Abstract

We introduce multi-directional optical coherence tomography (OCT), a technique for investigation of the scattering properties of directionally reflective tissue samples. By combining the concepts of multi-channel and directional OCT, this approach enables simultaneous acquisition of multiple reflectivity depth-scans probing a mutual sample location from differing angular orientations. The application of multi-directional OCT in retinal imaging allows for in-depth investigations on the directional reflectivity of the retinal nerve fiber layer, Henle’s fiber layer and the photoreceptor layer. Major ophthalmic diseases (such as glaucoma or age-related macular degeneration) have been reported to alter the directional reflectivity properties of these retinal layers. Hence, the concept of multi-directional OCT might help to gain improved understanding of pathology development and progression. As a first step, we demonstrate the capabilities of multi-directional OCT in the eyes of healthy human volunteers.

Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.

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2017 (4)

2016 (5)

R. Haindl, W. Trasischker, A. Wartak, B. Baumann, M. Pircher, and C. K. Hitzenberger, “Total retinal blood flow and reproducibility evaluation by three beam optical Doppler tomography,” Biomed. Opt. Express 7(2), 287–301 (2016).
[PubMed]

A. Wartak, R. Haindl, W. Trasischker, B. Baumann, M. Pircher, and C. K. Hitzenberger, “Active-passive path-length encoded (APPLE) Doppler OCT,” Biomed. Opt. Express 7(12), 5233–5251 (2016).
[PubMed]

M. Augustin, S. Fialová, T. Himmel, M. Glösmann, T. Lengheimer, D. J. Harper, R. Plasenzotti, M. Pircher, C. K. Hitzenberger, and B. Baumann, “Multi-functional OCT enables longitudinal study of retinal changes in a VLDLR knockout mouse model,” PLoS One 11(10), e0164419 (2016).
[PubMed]

Z. Liu, O. P. Kocaoglu, and D. T. Miller, “3D imaging of retinal pigment epithelial cells in the living human Retina,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT533 (2016).
[PubMed]

S. K. Gardiner, S. Demirel, J. Reynaud, and B. Fortune, “Changes in retinal nerve fiber layer reflectance intensity as a predictor of functional progression in glaucoma,” Invest. Ophthalmol. Vis. Sci. 57(3), 1221–1227 (2016).
[PubMed]

2015 (6)

B. J. Lujan, A. Roorda, J. A. Croskrey, A. M. Dubis, R. F. Cooper, J. K. Bayabo, J. L. Duncan, B. J. Antony, and J. Carroll, “Directional optical coherence tomography provides accurate outer nuclear layer and Henle fiber layer measurements,” Retina 35(8), 1511–1520 (2015).
[PubMed]

B. J. Antony, P. F. Stetson, M. D. Abramoff, K. Lee, J. M. Colijn, G. H. Buitendijk, C. C. Klaver, A. Roorda, and B. J. Lujan, “Characterizing the impact of off-axis scan acquisition on the reproducibility of total retinal thickness measurements in SDOCT volumes,” Transl. Vis. Sci. Technol. 4(4), 3 (2015).
[PubMed]

H. J. Morris, L. Blanco, J. L. Codona, S. L. Li, S. S. Choi, and N. Doble, “Directionality of individual cone photoreceptors in the parafoveal region,” Vision Res. 117, 67–80 (2015).
[PubMed]

R. Haindl, W. Trasischker, B. Baumann, M. Pircher, and C. K. Hitzenberger, “Three-beam Doppler optical coherence tomography using a facet prism telescope and MEMS mirror for improved transversal resolution,” J. Mod. Opt. 62(21), 1781–1788 (2015).
[PubMed]

O. Carrasco-Zevallos, D. Nankivil, B. Keller, C. Viehland, B. J. Lujan, and J. A. Izatt, “Pupil tracking optical coherence tomography for precise control of pupil entry position,” Biomed. Opt. Express 6(9), 3405–3419 (2015).
[PubMed]

X.-R. Huang, R. W. Knighton, W. J. Feuer, and J. Qiao, “Retinal nerve fiber layer reflectometry must consider directional reflectance,” Biomed. Opt. Express 7(1), 22–33 (2015).
[PubMed]

2014 (3)

P. P. Srinivasan, S. J. Heflin, J. A. Izatt, V. Y. Arshavsky, and S. Farsiu, “Automatic segmentation of up to ten layer boundaries in SD-OCT images of the mouse retina with and without missing layers due to pathology,” Biomed. Opt. Express 5(2), 348–365 (2014).
[PubMed]

R. S. Jonnal, O. P. Kocaoglu, R. J. Zawadzki, S.-H. Lee, J. S. Werner, and D. T. Miller, “The cellular origins of the outer retinal bands in optical coherence tomography images,” Invest. Ophthalmol. Vis. Sci. 55(12), 7904–7918 (2014).
[PubMed]

R. A. Leitgeb, R. M. Werkmeister, C. Blatter, and L. Schmetterer, “Doppler optical coherence tomography,” Prog. Retin. Eye Res. 41(100), 26–43 (2014).
[PubMed]

2013 (7)

M. T. Tsai, C. K. Lee, F. Y. Chang, J. T. Wu, C. P. Wu, T. T. Chi, and C. C. Yang, “Noninvasive imaging of heart chamber in Drosophila with dual-beam optical coherence tomography,” J. Biophotonics 6(9), 708–717 (2013).
[PubMed]

H. M. Subhash, N. Choudhury, F. Chen, R. K. Wang, S. L. Jacques, and A. L. Nuttall, “Depth-resolved dual-beamlet vibrometry based on Fourier domain low coherence interferometry,” J. Biomed. Opt. 18(3), 036003 (2013).
[PubMed]

V. S. Makhijani, A. Roorda, J. K. Bayabo, K. K. Tong, C. A. Rivera-Carpio, and B. J. Lujan, “Chromatic visualization of reflectivity variance within hybridized directional OCT images,” Proc. SPIE 8571, 857105 (2013).

W. Trasischker, R. M. Werkmeister, S. Zotter, B. Baumann, T. Torzicky, M. Pircher, and C. K. Hitzenberger, “In vitro and in vivo three-dimensional velocity vector measurement by three-beam spectral-domain Doppler optical coherence tomography,” J. Biomed. Opt. 18(11), 116010 (2013).
[PubMed]

T. Klein, R. André, W. Wieser, T. Pfeiffer, and R. Huber, “Joint aperture detection for speckle reduction and increased collection efficiency in ophthalmic MHz OCT,” Biomed. Opt. Express 4(4), 619–634 (2013).
[PubMed]

B. Cense, Q. Wang, S. Lee, L. Zhao, A. E. Elsner, C. K. Hitzenberger, and D. T. Miller, “Henle fiber layer phase retardation measured with polarization-sensitive optical coherence tomography,” Biomed. Opt. Express 4(11), 2296–2306 (2013).
[PubMed]

B. Wang, B. Yin, J. Dwelle, H. G. Rylander, M. K. Markey, and T. E. Milner, “Path-length-multiplexed scattering-angle-diverse optical coherence tomography for retinal imaging,” Opt. Lett. 38(21), 4374–4377 (2013).
[PubMed]

2012 (4)

F. Jaillon, S. Makita, and Y. Yasuno, “Variable velocity range imaging of the choroid with dual-beam optical coherence angiography,” Opt. Express 20(1), 385–396 (2012).
[PubMed]

J. van der Schoot, K. A. Vermeer, J. F. de Boer, and H. G. Lemij, “The Effect of glaucoma on the optical attenuation coefficient of the retinal nerve fiber layer in spectral domain optical coherence tomography images,” Invest. Ophthalmol. Vis. Sci. 53(4), 2424–2430 (2012).
[PubMed]

K. A. Vermeer, J. van der Schoot, H. G. Lemij, and J. F. de Boer, “RPE-normalized RNFL attenuation coefficient maps derived from volumetric OCT imaging for glaucoma assessment,” Invest. Ophthalmol. Vis. Sci. 53(10), 6102–6108 (2012).
[PubMed]

N. Suehira, S. Ooto, M. Hangai, K. Matsumoto, N. Tomatsu, T. Yuasa, K. Yamada, and N. Yoshimura, “Three-beam spectral-domain optical coherence tomography for retinal imaging,” J. Biomed. Opt. 17(10), 106001 (2012).
[PubMed]

2011 (6)

X.-R. Huang, Y. Zhou, W. Kong, and R. W. Knighton, “Reflectance decreases before thickness changes in the retinal nerve fiber layer in glaucomatous retinas,” Invest. Ophthalmol. Vis. Sci. 52(9), 6737–6742 (2011).
[PubMed]

B. J. Lujan, A. Roorda, R. W. Knighton, and J. Carroll, “Revealing Henle’s fiber layer using spectral domain optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 52(3), 1486–1492 (2011).
[PubMed]

T. Otani, Y. Yamaguchi, and S. Kishi, “Improved visualization of Henle fiber layer by changing the measurement beam angle on optical coherence tomography,” Retina 31(3), 497–501 (2011).
[PubMed]

S. Zotter, M. Pircher, T. Torzicky, M. Bonesi, E. Götzinger, R. A. Leitgeb, and C. K. Hitzenberger, “Visualization of microvasculature by dual-beam phase-resolved Doppler optical coherence tomography,” Opt. Express 19(2), 1217–1227 (2011).
[PubMed]

S. Makita, F. Jaillon, M. Yamanari, M. Miura, and Y. Yasuno, “Comprehensive in vivo micro-vascular imaging of the human eye by dual-beam-scan Doppler optical coherence angiography,” Opt. Express 19(2), 1271–1283 (2011).
[PubMed]

D. Rativa and B. Vohnsen, “Analysis of individual cone-photoreceptor directionality using scanning laser ophthalmoscopy,” Biomed. Opt. Express 2(6), 1423–1431 (2011).
[PubMed]

2010 (2)

2009 (2)

M. K. K. Leung, A. Mariampillai, B. A. Standish, K. K. C. Lee, N. R. Munce, I. A. Vitkin, and V. X. D. Yang, “High-power wavelength-swept laser in Littman telescope-less polygon filter and dual-amplifier configuration for multichannel optical coherence tomography,” Opt. Lett. 34(18), 2814–2816 (2009).
[PubMed]

S. G. Schuman, A. F. Koreishi, S. Farsiu, S.-H. Jung, J. A. Izatt, and C. A. Toth, “Photoreceptor layer thinning over drusen in eyes with age-related macular degeneration imaged in vivo with spectral-domain optical coherence tomography,” Ophthalmology 116(3), 488–496 (2009).
[PubMed]

2008 (5)

2007 (1)

2006 (1)

2004 (2)

2003 (2)

Y. L. Kim, L. Yang, R. K. Wali, H. K. Roy, M. J. Goldberg, A. K. Kromin, C. Kun, and V. Backman, “Simultaneous measurement of angular and spectral properties of light scattering for characterization of tissue microarchitecture and its alteration in early precancer,” IEEE J. Sel. Top. Quantum Electron. 9(2), 243–256 (2003).

N. Iftimia, B. E. Bouma, and G. J. Tearney, “Speckle reduction in optical coherence tomography by “path length encoded” angular compounding,” J. Biomed. Opt. 8(2), 260–263 (2003).
[PubMed]

1997 (2)

J. M. Schmitt, “Array detection for speckle reduction in optical coherence microscopy,” Phys. Med. Biol. 42(7), 1427–1439 (1997).
[PubMed]

S. A. Burns, S. Wu, J. C. He, and A. E. Elsner, “Variations in photoreceptor directionally across the central retina,” J. Opt. Soc. Am. A 14(9), 2033–2040 (1997).
[PubMed]

1995 (1)

1992 (1)

R. W. Knighton, C. Baverez, and A. Bhattacharya, “The directional reflectance of the retinal nerve fiber layer of the toad,” Invest. Ophthalmol. Vis. Sci. 33(9), 2603–2611 (1992).
[PubMed]

1971 (1)

A. M. Laties and J. M. Enoch, “An analysis of retinal receptor orientation. I. Angular relationship of neighboring photoreceptors,” Invest. Ophthalmol. 10(1), 69–77 (1971).
[PubMed]

1967 (1)

G. Westheimer, “Dependence of the magnitude of the Stiles-Crawford effect on retinal location,” J. Physiol. 192(2), 309–315 (1967).
[PubMed]

1961 (1)

F. Fankhauser, J. Enoch, and P. Cibis, “Receptor orientation in retinal pathology. A first study,” Am. J. Ophthalmol. 52(5), 767–783 (1961).
[PubMed]

1933 (1)

W. S. Stiles and B. H. Crawford, “The luminous efficiency of rays entering the eye pupil at different points,” Proc. R. Soc. Lond., B 112(778), 428–450 (1933).

Abramoff, M. D.

B. J. Antony, P. F. Stetson, M. D. Abramoff, K. Lee, J. M. Colijn, G. H. Buitendijk, C. C. Klaver, A. Roorda, and B. J. Lujan, “Characterizing the impact of off-axis scan acquisition on the reproducibility of total retinal thickness measurements in SDOCT volumes,” Transl. Vis. Sci. Technol. 4(4), 3 (2015).
[PubMed]

Adler, D. C.

André, R.

Antony, B. J.

B. J. Lujan, A. Roorda, J. A. Croskrey, A. M. Dubis, R. F. Cooper, J. K. Bayabo, J. L. Duncan, B. J. Antony, and J. Carroll, “Directional optical coherence tomography provides accurate outer nuclear layer and Henle fiber layer measurements,” Retina 35(8), 1511–1520 (2015).
[PubMed]

B. J. Antony, P. F. Stetson, M. D. Abramoff, K. Lee, J. M. Colijn, G. H. Buitendijk, C. C. Klaver, A. Roorda, and B. J. Lujan, “Characterizing the impact of off-axis scan acquisition on the reproducibility of total retinal thickness measurements in SDOCT volumes,” Transl. Vis. Sci. Technol. 4(4), 3 (2015).
[PubMed]

Arshavsky, V. Y.

Augustin, M.

A. Lichtenegger, D. J. Harper, M. Augustin, P. Eugui, M. Muck, J. Gesperger, C. K. Hitzenberger, A. Woehrer, and B. Baumann, “Spectroscopic imaging with spectral domain visible light optical coherence microscopy in Alzheimer’s disease brain samples,” Biomed. Opt. Express 8(9), 4007–4025 (2017).
[PubMed]

A. Wartak, M. Augustin, F. Beer, R. Haindl, B. Baumann, M. Pircher, and C. K. Hitzenberger, “Sequential multi-channel OCT in the retina using high-speed fiber optical switches,” Proc. SPIE 10416, 1041607 (2017).

M. Augustin, S. Fialová, T. Himmel, M. Glösmann, T. Lengheimer, D. J. Harper, R. Plasenzotti, M. Pircher, C. K. Hitzenberger, and B. Baumann, “Multi-functional OCT enables longitudinal study of retinal changes in a VLDLR knockout mouse model,” PLoS One 11(10), e0164419 (2016).
[PubMed]

Bachmann, A. H.

Backman, V.

Y. L. Kim, L. Yang, R. K. Wali, H. K. Roy, M. J. Goldberg, A. K. Kromin, C. Kun, and V. Backman, “Simultaneous measurement of angular and spectral properties of light scattering for characterization of tissue microarchitecture and its alteration in early precancer,” IEEE J. Sel. Top. Quantum Electron. 9(2), 243–256 (2003).

Barr, H.

J. Holmes, S. Hattersley, N. Stone, F. Bazant-Hegemark, and H. Barr, “Multi-channel Fourier domain OCT system with superior lateral resolution for biomedical applications,” Proc. SPIE 6847, 68470O (2008).

Baumann, B.

A. Wartak, M. Augustin, F. Beer, R. Haindl, B. Baumann, M. Pircher, and C. K. Hitzenberger, “Sequential multi-channel OCT in the retina using high-speed fiber optical switches,” Proc. SPIE 10416, 1041607 (2017).

A. Lichtenegger, D. J. Harper, M. Augustin, P. Eugui, M. Muck, J. Gesperger, C. K. Hitzenberger, A. Woehrer, and B. Baumann, “Spectroscopic imaging with spectral domain visible light optical coherence microscopy in Alzheimer’s disease brain samples,” Biomed. Opt. Express 8(9), 4007–4025 (2017).
[PubMed]

M. Augustin, S. Fialová, T. Himmel, M. Glösmann, T. Lengheimer, D. J. Harper, R. Plasenzotti, M. Pircher, C. K. Hitzenberger, and B. Baumann, “Multi-functional OCT enables longitudinal study of retinal changes in a VLDLR knockout mouse model,” PLoS One 11(10), e0164419 (2016).
[PubMed]

A. Wartak, R. Haindl, W. Trasischker, B. Baumann, M. Pircher, and C. K. Hitzenberger, “Active-passive path-length encoded (APPLE) Doppler OCT,” Biomed. Opt. Express 7(12), 5233–5251 (2016).
[PubMed]

R. Haindl, W. Trasischker, A. Wartak, B. Baumann, M. Pircher, and C. K. Hitzenberger, “Total retinal blood flow and reproducibility evaluation by three beam optical Doppler tomography,” Biomed. Opt. Express 7(2), 287–301 (2016).
[PubMed]

R. Haindl, W. Trasischker, B. Baumann, M. Pircher, and C. K. Hitzenberger, “Three-beam Doppler optical coherence tomography using a facet prism telescope and MEMS mirror for improved transversal resolution,” J. Mod. Opt. 62(21), 1781–1788 (2015).
[PubMed]

W. Trasischker, R. M. Werkmeister, S. Zotter, B. Baumann, T. Torzicky, M. Pircher, and C. K. Hitzenberger, “In vitro and in vivo three-dimensional velocity vector measurement by three-beam spectral-domain Doppler optical coherence tomography,” J. Biomed. Opt. 18(11), 116010 (2013).
[PubMed]

Baverez, C.

R. W. Knighton, C. Baverez, and A. Bhattacharya, “The directional reflectance of the retinal nerve fiber layer of the toad,” Invest. Ophthalmol. Vis. Sci. 33(9), 2603–2611 (1992).
[PubMed]

Bayabo, J. K.

B. J. Lujan, A. Roorda, J. A. Croskrey, A. M. Dubis, R. F. Cooper, J. K. Bayabo, J. L. Duncan, B. J. Antony, and J. Carroll, “Directional optical coherence tomography provides accurate outer nuclear layer and Henle fiber layer measurements,” Retina 35(8), 1511–1520 (2015).
[PubMed]

V. S. Makhijani, A. Roorda, J. K. Bayabo, K. K. Tong, C. A. Rivera-Carpio, and B. J. Lujan, “Chromatic visualization of reflectivity variance within hybridized directional OCT images,” Proc. SPIE 8571, 857105 (2013).

Bazant-Hegemark, F.

J. Holmes, S. Hattersley, N. Stone, F. Bazant-Hegemark, and H. Barr, “Multi-channel Fourier domain OCT system with superior lateral resolution for biomedical applications,” Proc. SPIE 6847, 68470O (2008).

Beer, F.

A. Wartak, M. Augustin, F. Beer, R. Haindl, B. Baumann, M. Pircher, and C. K. Hitzenberger, “Sequential multi-channel OCT in the retina using high-speed fiber optical switches,” Proc. SPIE 10416, 1041607 (2017).

Bhattacharya, A.

R. W. Knighton, C. Baverez, and A. Bhattacharya, “The directional reflectance of the retinal nerve fiber layer of the toad,” Invest. Ophthalmol. Vis. Sci. 33(9), 2603–2611 (1992).
[PubMed]

Biedermann, B. R.

Blanco, L.

H. J. Morris, L. Blanco, J. L. Codona, S. L. Li, S. S. Choi, and N. Doble, “Directionality of individual cone photoreceptors in the parafoveal region,” Vision Res. 117, 67–80 (2015).
[PubMed]

Blatter, C.

R. A. Leitgeb, R. M. Werkmeister, C. Blatter, and L. Schmetterer, “Doppler optical coherence tomography,” Prog. Retin. Eye Res. 41(100), 26–43 (2014).
[PubMed]

Bonesi, M.

Bouma, B. E.

A. E. Desjardins, B. J. Vakoc, G. J. Tearney, and B. E. Bouma, “Speckle reduction in OCT using massively-parallel detection and frequency-domain ranging,” Opt. Express 14(11), 4736–4745 (2006).
[PubMed]

N. Iftimia, B. E. Bouma, and G. J. Tearney, “Speckle reduction in optical coherence tomography by “path length encoded” angular compounding,” J. Biomed. Opt. 8(2), 260–263 (2003).
[PubMed]

Bouwens, A.

Buitendijk, G. H.

B. J. Antony, P. F. Stetson, M. D. Abramoff, K. Lee, J. M. Colijn, G. H. Buitendijk, C. C. Klaver, A. Roorda, and B. J. Lujan, “Characterizing the impact of off-axis scan acquisition on the reproducibility of total retinal thickness measurements in SDOCT volumes,” Transl. Vis. Sci. Technol. 4(4), 3 (2015).
[PubMed]

Burns, S. A.

Carrasco-Zevallos, O.

Carroll, J.

B. J. Lujan, A. Roorda, J. A. Croskrey, A. M. Dubis, R. F. Cooper, J. K. Bayabo, J. L. Duncan, B. J. Antony, and J. Carroll, “Directional optical coherence tomography provides accurate outer nuclear layer and Henle fiber layer measurements,” Retina 35(8), 1511–1520 (2015).
[PubMed]

B. J. Lujan, A. Roorda, R. W. Knighton, and J. Carroll, “Revealing Henle’s fiber layer using spectral domain optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 52(3), 1486–1492 (2011).
[PubMed]

Cense, B.

Chang, F. Y.

M. T. Tsai, C. K. Lee, F. Y. Chang, J. T. Wu, C. P. Wu, T. T. Chi, and C. C. Yang, “Noninvasive imaging of heart chamber in Drosophila with dual-beam optical coherence tomography,” J. Biophotonics 6(9), 708–717 (2013).
[PubMed]

Chen, F.

H. M. Subhash, N. Choudhury, F. Chen, R. K. Wang, S. L. Jacques, and A. L. Nuttall, “Depth-resolved dual-beamlet vibrometry based on Fourier domain low coherence interferometry,” J. Biomed. Opt. 18(3), 036003 (2013).
[PubMed]

Chi, T. T.

M. T. Tsai, C. K. Lee, F. Y. Chang, J. T. Wu, C. P. Wu, T. T. Chi, and C. C. Yang, “Noninvasive imaging of heart chamber in Drosophila with dual-beam optical coherence tomography,” J. Biophotonics 6(9), 708–717 (2013).
[PubMed]

Choi, S. S.

H. J. Morris, L. Blanco, J. L. Codona, S. L. Li, S. S. Choi, and N. Doble, “Directionality of individual cone photoreceptors in the parafoveal region,” Vision Res. 117, 67–80 (2015).
[PubMed]

Choudhury, N.

H. M. Subhash, N. Choudhury, F. Chen, R. K. Wang, S. L. Jacques, and A. L. Nuttall, “Depth-resolved dual-beamlet vibrometry based on Fourier domain low coherence interferometry,” J. Biomed. Opt. 18(3), 036003 (2013).
[PubMed]

Cibis, P.

F. Fankhauser, J. Enoch, and P. Cibis, “Receptor orientation in retinal pathology. A first study,” Am. J. Ophthalmol. 52(5), 767–783 (1961).
[PubMed]

Codona, J. L.

H. J. Morris, L. Blanco, J. L. Codona, S. L. Li, S. S. Choi, and N. Doble, “Directionality of individual cone photoreceptors in the parafoveal region,” Vision Res. 117, 67–80 (2015).
[PubMed]

Colijn, J. M.

B. J. Antony, P. F. Stetson, M. D. Abramoff, K. Lee, J. M. Colijn, G. H. Buitendijk, C. C. Klaver, A. Roorda, and B. J. Lujan, “Characterizing the impact of off-axis scan acquisition on the reproducibility of total retinal thickness measurements in SDOCT volumes,” Transl. Vis. Sci. Technol. 4(4), 3 (2015).
[PubMed]

Cooper, R. F.

B. J. Lujan, A. Roorda, J. A. Croskrey, A. M. Dubis, R. F. Cooper, J. K. Bayabo, J. L. Duncan, B. J. Antony, and J. Carroll, “Directional optical coherence tomography provides accurate outer nuclear layer and Henle fiber layer measurements,” Retina 35(8), 1511–1520 (2015).
[PubMed]

Coquoz, S.

Crawford, B. H.

W. S. Stiles and B. H. Crawford, “The luminous efficiency of rays entering the eye pupil at different points,” Proc. R. Soc. Lond., B 112(778), 428–450 (1933).

Croskrey, J. A.

B. J. Lujan, A. Roorda, J. A. Croskrey, A. M. Dubis, R. F. Cooper, J. K. Bayabo, J. L. Duncan, B. J. Antony, and J. Carroll, “Directional optical coherence tomography provides accurate outer nuclear layer and Henle fiber layer measurements,” Retina 35(8), 1511–1520 (2015).
[PubMed]

de Boer, J. F.

J. van der Schoot, K. A. Vermeer, J. F. de Boer, and H. G. Lemij, “The Effect of glaucoma on the optical attenuation coefficient of the retinal nerve fiber layer in spectral domain optical coherence tomography images,” Invest. Ophthalmol. Vis. Sci. 53(4), 2424–2430 (2012).
[PubMed]

K. A. Vermeer, J. van der Schoot, H. G. Lemij, and J. F. de Boer, “RPE-normalized RNFL attenuation coefficient maps derived from volumetric OCT imaging for glaucoma assessment,” Invest. Ophthalmol. Vis. Sci. 53(10), 6102–6108 (2012).
[PubMed]

Delori, F.

Demirel, S.

S. K. Gardiner, S. Demirel, J. Reynaud, and B. Fortune, “Changes in retinal nerve fiber layer reflectance intensity as a predictor of functional progression in glaucoma,” Invest. Ophthalmol. Vis. Sci. 57(3), 1221–1227 (2016).
[PubMed]

Descloux, A.

Desjardins, A. E.

Doble, N.

H. J. Morris, L. Blanco, J. L. Codona, S. L. Li, S. S. Choi, and N. Doble, “Directionality of individual cone photoreceptors in the parafoveal region,” Vision Res. 117, 67–80 (2015).
[PubMed]

Dragostinoff, N.

Drexler, W.

W. Drexler and J. G. Fujimoto, “State-of-the-art retinal optical coherence tomography,” Prog. Retin. Eye Res. 27(1), 45–88 (2008).
[PubMed]

Dubis, A. M.

B. J. Lujan, A. Roorda, J. A. Croskrey, A. M. Dubis, R. F. Cooper, J. K. Bayabo, J. L. Duncan, B. J. Antony, and J. Carroll, “Directional optical coherence tomography provides accurate outer nuclear layer and Henle fiber layer measurements,” Retina 35(8), 1511–1520 (2015).
[PubMed]

Duncan, J. L.

B. J. Lujan, A. Roorda, J. A. Croskrey, A. M. Dubis, R. F. Cooper, J. K. Bayabo, J. L. Duncan, B. J. Antony, and J. Carroll, “Directional optical coherence tomography provides accurate outer nuclear layer and Henle fiber layer measurements,” Retina 35(8), 1511–1520 (2015).
[PubMed]

Dwelle, J.

Eigenwillig, C. M.

Elsner, A. E.

Enoch, J.

F. Fankhauser, J. Enoch, and P. Cibis, “Receptor orientation in retinal pathology. A first study,” Am. J. Ophthalmol. 52(5), 767–783 (1961).
[PubMed]

Enoch, J. M.

A. M. Laties and J. M. Enoch, “An analysis of retinal receptor orientation. I. Angular relationship of neighboring photoreceptors,” Invest. Ophthalmol. 10(1), 69–77 (1971).
[PubMed]

Eugui, P.

Extermann, J.

Fankhauser, F.

F. Fankhauser, J. Enoch, and P. Cibis, “Receptor orientation in retinal pathology. A first study,” Am. J. Ophthalmol. 52(5), 767–783 (1961).
[PubMed]

Farsiu, S.

P. P. Srinivasan, S. J. Heflin, J. A. Izatt, V. Y. Arshavsky, and S. Farsiu, “Automatic segmentation of up to ten layer boundaries in SD-OCT images of the mouse retina with and without missing layers due to pathology,” Biomed. Opt. Express 5(2), 348–365 (2014).
[PubMed]

S. G. Schuman, A. F. Koreishi, S. Farsiu, S.-H. Jung, J. A. Izatt, and C. A. Toth, “Photoreceptor layer thinning over drusen in eyes with age-related macular degeneration imaged in vivo with spectral-domain optical coherence tomography,” Ophthalmology 116(3), 488–496 (2009).
[PubMed]

Ferguson, R. D.

Ferrante, A. A.

Feuer, W. J.

Fialová, S.

M. Augustin, S. Fialová, T. Himmel, M. Glösmann, T. Lengheimer, D. J. Harper, R. Plasenzotti, M. Pircher, C. K. Hitzenberger, and B. Baumann, “Multi-functional OCT enables longitudinal study of retinal changes in a VLDLR knockout mouse model,” PLoS One 11(10), e0164419 (2016).
[PubMed]

Fortune, B.

S. K. Gardiner, S. Demirel, J. Reynaud, and B. Fortune, “Changes in retinal nerve fiber layer reflectance intensity as a predictor of functional progression in glaucoma,” Invest. Ophthalmol. Vis. Sci. 57(3), 1221–1227 (2016).
[PubMed]

Fujimoto, J. G.

W. Drexler and J. G. Fujimoto, “State-of-the-art retinal optical coherence tomography,” Prog. Retin. Eye Res. 27(1), 45–88 (2008).
[PubMed]

D. C. Adler, T. H. Ko, and J. G. Fujimoto, “Speckle reduction in optical coherence tomography images by use of a spatially adaptive wavelet filter,” Opt. Lett. 29(24), 2878–2880 (2004).
[PubMed]

Gao, W.

Gardiner, S. K.

S. K. Gardiner, S. Demirel, J. Reynaud, and B. Fortune, “Changes in retinal nerve fiber layer reflectance intensity as a predictor of functional progression in glaucoma,” Invest. Ophthalmol. Vis. Sci. 57(3), 1221–1227 (2016).
[PubMed]

Gesperger, J.

Glösmann, M.

M. Augustin, S. Fialová, T. Himmel, M. Glösmann, T. Lengheimer, D. J. Harper, R. Plasenzotti, M. Pircher, C. K. Hitzenberger, and B. Baumann, “Multi-functional OCT enables longitudinal study of retinal changes in a VLDLR knockout mouse model,” PLoS One 11(10), e0164419 (2016).
[PubMed]

Goldberg, M. J.

Y. L. Kim, L. Yang, R. K. Wali, H. K. Roy, M. J. Goldberg, A. K. Kromin, C. Kun, and V. Backman, “Simultaneous measurement of angular and spectral properties of light scattering for characterization of tissue microarchitecture and its alteration in early precancer,” IEEE J. Sel. Top. Quantum Electron. 9(2), 243–256 (2003).

Gordon, M. L.

Götzinger, E.

Haindl, R.

A. Wartak, M. Augustin, F. Beer, R. Haindl, B. Baumann, M. Pircher, and C. K. Hitzenberger, “Sequential multi-channel OCT in the retina using high-speed fiber optical switches,” Proc. SPIE 10416, 1041607 (2017).

A. Wartak, R. Haindl, W. Trasischker, B. Baumann, M. Pircher, and C. K. Hitzenberger, “Active-passive path-length encoded (APPLE) Doppler OCT,” Biomed. Opt. Express 7(12), 5233–5251 (2016).
[PubMed]

R. Haindl, W. Trasischker, A. Wartak, B. Baumann, M. Pircher, and C. K. Hitzenberger, “Total retinal blood flow and reproducibility evaluation by three beam optical Doppler tomography,” Biomed. Opt. Express 7(2), 287–301 (2016).
[PubMed]

R. Haindl, W. Trasischker, B. Baumann, M. Pircher, and C. K. Hitzenberger, “Three-beam Doppler optical coherence tomography using a facet prism telescope and MEMS mirror for improved transversal resolution,” J. Mod. Opt. 62(21), 1781–1788 (2015).
[PubMed]

Hammer, D. X.

Hangai, M.

N. Suehira, S. Ooto, M. Hangai, K. Matsumoto, N. Tomatsu, T. Yuasa, K. Yamada, and N. Yoshimura, “Three-beam spectral-domain optical coherence tomography for retinal imaging,” J. Biomed. Opt. 17(10), 106001 (2012).
[PubMed]

Harper, D. J.

A. Lichtenegger, D. J. Harper, M. Augustin, P. Eugui, M. Muck, J. Gesperger, C. K. Hitzenberger, A. Woehrer, and B. Baumann, “Spectroscopic imaging with spectral domain visible light optical coherence microscopy in Alzheimer’s disease brain samples,” Biomed. Opt. Express 8(9), 4007–4025 (2017).
[PubMed]

M. Augustin, S. Fialová, T. Himmel, M. Glösmann, T. Lengheimer, D. J. Harper, R. Plasenzotti, M. Pircher, C. K. Hitzenberger, and B. Baumann, “Multi-functional OCT enables longitudinal study of retinal changes in a VLDLR knockout mouse model,” PLoS One 11(10), e0164419 (2016).
[PubMed]

Hattersley, S.

J. Holmes, S. Hattersley, N. Stone, F. Bazant-Hegemark, and H. Barr, “Multi-channel Fourier domain OCT system with superior lateral resolution for biomedical applications,” Proc. SPIE 6847, 68470O (2008).

He, J. C.

Heflin, S. J.

Himmel, T.

M. Augustin, S. Fialová, T. Himmel, M. Glösmann, T. Lengheimer, D. J. Harper, R. Plasenzotti, M. Pircher, C. K. Hitzenberger, and B. Baumann, “Multi-functional OCT enables longitudinal study of retinal changes in a VLDLR knockout mouse model,” PLoS One 11(10), e0164419 (2016).
[PubMed]

Hitzenberger, C. K.

A. Lichtenegger, D. J. Harper, M. Augustin, P. Eugui, M. Muck, J. Gesperger, C. K. Hitzenberger, A. Woehrer, and B. Baumann, “Spectroscopic imaging with spectral domain visible light optical coherence microscopy in Alzheimer’s disease brain samples,” Biomed. Opt. Express 8(9), 4007–4025 (2017).
[PubMed]

A. Wartak, M. Augustin, F. Beer, R. Haindl, B. Baumann, M. Pircher, and C. K. Hitzenberger, “Sequential multi-channel OCT in the retina using high-speed fiber optical switches,” Proc. SPIE 10416, 1041607 (2017).

A. Wartak, R. Haindl, W. Trasischker, B. Baumann, M. Pircher, and C. K. Hitzenberger, “Active-passive path-length encoded (APPLE) Doppler OCT,” Biomed. Opt. Express 7(12), 5233–5251 (2016).
[PubMed]

M. Augustin, S. Fialová, T. Himmel, M. Glösmann, T. Lengheimer, D. J. Harper, R. Plasenzotti, M. Pircher, C. K. Hitzenberger, and B. Baumann, “Multi-functional OCT enables longitudinal study of retinal changes in a VLDLR knockout mouse model,” PLoS One 11(10), e0164419 (2016).
[PubMed]

R. Haindl, W. Trasischker, A. Wartak, B. Baumann, M. Pircher, and C. K. Hitzenberger, “Total retinal blood flow and reproducibility evaluation by three beam optical Doppler tomography,” Biomed. Opt. Express 7(2), 287–301 (2016).
[PubMed]

R. Haindl, W. Trasischker, B. Baumann, M. Pircher, and C. K. Hitzenberger, “Three-beam Doppler optical coherence tomography using a facet prism telescope and MEMS mirror for improved transversal resolution,” J. Mod. Opt. 62(21), 1781–1788 (2015).
[PubMed]

B. Cense, Q. Wang, S. Lee, L. Zhao, A. E. Elsner, C. K. Hitzenberger, and D. T. Miller, “Henle fiber layer phase retardation measured with polarization-sensitive optical coherence tomography,” Biomed. Opt. Express 4(11), 2296–2306 (2013).
[PubMed]

W. Trasischker, R. M. Werkmeister, S. Zotter, B. Baumann, T. Torzicky, M. Pircher, and C. K. Hitzenberger, “In vitro and in vivo three-dimensional velocity vector measurement by three-beam spectral-domain Doppler optical coherence tomography,” J. Biomed. Opt. 18(11), 116010 (2013).
[PubMed]

S. Zotter, M. Pircher, T. Torzicky, M. Bonesi, E. Götzinger, R. A. Leitgeb, and C. K. Hitzenberger, “Visualization of microvasculature by dual-beam phase-resolved Doppler optical coherence tomography,” Opt. Express 19(2), 1217–1227 (2011).
[PubMed]

S. Zotter, M. Pircher, E. Götzinger, T. Torzicky, M. Bonesi, and C. K. Hitzenberger, “Sample motion-insensitive, full-range, complex, spectral-domain optical-coherence tomography,” Opt. Lett. 35(23), 3913–3915 (2010).
[PubMed]

R. M. Werkmeister, N. Dragostinoff, M. Pircher, E. Götzinger, C. K. Hitzenberger, R. A. Leitgeb, and L. Schmetterer, “Bidirectional Doppler Fourier-domain optical coherence tomography for measurement of absolute flow velocities in human retinal vessels,” Opt. Lett. 33(24), 2967–2969 (2008).
[PubMed]

Holmes, J.

J. Holmes, S. Hattersley, N. Stone, F. Bazant-Hegemark, and H. Barr, “Multi-channel Fourier domain OCT system with superior lateral resolution for biomedical applications,” Proc. SPIE 6847, 68470O (2008).

Huang, X.-R.

X.-R. Huang, R. W. Knighton, W. J. Feuer, and J. Qiao, “Retinal nerve fiber layer reflectometry must consider directional reflectance,” Biomed. Opt. Express 7(1), 22–33 (2015).
[PubMed]

X.-R. Huang, Y. Zhou, W. Kong, and R. W. Knighton, “Reflectance decreases before thickness changes in the retinal nerve fiber layer in glaucomatous retinas,” Invest. Ophthalmol. Vis. Sci. 52(9), 6737–6742 (2011).
[PubMed]

Huber, R.

Iftimia, N.

N. Iftimia, B. E. Bouma, and G. J. Tearney, “Speckle reduction in optical coherence tomography by “path length encoded” angular compounding,” J. Biomed. Opt. 8(2), 260–263 (2003).
[PubMed]

Iftimia, N. V.

Izatt, J. A.

Jacques, S. L.

H. M. Subhash, N. Choudhury, F. Chen, R. K. Wang, S. L. Jacques, and A. L. Nuttall, “Depth-resolved dual-beamlet vibrometry based on Fourier domain low coherence interferometry,” J. Biomed. Opt. 18(3), 036003 (2013).
[PubMed]

Jaillon, F.

Jonnal, R. S.

R. S. Jonnal, O. P. Kocaoglu, R. J. Zawadzki, S.-H. Lee, J. S. Werner, and D. T. Miller, “The cellular origins of the outer retinal bands in optical coherence tomography images,” Invest. Ophthalmol. Vis. Sci. 55(12), 7904–7918 (2014).
[PubMed]

W. Gao, B. Cense, Y. Zhang, R. S. Jonnal, and D. T. Miller, “Measuring retinal contributions to the optical Stiles-Crawford effect with optical coherence tomography,” Opt. Express 16(9), 6486–6501 (2008).
[PubMed]

Jung, S.-H.

S. G. Schuman, A. F. Koreishi, S. Farsiu, S.-H. Jung, J. A. Izatt, and C. A. Toth, “Photoreceptor layer thinning over drusen in eyes with age-related macular degeneration imaged in vivo with spectral-domain optical coherence tomography,” Ophthalmology 116(3), 488–496 (2009).
[PubMed]

Keller, B.

Kim, Y. L.

Y. L. Kim, L. Yang, R. K. Wali, H. K. Roy, M. J. Goldberg, A. K. Kromin, C. Kun, and V. Backman, “Simultaneous measurement of angular and spectral properties of light scattering for characterization of tissue microarchitecture and its alteration in early precancer,” IEEE J. Sel. Top. Quantum Electron. 9(2), 243–256 (2003).

Kishi, S.

T. Otani, Y. Yamaguchi, and S. Kishi, “Improved visualization of Henle fiber layer by changing the measurement beam angle on optical coherence tomography,” Retina 31(3), 497–501 (2011).
[PubMed]

Klaver, C. C.

B. J. Antony, P. F. Stetson, M. D. Abramoff, K. Lee, J. M. Colijn, G. H. Buitendijk, C. C. Klaver, A. Roorda, and B. J. Lujan, “Characterizing the impact of off-axis scan acquisition on the reproducibility of total retinal thickness measurements in SDOCT volumes,” Transl. Vis. Sci. Technol. 4(4), 3 (2015).
[PubMed]

Klein, T.

Knighton, R. W.

X.-R. Huang, R. W. Knighton, W. J. Feuer, and J. Qiao, “Retinal nerve fiber layer reflectometry must consider directional reflectance,” Biomed. Opt. Express 7(1), 22–33 (2015).
[PubMed]

X.-R. Huang, Y. Zhou, W. Kong, and R. W. Knighton, “Reflectance decreases before thickness changes in the retinal nerve fiber layer in glaucomatous retinas,” Invest. Ophthalmol. Vis. Sci. 52(9), 6737–6742 (2011).
[PubMed]

B. J. Lujan, A. Roorda, R. W. Knighton, and J. Carroll, “Revealing Henle’s fiber layer using spectral domain optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 52(3), 1486–1492 (2011).
[PubMed]

R. W. Knighton, C. Baverez, and A. Bhattacharya, “The directional reflectance of the retinal nerve fiber layer of the toad,” Invest. Ophthalmol. Vis. Sci. 33(9), 2603–2611 (1992).
[PubMed]

Ko, T. H.

Kocaoglu, O. P.

Z. Liu, O. P. Kocaoglu, and D. T. Miller, “3D imaging of retinal pigment epithelial cells in the living human Retina,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT533 (2016).
[PubMed]

R. S. Jonnal, O. P. Kocaoglu, R. J. Zawadzki, S.-H. Lee, J. S. Werner, and D. T. Miller, “The cellular origins of the outer retinal bands in optical coherence tomography images,” Invest. Ophthalmol. Vis. Sci. 55(12), 7904–7918 (2014).
[PubMed]

Kong, W.

X.-R. Huang, Y. Zhou, W. Kong, and R. W. Knighton, “Reflectance decreases before thickness changes in the retinal nerve fiber layer in glaucomatous retinas,” Invest. Ophthalmol. Vis. Sci. 52(9), 6737–6742 (2011).
[PubMed]

Koreishi, A. F.

S. G. Schuman, A. F. Koreishi, S. Farsiu, S.-H. Jung, J. A. Izatt, and C. A. Toth, “Photoreceptor layer thinning over drusen in eyes with age-related macular degeneration imaged in vivo with spectral-domain optical coherence tomography,” Ophthalmology 116(3), 488–496 (2009).
[PubMed]

Kromin, A. K.

Y. L. Kim, L. Yang, R. K. Wali, H. K. Roy, M. J. Goldberg, A. K. Kromin, C. Kun, and V. Backman, “Simultaneous measurement of angular and spectral properties of light scattering for characterization of tissue microarchitecture and its alteration in early precancer,” IEEE J. Sel. Top. Quantum Electron. 9(2), 243–256 (2003).

Kun, C.

Y. L. Kim, L. Yang, R. K. Wali, H. K. Roy, M. J. Goldberg, A. K. Kromin, C. Kun, and V. Backman, “Simultaneous measurement of angular and spectral properties of light scattering for characterization of tissue microarchitecture and its alteration in early precancer,” IEEE J. Sel. Top. Quantum Electron. 9(2), 243–256 (2003).

Lasser, T.

Laties, A. M.

A. M. Laties and J. M. Enoch, “An analysis of retinal receptor orientation. I. Angular relationship of neighboring photoreceptors,” Invest. Ophthalmol. 10(1), 69–77 (1971).
[PubMed]

Lee, C. K.

M. T. Tsai, C. K. Lee, F. Y. Chang, J. T. Wu, C. P. Wu, T. T. Chi, and C. C. Yang, “Noninvasive imaging of heart chamber in Drosophila with dual-beam optical coherence tomography,” J. Biophotonics 6(9), 708–717 (2013).
[PubMed]

Lee, K.

B. J. Antony, P. F. Stetson, M. D. Abramoff, K. Lee, J. M. Colijn, G. H. Buitendijk, C. C. Klaver, A. Roorda, and B. J. Lujan, “Characterizing the impact of off-axis scan acquisition on the reproducibility of total retinal thickness measurements in SDOCT volumes,” Transl. Vis. Sci. Technol. 4(4), 3 (2015).
[PubMed]

Lee, K. K. C.

Lee, S.

Lee, S.-H.

R. S. Jonnal, O. P. Kocaoglu, R. J. Zawadzki, S.-H. Lee, J. S. Werner, and D. T. Miller, “The cellular origins of the outer retinal bands in optical coherence tomography images,” Invest. Ophthalmol. Vis. Sci. 55(12), 7904–7918 (2014).
[PubMed]

Leitgeb, R. A.

Lemij, H. G.

J. van der Schoot, K. A. Vermeer, J. F. de Boer, and H. G. Lemij, “The Effect of glaucoma on the optical attenuation coefficient of the retinal nerve fiber layer in spectral domain optical coherence tomography images,” Invest. Ophthalmol. Vis. Sci. 53(4), 2424–2430 (2012).
[PubMed]

K. A. Vermeer, J. van der Schoot, H. G. Lemij, and J. F. de Boer, “RPE-normalized RNFL attenuation coefficient maps derived from volumetric OCT imaging for glaucoma assessment,” Invest. Ophthalmol. Vis. Sci. 53(10), 6102–6108 (2012).
[PubMed]

Lengheimer, T.

M. Augustin, S. Fialová, T. Himmel, M. Glösmann, T. Lengheimer, D. J. Harper, R. Plasenzotti, M. Pircher, C. K. Hitzenberger, and B. Baumann, “Multi-functional OCT enables longitudinal study of retinal changes in a VLDLR knockout mouse model,” PLoS One 11(10), e0164419 (2016).
[PubMed]

Leung, M. K. K.

Li, S. L.

H. J. Morris, L. Blanco, J. L. Codona, S. L. Li, S. S. Choi, and N. Doble, “Directionality of individual cone photoreceptors in the parafoveal region,” Vision Res. 117, 67–80 (2015).
[PubMed]

Lichtenegger, A.

Liu, Z.

Z. Liu, O. P. Kocaoglu, and D. T. Miller, “3D imaging of retinal pigment epithelial cells in the living human Retina,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT533 (2016).
[PubMed]

Lo, S.

Lujan, B. J.

O. Carrasco-Zevallos, D. Nankivil, B. Keller, C. Viehland, B. J. Lujan, and J. A. Izatt, “Pupil tracking optical coherence tomography for precise control of pupil entry position,” Biomed. Opt. Express 6(9), 3405–3419 (2015).
[PubMed]

B. J. Lujan, A. Roorda, J. A. Croskrey, A. M. Dubis, R. F. Cooper, J. K. Bayabo, J. L. Duncan, B. J. Antony, and J. Carroll, “Directional optical coherence tomography provides accurate outer nuclear layer and Henle fiber layer measurements,” Retina 35(8), 1511–1520 (2015).
[PubMed]

B. J. Antony, P. F. Stetson, M. D. Abramoff, K. Lee, J. M. Colijn, G. H. Buitendijk, C. C. Klaver, A. Roorda, and B. J. Lujan, “Characterizing the impact of off-axis scan acquisition on the reproducibility of total retinal thickness measurements in SDOCT volumes,” Transl. Vis. Sci. Technol. 4(4), 3 (2015).
[PubMed]

V. S. Makhijani, A. Roorda, J. K. Bayabo, K. K. Tong, C. A. Rivera-Carpio, and B. J. Lujan, “Chromatic visualization of reflectivity variance within hybridized directional OCT images,” Proc. SPIE 8571, 857105 (2013).

B. J. Lujan, A. Roorda, R. W. Knighton, and J. Carroll, “Revealing Henle’s fiber layer using spectral domain optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 52(3), 1486–1492 (2011).
[PubMed]

Makhijani, V. S.

V. S. Makhijani, A. Roorda, J. K. Bayabo, K. K. Tong, C. A. Rivera-Carpio, and B. J. Lujan, “Chromatic visualization of reflectivity variance within hybridized directional OCT images,” Proc. SPIE 8571, 857105 (2013).

Makita, S.

Marchand, P. J.

Marcon, N. E.

Mariampillai, A.

Markey, M. K.

Matsumoto, K.

N. Suehira, S. Ooto, M. Hangai, K. Matsumoto, N. Tomatsu, T. Yuasa, K. Yamada, and N. Yoshimura, “Three-beam spectral-domain optical coherence tomography for retinal imaging,” J. Biomed. Opt. 17(10), 106001 (2012).
[PubMed]

Michaely, R.

Miller, D. T.

Z. Liu, O. P. Kocaoglu, and D. T. Miller, “3D imaging of retinal pigment epithelial cells in the living human Retina,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT533 (2016).
[PubMed]

R. S. Jonnal, O. P. Kocaoglu, R. J. Zawadzki, S.-H. Lee, J. S. Werner, and D. T. Miller, “The cellular origins of the outer retinal bands in optical coherence tomography images,” Invest. Ophthalmol. Vis. Sci. 55(12), 7904–7918 (2014).
[PubMed]

B. Cense, Q. Wang, S. Lee, L. Zhao, A. E. Elsner, C. K. Hitzenberger, and D. T. Miller, “Henle fiber layer phase retardation measured with polarization-sensitive optical coherence tomography,” Biomed. Opt. Express 4(11), 2296–2306 (2013).
[PubMed]

W. Gao, B. Cense, Y. Zhang, R. S. Jonnal, and D. T. Miller, “Measuring retinal contributions to the optical Stiles-Crawford effect with optical coherence tomography,” Opt. Express 16(9), 6486–6501 (2008).
[PubMed]

Milner, T. E.

Miura, M.

Morris, H. J.

H. J. Morris, L. Blanco, J. L. Codona, S. L. Li, S. S. Choi, and N. Doble, “Directionality of individual cone photoreceptors in the parafoveal region,” Vision Res. 117, 67–80 (2015).
[PubMed]

Muck, M.

Mujat, M.

Munce, N.

Munce, N. R.

Nankivil, D.

Nguyen, D.

Nuttall, A. L.

H. M. Subhash, N. Choudhury, F. Chen, R. K. Wang, S. L. Jacques, and A. L. Nuttall, “Depth-resolved dual-beamlet vibrometry based on Fourier domain low coherence interferometry,” J. Biomed. Opt. 18(3), 036003 (2013).
[PubMed]

Ooto, S.

N. Suehira, S. Ooto, M. Hangai, K. Matsumoto, N. Tomatsu, T. Yuasa, K. Yamada, and N. Yoshimura, “Three-beam spectral-domain optical coherence tomography for retinal imaging,” J. Biomed. Opt. 17(10), 106001 (2012).
[PubMed]

Otani, T.

T. Otani, Y. Yamaguchi, and S. Kishi, “Improved visualization of Henle fiber layer by changing the measurement beam angle on optical coherence tomography,” Retina 31(3), 497–501 (2011).
[PubMed]

Pekar, J.

Pfeiffer, T.

Pircher, M.

M. Pircher and R. J. Zawadzki, “Review of adaptive optics OCT (AO-OCT): principles and applications for retinal imaging [Invited],” Biomed. Opt. Express 8(5), 2536–2562 (2017).
[PubMed]

A. Wartak, M. Augustin, F. Beer, R. Haindl, B. Baumann, M. Pircher, and C. K. Hitzenberger, “Sequential multi-channel OCT in the retina using high-speed fiber optical switches,” Proc. SPIE 10416, 1041607 (2017).

A. Wartak, R. Haindl, W. Trasischker, B. Baumann, M. Pircher, and C. K. Hitzenberger, “Active-passive path-length encoded (APPLE) Doppler OCT,” Biomed. Opt. Express 7(12), 5233–5251 (2016).
[PubMed]

M. Augustin, S. Fialová, T. Himmel, M. Glösmann, T. Lengheimer, D. J. Harper, R. Plasenzotti, M. Pircher, C. K. Hitzenberger, and B. Baumann, “Multi-functional OCT enables longitudinal study of retinal changes in a VLDLR knockout mouse model,” PLoS One 11(10), e0164419 (2016).
[PubMed]

R. Haindl, W. Trasischker, A. Wartak, B. Baumann, M. Pircher, and C. K. Hitzenberger, “Total retinal blood flow and reproducibility evaluation by three beam optical Doppler tomography,” Biomed. Opt. Express 7(2), 287–301 (2016).
[PubMed]

R. Haindl, W. Trasischker, B. Baumann, M. Pircher, and C. K. Hitzenberger, “Three-beam Doppler optical coherence tomography using a facet prism telescope and MEMS mirror for improved transversal resolution,” J. Mod. Opt. 62(21), 1781–1788 (2015).
[PubMed]

W. Trasischker, R. M. Werkmeister, S. Zotter, B. Baumann, T. Torzicky, M. Pircher, and C. K. Hitzenberger, “In vitro and in vivo three-dimensional velocity vector measurement by three-beam spectral-domain Doppler optical coherence tomography,” J. Biomed. Opt. 18(11), 116010 (2013).
[PubMed]

S. Zotter, M. Pircher, T. Torzicky, M. Bonesi, E. Götzinger, R. A. Leitgeb, and C. K. Hitzenberger, “Visualization of microvasculature by dual-beam phase-resolved Doppler optical coherence tomography,” Opt. Express 19(2), 1217–1227 (2011).
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S. Zotter, M. Pircher, E. Götzinger, T. Torzicky, M. Bonesi, and C. K. Hitzenberger, “Sample motion-insensitive, full-range, complex, spectral-domain optical-coherence tomography,” Opt. Lett. 35(23), 3913–3915 (2010).
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R. M. Werkmeister, N. Dragostinoff, M. Pircher, E. Götzinger, C. K. Hitzenberger, R. A. Leitgeb, and L. Schmetterer, “Bidirectional Doppler Fourier-domain optical coherence tomography for measurement of absolute flow velocities in human retinal vessels,” Opt. Lett. 33(24), 2967–2969 (2008).
[PubMed]

Plasenzotti, R.

M. Augustin, S. Fialová, T. Himmel, M. Glösmann, T. Lengheimer, D. J. Harper, R. Plasenzotti, M. Pircher, C. K. Hitzenberger, and B. Baumann, “Multi-functional OCT enables longitudinal study of retinal changes in a VLDLR knockout mouse model,” PLoS One 11(10), e0164419 (2016).
[PubMed]

Qiao, J.

Rativa, D.

Reynaud, J.

S. K. Gardiner, S. Demirel, J. Reynaud, and B. Fortune, “Changes in retinal nerve fiber layer reflectance intensity as a predictor of functional progression in glaucoma,” Invest. Ophthalmol. Vis. Sci. 57(3), 1221–1227 (2016).
[PubMed]

Rivera-Carpio, C. A.

V. S. Makhijani, A. Roorda, J. K. Bayabo, K. K. Tong, C. A. Rivera-Carpio, and B. J. Lujan, “Chromatic visualization of reflectivity variance within hybridized directional OCT images,” Proc. SPIE 8571, 857105 (2013).

Roorda, A.

B. J. Antony, P. F. Stetson, M. D. Abramoff, K. Lee, J. M. Colijn, G. H. Buitendijk, C. C. Klaver, A. Roorda, and B. J. Lujan, “Characterizing the impact of off-axis scan acquisition on the reproducibility of total retinal thickness measurements in SDOCT volumes,” Transl. Vis. Sci. Technol. 4(4), 3 (2015).
[PubMed]

B. J. Lujan, A. Roorda, J. A. Croskrey, A. M. Dubis, R. F. Cooper, J. K. Bayabo, J. L. Duncan, B. J. Antony, and J. Carroll, “Directional optical coherence tomography provides accurate outer nuclear layer and Henle fiber layer measurements,” Retina 35(8), 1511–1520 (2015).
[PubMed]

V. S. Makhijani, A. Roorda, J. K. Bayabo, K. K. Tong, C. A. Rivera-Carpio, and B. J. Lujan, “Chromatic visualization of reflectivity variance within hybridized directional OCT images,” Proc. SPIE 8571, 857105 (2013).

B. J. Lujan, A. Roorda, R. W. Knighton, and J. Carroll, “Revealing Henle’s fiber layer using spectral domain optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 52(3), 1486–1492 (2011).
[PubMed]

Roy, H. K.

Y. L. Kim, L. Yang, R. K. Wali, H. K. Roy, M. J. Goldberg, A. K. Kromin, C. Kun, and V. Backman, “Simultaneous measurement of angular and spectral properties of light scattering for characterization of tissue microarchitecture and its alteration in early precancer,” IEEE J. Sel. Top. Quantum Electron. 9(2), 243–256 (2003).

Rylander, H. G.

Schmetterer, L.

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S. G. Schuman, A. F. Koreishi, S. Farsiu, S.-H. Jung, J. A. Izatt, and C. A. Toth, “Photoreceptor layer thinning over drusen in eyes with age-related macular degeneration imaged in vivo with spectral-domain optical coherence tomography,” Ophthalmology 116(3), 488–496 (2009).
[PubMed]

Sison, M.

Srinivasan, P. P.

Standish, B. A.

Stetson, P. F.

B. J. Antony, P. F. Stetson, M. D. Abramoff, K. Lee, J. M. Colijn, G. H. Buitendijk, C. C. Klaver, A. Roorda, and B. J. Lujan, “Characterizing the impact of off-axis scan acquisition on the reproducibility of total retinal thickness measurements in SDOCT volumes,” Transl. Vis. Sci. Technol. 4(4), 3 (2015).
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W. S. Stiles and B. H. Crawford, “The luminous efficiency of rays entering the eye pupil at different points,” Proc. R. Soc. Lond., B 112(778), 428–450 (1933).

Stone, N.

J. Holmes, S. Hattersley, N. Stone, F. Bazant-Hegemark, and H. Barr, “Multi-channel Fourier domain OCT system with superior lateral resolution for biomedical applications,” Proc. SPIE 6847, 68470O (2008).

Subhash, H. M.

H. M. Subhash, N. Choudhury, F. Chen, R. K. Wang, S. L. Jacques, and A. L. Nuttall, “Depth-resolved dual-beamlet vibrometry based on Fourier domain low coherence interferometry,” J. Biomed. Opt. 18(3), 036003 (2013).
[PubMed]

Suehira, N.

N. Suehira, S. Ooto, M. Hangai, K. Matsumoto, N. Tomatsu, T. Yuasa, K. Yamada, and N. Yoshimura, “Three-beam spectral-domain optical coherence tomography for retinal imaging,” J. Biomed. Opt. 17(10), 106001 (2012).
[PubMed]

Szlag, D.

Tearney, G. J.

A. E. Desjardins, B. J. Vakoc, G. J. Tearney, and B. E. Bouma, “Speckle reduction in OCT using massively-parallel detection and frequency-domain ranging,” Opt. Express 14(11), 4736–4745 (2006).
[PubMed]

N. Iftimia, B. E. Bouma, and G. J. Tearney, “Speckle reduction in optical coherence tomography by “path length encoded” angular compounding,” J. Biomed. Opt. 8(2), 260–263 (2003).
[PubMed]

Tomatsu, N.

N. Suehira, S. Ooto, M. Hangai, K. Matsumoto, N. Tomatsu, T. Yuasa, K. Yamada, and N. Yoshimura, “Three-beam spectral-domain optical coherence tomography for retinal imaging,” J. Biomed. Opt. 17(10), 106001 (2012).
[PubMed]

Tong, K. K.

V. S. Makhijani, A. Roorda, J. K. Bayabo, K. K. Tong, C. A. Rivera-Carpio, and B. J. Lujan, “Chromatic visualization of reflectivity variance within hybridized directional OCT images,” Proc. SPIE 8571, 857105 (2013).

Torzicky, T.

Toth, C. A.

S. G. Schuman, A. F. Koreishi, S. Farsiu, S.-H. Jung, J. A. Izatt, and C. A. Toth, “Photoreceptor layer thinning over drusen in eyes with age-related macular degeneration imaged in vivo with spectral-domain optical coherence tomography,” Ophthalmology 116(3), 488–496 (2009).
[PubMed]

Trasischker, W.

A. Wartak, R. Haindl, W. Trasischker, B. Baumann, M. Pircher, and C. K. Hitzenberger, “Active-passive path-length encoded (APPLE) Doppler OCT,” Biomed. Opt. Express 7(12), 5233–5251 (2016).
[PubMed]

R. Haindl, W. Trasischker, A. Wartak, B. Baumann, M. Pircher, and C. K. Hitzenberger, “Total retinal blood flow and reproducibility evaluation by three beam optical Doppler tomography,” Biomed. Opt. Express 7(2), 287–301 (2016).
[PubMed]

R. Haindl, W. Trasischker, B. Baumann, M. Pircher, and C. K. Hitzenberger, “Three-beam Doppler optical coherence tomography using a facet prism telescope and MEMS mirror for improved transversal resolution,” J. Mod. Opt. 62(21), 1781–1788 (2015).
[PubMed]

W. Trasischker, R. M. Werkmeister, S. Zotter, B. Baumann, T. Torzicky, M. Pircher, and C. K. Hitzenberger, “In vitro and in vivo three-dimensional velocity vector measurement by three-beam spectral-domain Doppler optical coherence tomography,” J. Biomed. Opt. 18(11), 116010 (2013).
[PubMed]

Tsai, M. T.

M. T. Tsai, C. K. Lee, F. Y. Chang, J. T. Wu, C. P. Wu, T. T. Chi, and C. C. Yang, “Noninvasive imaging of heart chamber in Drosophila with dual-beam optical coherence tomography,” J. Biophotonics 6(9), 708–717 (2013).
[PubMed]

Vakoc, B. J.

van der Schoot, J.

K. A. Vermeer, J. van der Schoot, H. G. Lemij, and J. F. de Boer, “RPE-normalized RNFL attenuation coefficient maps derived from volumetric OCT imaging for glaucoma assessment,” Invest. Ophthalmol. Vis. Sci. 53(10), 6102–6108 (2012).
[PubMed]

J. van der Schoot, K. A. Vermeer, J. F. de Boer, and H. G. Lemij, “The Effect of glaucoma on the optical attenuation coefficient of the retinal nerve fiber layer in spectral domain optical coherence tomography images,” Invest. Ophthalmol. Vis. Sci. 53(4), 2424–2430 (2012).
[PubMed]

Vermeer, K. A.

J. van der Schoot, K. A. Vermeer, J. F. de Boer, and H. G. Lemij, “The Effect of glaucoma on the optical attenuation coefficient of the retinal nerve fiber layer in spectral domain optical coherence tomography images,” Invest. Ophthalmol. Vis. Sci. 53(4), 2424–2430 (2012).
[PubMed]

K. A. Vermeer, J. van der Schoot, H. G. Lemij, and J. F. de Boer, “RPE-normalized RNFL attenuation coefficient maps derived from volumetric OCT imaging for glaucoma assessment,” Invest. Ophthalmol. Vis. Sci. 53(10), 6102–6108 (2012).
[PubMed]

Viehland, C.

Vitkin, I. A.

Vohnsen, B.

Vu, D.

Wali, R. K.

Y. L. Kim, L. Yang, R. K. Wali, H. K. Roy, M. J. Goldberg, A. K. Kromin, C. Kun, and V. Backman, “Simultaneous measurement of angular and spectral properties of light scattering for characterization of tissue microarchitecture and its alteration in early precancer,” IEEE J. Sel. Top. Quantum Electron. 9(2), 243–256 (2003).

Wang, B.

Wang, Q.

Wang, R. K.

H. M. Subhash, N. Choudhury, F. Chen, R. K. Wang, S. L. Jacques, and A. L. Nuttall, “Depth-resolved dual-beamlet vibrometry based on Fourier domain low coherence interferometry,” J. Biomed. Opt. 18(3), 036003 (2013).
[PubMed]

Wartak, A.

Werkmeister, R. M.

R. A. Leitgeb, R. M. Werkmeister, C. Blatter, and L. Schmetterer, “Doppler optical coherence tomography,” Prog. Retin. Eye Res. 41(100), 26–43 (2014).
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Figures (10)

Fig. 1
Fig. 1 (a) Fundus photo of a healthy eye indicating the two retinal regions of interest (ROIs) investigated in this work: the perpapillary (including the ONH) and the macular region (including the fovea). The applied scanning patterns per ROI are indicated by black arrows (ONH: circumpapillary (CP); fovea: linear and raster). (b) Representative linear scan through the macular region of the same eye. Retinal and choroidal layers (labelled according to [36]): ILM – inner limiting membrane; RNFL – retinal nerve fiber layer; GCL – ganglion cell layer; IPL – inner plexiform layer; INL – inner nuclear layer; OPL – outer plexiform layer; HFL – Henle’s fiber layer; ONL – outer nuclear layer; ELM – external limiting membrane; IS/OS – inner segment/outer segment junction; OS – outer segments; COST/RPE – cone outer segment tips/retinal pigment epithelium; ICH – inner choroid; OCH – outer choroid. (c) Schematics of the three-channel illumination (equilateral triangle geometry). (d) Beam configuration on the 2D-MEMS scanner (in the equilateral triangle geometry all three beams are positioned off-pivot).

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Fig. 2
Fig. 2 Flowchart diagram of image analysis for revealing directional contrast among the three simultaneously acquired intensity B-scans. (a) Single-frame registered B-scans of the three channels. (b) Color coded B-scans of (a). (c) Intensity/color averaged and intensity/color maximum intensity projection (MIP) of the three respective fused B-scans. (d) Additive color scheme of primary and secondary colors.

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Fig. 3
Fig. 3 CP intensity B-scans of the ONH region. (a) Channel-1 (cyan). (b) Channel-2 (magenta). (c) Channel-3 (yellow). (d) Color averaged image of the three channels. (e)-(h) Zoom-ins of the indicated respective ROI. Scale bars: 0.5 mm (horizontally), 0.2 mm (vertically).

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Fig. 4
Fig. 4 Quantitative evaluation of the IS/OS-COST complex. (a) Representative CP B-scan indicating the evaluation window in between the red lines (20 depth-pixels or ~70 μm). (b) Normalized and smoothed intensity distribution within the evaluation window as a function of the azimuth angle (channel-1: cyan; channel-2: magenta; channel-3: yellow). (c) Polar plot of (b): intensity (radius) as a function of the azimuth angle. (d) Color fundus photo (grayscale) overlay of (c) and indication of the respective equilateral triangle beam geometry.

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Fig. 5
Fig. 5 Investigation of the repeatability of the quantitative evaluation of the IS/OS-COST complex in one eye of a healthy volunteer. (a) Mean and standard deviation (shaded area indicates ± one standard deviation) of five measurements (acquired within two consecutive days) per channel (channel-1: cyan; channel-2: magenta; channel-3: yellow). Normalized intensity as a function of the A-scan number (or the respective azimuth angle). (b) Polar plot of the mean data of (a): intensity (radius) as a function of the azimuth angle.

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Fig. 6
Fig. 6 Investigation of the variability among subjects of multi-directional OCT findings in two additional eyes of two healthy volunteers. (a), (c) Color averaged images of two eyes of two subjects. (b), (d) Respective normalized and smoothed polar plots of the intensity distribution within the evaluation window as a function of the azimuth angle (channel-1: cyan; channel-2: magenta; channel-3: yellow). Scale bars: 0.5 mm (horizontally), 0.2 mm (vertically).

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Fig. 7
Fig. 7 Quantitative evaluation of the RNFL. (a) Representative CP B-scan indicating the evaluation window in between the green lines (15 depth-pixels or ~53 μm). (b) Normalized and smoothed intensity distribution within the evaluation window as a function of the azimuth angle (channel-1: cyan; channel-2: magenta; channel-3: yellow). (c) Polar plot of (b): intensity (radius) as a function of the azimuth angle.

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Fig. 8
Fig. 8 Linear ((a)-(o); 16-times averaged) and volumetric ((p)-(s); single-frame) intensity macular imaging results. (a) Channel-1 (cyan). (b) Channel-2 (magenta). (c) Channel-3 (yellow). (d) Intensity average of the three channels. (e) Color averaged image of the three channels. (f)-(o) Zoom-ins of the indicated respective ROIs. (p) Cross-sectional view of a 3D rendering of a color MIP near the foveal pit. (q) Zoom-in of the indicated ROI in (p) to better visualize HFL. (r) 3D rendering of the volumetric data cube (channel-2). (s) Visualization of HFL in a color MIP en-face projection including indication of the respective equilateral triangle beam geometry. Scale bars: 0.5 mm (horizontally), 0.2 mm (vertically).

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Fig. 9
Fig. 9 Compensation of directional reflectivity and comparison of pupil entry position. (a) Single-frame CP intensity B-scan of the off-centered channel-2. (b) Three-channel off-center CP intensity B-scan MIP. (c), (d) Indicated ROI zoom-ins of the PR-layer. (e) Single-frame CP intensity B-scan of the pupil-centered channel-1. (f) MIP of a CP intensity B-scan of the three-frame averaged pupil centered channel-1. Scale bars: 0.5 mm (horizontally), 0.2 mm (vertically).

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Fig. 10
Fig. 10 Speckle reduction comparison. (a) Single-frame CP intensity B-scan of channel-1 (a). (b) Three-channel-averaged CP intensity B-scan. (c), (d) Indicated ROI-1 zoom-in on the entire retinal cross-section. (e), (f) Indicated ROI-2 zoom-in on the RNFL. Scale bars: 0.5 mm (horizontally), 0.2 mm (vertically).

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Tables (1)

Tables Icon

Table 1 Speckle reduction performance metrics SNR, CNR and ENL for the CP scans depicted in Fig. 10 averaged over five ROIs per image (homogenous signal part from within the RNFL). The single-frame CP B-scans of the three individual channels were evaluated and the respective mean values were compared to the values obtained from the intensity averaged CP B-scan.

View Table

Equations (3)

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SNR=10× log 10 ( μ s.lin 2 σ b,lin 2 ),
CNR= μ s,log − μ b,log σ s,log 2 + σ b,log 2 ,
ENL= μ s,log 2 σ s,log 2 ,

Metrics