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Optics Express

Optics Express

  • Editor: C. Martijn de Sterke
  • Vol. 20, Iss. 7 — Mar. 26, 2012
  • pp: 7564–7574
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Automated measurement of choroidal thickness in the human eye by polarization sensitive optical coherence tomography

Teresa Torzicky, Michael Pircher, Stefan Zotter, Marco Bonesi, Erich Götzinger, and Christoph K. Hitzenberger  »View Author Affiliations


Optics Express, Vol. 20, Issue 7, pp. 7564-7574 (2012)
http://dx.doi.org/10.1364/OE.20.007564


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Abstract

We present a new method to automatically segment the thickness of the choroid in the human eye by polarization sensitive optical coherence tomography (PS-OCT). A swept source PS-OCT instrument operating at a center wavelength of 1040 nm is used. The segmentation method is based entirely on intrinsic, tissue specific polarization contrast mechanisms. In a first step, the anterior boundary of the choroid, the retinal pigment epithelium, is segmented based on depolarization. In a second step, the choroid-sclera interface is found by using the birefringence of the sclera. The method is demonstrated in five healthy eyes. The mean repeatability (standard deviation) of thickness measurement was found to be 18.3 µm.

© 2012 OSA

1. Introduction

Optical coherence tomography (OCT) was introduced two decades ago [1

1. D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991). [CrossRef] [PubMed]

] as a non-invasive modality for imaging transparent and translucent samples and tissues with resolution of a few µm [2

2. A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, “Optical coherence tomography - principles and applications,” Rep. Prog. Phys. 66(2), 239–303 (2003). [CrossRef]

, 3

3. W. Drexler and J. G. Fujimoto, Optical coherence tomography. Technology and Applications (Springer, Berlin, 2008).

]. The first (and still dominating) application field of OCT was ophthalmology, where OCT revolutionized retinal imaging and diagnostics [4

4. W. Drexler and J. G. Fujimoto, “Optical coherence tomography in ophthalmology,” J. Biomed. Opt. 12(4), 041201 (2007). [CrossRef]

, 5

5. W. Geitzenauer, C. K. Hitzenberger, and U. M. Schmidt-Erfurth, “Retinal optical coherence tomography: past, present and future perspectives,” Br. J. Ophthalmol. 95(2), 171–177 (2011). [CrossRef] [PubMed]

]. The introduction of the spectral domain (SD) principle [6

6. A. F. Fercher, C. K. Hitzenberger, G. Kamp, and S. Y. Elzaiat, “Measurement of intraocular distances by backscattering spectral interferometry,” Opt. Commun. 117(1-2), 43–48 (1995). [CrossRef]

8

8. M. Wojtkowski, R. Leitgeb, A. Kowalczyk, T. Bajraszewski, and A. F. Fercher, “In vivo human retinal imaging by Fourier domain optical coherence tomography,” J. Biomed. Opt. 7(3), 457–463 (2002). [CrossRef] [PubMed]

] caused a paradigm shift in OCT technology. Its improved sensitivity [9

9. R. Leitgeb, C. K. Hitzenberger, and A. F. Fercher, “Performance of fourier domain vs. time domain optical coherence tomography,” Opt. Express 11(8), 889–894 (2003). [CrossRef] [PubMed]

11

11. M. A. Choma, M. V. Sarunic, C. H. Yang, and J. A. Izatt, “Sensitivity advantage of swept source and Fourier domain optical coherence tomography,” Opt. Express 11(18), 2183–2189 (2003). [CrossRef] [PubMed]

] enables modern commercial OCT scanners to operate at imaging speeds beyond 20 kA-lines/s. They operate in the 800 nm wavelength regime and achieve an axial resolution on the order of 5 µm, providing high-quality images of the retina, from the inner limiting membrane down to the retinal pigment epithelium (RPE). However, presently available commercial OCT systems still have two shortcomings: (i) Imaging of deeper layers, beyond the RPE, is hindered by scattering and absorption of the sampling light in the RPE. (ii) They acquire images just based on backscattered intensity which does not provide a tissue specific contrast.

It has been shown that the use of longer wavelengths can overcome the first problem. The optimum wavelength regime for OCT imaging beyond the RPE is around 1050 nm where scattering and absorption of the RPE are reduced and water absorption has a local minimum [12

12. A. Unterhuber, B. Povazay, B. Hermann, H. Sattmann, A. Chavez-Pirson, and W. Drexler, “In vivo retinal optical coherence tomography at 1040 nm - enhanced penetration into the choroid,” Opt. Express 13(9), 3252–3258 (2005). [CrossRef] [PubMed]

15

15. P. Puvanathasan, P. Forbes, Z. Ren, D. Malchow, S. Boyd, and K. Bizheva, “High-speed, high-resolution Fourier-domain optical coherence tomography system for retinal imaging in the 1060 nm wavelength region,” Opt. Lett. 33(21), 2479–2481 (2008). [PubMed]

]. The use of this wavelength enabled imaging of the choroid down to the choroid-sclera interface (CSI). The introduction of this method allowed to measure the thickness of the choroid, a quantity of great interest for the study of ocular disorders like high myopia, diabetic retinopathy, central serous chorioretinopathy, etc. Recent studies demonstrate the interest to measure the choroidal thickness by this technique (cf., e.g., [16

16. M. Esmaeelpour, B. Povazay, B. Hermann, B. Hofer, V. Kajic, K. Kapoor, N. J. L. Sheen, R. V. North, and W. Drexler, “Three-dimensional 1060-nm OCT: choroidal thickness maps in normal subjects and improved posterior segment visualization in cataract patients,” Invest. Ophthalmol. Vis. Sci. 51(10), 5260–5266 (2010). [CrossRef] [PubMed]

18

18. Y. Ikuno, I. Maruko, Y. Yasuno, M. Miura, T. Sekiryu, K. Nishida, and T. Iida, “Reproducibility of retinal and choroidal thickness measurements in enhanced depth imaging and high-penetration optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 52(8), 5536–5540 (2011). [CrossRef] [PubMed]

]). However, in most of these studies, the CSI is segmented manually, which is problematic since it is time consuming and largely subjective. Only very recently, a first study employing an automated segmentation algorithm based on a statistical model and texture analysis was reported [19

19. V. Kajić, M. Esmaeelpour, B. Považay, D. Marshall, P. L. Rosin, and W. Drexler, “Automated choroidal segmentation of 1060 nm OCT in healthy and pathologic eyes using a statistical model,” Biomed. Opt. Express 3(1), 86–103 (2012). [CrossRef] [PubMed]

]. This study used exclusively intensity based data.

Polarization sensitive (PS) OCT [20

20. M. R. Hee, D. Huang, E. A. Swanson, and J. G. Fujimoto, “Polarization-sensitive low-coherence reflectometer for birefringence characterization and ranging,” J. Opt. Soc. Am. B 9(6), 903–908 (1992). [CrossRef]

, 21

21. J. F. de Boer, T. E. Milner, M. J. C. van Gemert, and J. S. Nelson, “Two-dimensional birefringence imaging in biological tissue by polarization-sensitive optical coherence tomography,” Opt. Lett. 22(12), 934–936 (1997). [CrossRef] [PubMed]

] is a functional extension of OCT that takes advantage of the additional information carried in the light's polarization state. Thereby, PS-OCT can be used to solve the second problem mentioned above. Several structures in the ocular fundus can change the polarization state of the sampling beam: there are birefringent structures like the retinal nerve fiber layer [22

22. R. N. Weinreb, A. W. Dreher, A. Coleman, H. Quigley, B. Shaw, and K. Reiter, “Histopathologic validation of Fourier-ellipsometry measurements of retinal nerve fiber layer thickness,” Arch. Ophthalmol. 108(4), 557–560 (1990). [CrossRef] [PubMed]

, 23

23. B. Cense, T. C. Chen, B. H. Park, M. C. Pierce, and J. F. de Boer, “In vivo depth-resolved birefringence measurements of the human retinal nerve fiber layer by polarization-sensitive optical coherence tomography,” Opt. Lett. 27(18), 1610–1612 (2002). [CrossRef] [PubMed]

], Henle’s fiber layer [24

24. H. B. Brink and G. J. van Blokland, “Birefringence of the human foveal area assessed in vivo with Mueller-matrix ellipsometry,” J. Opt. Soc. Am. A 5(1), 49–57 (1988). [CrossRef] [PubMed]

, 25

25. M. Pircher, E. Götzinger, R. Leitgeb, H. Sattmann, O. Findl, and C. K. Hitzenberger, “Imaging of polarization properties of human retina in vivo with phase resolved transversal PS-OCT,” Opt. Express 12(24), 5940–5951 (2004). [CrossRef] [PubMed]

], the sclera [26

26. B. Baumann, E. Götzinger, M. Pircher, and C. K. Hitzenberger, “Single camera based spectral domain polarization sensitive optical coherence tomography,” Opt. Express 15(3), 1054–1063 (2007). [CrossRef] [PubMed]

, 27

27. M. Yamanari, S. Makita, and Y. Yasuno, “Polarization-sensitive swept-source optical coherence tomography with continuous source polarization modulation,” Opt. Express 16(8), 5892–5906 (2008). [CrossRef] [PubMed]

], or scar tissue [28

28. S. Michels, M. Pircher, W. Geitzenauer, C. Simader, E. Götzinger, O. Findl, U. Schmidt-Erfurth, and C. K. Hitzenberger, “Value of polarisation-sensitive optical coherence tomography in diseases affecting the retinal pigment epithelium,” Br. J. Ophthalmol. 92(2), 204–209 (2008). [CrossRef] [PubMed]

]. These structures introduce a phase retardation between beam components of orthogonal polarization state which can be used for contrasting or to perform quantitative measurements [29

29. B. Cense, T. C. Chen, B. H. Park, M. C. Pierce, and J. F. de Boer, “Thickness and birefringence of healthy retinal nerve fiber layer tissue measured with polarization-sensitive optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 45(8), 2606–2612 (2004). [CrossRef] [PubMed]

32

32. E. Götzinger, M. Pircher, B. Baumann, C. Hirn, C. Vass, and C. K. Hitzenberger, “Retinal nerve fiber layer birefringence evaluated with polarization sensitive spectral domain OCT and scanning laser polarimetry: A comparison,” J Biophoton. 1(2), 129–139 (2008). [CrossRef] [PubMed]

]. The RPE and other pigmented tissues like choroidal melanoma or naevi act as depolarizers, i.e. scramble the polarization state of backscattered light [25

25. M. Pircher, E. Götzinger, R. Leitgeb, H. Sattmann, O. Findl, and C. K. Hitzenberger, “Imaging of polarization properties of human retina in vivo with phase resolved transversal PS-OCT,” Opt. Express 12(24), 5940–5951 (2004). [CrossRef] [PubMed]

, 33

33. M. Pircher, E. Götzinger, O. Findl, S. Michels, W. Geitzenauer, C. Leydolt, U. Schmidt-Erfurth, and C. K. Hitzenberger, “Human macula investigated in vivo with polarization-sensitive optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 47(12), 5487–5494 (2006). [CrossRef] [PubMed]

, 34

34. E. Götzinger, M. Pircher, B. Baumann, C. Ahlers, W. Geitzenauer, U. Schmidt-Erfurth, and C. K. Hitzenberger, “Three-dimensional polarization sensitive OCT imaging and interactive display of the human retina,” Opt. Express 17(5), 4151–4165 (2009). [CrossRef] [PubMed]

]. This effect can be used to segment the RPE and associated lesions by its intrinsic, tissue specific polarization contrast [35

35. E. Götzinger, M. Pircher, W. Geitzenauer, C. Ahlers, B. Baumann, S. Michels, U. Schmidt-Erfurth, and C. K. Hitzenberger, “Retinal pigment epithelium segmentation by polarization sensitive optical coherence tomography,” Opt. Express 16(21), 16410–16422 (2008). [CrossRef] [PubMed]

37

37. C. Ahlers, E. Götzinger, M. Pircher, I. Golbaz, F. Prager, C. Schütze, B. Baumann, C. K. Hitzenberger, and U. Schmidt-Erfurth, “Imaging of the retinal pigment epithelium in age-related macular degeneration using polarization-sensitive optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 51(4), 2149–2157 (2010). [CrossRef] [PubMed]

].

In this paper, we use PS-OCT at 1040 nm, to the best of our knowledge for the first time, to automatically segment the thickness of the choroid by an algorithm that exploits two tissue polarization properties: in a first step, the RPE is segmented based on its depolarizing effect; in a second step, the CSI is segmented based on the birefringence of the sclera. Finally, the difference between the two layers is calculated. We demonstrate the method in five healthy volunteers, present repeatability data, and discuss the results in relation to intensity based manual measurements.

2. Methods

2.1 Instrument

We used a PS-OCT setup based on principles reported previously [38

38. E. Götzinger, M. Pircher, and C. K. Hitzenberger, “High speed spectral domain polarization sensitive optical coherence tomography of the human retina,” Opt. Express 13(25), 10217–10229 (2005). [CrossRef] [PubMed]

]. The main changes made were as follows: (i) The super luminescent diode (SLD; center wavelength 840 nm) was replaced by a swept source (Axsun Inc.) operating at a center wavelength of 1040 nm at a scanning speed of 100 kHz. The sweep range is 110 nm, providing an axial resolution of 7.9 µm in air or 5.6 µm in tissue (assuming a refractive index of 1.4). (ii) The bulk optic Michelson interferometer was replaced by a bulk optic Mach Zehnder interferometer. (iii) The spectrometer based detection unit was replaced by a dual balanced detection scheme employing InGaAs detectors with a cutoff frequency of 350 MHz (Thorlabs Inc.) and a 2-channel 12 bit AD board operating at 500 MSamples/s (Alazartech). The eye was illuminated by a power of 2 mW providing a sensitivity of ~102 dB and a roll off of ~4 dB over 3 mm optical imaging depth.

2.2 Imaging protocol

In this work, B-scan series of the human retina were recorded centrally through the fovea. A B-scan series consisted of 50 B-scans (1000 A-scans each, scan angle ~20°) recorded at the same position within 0.5 s. B-scans were averaged (see below) to reduce speckle noise and improve image quality. To determine the repeatability of our results, each subject was imaged five times. The subjects sat back and were re-aligned between the measurements.

2.3 Data processing

After standard Fourier domain OCT data preprocessing (fixed pattern noise removal, rescaling of the spectral data to remove sweep nonlinearities, spectral side lobe suppression by a Hanning window, zero padding, dispersion compensation) an inverse FFT is performed. From the resulting complex data set, amplitude and phase information is derived for each polarization channel. From these quantities, the reflectivity, retardation, and optic axis orientation can be calculated as described previously [38

38. E. Götzinger, M. Pircher, and C. K. Hitzenberger, “High speed spectral domain polarization sensitive optical coherence tomography of the human retina,” Opt. Express 13(25), 10217–10229 (2005). [CrossRef] [PubMed]

, 39

39. C. K. Hitzenberger, E. Goetzinger, M. Sticker, M. Pircher, and A. F. Fercher, “Measurement and imaging of birefringence and optic axis orientation by phase resolved polarization sensitive optical coherence tomography,” Opt. Express 9(13), 780–790 (2001). [CrossRef] [PubMed]

].

In the following step, the RPE and the CSI were segmented based on their polarization properties. The individual segmentation procedures are described with reference to Fig. 1
Fig. 1 PS-OCT images of human fovea region to illustrate segmentation of choroid. a) Intensity B-scan; b) DOPU B-scan (color bar: 0-1); c) retardation B-scan (color bar: 0° - 90°); d) retardation A-scan (position shown by orange line in a)); e) intensity B-scan with segmentation lines (red: RPE, green: CSI); f) retardation B-scan with segmentation lines (top white line: RPE, bottom white line: CSI, color bar: 0° - 90°). B-scan dimensions: 19° (horizontal) x 1 mm (vertical; geometric distance).
which shows an example of averaged images derived from a B-scan series. The intensity image (Fig. 1(a)) shows a cross section where all the major retinal layers can be seen. The choroid can be clearly identified, demonstrating the improved imaging depth of the 1040 nm SS PS-OCT system. Behind the area showing large blood vessels (dark patches surrounded by brighter structures, perhaps vessel walls), an area of rather uniform backscattered intensity that decreases with depth can be observed.

We start by segmenting the RPE which can be regarded as the anterior boundary of the choroid (in healthy eyes, the RPE is indistinguishable from Bruch's membrane). In the intensity image, the RPE is observed as the last bright boundary at the posterior side of the retina. Its intensity is approximately similar to that of the two boundaries located immediately anterior to the RPE, the end tips of the photoreceptors (ETPR, the layer immediately adjacent to the RPE), and the boundary between inner and outer photoreceptor segments (IS/OS, the layer anterior to the ETPR). However, the RPE shows a very different contrast behavior in polarization sensitive images. As can be seen in the DOPU image (Fig. 1(b)), the RPE strongly depolarizes backscattered light (greenish band). This intrinsic, tissue specific contrast can be used to directly segment the RPE. We extract the RPE by applying a thresholding algorithm that segments pixels below a DOPU threshold of DOPUthr < 0.8. We then fit a polynomial of 4th order to the segmented pixels. The result is a line that marks the position of the RPE. Figure 1(e) shows an intensity image with the segmented RPE line shown in red. This line is taken as the anterior boundary of the choroid.

Figure 1(c) shows the retardation image. The rather constant blue color observed in the layers anterior to the RPE indicates that these layers essentially preserve the polarization state of the incident beam. The RPE is observed as a cyan-green band; this color is caused by averaging the randomly distributed polarization states generated by the depolarizing RPE over the 50 successive frames. Beneath the RPE, the choroid shows again blue color, indicating polarization preservation. The patches of somewhat lighter blue and cyan indicate slight depolarization by choroidal pigments and are also partly caused by noise due to low signal intensity; this can be observed especially in the areas corresponding to vessels (dark patches in the intensity image). Further below, a color change to cyan, green, and yellow can be observed. This indicates phase retardation caused by the birefringent sclera. Deeper areas of the sclera are shown in grey. This indicates that the signal obtained from the corresponding area is not reliable enough to calculate correct retardation values. Two conditions can lead to this gating out of signals: (i) the intensity is too low, which distorts measured retardation [41

41. K. Schoenenberger, B. W. Colston, D. J. Maitland, L. B. Da Silva, and M. J. Everett, “Mapping of birefringence and thermal damage in tissue by use of polarization-sensitive optical coherence tomography,” Appl. Opt. 37(25), 6026–6036 (1998). [CrossRef] [PubMed]

]; this is checked by applying an intensity threshold (areas of signal-to-noise ratio below 7 dB in the averaged B-scans are excluded). (ii) The signal originates from multiple scattering which causes a random polarization state. This is checked by applying a DOPU threshold (signals with DOPU < 0.3 are excluded).

We now segment the CSI based on the birefringence of the sclera. The idea is as follows: we observe a certain, well defined retardation value δpr in the photoreceptor layer (averaged over the IS/OS and ETPR boundaries). The RPE and the choroid are non-birefringent, therefore the retardation value should stay constant within these layers. The retardation rises within the sclera, so we have to find the position where the retardation starts to increase; this position should correspond to the CSI. However, the depolarization of light backscattered from the RPE and parts of the choroid mimic an increased retardation of parts of the signal observed in these layers (cf. the retardation A-scan shown in Fig. 1(d), which shows noisy peaks in front of the sclera). Therefore, our segmentation algorithm starts searching a retardation gradient from the posterior side of the image, excluding areas of unreliable signal (the grey areas of Fig. 1(c)). Within the slope of the gradient (dashed red line), the depth position z1 where the retardation drops below a predetermined value δ1 is located. Ideally, δ1 would be equal to δpr. However, because of the noisy retardation signal in the choroid, the retardation does not drop to the value of δpr. Therefore, we add an offset to define δ1: δ1 = δpr + δoffset. The optimum choice of δoffset was empirically found to be δoffset = 14°. The position z1 of δ1 is slightly deeper than the theoretic CSI position zCSI (which is where the retardation value would have dropped to δpr if there were no disturbance by the noisy choroid signal). We approximate zCSI = z1 - (dz/dδ)δoffset, where (dz/dδ) is the inverse gradient of the retardation (we take a mean retardation gradient (i.e., birefringence) of 0.62°/µm optical imaging depth for all subjects).

3. Results

Horizontal cross sections of the fovea region of the right eye of five healthy subjects were recorded, and RPE and CSI were segmented as described above. Figure 2
Fig. 2 Segmentation of choroid in five healthy volunteers by PS-OCT. Left column: intensity B-scans (red line: RPE, green line: CSI). Right column: retardation B-scans (top white line: RPE, bottom white line: CSI; color scale: cf. Figure 1). B-scan dimensions: 19° (horizontal) x 1060 µm (vertical; geometric distance).
shows the results. Left and right hand columns show intensity and retardation images, respectively. RPE and CSI segmentation lines are shown in red and green in the intensity images, respectively, and as two white lines in the retardation images.

Figure 3
Fig. 3 Plots of choroidal thickness obtained by PS-OCT in five healthy volunteers. The foveola is at 0° (left and right sides are cropped to cover only those parts of the horizontal scans that are imaged in all eyes; the cropping was necessary because of decentration of some scans, cf. Figure 2).
shows a plot of the choroidal thickness (CT) extracted from these images. CT was calculated as the difference between the CSI and RPE line, divided by an estimated refractive index of 1.4. CT varies among subjects, with mean CT values ranging from 271 to 383 µm (averaged over the width of the individual B-scans). The CT within a B-scan is not uniform but can show a strong asymmetry, e.g., in Fig. 2(a) and 2(b) the maximum value is 343 µm (slightly temporal to the foveola), while the minimum value is 205 µm (at the nasal edge of the imaged region).

Figure 4
Fig. 4 Repeatability of CT segmentation by PS-OCT. The center line (black) shows the mean value of 5 CT thickness measurements obtained in a single subject. The other lines (red and green) show mean ± standard deviation. The foveola is at 0°.
shows results of a repeatability measurement (same eye as in Fig. 2(a) and 2(b)). The eye was repeatedly measured 5 times. The mean CT line and the interval of the standard deviation (SD) are shown. The mean SD (across the width of the B-scan) was 17.5 µm. The mean SD value of all 5 eyes was 18.3 µm (range: 13 – 28 µm).

4. Discussion

We developed and demonstrated a new method to measure choroidal thickness by PS-OCT, based entirely on polarization sensitive, intrinsic, tissue specific contrast mechanisms. While the anterior boundary of the choroid, the RPE, was segmented based on depolarization, the segmentation of the posterior boundary, the CSI, is based on the birefringence of the sclera.

The segmentation of the CSI by exploiting the scleral birefringence is somewhat more complicated, for two reasons:

  • (i) The penetration depth of 840 nm OCT systems is usually not good enough to image the CSI. The reasons are the increased scattering of the shorter wavelength in RPE and choroid, and the stronger sensitivity roll off of usual spectrometer based 840 nm SD-OCT systems. The use of the less scattered longer wavelength of ~1050 nm, emitted by a swept source with low sensitivity roll off, improved the penetration depth considerably, enabling reliable identification of the CSI in most cases. (It should, however, be mentioned that intensity based imaging of the CSI by 840 nm OCT systems operated in reverse mode (“enhanced depth imaging”, or EDI mode), in combination with averaging supported by a retinal tracker, has recently been successfully demonstrated [18

    18. Y. Ikuno, I. Maruko, Y. Yasuno, M. Miura, T. Sekiryu, K. Nishida, and T. Iida, “Reproducibility of retinal and choroidal thickness measurements in enhanced depth imaging and high-penetration optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 52(8), 5536–5540 (2011). [CrossRef] [PubMed]

    , 42

    42. R. F. Spaide, H. Koizumi, and M. C. Pozzoni, “Enhanced depth imaging spectral-domain optical coherence tomography,” Am. J. Ophthalmol. 146(4), 496–500 (2008). [CrossRef] [PubMed]

    , 43

    43. W. Rahman, F. K. Chen, J. Yeoh, P. Patel, A. Tufail, and L. Da Cruz, “Repeatability of manual subfoveal choroidal thickness measurements in healthy subjects using the technique of enhanced depth imaging optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 52(5), 2267–2271 (2011). [CrossRef] [PubMed]

    ].)
  • (ii) Contrary to depolarization, which can easily be identified also in very thin layers like the mono-cell RPE layer, retardation caused by birefringence requires a certain layer thickness to build up a measurable retardation: a gradient has to be searched, and the position where this gradient starts has to be identified. The search for the gradient is complicated by two effects: the noisy retardation signal caused by the depolarizing pigments in the choroid, and the multiple scattering observed at very deep positions, which also leads to confounding noise of the measured retardation signal. Our solution to these problems was to gate out multiply scattered light via the DOPU value, and to start the search for the retardation gradient from the posterior side of the image. While this method worked well in the majority of the subjects imaged in this study, it can lead to limitations: In case of very thick choroids (CT > ~380 - 400 µm), the signal from the sclera might be dominated by multiply scattered light, preventing the measurement of reliable retardation signals from the sclera over a depth interval that is necessary to identify the retardation gradient. We observed such an effect in one of our subjects (cf. Figs. 2(g), 2(h)). In this case, most of the data points below the choroid are associated with low DOPU values, so the resulting segmentation line is questionable. This is in agreement with the fact that the repeatability of CT measurement was worst in this subject (SD = 28 µm).

Figure 5
Fig. 5 PS-OCT B-scans of a human retina to illustrate deviations between PS-OCT based choroidal segmentation and results derived manually from intensity image. See text for details. a) Intensity (red line: RPE, green line: CSI by PS-OCT, orange line: CSI by manual segmentation); b) retardation (top white line: RPE, bottom white line: CSI by PS-OCT, orange line: CSI by manual segmentation; color bar: cf. Fig. 1). B-scan dimensions: 19° (horizontal) x 1060 µm (vertical; geometric distance).
shows an example of B-scans with segmentation lines for a detailed comparison (same subject as in Fig. 2 (c), 2(d)). Figure 5(a) shows the intensity image, Fig. 5(b) the retardation image. In addition to the PS-OCT based segmentation lines, the manually drawn lines are shown in orange (the line was drawn into the intensity image and copied into the retardation image). On the right hand side (nasal, area is close to the optic nerve head) the PS-OCT based CSI segmentation line is close to the manually drawn line. However, in other parts (left hand side), there is a distinct deviation: the PS-OCT segmentation line is placed deeper than the intensity based line. Part of that deviation might be caused by the fact that we used an average scleral birefringence to correct for the retardation offset δoffset (cf. section 2.3). The retardation image clearly shows that the birefringence (color gradient) is not constant along the B-scan. An individually and locally varying birefringence could be implemented in future improvements of our algorithm. However, this effect can only explain a minor part of the observed deviation. The retardation image clearly shows that the PS-OCT line is at the position where the retardation gradient (i.e. the birefringence) starts, the intensity-based line is within an area that shows constant retardation (no birefringence).

A comparison of Figs. 5(a) and 5(b) clearly shows that in the corresponding areas there are quite thick regions within the tissue of rather uniform reflectivity that show no birefringence (constant blue color in Fig. 5(b), cf. asterisks). This leads to a unilateral deviation of PS-OCT and intensity based CSI segmentation. The PS algorithm tends to draw the segmentation line at a deeper position than intensity based manual segmentation. In Fig. 5, the deviation ranges from 0 to ~70 µm, with an average of ~25 µm. Across all five volunteers, the mean deviation is ~35 µm.

The reasons for these discrepancies are still under discussion: either the tissue layer where the discrepancy is observed is not part of the sclera or the corresponding scleral tissue is non-birefringent. Therefore, the true CSI position remains unclear in these areas, and further research and comparison with histology is needed.

Despite this unresolved discrepancy, we think CT segmentation by PS-OCT is an interesting alternative to intensity based methods because it can be fully automated and provides additional, complementary information to intensity based data.

Acknowledgments

Financial support from the European Union (project FUN OCT, FP7 HEALTH, contract no. 201880) and from the Austrian Science Fund (FWF grant P19624-B02) is gratefully acknowledged.

References and Links

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W. Geitzenauer, C. K. Hitzenberger, and U. M. Schmidt-Erfurth, “Retinal optical coherence tomography: past, present and future perspectives,” Br. J. Ophthalmol. 95(2), 171–177 (2011). [CrossRef] [PubMed]

6.

A. F. Fercher, C. K. Hitzenberger, G. Kamp, and S. Y. Elzaiat, “Measurement of intraocular distances by backscattering spectral interferometry,” Opt. Commun. 117(1-2), 43–48 (1995). [CrossRef]

7.

G. Häusler and M. W. Lindner, “Coherence radar” and “spectral radar” - new tools for dermatological diagnosis,” J. Biomed. Opt. 3(1), 21–31 (1998). [CrossRef]

8.

M. Wojtkowski, R. Leitgeb, A. Kowalczyk, T. Bajraszewski, and A. F. Fercher, “In vivo human retinal imaging by Fourier domain optical coherence tomography,” J. Biomed. Opt. 7(3), 457–463 (2002). [CrossRef] [PubMed]

9.

R. Leitgeb, C. K. Hitzenberger, and A. F. Fercher, “Performance of fourier domain vs. time domain optical coherence tomography,” Opt. Express 11(8), 889–894 (2003). [CrossRef] [PubMed]

10.

J. F. de Boer, B. Cense, B. H. Park, M. C. Pierce, G. J. Tearney, and B. E. Bouma, “Improved signal-to-noise ratio in spectral-domain compared with time-domain optical coherence tomography,” Opt. Lett. 28(21), 2067–2069 (2003). [CrossRef] [PubMed]

11.

M. A. Choma, M. V. Sarunic, C. H. Yang, and J. A. Izatt, “Sensitivity advantage of swept source and Fourier domain optical coherence tomography,” Opt. Express 11(18), 2183–2189 (2003). [CrossRef] [PubMed]

12.

A. Unterhuber, B. Povazay, B. Hermann, H. Sattmann, A. Chavez-Pirson, and W. Drexler, “In vivo retinal optical coherence tomography at 1040 nm - enhanced penetration into the choroid,” Opt. Express 13(9), 3252–3258 (2005). [CrossRef] [PubMed]

13.

Y. Yasuno, Y. J. Hong, S. Makita, M. Yamanari, M. Akiba, M. Miura, and T. Yatagai, “In vivo high-contrast imaging of deep posterior eye by 1-microm swept source optical coherence tomography and scattering optical coherence angiography,” Opt. Express 15(10), 6121–6139 (2007). [CrossRef] [PubMed]

14.

E. C. W. Lee, J. F. de Boer, M. Mujat, H. Lim, and S. H. Yun, “In vivo optical frequency domain imaging of human retina and choroid,” Opt. Express 14(10), 4403–4411 (2006). [CrossRef] [PubMed]

15.

P. Puvanathasan, P. Forbes, Z. Ren, D. Malchow, S. Boyd, and K. Bizheva, “High-speed, high-resolution Fourier-domain optical coherence tomography system for retinal imaging in the 1060 nm wavelength region,” Opt. Lett. 33(21), 2479–2481 (2008). [PubMed]

16.

M. Esmaeelpour, B. Povazay, B. Hermann, B. Hofer, V. Kajic, K. Kapoor, N. J. L. Sheen, R. V. North, and W. Drexler, “Three-dimensional 1060-nm OCT: choroidal thickness maps in normal subjects and improved posterior segment visualization in cataract patients,” Invest. Ophthalmol. Vis. Sci. 51(10), 5260–5266 (2010). [CrossRef] [PubMed]

17.

M. Esmaeelpour, B. Považay, B. Hermann, B. Hofer, V. Kajic, S. L. Hale, R. V. North, W. Drexler, and N. J. L. Sheen, “Mapping choroidal and retinal thickness variation in type 2 diabetes using three-dimensional 1060-nm optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 52(8), 5311–5316 (2011). [CrossRef] [PubMed]

18.

Y. Ikuno, I. Maruko, Y. Yasuno, M. Miura, T. Sekiryu, K. Nishida, and T. Iida, “Reproducibility of retinal and choroidal thickness measurements in enhanced depth imaging and high-penetration optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 52(8), 5536–5540 (2011). [CrossRef] [PubMed]

19.

V. Kajić, M. Esmaeelpour, B. Považay, D. Marshall, P. L. Rosin, and W. Drexler, “Automated choroidal segmentation of 1060 nm OCT in healthy and pathologic eyes using a statistical model,” Biomed. Opt. Express 3(1), 86–103 (2012). [CrossRef] [PubMed]

20.

M. R. Hee, D. Huang, E. A. Swanson, and J. G. Fujimoto, “Polarization-sensitive low-coherence reflectometer for birefringence characterization and ranging,” J. Opt. Soc. Am. B 9(6), 903–908 (1992). [CrossRef]

21.

J. F. de Boer, T. E. Milner, M. J. C. van Gemert, and J. S. Nelson, “Two-dimensional birefringence imaging in biological tissue by polarization-sensitive optical coherence tomography,” Opt. Lett. 22(12), 934–936 (1997). [CrossRef] [PubMed]

22.

R. N. Weinreb, A. W. Dreher, A. Coleman, H. Quigley, B. Shaw, and K. Reiter, “Histopathologic validation of Fourier-ellipsometry measurements of retinal nerve fiber layer thickness,” Arch. Ophthalmol. 108(4), 557–560 (1990). [CrossRef] [PubMed]

23.

B. Cense, T. C. Chen, B. H. Park, M. C. Pierce, and J. F. de Boer, “In vivo depth-resolved birefringence measurements of the human retinal nerve fiber layer by polarization-sensitive optical coherence tomography,” Opt. Lett. 27(18), 1610–1612 (2002). [CrossRef] [PubMed]

24.

H. B. Brink and G. J. van Blokland, “Birefringence of the human foveal area assessed in vivo with Mueller-matrix ellipsometry,” J. Opt. Soc. Am. A 5(1), 49–57 (1988). [CrossRef] [PubMed]

25.

M. Pircher, E. Götzinger, R. Leitgeb, H. Sattmann, O. Findl, and C. K. Hitzenberger, “Imaging of polarization properties of human retina in vivo with phase resolved transversal PS-OCT,” Opt. Express 12(24), 5940–5951 (2004). [CrossRef] [PubMed]

26.

B. Baumann, E. Götzinger, M. Pircher, and C. K. Hitzenberger, “Single camera based spectral domain polarization sensitive optical coherence tomography,” Opt. Express 15(3), 1054–1063 (2007). [CrossRef] [PubMed]

27.

M. Yamanari, S. Makita, and Y. Yasuno, “Polarization-sensitive swept-source optical coherence tomography with continuous source polarization modulation,” Opt. Express 16(8), 5892–5906 (2008). [CrossRef] [PubMed]

28.

S. Michels, M. Pircher, W. Geitzenauer, C. Simader, E. Götzinger, O. Findl, U. Schmidt-Erfurth, and C. K. Hitzenberger, “Value of polarisation-sensitive optical coherence tomography in diseases affecting the retinal pigment epithelium,” Br. J. Ophthalmol. 92(2), 204–209 (2008). [CrossRef] [PubMed]

29.

B. Cense, T. C. Chen, B. H. Park, M. C. Pierce, and J. F. de Boer, “Thickness and birefringence of healthy retinal nerve fiber layer tissue measured with polarization-sensitive optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 45(8), 2606–2612 (2004). [CrossRef] [PubMed]

30.

M. Mujat, B. H. Park, B. Cense, T. C. Chen, and J. F. de Boer, “Autocalibration of spectral-domain optical coherence tomography spectrometers for in vivo quantitative retinal nerve fiber layer birefringence determination,” J. Biomed. Opt. 12(4), 041205 (2007). [CrossRef] [PubMed]

31.

M. Yamanari, M. Miura, S. Makita, T. Yatagai, and Y. Yasuno, “Phase retardation measurement of retinal nerve fiber layer by polarization-sensitive spectral-domain optical coherence tomography and scanning laser polarimetry,” J. Biomed. Opt. 13(1), 014013 (2008). [CrossRef] [PubMed]

32.

E. Götzinger, M. Pircher, B. Baumann, C. Hirn, C. Vass, and C. K. Hitzenberger, “Retinal nerve fiber layer birefringence evaluated with polarization sensitive spectral domain OCT and scanning laser polarimetry: A comparison,” J Biophoton. 1(2), 129–139 (2008). [CrossRef] [PubMed]

33.

M. Pircher, E. Götzinger, O. Findl, S. Michels, W. Geitzenauer, C. Leydolt, U. Schmidt-Erfurth, and C. K. Hitzenberger, “Human macula investigated in vivo with polarization-sensitive optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 47(12), 5487–5494 (2006). [CrossRef] [PubMed]

34.

E. Götzinger, M. Pircher, B. Baumann, C. Ahlers, W. Geitzenauer, U. Schmidt-Erfurth, and C. K. Hitzenberger, “Three-dimensional polarization sensitive OCT imaging and interactive display of the human retina,” Opt. Express 17(5), 4151–4165 (2009). [CrossRef] [PubMed]

35.

E. Götzinger, M. Pircher, W. Geitzenauer, C. Ahlers, B. Baumann, S. Michels, U. Schmidt-Erfurth, and C. K. Hitzenberger, “Retinal pigment epithelium segmentation by polarization sensitive optical coherence tomography,” Opt. Express 16(21), 16410–16422 (2008). [CrossRef] [PubMed]

36.

B. Baumann, E. Götzinger, M. Pircher, H. Sattmann, C. Schuutze, F. Schlanitz, C. Ahlers, U. Schmidt-Erfurth, and C. K. Hitzenberger, “Segmentation and quantification of retinal lesions in age-related macular degeneration using polarization-sensitive optical coherence tomography,” J. Biomed. Opt. 15(6), 061704 (2010). [CrossRef] [PubMed]

37.

C. Ahlers, E. Götzinger, M. Pircher, I. Golbaz, F. Prager, C. Schütze, B. Baumann, C. K. Hitzenberger, and U. Schmidt-Erfurth, “Imaging of the retinal pigment epithelium in age-related macular degeneration using polarization-sensitive optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 51(4), 2149–2157 (2010). [CrossRef] [PubMed]

38.

E. Götzinger, M. Pircher, and C. K. Hitzenberger, “High speed spectral domain polarization sensitive optical coherence tomography of the human retina,” Opt. Express 13(25), 10217–10229 (2005). [CrossRef] [PubMed]

39.

C. K. Hitzenberger, E. Goetzinger, M. Sticker, M. Pircher, and A. F. Fercher, “Measurement and imaging of birefringence and optic axis orientation by phase resolved polarization sensitive optical coherence tomography,” Opt. Express 9(13), 780–790 (2001). [CrossRef] [PubMed]

40.

E. Götzinger, M. Pircher, B. Baumann, T. Schmoll, H. Sattmann, R. A. Leitgeb, and C. K. Hitzenberger, “Speckle noise reduction in high speed polarization sensitive spectral domain optical coherence tomography,” Opt. Express 19(15), 14568–14585 (2011). [CrossRef] [PubMed]

41.

K. Schoenenberger, B. W. Colston, D. J. Maitland, L. B. Da Silva, and M. J. Everett, “Mapping of birefringence and thermal damage in tissue by use of polarization-sensitive optical coherence tomography,” Appl. Opt. 37(25), 6026–6036 (1998). [CrossRef] [PubMed]

42.

R. F. Spaide, H. Koizumi, and M. C. Pozzoni, “Enhanced depth imaging spectral-domain optical coherence tomography,” Am. J. Ophthalmol. 146(4), 496–500 (2008). [CrossRef] [PubMed]

43.

W. Rahman, F. K. Chen, J. Yeoh, P. Patel, A. Tufail, and L. Da Cruz, “Repeatability of manual subfoveal choroidal thickness measurements in healthy subjects using the technique of enhanced depth imaging optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 52(5), 2267–2271 (2011). [CrossRef] [PubMed]

44.

C. S. Tan, Y. Ouyang, H. Ruiz, and S. R. Sadda, “Diurnal variation of choroidal thickness in normal, healthy subjects measured by spectral domain optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 53(1), 261–266 (2012). [CrossRef] [PubMed]

45.

L. Duan, M. Yamanari, and Y. Yasuno, “Automated phase retardation oriented segmentation of chorio-scleral interface by polarization sensitive optical coherence tomography,” Opt. Express 20(3), 3353–3366 (2012). [CrossRef] [PubMed]

OCIS Codes
(170.4470) Medical optics and biotechnology : Ophthalmology
(170.4500) Medical optics and biotechnology : Optical coherence tomography
(170.4580) Medical optics and biotechnology : Optical diagnostics for medicine
(230.5440) Optical devices : Polarization-selective devices

ToC Category:
Medical Optics and Biotechnology

History
Original Manuscript: January 18, 2012
Revised Manuscript: March 14, 2012
Manuscript Accepted: March 15, 2012
Published: March 19, 2012

Virtual Issues
Vol. 7, Iss. 5 Virtual Journal for Biomedical Optics

Citation
Teresa Torzicky, Michael Pircher, Stefan Zotter, Marco Bonesi, Erich Götzinger, and Christoph K. Hitzenberger, "Automated measurement of choroidal thickness in the human eye by polarization sensitive optical coherence tomography," Opt. Express 20, 7564-7574 (2012)
http://www.opticsinfobase.org/oe/abstract.cfm?URI=oe-20-7-7564


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References

  1. D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991). [CrossRef] [PubMed]
  2. A. F. Fercher, W. Drexler, C. K. Hitzenberger, T. Lasser, “Optical coherence tomography - principles and applications,” Rep. Prog. Phys. 66(2), 239–303 (2003). [CrossRef]
  3. W. Drexler and J. G. Fujimoto, Optical coherence tomography. Technology and Applications (Springer, Berlin, 2008).
  4. W. Drexler, J. G. Fujimoto, “Optical coherence tomography in ophthalmology,” J. Biomed. Opt. 12(4), 041201 (2007). [CrossRef]
  5. W. Geitzenauer, C. K. Hitzenberger, U. M. Schmidt-Erfurth, “Retinal optical coherence tomography: past, present and future perspectives,” Br. J. Ophthalmol. 95(2), 171–177 (2011). [CrossRef] [PubMed]
  6. A. F. Fercher, C. K. Hitzenberger, G. Kamp, S. Y. Elzaiat, “Measurement of intraocular distances by backscattering spectral interferometry,” Opt. Commun. 117(1-2), 43–48 (1995). [CrossRef]
  7. G. Häusler, M. W. Lindner, “Coherence radar” and “spectral radar” - new tools for dermatological diagnosis,” J. Biomed. Opt. 3(1), 21–31 (1998). [CrossRef]
  8. M. Wojtkowski, R. Leitgeb, A. Kowalczyk, T. Bajraszewski, A. F. Fercher, “In vivo human retinal imaging by Fourier domain optical coherence tomography,” J. Biomed. Opt. 7(3), 457–463 (2002). [CrossRef] [PubMed]
  9. R. Leitgeb, C. K. Hitzenberger, A. F. Fercher, “Performance of fourier domain vs. time domain optical coherence tomography,” Opt. Express 11(8), 889–894 (2003). [CrossRef] [PubMed]
  10. J. F. de Boer, B. Cense, B. H. Park, M. C. Pierce, G. J. Tearney, B. E. Bouma, “Improved signal-to-noise ratio in spectral-domain compared with time-domain optical coherence tomography,” Opt. Lett. 28(21), 2067–2069 (2003). [CrossRef] [PubMed]
  11. M. A. Choma, M. V. Sarunic, C. H. Yang, J. A. Izatt, “Sensitivity advantage of swept source and Fourier domain optical coherence tomography,” Opt. Express 11(18), 2183–2189 (2003). [CrossRef] [PubMed]
  12. A. Unterhuber, B. Povazay, B. Hermann, H. Sattmann, A. Chavez-Pirson, W. Drexler, “In vivo retinal optical coherence tomography at 1040 nm - enhanced penetration into the choroid,” Opt. Express 13(9), 3252–3258 (2005). [CrossRef] [PubMed]
  13. Y. Yasuno, Y. J. Hong, S. Makita, M. Yamanari, M. Akiba, M. Miura, T. Yatagai, “In vivo high-contrast imaging of deep posterior eye by 1-microm swept source optical coherence tomography and scattering optical coherence angiography,” Opt. Express 15(10), 6121–6139 (2007). [CrossRef] [PubMed]
  14. E. C. W. Lee, J. F. de Boer, M. Mujat, H. Lim, S. H. Yun, “In vivo optical frequency domain imaging of human retina and choroid,” Opt. Express 14(10), 4403–4411 (2006). [CrossRef] [PubMed]
  15. P. Puvanathasan, P. Forbes, Z. Ren, D. Malchow, S. Boyd, K. Bizheva, “High-speed, high-resolution Fourier-domain optical coherence tomography system for retinal imaging in the 1060 nm wavelength region,” Opt. Lett. 33(21), 2479–2481 (2008). [PubMed]
  16. M. Esmaeelpour, B. Povazay, B. Hermann, B. Hofer, V. Kajic, K. Kapoor, N. J. L. Sheen, R. V. North, W. Drexler, “Three-dimensional 1060-nm OCT: choroidal thickness maps in normal subjects and improved posterior segment visualization in cataract patients,” Invest. Ophthalmol. Vis. Sci. 51(10), 5260–5266 (2010). [CrossRef] [PubMed]
  17. M. Esmaeelpour, B. Považay, B. Hermann, B. Hofer, V. Kajic, S. L. Hale, R. V. North, W. Drexler, N. J. L. Sheen, “Mapping choroidal and retinal thickness variation in type 2 diabetes using three-dimensional 1060-nm optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 52(8), 5311–5316 (2011). [CrossRef] [PubMed]
  18. Y. Ikuno, I. Maruko, Y. Yasuno, M. Miura, T. Sekiryu, K. Nishida, T. Iida, “Reproducibility of retinal and choroidal thickness measurements in enhanced depth imaging and high-penetration optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 52(8), 5536–5540 (2011). [CrossRef] [PubMed]
  19. V. Kajić, M. Esmaeelpour, B. Považay, D. Marshall, P. L. Rosin, W. Drexler, “Automated choroidal segmentation of 1060 nm OCT in healthy and pathologic eyes using a statistical model,” Biomed. Opt. Express 3(1), 86–103 (2012). [CrossRef] [PubMed]
  20. M. R. Hee, D. Huang, E. A. Swanson, J. G. Fujimoto, “Polarization-sensitive low-coherence reflectometer for birefringence characterization and ranging,” J. Opt. Soc. Am. B 9(6), 903–908 (1992). [CrossRef]
  21. J. F. de Boer, T. E. Milner, M. J. C. van Gemert, J. S. Nelson, “Two-dimensional birefringence imaging in biological tissue by polarization-sensitive optical coherence tomography,” Opt. Lett. 22(12), 934–936 (1997). [CrossRef] [PubMed]
  22. R. N. Weinreb, A. W. Dreher, A. Coleman, H. Quigley, B. Shaw, K. Reiter, “Histopathologic validation of Fourier-ellipsometry measurements of retinal nerve fiber layer thickness,” Arch. Ophthalmol. 108(4), 557–560 (1990). [CrossRef] [PubMed]
  23. B. Cense, T. C. Chen, B. H. Park, M. C. Pierce, J. F. de Boer, “In vivo depth-resolved birefringence measurements of the human retinal nerve fiber layer by polarization-sensitive optical coherence tomography,” Opt. Lett. 27(18), 1610–1612 (2002). [CrossRef] [PubMed]
  24. H. B. Brink, G. J. van Blokland, “Birefringence of the human foveal area assessed in vivo with Mueller-matrix ellipsometry,” J. Opt. Soc. Am. A 5(1), 49–57 (1988). [CrossRef] [PubMed]
  25. M. Pircher, E. Götzinger, R. Leitgeb, H. Sattmann, O. Findl, C. K. Hitzenberger, “Imaging of polarization properties of human retina in vivo with phase resolved transversal PS-OCT,” Opt. Express 12(24), 5940–5951 (2004). [CrossRef] [PubMed]
  26. B. Baumann, E. Götzinger, M. Pircher, C. K. Hitzenberger, “Single camera based spectral domain polarization sensitive optical coherence tomography,” Opt. Express 15(3), 1054–1063 (2007). [CrossRef] [PubMed]
  27. M. Yamanari, S. Makita, Y. Yasuno, “Polarization-sensitive swept-source optical coherence tomography with continuous source polarization modulation,” Opt. Express 16(8), 5892–5906 (2008). [CrossRef] [PubMed]
  28. S. Michels, M. Pircher, W. Geitzenauer, C. Simader, E. Götzinger, O. Findl, U. Schmidt-Erfurth, C. K. Hitzenberger, “Value of polarisation-sensitive optical coherence tomography in diseases affecting the retinal pigment epithelium,” Br. J. Ophthalmol. 92(2), 204–209 (2008). [CrossRef] [PubMed]
  29. B. Cense, T. C. Chen, B. H. Park, M. C. Pierce, J. F. de Boer, “Thickness and birefringence of healthy retinal nerve fiber layer tissue measured with polarization-sensitive optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 45(8), 2606–2612 (2004). [CrossRef] [PubMed]
  30. M. Mujat, B. H. Park, B. Cense, T. C. Chen, J. F. de Boer, “Autocalibration of spectral-domain optical coherence tomography spectrometers for in vivo quantitative retinal nerve fiber layer birefringence determination,” J. Biomed. Opt. 12(4), 041205 (2007). [CrossRef] [PubMed]
  31. M. Yamanari, M. Miura, S. Makita, T. Yatagai, Y. Yasuno, “Phase retardation measurement of retinal nerve fiber layer by polarization-sensitive spectral-domain optical coherence tomography and scanning laser polarimetry,” J. Biomed. Opt. 13(1), 014013 (2008). [CrossRef] [PubMed]
  32. E. Götzinger, M. Pircher, B. Baumann, C. Hirn, C. Vass, C. K. Hitzenberger, “Retinal nerve fiber layer birefringence evaluated with polarization sensitive spectral domain OCT and scanning laser polarimetry: A comparison,” J Biophoton. 1(2), 129–139 (2008). [CrossRef] [PubMed]
  33. M. Pircher, E. Götzinger, O. Findl, S. Michels, W. Geitzenauer, C. Leydolt, U. Schmidt-Erfurth, C. K. Hitzenberger, “Human macula investigated in vivo with polarization-sensitive optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 47(12), 5487–5494 (2006). [CrossRef] [PubMed]
  34. E. Götzinger, M. Pircher, B. Baumann, C. Ahlers, W. Geitzenauer, U. Schmidt-Erfurth, C. K. Hitzenberger, “Three-dimensional polarization sensitive OCT imaging and interactive display of the human retina,” Opt. Express 17(5), 4151–4165 (2009). [CrossRef] [PubMed]
  35. E. Götzinger, M. Pircher, W. Geitzenauer, C. Ahlers, B. Baumann, S. Michels, U. Schmidt-Erfurth, C. K. Hitzenberger, “Retinal pigment epithelium segmentation by polarization sensitive optical coherence tomography,” Opt. Express 16(21), 16410–16422 (2008). [CrossRef] [PubMed]
  36. B. Baumann, E. Götzinger, M. Pircher, H. Sattmann, C. Schuutze, F. Schlanitz, C. Ahlers, U. Schmidt-Erfurth, C. K. Hitzenberger, “Segmentation and quantification of retinal lesions in age-related macular degeneration using polarization-sensitive optical coherence tomography,” J. Biomed. Opt. 15(6), 061704 (2010). [CrossRef] [PubMed]
  37. C. Ahlers, E. Götzinger, M. Pircher, I. Golbaz, F. Prager, C. Schütze, B. Baumann, C. K. Hitzenberger, U. Schmidt-Erfurth, “Imaging of the retinal pigment epithelium in age-related macular degeneration using polarization-sensitive optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 51(4), 2149–2157 (2010). [CrossRef] [PubMed]
  38. E. Götzinger, M. Pircher, C. K. Hitzenberger, “High speed spectral domain polarization sensitive optical coherence tomography of the human retina,” Opt. Express 13(25), 10217–10229 (2005). [CrossRef] [PubMed]
  39. C. K. Hitzenberger, E. Goetzinger, M. Sticker, M. Pircher, A. F. Fercher, “Measurement and imaging of birefringence and optic axis orientation by phase resolved polarization sensitive optical coherence tomography,” Opt. Express 9(13), 780–790 (2001). [CrossRef] [PubMed]
  40. E. Götzinger, M. Pircher, B. Baumann, T. Schmoll, H. Sattmann, R. A. Leitgeb, C. K. Hitzenberger, “Speckle noise reduction in high speed polarization sensitive spectral domain optical coherence tomography,” Opt. Express 19(15), 14568–14585 (2011). [CrossRef] [PubMed]
  41. K. Schoenenberger, B. W. Colston, D. J. Maitland, L. B. Da Silva, M. J. Everett, “Mapping of birefringence and thermal damage in tissue by use of polarization-sensitive optical coherence tomography,” Appl. Opt. 37(25), 6026–6036 (1998). [CrossRef] [PubMed]
  42. R. F. Spaide, H. Koizumi, M. C. Pozzoni, “Enhanced depth imaging spectral-domain optical coherence tomography,” Am. J. Ophthalmol. 146(4), 496–500 (2008). [CrossRef] [PubMed]
  43. W. Rahman, F. K. Chen, J. Yeoh, P. Patel, A. Tufail, L. Da Cruz, “Repeatability of manual subfoveal choroidal thickness measurements in healthy subjects using the technique of enhanced depth imaging optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 52(5), 2267–2271 (2011). [CrossRef] [PubMed]
  44. C. S. Tan, Y. Ouyang, H. Ruiz, S. R. Sadda, “Diurnal variation of choroidal thickness in normal, healthy subjects measured by spectral domain optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 53(1), 261–266 (2012). [CrossRef] [PubMed]
  45. L. Duan, M. Yamanari, Y. Yasuno, “Automated phase retardation oriented segmentation of chorio-scleral interface by polarization sensitive optical coherence tomography,” Opt. Express 20(3), 3353–3366 (2012). [CrossRef] [PubMed]

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