minutes walk to the restaurant along the Ringstraße.

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FRIDAY:

8.30 – 12.30: meeting 13.00 – 14.00: lunch 14.30 – 18.00: Guided Vienna City Tour (optional)

Meet at 14.20 in hotel lobby

Our host in Vienna will be Clemens Vass (clemens.vass@meduniwien.ac.at; mobile phone: + 43676 5104678) You may also try to contact Hans Lemij (hlemij@me.com; mobile phone +31655863578).

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Comparison of birefringence-related data between scanning laser polarimetry (GDx) and polarization sensitive optical coherence tomography (PS-OCT). Clemens Vass1, Ivania Pereira1, Stefan Zotter2, Stephan Holzer1, Hemma Resch1, Michael Pircher2; Christoph Hitzenberger2 1. Dept of Ophthalmology, Medical University of Vienna, Vienna, Austria. 2. Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria. Purpose: To compare the retardation of the retinal nerve fiber layer (RNFL) measured with the scanning laser polarimeter GDx-VCC and GDx-ECC (Carl Zeiss Meditec Inc.) with the retardation as measured with polarization sensitive optical coherence tomography (PS-OCT). Methods: A sample of 8 healthy volunteers, 13 glaucoma suspects and 5 early glaucoma patients underwent complete ophthalmologic examination, including visual field testing, GDx-VCC and GDx-ECC and PS-OCT. Early glaucoma was defined as glaucomatous optic neuropathy with a visual field mean deviation (VF-MD) of -4 dB or better. The definition of glaucoma suspect was based on the suspect appearance of the optic disc while VF was normal. PS-OCT was measured with a system operating at 70kHz A-scan rate (scan angle 30°x30° or 40°x40°, scan pattern 1024x250 A-scans). We compared the average retardation of the superior and inferior sectors. The thickness values of the GDx were converted to degree of retardation for comparison using the published fixed conversion factor. When converting the data we furthermore took into account for the different wavelengths of the GDx and our PS-OCT. Results: For the mean values (deg.) and standard deviations of the three different measurements please see the table. For GDx-ECC, GDx-VCC and PS-OCT we found statistically significant differences between the healthy and the suspect groups (p<0.05). There was also a small but statistically significant difference between the retardation found with the GDx and the PS-OCT, the latter giving slightly higher values (p<0.05). Healthy Suspects Early glaucoma Age 49.5 60.2 59.9 PS-OCT superior 20.84 (±2.35) 17.36 (±3.68) 16.71 (±6.60) PS-OCT inferior 22.36 (±1.80) 18.37 (±3.30) 16.94 (±4.40) GDx-ECC superior 19.01 (±1.20) 16.06 (±1.60) 14.87 (±4.05) GDx-ECC inferior 18.57 (±2.07) 15.34 (±2.08) 13.14 (±2.64) GDx-VCC superior 19.53 (±0.93) 16.22 (±1.71) 14.98 (±4.05) GDx-VCC inferior 19.22 (±2.23) 15.53 (±2.26) 12.86 (±3.02) Conclusions: The retardation values given by the GDx and the PS-OCT are comparable as are the differences between the groups. !

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Doppler OCT

Leopold Schmetterer

Department of Clinical Pharmacology, Center of Medical Physics and Biomedcial Engineering, Medical University of Vienna, Vienna, Austria

Optical coherence tomography (OCT) has become a standard tool for assessing optic disc morphology and retinal nerve fiber layer thickness in glaucoma. In the recent years several functional extensions of the technique have been proposed. One approach is Doppler OCT, which combines the principles of laser Doppler velocimetry with those of OCT. This yields in principle information on both, retinal blood velocity and retinal vessel diameter. We developed a technique based on diameter measurements with a fundus-camera based system and bi-directional Fourier Domain Doppler OCT. Using this technique it is possible to measure total blood flow in both arteris and veins. Comparison of velocity data as obtained with bi-directional Fourier Domain Doppler OCT showed good correlation with laser Doppler velocimetry data during both normoxic and hyperopic conditions. In addition, data measured at retinal bifurcations indicate the validity of the technique. Finally, measurements at retinal arterial and venous vessels show that absolute retinal blood flow can be extracted with high precision. The technique may be suitable to test the hypothesis that reduced retinal blood flow is a risk factor for primary open angle glaucoma.

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Figure 2: Automated segmentation obtained on a B-scan superior to the optical nerve head of a glaucoma eye. Figure 1: Automated (yellow) and manual (red) segmentation obtained on a B-scan superior to the optical nerve head of a normal eye.

! "P!

Structural and functional monitoring of glaucoma patients: a comparison using regression

analysis

Gijs Thepass1, Koenraad A. Vermeer1, Josine van der Schoot1, Hans G. Lemij1,2

1 Rotterdam Ophthalmic Institute, Rotterdam Eye Hospital, Rotterdam, The Netherlands

3 Glaucoma Service, Rotterdam Eye Hospital, Rotterdam, The Netherlands

Purpose

Structural and functional measurements play a key role in the follow-up of glaucoma patients.

Unfortunately the agreement between structural and functional measurements in glaucomatous

progression is generally poor. For Scanning Laser Polarimetry (SLP), the agreement with functional

measurements has been explored relatively little.

Methods

All eligible eyes of glaucoma patients from the Rotterdam Glaucoma Imaging Study with at least 5

follow-up measurements were enrolled (n=90) in this study. The average time between the first and last

visit was 28 months (22-32). The proprietary progression programs for both SLP (GDx ECC, Carl Zeiss

Meditec) and Standard Automated Perimetry (SAP) (Humphrey Field Analyzer II, 24-2 white on white

SITA test program, Carl Zeiss Meditec) were used (GDx GPA Fast mode and HFA GPA, respectively).

The GDx GPA flags any progression either as no progression, as possible or as likely. As an

comparison we also calculated linear regression coefficients for each series of measurements of the

SAP Visual Field Index (VFI) and Mean Deviation (MD), and the GDx peripapillary retinal nerve fibre

layer thickness (TSNIT average).

Results

All results of the regression analyses are presented in Figs. 1 & 2. None of the tested eyes showed

statistically significant progression by HFA GPA, but 5 (6%) eyes showed likely progression by GDx

GPA (marked by red triangles in Figs. 1&2). Eight eyes (9%) showed TSNIT average increases (marked

by green diamonds in figures 1&2). In our own regression analyses, 52 eyes (58%) showed disease

progression by HFA VFI, 60 eyes (67%) by HFA MD and 49 eyes (54%) by GDx TSNIT average. In 31

eyes (34%), there was both structural and functional progression by HFA VFI and TSNIT average (see

Figs.). Both structural and functional regression occurred in 18 eyes (20%).

! "R!

Conclusions

Glaucomatous progression may be detected by SLP and by SAP. There was poor agreement between

GDx and HFA progression, regardless of the used analysis. HFA GPA was more conservative than

linear regression analysis. One of the limitations of this study is the relatively short average follow-up

time. Plots that combine data from both structural and functional test methods (such as in Figs. 1 & 2)

may help clinicians appreciate whether structural and functional measurements agree. In case of such

agreement, they may feel more confident in their glaucoma management.

! "S!

Nomdo M. Jansonius,1,2 Julia Schiefer,3 Jukka Nevalainen,4 Jens Paetzold,5 Ulrich Schiefer5

1.Department of Ophthalmology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands 2.Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands 3.University Eye Hospital Munich, Ludwig Maximilians University, Munich, Germany 4.University Eye Hospital Oulu, Oulu, Finland 5.Centre for Ophthalmology, University of Tübingen, Tübingen, Germany

Relationship between Retinal Vessel Course and Retinal Nerve Fiber Bundle

Trajectories in the Human Eye

Purpose: Jansonius et al. developed a mathematical model for the description of retinal nerve

fiber bundle trajectories in the human eye (Vision Res 2009; Exp Eye Res 2012). Refraction

and possibly optic disc inclination explained some of the observed variability in the superior-

temporal region but not in the inferior-temporal region. Aim of the current study was to

determine the relationship between the retinal vessel course and the retinal nerve fiber bundle

trajectories.

Methods: The previous dataset of high-quality fundus photographs was used, comprising 28

eyes of 28 subjects (Exp Eye Res 2012). In this dataset, refraction ranged from -8.75 to +6.25

D, with a mean value (standard deviation) of -0.4 (3.3) D. Optic disc inclination ranged from

0.8 to 10.6 deg, with a mean value of 5.1 (2.4) deg. In total 625 retinal nerve fiber bundle

trajectories were traced. For all individual trajectories, the departure from the model was

calculated. Subsequently, we calculated, per subject, a 'mean departure' for the superior-

temporal and inferior-temporal regions. To quantify the retinal vessel course, we measured the

vertical distance between the fovea and the superior-temporal and inferior-temporal veins

(venous arcades). These distances were normalized to the distance between fovea and optic

nerve head center. Multiple linear regression analysis was performed for the superior-temporal

and inferior-temporal regions separately, with the mean departure as dependent variable and

refraction, optic disc inclination and retinal vessel course as independent variables.

Results: In the superior-temporal region, refraction was significantly associated with mean

departure (P=0.03) but optic disc inclination (P=0.13) and retinal vessel course (P=0.28) were

not. The addition of the retinal vessel course to the regression analysis increased the explained

variance from 0.26 to 0.29. In the inferior-temporal region, non of the independent variables

were significantly associated with mean departure (P=0.20, 0.87 and 0.13 for refraction, optic

! "K!

disc inclination and retinal vessel course, respectively). The addition of the retinal vessel course

to the regression analysis increased the explained variance from 0.07 to 0.16.

Conclusions: The wiring of the human retina displays a considerable variability. Refraction,

optic disc inclination and the position of the venous arcades explain some of this variability.

! QD!

Optimizing the correspondence between visual field defects and mathematical models of retinal nerve fiber morphometry N.S. Erler1, S.R. Bryan1, P.H.C. Eilers2, E.M.E.H. Lesaffre2, H.G. Lemij3, K.A. Vermeer1 1 Rotterdam Ophthalmic Institute, Rotterdam Eye Hospital, Rotterdam, The Netherlands 2 Erasmus Medical Center, Rotterdam, The Netherlands 3 Glaucoma Service, Rotterdam Eye Hospital, Rotterdam, The Netherlands Purpose: Visual fields, as determined by automated perimetry, are notoriously noisy. The purpose of this study was to evaluate the correspondence of visual field defects with a model of the retinal nerve fiber layer’s morphology and to develop a way to adjust the model parameters for optimal correspondence. Visual fields can then be smoothed according to the nerve fiber bundles' orientation for noise reduction. Figure 1: Correlation vs. distance, for the conventional visual fields We applied a model that describes the paths of retinal nerve fibers (Airaksinen et al, 2008) to the 24-2 threshold test locations. This model associates every test location with the angle of the nerve fiber at the optic nerve head and the nerve fiber's length. The model's two shape parameters (A and B) steer the spatial distribution of nerve fibers. The correlation coefficient between every combination of two visual field locations were calculated from threshold deviation values from 104 visual fields with moderate glaucoma (MD between -12 dB and -6 dB) from an ongoing study at the Rotterdam Eye Hospital. Figure 2: Correlation vs. distance, for the nerve fibre model with A=0.8 and B=0.015 Results: A scatter plot of the correlation coefficients versus the Euclidean distance in the conventional visual field is shown in Figure 1. The correlation is very inconsistent, i.e., for the same distance between two locations the correlation coefficient varies considerably. This is expressed by the large root-mean-squared error (RMSE) which is determined from the residuals. A similar plot is shown in Figure 2 for distances in nerve fiber angles, with shape parameters A=0.8 and B=0.015. The consistency of correlation coefficients is much smaller than for the Euclidean distance. Optimal consistency (minimal RMSE) was found for A=0.4 and B=0.03, as shown in Figure 3. Conclusion: We developed a method to optimize the shape parameters of a mathematical nerve fiber model to visual field defects. The optimal model considerably improves the consistency of the correlation between visual field locations. The estimated optimum is in agreement with the parameter values that were determined by Airaksinen et al based on fundus photos.

! Q"!

Advancements in high resolution retinal microangiography and blood flow assessment using Doppler OCT R.A. Leitgeb, Center for Med Physics & Biomed Engineering, Medical University Vienna, Vienna, Austria. Purpose: To assess the blood flow dynamics quantitatively and to contrast the microvasculature network label free of the posterior segment in healthy and diseased human subjects using a high-speed Doppler OCT platform. Methods: Traditional Doppler OCT is highly sensitive to motion artifacts due to the dependence on the Doppler angle, limiting its accuracy in clinical practice. To overcome this limitation, we use a bidirectional dual beam platform with flexible aligning of the incidence plane allowing reconstruction of the true flow velocity in the range of 5 to 500mm/s. The angle independent quantitative flow dynamics are extracted from specific vessel cross-sections of arteries and veins, acquired from circumpapillary and segment DOCT scan series over time at 100kA-scans/s. Microangiography is used to assess the vascular network branching and integrity. Contrast of flow towards static tissue is achieved by using an intensity difference algorithm between successive B-scans. Novel High Speed OCT platforms operating in the MHz A-scan rate range allow for 45x45 degree wide field imaging of retinal and choroidal microvasculature. Results: The quantitative analysis profits from the intrinsic stability with respect to motion. The use of 1060nm center wavelength shows enhanced penetration into choroidal structures. The flow values in retinal vessels of healthy subjects of 20-50mm/s and 10-20mm/s for arteries and veins respectively fit well with previous findings. Highly sensitive flow contrasting has been performed on healthy subjects over a wide field of view of 45degree using novel laser technology. The images show impressive contrast down to individual capillaries in both retina and choroid. Choroidal imaging is optimal due to the better penetration at the operating wavelength of 1060nm. Conclusions: We apply a dual beam bidirectional Doppler OCT system to accurately quantify flow dynamics together with high speed OCT for non-invasive 3D microangiography of the posterior segment in the human eye with unpredecented filed of view and vascular contrast. The measurements performed in healthy subjects allow deriving characteristic vascular patterns of the pathological tissue. The motion artifact stable and accurate flow quantification and visualization may therefore lead ultimately to a better understanding and an enhanced early diagnosis of major retinal diseases. I acknowledge my group members Cedric Blatter, Branislaw Grajcar, Amardeep Singh, Tilman Schmoll, and Severine Couquoz, collaboration with Dr. Christoph Mitsch, Dr. Sonja Prager, and Prof. Ursula Schmidt-Erfurth from the Department of Ophthalmology and Optometry at the Medical University Vienna, Dr. Robert Huber from the LMU Munich, as well as financial support from European Commision (FP7-HEALTH FUN-OCT) and the Austrian Christian Doppler Association.

22

L ReLoaded: A Metamorphosis and Transfiguration. Application to Data from the Heidelberg Retina Tomograph. Martin Diller, Heidelberg; Paul Artes, Halifax “Anything that can be said can be said clearly. What cannot be said, thereof one must be silent.” L Wittgenstein (1889 – 1951). www.youtube.com/watch?v=57PWqFowq-4 “God is in the details.” L Mies van der Rohe (1886 – 1969)

Ophthalmic imaging technologies yield complex data – data that are difficult to interpret without more or less sophisticated statistical tools. Yet clinicians, technicians, and patients often do not have a background in statistics or probability theory, and thus there is a danger that results are misinterpreted. L is our yet incomplete attempt to find a generalisable solution to this dilemma, applied to data from the HRT.

L aims to translate progression data from series of HRT images a) into a simple graphical representation, and b) into clear, jargon-free yet technically accurate, verbal statements that provide clinically relevant guidance to non-experts. L makes statements on the most important dimensions (speed, clinical and statistical significance of change, and the power to detect it; validity of linearity assumptions made by the analysis; image quality). Each dimension is quantified by an appropriate combination of indices (for example, image quality ~ mean pixel height standard deviation [MPHSD] + uniformity of illumination + … + etc.), providing a hierarchy of statements that users are invited but not forced to explore. These dimensions are scaled into an [0, 100] interval by comparison with reference quantiles from a previously published population (Reis et al, Ophthalmology 2012).

We look forward to discussing the L approach with the critical audience of IMAGE.

! QO!

Confocal Laser Scanning Tomography to predict Visual Field Conversion in Glaucoma Suspects and Ocular Hypertension

Schrems-Hoesl LM*, Schrems WA*, Horn FK, Mardin CY, Kruse FE, Juenemann AG, Laemmer R.

Department of Ophthalmology, University of Erlangen-Nuremberg, Erlangen, Germany

*These authors contributed equally to this work.

Purpose: To compare Moorfields regression analysis (MRA), Glaucoma probability score (GPS) and different discriminant functions to predict future visual field conversion of glaucoma suspects and ocular hypertensive subjects.

Methods: 120 patients with ocular hypertension and 110 patients with suspected glaucoma were recruited from the Erlangen glaucoma registry for this study. Annually, all patients underwent standard automated perimetry, 24-hour intraocular pressure profile, optic disc photography and HRT (Heidelberg Retina Tomograph; Heidelberg Engineering) measurements. One randomly selected eye of each patient was used in the study. The cohort was divided into two groups based on the development of repeatable glaucomatous visual fields during follow-up. Positive (PPV) and negative predictive values (NPV) were compared for MRA, GPS and the classification of Bathija, Mikelberg and Mardin at baseline. Kaplan-Meier Survival curves and logrank tests were used to evaluate equality of survival distributions for different test results.

Results: Mean follow-up time was 9.47 +/- 2.81 years (minimum = 3.42 years; maximum = 14.33 years). 26 eyes (11.3 %) demonstrated glaucomatous visual field loss in the follow-up period. MRA temporal-superior and temporal-inferior outside normal limits were predictive of future visual field loss with PPVs of 33.3% and 28.6%. Normal GPS Temporal Sector demonstrated a NPV of 96.4% and normal results in discriminant functions between 94.7% and 95.5%.

Conclusions: HRT is an useful tool 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 were normal. MRA temporal-superior and temporal-inferior outside normal limits are associated with future VF conversion.!

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! QN!

Additional topics

“Mystery cases” In previous years, it was interesting to discuss mysterious features

that we had come across in various images. Please bring along and present any of

those “mystery cases”. Maybe we can come up with reasonable solutions, or good

suggestions to further explore the mysteries.

OCT standards The differences between the various OCT imaging devices may be

large and subject to continual change. This limits comparative studies across

instruments as well as longitudinal studies with devices that undergo repeated

upgrades. It would therefore be useful to set specific standards; one could think of

scanning protocols, (pre)processing procedures, data display standards, selection of

normative databases, etc., etc. Are we ready for setting any such standards? Will

those standards hamper or promote the further defvelopment of OCT technology in

glaucoma management?

Next IMAGE meeting The turn-out and number of abstracts have been lower this year

than in previous years. Is this due to timing, the venue, bad luck, or to other, yet

unknown factors? How does this impact on setting the next date and venue for future

IMAGE meetings? What can we learn, and should we do, to promote future meetings?

Where and when will we have IMAGE 2014? Any candidate cities?

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