Abstract

We present the first spectral domain optical coherence tomography (SD-OCT) system that combines an isotropic imaging resolution of ~1.5 µm in biological tissue with a 250 kHz image acquisition rate, for in vivo non-contact, volumetric imaging of the cellular structure of the human cornea. OCT images of the healthy human cornea acquired with this system reveal the cellular structure of the corneal epithelium, cellular debris and mucin clusters in the tear film, the shape, size and spatial distribution of the sub-basal corneal nerves and keratocytes in the corneal stroma, as well as reflections from endothelial nuclei. The corneal images presented here demonstrate the potential clinical value of the new high speed, high resolution OCT system for non-invasive diagnostics and monitoring the treatment of corneal diseases.

© 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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2018 (2)

V. Mazlin, P. Xiao, E. Dalimier, K. Grieve, K. Irsch, J. A. Sahel, M. Fink, and A. C. Boccara, “In vivo high resolution human corneal imaging using full-field OCT,” Biomed. Opt. Express 8(2), 557–568 (2018).
[Crossref] [PubMed]

L. Ginner, T. Schmoll, A. Kumar, M. Salas, N. Pricoupenko, L. M. Wurster, and R. A. Leitgeb, “Holographic line field en-face OCT with digital adaptive optics in the retina in vivo,” Biomed. Opt. Express 9(2), 472–485 (2018).
[Crossref] [PubMed]

2017 (4)

2016 (2)

K. Grieve, C. Georgeon, F. Andreiuolo, M. Borderie, D. Ghoubay, J. Rault, and V. M. Borderie, “Imaging microscopic features of keratoconic corneal morphology,” Cornea 35(12), 1621–1630 (2016).
[Crossref] [PubMed]

K. Bizheva, L. Haines, E. Mason, B. MacLellan, B. Tan, D. Hileeto, and L. Sorbara, “In vivo imaging and morphometry of the human pre-Descemet’s layer and endothelium with ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 57(6), 2782–2787 (2016).
[Crossref] [PubMed]

2015 (1)

2014 (2)

D. Cui, X. Liu, J. Zhang, X. Yu, S. Ding, Y. Luo, J. Gu, P. Shum, and L. Liu, “Dual spectrometer system with spectral compounding for 1-μm optical coherence tomography in vivo,” Opt. Lett. 39(23), 6727–6730 (2014).
[Crossref] [PubMed]

E. Villani, C. Baudouin, N. Efron, P. Hamrah, T. Kojima, S. V. Patel, S. C. Pflugfelder, A. Zhivov, and M. Dogru, “In vivo confocal microscopy of the ocular surface: from bench to bedside,” Curr. Eye Res. 39(3), 213–231 (2014).
[Crossref] [PubMed]

2013 (1)

R. M. Werkmeister, A. Alex, S. Kaya, A. Unterhuber, N. Hofer, J. Riedl, M. Bronhagl, and et al.., “Measurement of tear film thickness using ultrahigh-resolution OCT,” Invest. Ophthalmol. Vis. Sci 54, 5578–5583 (2013).
[PubMed]

2012 (3)

R. Yadav, R. Kottaiyan, K. Ahmad, and G. Yoon, “Epithelium and Bowman’s layer thickness and light scatter in keratoconic cornea evaluated using ultrahigh resolution optical coherence tomography,” J. Biomed. Opt. 17(11), 116010 (2012).
[Crossref] [PubMed]

M. S. Oliva, T. Schottman, and M. Gulati, “Turning the tide of corneal blindness,” Indian J. Ophthalmol. 60(5), 423–427 (2012).
[Crossref] [PubMed]

D. Pascolini and S. P. Mariotti, “Global estimates of visual impairment: 2010,” Br. J. Ophthalmol. 96(5), 614–618 (2012).
[Crossref] [PubMed]

2011 (6)

J. Wang, M. Abou Shousha, V. L. Perez, C. L. Karp, S. H. Yoo, M. Shen, L. Cui, V. Hurmeric, C. Du, D. Zhu, Q. Chen, and M. Li, “Ultra-high resolution optical coherence tomography for imaging the anterior segment of the eye,” Ophthalmic Surg. Lasers Imaging 42(4Suppl), S15–S27 (2011).
[Crossref] [PubMed]

L. Liu, J. A. Gardecki, S. K. Nadkarni, J. D. Toussaint, Y. Yagi, B. E. Bouma, and G. J. Tearney, “Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography,” Nat. Med. 17(8), 1010–1014 (2011).
[Crossref] [PubMed]

L. An, P. Li, T. T. Shen, and R. Wang, “High speed spectral domain optical coherence tomography for retinal imaging at 500,000 A‑lines per second,” Biomed. Opt. Express 2(10), 2770–2783 (2011).
[Crossref] [PubMed]

A. H. Karimi, A. Wong, and K. Bizheva, “Automated detection and cell density assessment of keratocytes in the human corneal stroma from ultrahigh resolution optical coherence tomograms,” Biomed. Opt. Express 2(10), 2905–2916 (2011).
[Crossref] [PubMed]

R. Yadav, K. S. Lee, J. P. Rolland, J. M. Zavislan, J. V. Aquavella, and G. Yoon, “Micrometer axial resolution OCT for corneal imaging,” Biomed. Opt. Express 2(11), 3037–3046 (2011).
[Crossref] [PubMed]

M. Tavakoli and R. A. Malik, “Corneal confocal microscopy: a novel non-invasive technique to quantify small fibre pathology in peripheral neuropathies,” J. Vis. Exp. 47, 47 (2011).
[Crossref] [PubMed]

2010 (3)

W. Wieser, B. R. Biedermann, T. Klein, C. M. Eigenwillig, and R. Huber, “Multi-megahertz OCT: High quality 3D imaging at 20 million A-scans and 4.5 GVoxels per second,” Opt. Express 18(14), 14685–14704 (2010).
[Crossref] [PubMed]

N. Hutchings, T. L. Simpson, C. Hyun, A. A. Moayed, S. Hariri, L. Sorbara, and K. Bizheva, “Swelling of the human cornea revealed by high-speed, ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 51(9), 4579–4584 (2010).
[Crossref] [PubMed]

R. L. Niederer and C. N. J. McGhee, “Clinical in vivo confocal microscopy of the human cornea in health and disease,” Prog. Retin. Eye Res. 29(1), 30–58 (2010).
[Crossref] [PubMed]

2009 (3)

M. Burton, “Corneal blindness: prevention, treatment and rehabilitaiton,” Community Eye Health 22(71), 33–35 (2009).
[PubMed]

J. L. Ramos, Y. Li, and D. Huang, “Clinical and research applications of anterior segment optical coherence tomography - a review,” Clin. Exp. Ophthalmol. 37(1), 81–89 (2009).
[Crossref] [PubMed]

T. Schmoll, C. Kolbitsch, and R. A. Leitgeb, “Ultra-high-speed volumetric tomography of human retinal blood flow,” Opt. Express 17(5), 4166–4176 (2009).
[Crossref] [PubMed]

2008 (1)

2004 (1)

2003 (1)

I. Jalbert, F. Stapleton, E. Papas, D. F. Sweeney, and M. Coroneo, “In vivo confocal microscopy of the human cornea,” Br. J. Ophthalmol. 87(2), 225–236 (2003).
[Crossref] [PubMed]

2002 (2)

2001 (1)

J. P. Whitcher, M. Srinivasan, and M. P. Upadhyay, “Corneal blindness: a global perspective,” Bull. World Health Organ. 79(3), 214–221 (2001).
[PubMed]

1996 (1)

A. F. Fercher, “Optical coherence tomography,” J. Biomed. Opt. 1(2), 157–173 (1996).
[Crossref] [PubMed]

1991 (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]

Abou Shousha, M.

J. Wang, M. Abou Shousha, V. L. Perez, C. L. Karp, S. H. Yoo, M. Shen, L. Cui, V. Hurmeric, C. Du, D. Zhu, Q. Chen, and M. Li, “Ultra-high resolution optical coherence tomography for imaging the anterior segment of the eye,” Ophthalmic Surg. Lasers Imaging 42(4Suppl), S15–S27 (2011).
[Crossref] [PubMed]

Ahmad, K.

R. Yadav, R. Kottaiyan, K. Ahmad, and G. Yoon, “Epithelium and Bowman’s layer thickness and light scatter in keratoconic cornea evaluated using ultrahigh resolution optical coherence tomography,” J. Biomed. Opt. 17(11), 116010 (2012).
[Crossref] [PubMed]

Alex, A.

R. M. Werkmeister, A. Alex, S. Kaya, A. Unterhuber, N. Hofer, J. Riedl, M. Bronhagl, and et al.., “Measurement of tear film thickness using ultrahigh-resolution OCT,” Invest. Ophthalmol. Vis. Sci 54, 5578–5583 (2013).
[PubMed]

An, L.

Andreiuolo, F.

K. Grieve, C. Georgeon, F. Andreiuolo, M. Borderie, D. Ghoubay, J. Rault, and V. M. Borderie, “Imaging microscopic features of keratoconic corneal morphology,” Cornea 35(12), 1621–1630 (2016).
[Crossref] [PubMed]

Apolonski, A.

Aquavella, J. V.

Aranha Dos Santos, V.

Aschinger, G. C.

Baudouin, C.

E. Villani, C. Baudouin, N. Efron, P. Hamrah, T. Kojima, S. V. Patel, S. C. Pflugfelder, A. Zhivov, and M. Dogru, “In vivo confocal microscopy of the ocular surface: from bench to bedside,” Curr. Eye Res. 39(3), 213–231 (2014).
[Crossref] [PubMed]

Baumgartner, I.

Biedermann, B. R.

Bizheva, K.

K. Bizheva, B. Tan, B. MacLelan, O. Kralj, M. Hajialamdari, D. Hileeto, and L. Sorbara, “Sub-micrometer axial resolution OCT for in-vivo imaging of the cellular structure of healthy and keratoconic human corneas,” Biomed. Opt. Express 8(2), 800–812 (2017).
[Crossref] [PubMed]

K. Bizheva, B. Tan, B. MacLellan, Z. Hosseinaee, E. Mason, D. Hileeto, and L. Sorbara, “In-vivo imaging of the palisades of Vogt and the limbal crypts with sub-micrometer axial resolution optical coherence tomography,” Biomed. Opt. Express 8(9), 4141–4151 (2017).
[Crossref] [PubMed]

K. Bizheva, L. Haines, E. Mason, B. MacLellan, B. Tan, D. Hileeto, and L. Sorbara, “In vivo imaging and morphometry of the human pre-Descemet’s layer and endothelium with ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 57(6), 2782–2787 (2016).
[Crossref] [PubMed]

A. H. Karimi, A. Wong, and K. Bizheva, “Automated detection and cell density assessment of keratocytes in the human corneal stroma from ultrahigh resolution optical coherence tomograms,” Biomed. Opt. Express 2(10), 2905–2916 (2011).
[Crossref] [PubMed]

N. Hutchings, T. L. Simpson, C. Hyun, A. A. Moayed, S. Hariri, L. Sorbara, and K. Bizheva, “Swelling of the human cornea revealed by high-speed, ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 51(9), 4579–4584 (2010).
[Crossref] [PubMed]

B. Povazay, K. Bizheva, A. Unterhuber, B. Hermann, H. Sattmann, A. F. Fercher, W. Drexler, A. Apolonski, W. J. Wadsworth, J. C. Knight, P. S. Russell, M. Vetterlein, and E. Scherzer, “Submicrometer axial resolution optical coherence tomography,” Opt. Lett. 27(20), 1800–1802 (2002).
[Crossref] [PubMed]

Boccara, A. C.

V. Mazlin, P. Xiao, E. Dalimier, K. Grieve, K. Irsch, J. A. Sahel, M. Fink, and A. C. Boccara, “In vivo high resolution human corneal imaging using full-field OCT,” Biomed. Opt. Express 8(2), 557–568 (2018).
[Crossref] [PubMed]

Boccara, A.C.

K. Grieve, M. Paques, A. Dubois, J. Sahe, A.C. Boccara, and J.F. Gargasson, “Ocular tissue imaging using ultrahigh-resolution, full-field optical coherence tomography,” Invest. Ophthalmol. Vis. Sci45, 4126–4131 (2004).
[Crossref]

Boccara, C.

Borderie, M.

K. Grieve, C. Georgeon, F. Andreiuolo, M. Borderie, D. Ghoubay, J. Rault, and V. M. Borderie, “Imaging microscopic features of keratoconic corneal morphology,” Cornea 35(12), 1621–1630 (2016).
[Crossref] [PubMed]

Borderie, V. M.

K. Grieve, C. Georgeon, F. Andreiuolo, M. Borderie, D. Ghoubay, J. Rault, and V. M. Borderie, “Imaging microscopic features of keratoconic corneal morphology,” Cornea 35(12), 1621–1630 (2016).
[Crossref] [PubMed]

Bouma, B. E.

L. Liu, J. A. Gardecki, S. K. Nadkarni, J. D. Toussaint, Y. Yagi, B. E. Bouma, and G. J. Tearney, “Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography,” Nat. Med. 17(8), 1010–1014 (2011).
[Crossref] [PubMed]

Bronhagl, M.

R. M. Werkmeister, A. Alex, S. Kaya, A. Unterhuber, N. Hofer, J. Riedl, M. Bronhagl, and et al.., “Measurement of tear film thickness using ultrahigh-resolution OCT,” Invest. Ophthalmol. Vis. Sci 54, 5578–5583 (2013).
[PubMed]

Burton, M.

M. Burton, “Corneal blindness: prevention, treatment and rehabilitaiton,” Community Eye Health 22(71), 33–35 (2009).
[PubMed]

Cable, A.

Canavesi, C.

Chang, W.

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]

Chen, Q.

J. Wang, M. Abou Shousha, V. L. Perez, C. L. Karp, S. H. Yoo, M. Shen, L. Cui, V. Hurmeric, C. Du, D. Zhu, Q. Chen, and M. Li, “Ultra-high resolution optical coherence tomography for imaging the anterior segment of the eye,” Ophthalmic Surg. Lasers Imaging 42(4Suppl), S15–S27 (2011).
[Crossref] [PubMed]

Chen, Y.

Chen, Z.

Chu, Y. J.

Coroneo, M.

I. Jalbert, F. Stapleton, E. Papas, D. F. Sweeney, and M. Coroneo, “In vivo confocal microscopy of the human cornea,” Br. J. Ophthalmol. 87(2), 225–236 (2003).
[Crossref] [PubMed]

Cui, D.

Cui, L.

J. Wang, M. Abou Shousha, V. L. Perez, C. L. Karp, S. H. Yoo, M. Shen, L. Cui, V. Hurmeric, C. Du, D. Zhu, Q. Chen, and M. Li, “Ultra-high resolution optical coherence tomography for imaging the anterior segment of the eye,” Ophthalmic Surg. Lasers Imaging 42(4Suppl), S15–S27 (2011).
[Crossref] [PubMed]

Dalimier, E.

V. Mazlin, P. Xiao, E. Dalimier, K. Grieve, K. Irsch, J. A. Sahel, M. Fink, and A. C. Boccara, “In vivo high resolution human corneal imaging using full-field OCT,” Biomed. Opt. Express 8(2), 557–568 (2018).
[Crossref] [PubMed]

Ding, S.

Ding, Z.

Dogru, M.

E. Villani, C. Baudouin, N. Efron, P. Hamrah, T. Kojima, S. V. Patel, S. C. Pflugfelder, A. Zhivov, and M. Dogru, “In vivo confocal microscopy of the ocular surface: from bench to bedside,” Curr. Eye Res. 39(3), 213–231 (2014).
[Crossref] [PubMed]

Drexler, W.

Du, C.

J. Wang, M. Abou Shousha, V. L. Perez, C. L. Karp, S. H. Yoo, M. Shen, L. Cui, V. Hurmeric, C. Du, D. Zhu, Q. Chen, and M. Li, “Ultra-high resolution optical coherence tomography for imaging the anterior segment of the eye,” Ophthalmic Surg. Lasers Imaging 42(4Suppl), S15–S27 (2011).
[Crossref] [PubMed]

Dua, H.

Dubois, A.

A. Dubois, K. Grieve, G. Moneron, R. Lecaque, L. Vabre, and C. Boccara, “Ultrahigh-resolution full-field optical coherence tomography,” Appl. Opt. 43(14), 2874–2883 (2004).
[Crossref] [PubMed]

K. Grieve, M. Paques, A. Dubois, J. Sahe, A.C. Boccara, and J.F. Gargasson, “Ocular tissue imaging using ultrahigh-resolution, full-field optical coherence tomography,” Invest. Ophthalmol. Vis. Sci45, 4126–4131 (2004).
[Crossref]

Efron, N.

E. Villani, C. Baudouin, N. Efron, P. Hamrah, T. Kojima, S. V. Patel, S. C. Pflugfelder, A. Zhivov, and M. Dogru, “In vivo confocal microscopy of the ocular surface: from bench to bedside,” Curr. Eye Res. 39(3), 213–231 (2014).
[Crossref] [PubMed]

Eigenwillig, C. M.

Fercher, A. F.

Fink, M.

V. Mazlin, P. Xiao, E. Dalimier, K. Grieve, K. Irsch, J. A. Sahel, M. Fink, and A. C. Boccara, “In vivo high resolution human corneal imaging using full-field OCT,” Biomed. Opt. Express 8(2), 557–568 (2018).
[Crossref] [PubMed]

Flotte, T.

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]

Fujimoto, J. G.

B. Potsaid, I. Gorczynska, V. J. Srinivasan, Y. Chen, J. Jiang, A. Cable, and J. G. Fujimoto, “Ultrahigh speed spectral / Fourier domain OCT ophthalmic imaging at 70,000 to 312,500 axial scans per second,” Opt. Express 16(19), 15149–15169 (2008).
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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]

Gain, P.

Gardecki, J. A.

L. Liu, J. A. Gardecki, S. K. Nadkarni, J. D. Toussaint, Y. Yagi, B. E. Bouma, and G. J. Tearney, “Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography,” Nat. Med. 17(8), 1010–1014 (2011).
[Crossref] [PubMed]

Gargasson, J.F.

K. Grieve, M. Paques, A. Dubois, J. Sahe, A.C. Boccara, and J.F. Gargasson, “Ocular tissue imaging using ultrahigh-resolution, full-field optical coherence tomography,” Invest. Ophthalmol. Vis. Sci45, 4126–4131 (2004).
[Crossref]

Garhöfer, G.

Georgeon, C.

K. Grieve, C. Georgeon, F. Andreiuolo, M. Borderie, D. Ghoubay, J. Rault, and V. M. Borderie, “Imaging microscopic features of keratoconic corneal morphology,” Cornea 35(12), 1621–1630 (2016).
[Crossref] [PubMed]

Ghoubay, D.

K. Grieve, C. Georgeon, F. Andreiuolo, M. Borderie, D. Ghoubay, J. Rault, and V. M. Borderie, “Imaging microscopic features of keratoconic corneal morphology,” Cornea 35(12), 1621–1630 (2016).
[Crossref] [PubMed]

Ginner, L.

Gorczynska, I.

Gregory, K.

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]

Grieve, K.

V. Mazlin, P. Xiao, E. Dalimier, K. Grieve, K. Irsch, J. A. Sahel, M. Fink, and A. C. Boccara, “In vivo high resolution human corneal imaging using full-field OCT,” Biomed. Opt. Express 8(2), 557–568 (2018).
[Crossref] [PubMed]

K. Grieve, C. Georgeon, F. Andreiuolo, M. Borderie, D. Ghoubay, J. Rault, and V. M. Borderie, “Imaging microscopic features of keratoconic corneal morphology,” Cornea 35(12), 1621–1630 (2016).
[Crossref] [PubMed]

A. Dubois, K. Grieve, G. Moneron, R. Lecaque, L. Vabre, and C. Boccara, “Ultrahigh-resolution full-field optical coherence tomography,” Appl. Opt. 43(14), 2874–2883 (2004).
[Crossref] [PubMed]

K. Grieve, M. Paques, A. Dubois, J. Sahe, A.C. Boccara, and J.F. Gargasson, “Ocular tissue imaging using ultrahigh-resolution, full-field optical coherence tomography,” Invest. Ophthalmol. Vis. Sci45, 4126–4131 (2004).
[Crossref]

Gu, J.

Gulati, M.

M. S. Oliva, T. Schottman, and M. Gulati, “Turning the tide of corneal blindness,” Indian J. Ophthalmol. 60(5), 423–427 (2012).
[Crossref] [PubMed]

Haines, L.

K. Bizheva, L. Haines, E. Mason, B. MacLellan, B. Tan, D. Hileeto, and L. Sorbara, “In vivo imaging and morphometry of the human pre-Descemet’s layer and endothelium with ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 57(6), 2782–2787 (2016).
[Crossref] [PubMed]

Hajialamdari, M.

Hamrah, P.

E. Villani, C. Baudouin, N. Efron, P. Hamrah, T. Kojima, S. V. Patel, S. C. Pflugfelder, A. Zhivov, and M. Dogru, “In vivo confocal microscopy of the ocular surface: from bench to bedside,” Curr. Eye Res. 39(3), 213–231 (2014).
[Crossref] [PubMed]

Hariri, S.

N. Hutchings, T. L. Simpson, C. Hyun, A. A. Moayed, S. Hariri, L. Sorbara, and K. Bizheva, “Swelling of the human cornea revealed by high-speed, ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 51(9), 4579–4584 (2010).
[Crossref] [PubMed]

He, Z.

Hee, M. R.

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]

Hermann, B.

Hileeto, D.

Hindman, H. B.

Hofer, N.

R. M. Werkmeister, A. Alex, S. Kaya, A. Unterhuber, N. Hofer, J. Riedl, M. Bronhagl, and et al.., “Measurement of tear film thickness using ultrahigh-resolution OCT,” Invest. Ophthalmol. Vis. Sci 54, 5578–5583 (2013).
[PubMed]

Hosseinaee, Z.

Huang, D.

J. L. Ramos, Y. Li, and D. Huang, “Clinical and research applications of anterior segment optical coherence tomography - a review,” Clin. Exp. Ophthalmol. 37(1), 81–89 (2009).
[Crossref] [PubMed]

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]

Huber, R.

Hurmeric, V.

J. Wang, M. Abou Shousha, V. L. Perez, C. L. Karp, S. H. Yoo, M. Shen, L. Cui, V. Hurmeric, C. Du, D. Zhu, Q. Chen, and M. Li, “Ultra-high resolution optical coherence tomography for imaging the anterior segment of the eye,” Ophthalmic Surg. Lasers Imaging 42(4Suppl), S15–S27 (2011).
[Crossref] [PubMed]

Hutchings, N.

N. Hutchings, T. L. Simpson, C. Hyun, A. A. Moayed, S. Hariri, L. Sorbara, and K. Bizheva, “Swelling of the human cornea revealed by high-speed, ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 51(9), 4579–4584 (2010).
[Crossref] [PubMed]

Hyun, C.

N. Hutchings, T. L. Simpson, C. Hyun, A. A. Moayed, S. Hariri, L. Sorbara, and K. Bizheva, “Swelling of the human cornea revealed by high-speed, ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 51(9), 4579–4584 (2010).
[Crossref] [PubMed]

Irsch, K.

V. Mazlin, P. Xiao, E. Dalimier, K. Grieve, K. Irsch, J. A. Sahel, M. Fink, and A. C. Boccara, “In vivo high resolution human corneal imaging using full-field OCT,” Biomed. Opt. Express 8(2), 557–568 (2018).
[Crossref] [PubMed]

Jalbert, I.

I. Jalbert, F. Stapleton, E. Papas, D. F. Sweeney, and M. Coroneo, “In vivo confocal microscopy of the human cornea,” Br. J. Ophthalmol. 87(2), 225–236 (2003).
[Crossref] [PubMed]

Jiang, J.

Karimi, A. H.

Karp, C. L.

J. Wang, M. Abou Shousha, V. L. Perez, C. L. Karp, S. H. Yoo, M. Shen, L. Cui, V. Hurmeric, C. Du, D. Zhu, Q. Chen, and M. Li, “Ultra-high resolution optical coherence tomography for imaging the anterior segment of the eye,” Ophthalmic Surg. Lasers Imaging 42(4Suppl), S15–S27 (2011).
[Crossref] [PubMed]

Kaya, S.

R. M. Werkmeister, A. Alex, S. Kaya, A. Unterhuber, N. Hofer, J. Riedl, M. Bronhagl, and et al.., “Measurement of tear film thickness using ultrahigh-resolution OCT,” Invest. Ophthalmol. Vis. Sci 54, 5578–5583 (2013).
[PubMed]

Klein, T.

Knight, J. C.

Kojima, T.

E. Villani, C. Baudouin, N. Efron, P. Hamrah, T. Kojima, S. V. Patel, S. C. Pflugfelder, A. Zhivov, and M. Dogru, “In vivo confocal microscopy of the ocular surface: from bench to bedside,” Curr. Eye Res. 39(3), 213–231 (2014).
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Kolbitsch, C.

Kottaiyan, R.

R. Yadav, R. Kottaiyan, K. Ahmad, and G. Yoon, “Epithelium and Bowman’s layer thickness and light scatter in keratoconic cornea evaluated using ultrahigh resolution optical coherence tomography,” J. Biomed. Opt. 17(11), 116010 (2012).
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Kralj, O.

Kumar, A.

Lecaque, R.

Lee, K. S.

Leitgeb, R. A.

Lepine, T.

Li, M.

J. Wang, M. Abou Shousha, V. L. Perez, C. L. Karp, S. H. Yoo, M. Shen, L. Cui, V. Hurmeric, C. Du, D. Zhu, Q. Chen, and M. Li, “Ultra-high resolution optical coherence tomography for imaging the anterior segment of the eye,” Ophthalmic Surg. Lasers Imaging 42(4Suppl), S15–S27 (2011).
[Crossref] [PubMed]

Li, P.

Li, Y.

J. L. Ramos, Y. Li, and D. Huang, “Clinical and research applications of anterior segment optical coherence tomography - a review,” Clin. Exp. Ophthalmol. 37(1), 81–89 (2009).
[Crossref] [PubMed]

Lin, C. P.

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]

Liu, L.

D. Cui, X. Liu, J. Zhang, X. Yu, S. Ding, Y. Luo, J. Gu, P. Shum, and L. Liu, “Dual spectrometer system with spectral compounding for 1-μm optical coherence tomography in vivo,” Opt. Lett. 39(23), 6727–6730 (2014).
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L. Liu, J. A. Gardecki, S. K. Nadkarni, J. D. Toussaint, Y. Yagi, B. E. Bouma, and G. J. Tearney, “Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography,” Nat. Med. 17(8), 1010–1014 (2011).
[Crossref] [PubMed]

Liu, X.

Luo, Y.

MacLelan, B.

MacLellan, B.

K. Bizheva, B. Tan, B. MacLellan, Z. Hosseinaee, E. Mason, D. Hileeto, and L. Sorbara, “In-vivo imaging of the palisades of Vogt and the limbal crypts with sub-micrometer axial resolution optical coherence tomography,” Biomed. Opt. Express 8(9), 4141–4151 (2017).
[Crossref] [PubMed]

K. Bizheva, L. Haines, E. Mason, B. MacLellan, B. Tan, D. Hileeto, and L. Sorbara, “In vivo imaging and morphometry of the human pre-Descemet’s layer and endothelium with ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 57(6), 2782–2787 (2016).
[Crossref] [PubMed]

Malik, R. A.

M. Tavakoli and R. A. Malik, “Corneal confocal microscopy: a novel non-invasive technique to quantify small fibre pathology in peripheral neuropathies,” J. Vis. Exp. 47, 47 (2011).
[Crossref] [PubMed]

Mariotti, S. P.

D. Pascolini and S. P. Mariotti, “Global estimates of visual impairment: 2010,” Br. J. Ophthalmol. 96(5), 614–618 (2012).
[Crossref] [PubMed]

Mason, E.

K. Bizheva, B. Tan, B. MacLellan, Z. Hosseinaee, E. Mason, D. Hileeto, and L. Sorbara, “In-vivo imaging of the palisades of Vogt and the limbal crypts with sub-micrometer axial resolution optical coherence tomography,” Biomed. Opt. Express 8(9), 4141–4151 (2017).
[Crossref] [PubMed]

K. Bizheva, L. Haines, E. Mason, B. MacLellan, B. Tan, D. Hileeto, and L. Sorbara, “In vivo imaging and morphometry of the human pre-Descemet’s layer and endothelium with ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 57(6), 2782–2787 (2016).
[Crossref] [PubMed]

Mazlin, V.

V. Mazlin, P. Xiao, E. Dalimier, K. Grieve, K. Irsch, J. A. Sahel, M. Fink, and A. C. Boccara, “In vivo high resolution human corneal imaging using full-field OCT,” Biomed. Opt. Express 8(2), 557–568 (2018).
[Crossref] [PubMed]

McGhee, C. N. J.

R. L. Niederer and C. N. J. McGhee, “Clinical in vivo confocal microscopy of the human cornea in health and disease,” Prog. Retin. Eye Res. 29(1), 30–58 (2010).
[Crossref] [PubMed]

Moayed, A. A.

N. Hutchings, T. L. Simpson, C. Hyun, A. A. Moayed, S. Hariri, L. Sorbara, and K. Bizheva, “Swelling of the human cornea revealed by high-speed, ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 51(9), 4579–4584 (2010).
[Crossref] [PubMed]

Moneron, G.

Nadkarni, S. K.

L. Liu, J. A. Gardecki, S. K. Nadkarni, J. D. Toussaint, Y. Yagi, B. E. Bouma, and G. J. Tearney, “Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography,” Nat. Med. 17(8), 1010–1014 (2011).
[Crossref] [PubMed]

Nelson, J. S.

Niederer, R. L.

R. L. Niederer and C. N. J. McGhee, “Clinical in vivo confocal microscopy of the human cornea in health and disease,” Prog. Retin. Eye Res. 29(1), 30–58 (2010).
[Crossref] [PubMed]

Oliva, M. S.

M. S. Oliva, T. Schottman, and M. Gulati, “Turning the tide of corneal blindness,” Indian J. Ophthalmol. 60(5), 423–427 (2012).
[Crossref] [PubMed]

Pantalon, A.

Papas, E.

I. Jalbert, F. Stapleton, E. Papas, D. F. Sweeney, and M. Coroneo, “In vivo confocal microscopy of the human cornea,” Br. J. Ophthalmol. 87(2), 225–236 (2003).
[Crossref] [PubMed]

Paques, M.

K. Grieve, M. Paques, A. Dubois, J. Sahe, A.C. Boccara, and J.F. Gargasson, “Ocular tissue imaging using ultrahigh-resolution, full-field optical coherence tomography,” Invest. Ophthalmol. Vis. Sci45, 4126–4131 (2004).
[Crossref]

Pascolini, D.

D. Pascolini and S. P. Mariotti, “Global estimates of visual impairment: 2010,” Br. J. Ophthalmol. 96(5), 614–618 (2012).
[Crossref] [PubMed]

Patel, S. V.

E. Villani, C. Baudouin, N. Efron, P. Hamrah, T. Kojima, S. V. Patel, S. C. Pflugfelder, A. Zhivov, and M. Dogru, “In vivo confocal microscopy of the ocular surface: from bench to bedside,” Curr. Eye Res. 39(3), 213–231 (2014).
[Crossref] [PubMed]

Perez, V. L.

J. Wang, M. Abou Shousha, V. L. Perez, C. L. Karp, S. H. Yoo, M. Shen, L. Cui, V. Hurmeric, C. Du, D. Zhu, Q. Chen, and M. Li, “Ultra-high resolution optical coherence tomography for imaging the anterior segment of the eye,” Ophthalmic Surg. Lasers Imaging 42(4Suppl), S15–S27 (2011).
[Crossref] [PubMed]

Pflugfelder, S. C.

E. Villani, C. Baudouin, N. Efron, P. Hamrah, T. Kojima, S. V. Patel, S. C. Pflugfelder, A. Zhivov, and M. Dogru, “In vivo confocal microscopy of the ocular surface: from bench to bedside,” Curr. Eye Res. 39(3), 213–231 (2014).
[Crossref] [PubMed]

Pircher, M.

Pircher, N.

Potsaid, B.

Povazay, B.

Pricoupenko, N.

Puliafito, C. A.

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]

Ramos, J. L.

J. L. Ramos, Y. Li, and D. Huang, “Clinical and research applications of anterior segment optical coherence tomography - a review,” Clin. Exp. Ophthalmol. 37(1), 81–89 (2009).
[Crossref] [PubMed]

Rault, J.

K. Grieve, C. Georgeon, F. Andreiuolo, M. Borderie, D. Ghoubay, J. Rault, and V. M. Borderie, “Imaging microscopic features of keratoconic corneal morphology,” Cornea 35(12), 1621–1630 (2016).
[Crossref] [PubMed]

Ren, H.

Riedl, J.

R. M. Werkmeister, A. Alex, S. Kaya, A. Unterhuber, N. Hofer, J. Riedl, M. Bronhagl, and et al.., “Measurement of tear film thickness using ultrahigh-resolution OCT,” Invest. Ophthalmol. Vis. Sci 54, 5578–5583 (2013).
[PubMed]

Rolland, J. P.

Russell, P. S.

Sahe, J.

K. Grieve, M. Paques, A. Dubois, J. Sahe, A.C. Boccara, and J.F. Gargasson, “Ocular tissue imaging using ultrahigh-resolution, full-field optical coherence tomography,” Invest. Ophthalmol. Vis. Sci45, 4126–4131 (2004).
[Crossref]

Sahel, J. A.

V. Mazlin, P. Xiao, E. Dalimier, K. Grieve, K. Irsch, J. A. Sahel, M. Fink, and A. C. Boccara, “In vivo high resolution human corneal imaging using full-field OCT,” Biomed. Opt. Express 8(2), 557–568 (2018).
[Crossref] [PubMed]

Salas, M.

Sapeta, S.

Sattmann, H.

Scherzer, E.

Schmetterer, L.

Schmidinger, G.

Schmidl, D.

Schmoll, T.

Schottman, T.

M. S. Oliva, T. Schottman, and M. Gulati, “Turning the tide of corneal blindness,” Indian J. Ophthalmol. 60(5), 423–427 (2012).
[Crossref] [PubMed]

Schuman, J. S.

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]

Schwarzhans, F.

Shen, M.

J. Wang, M. Abou Shousha, V. L. Perez, C. L. Karp, S. H. Yoo, M. Shen, L. Cui, V. Hurmeric, C. Du, D. Zhu, Q. Chen, and M. Li, “Ultra-high resolution optical coherence tomography for imaging the anterior segment of the eye,” Ophthalmic Surg. Lasers Imaging 42(4Suppl), S15–S27 (2011).
[Crossref] [PubMed]

Shen, T. T.

Shum, P.

Simpson, T. L.

N. Hutchings, T. L. Simpson, C. Hyun, A. A. Moayed, S. Hariri, L. Sorbara, and K. Bizheva, “Swelling of the human cornea revealed by high-speed, ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 51(9), 4579–4584 (2010).
[Crossref] [PubMed]

Sorbara, L.

K. Bizheva, B. Tan, B. MacLelan, O. Kralj, M. Hajialamdari, D. Hileeto, and L. Sorbara, “Sub-micrometer axial resolution OCT for in-vivo imaging of the cellular structure of healthy and keratoconic human corneas,” Biomed. Opt. Express 8(2), 800–812 (2017).
[Crossref] [PubMed]

K. Bizheva, B. Tan, B. MacLellan, Z. Hosseinaee, E. Mason, D. Hileeto, and L. Sorbara, “In-vivo imaging of the palisades of Vogt and the limbal crypts with sub-micrometer axial resolution optical coherence tomography,” Biomed. Opt. Express 8(9), 4141–4151 (2017).
[Crossref] [PubMed]

K. Bizheva, L. Haines, E. Mason, B. MacLellan, B. Tan, D. Hileeto, and L. Sorbara, “In vivo imaging and morphometry of the human pre-Descemet’s layer and endothelium with ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 57(6), 2782–2787 (2016).
[Crossref] [PubMed]

N. Hutchings, T. L. Simpson, C. Hyun, A. A. Moayed, S. Hariri, L. Sorbara, and K. Bizheva, “Swelling of the human cornea revealed by high-speed, ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 51(9), 4579–4584 (2010).
[Crossref] [PubMed]

Srinivasan, M.

J. P. Whitcher, M. Srinivasan, and M. P. Upadhyay, “Corneal blindness: a global perspective,” Bull. World Health Organ. 79(3), 214–221 (2001).
[PubMed]

Srinivasan, V. J.

Stapleton, F.

I. Jalbert, F. Stapleton, E. Papas, D. F. Sweeney, and M. Coroneo, “In vivo confocal microscopy of the human cornea,” Br. J. Ophthalmol. 87(2), 225–236 (2003).
[Crossref] [PubMed]

Stinson, W. G.

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]

Swanson, E. A.

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]

Sweeney, D. F.

I. Jalbert, F. Stapleton, E. Papas, D. F. Sweeney, and M. Coroneo, “In vivo confocal microscopy of the human cornea,” Br. J. Ophthalmol. 87(2), 225–236 (2003).
[Crossref] [PubMed]

Tan, B.

Tankam, P.

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L. An, P. Li, T. T. Shen, and R. Wang, “High speed spectral domain optical coherence tomography for retinal imaging at 500,000 A‑lines per second,” Biomed. Opt. Express 2(10), 2770–2783 (2011).
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L. Ginner, T. Schmoll, A. Kumar, M. Salas, N. Pricoupenko, L. M. Wurster, and R. A. Leitgeb, “Holographic line field en-face OCT with digital adaptive optics in the retina in vivo,” Biomed. Opt. Express 9(2), 472–485 (2018).
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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).
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Figures (7)

Fig. 1
Fig. 1 Schematic of the 250 kHz SD-OCT system. CL – collimator; DCP – dispersion compensation prisms; FC – broadband fiber coupler; FFT – fast Fourier transform; L1 to L4 – broadband achromat doublets; M – mirror; MEFO - Multi-element Focusing Objective; MO – microscope objective; NDF – neutral density filter; PC – polarization controllers; X,Y – a pair of galvanometric scanners; VPHG – volume phase holographic grating.
Fig. 2
Fig. 2 Sample and reference arm spectra measured at the detection end of the SD-OCT system (A). Axial PSF measured in free space (B). Sensitivity roll-off (C). Image of an USAF target acquired with a 10x microscope objective (D). Magnified view of the USAF target marked with the blue square (E). Red and green lines show the intensity profiles of group 7, elements 6 and 7 of the USAF target image (F).
Fig. 3
Fig. 3 Typical cross-sectional H&E histology image of a healthy human cornea with red arrows marking keratocytes in the stroma (A). EPI – epithelium, BM – Bowman’s membrane, STR – stroma. Representative B-scan acquired in-vivo from a healthy human cornea with the blue and red arrows marking the tear film and keratocytes respectively (B). A volumetric OCT image of the anterior cornea with yellow arrows marking hyper-reflective features in the tear film (C). Enface image of the tear film showing hyper-reflective structures (yellow arrows) that may correspond to cellular debris and mucin clusters (D). Enface images of the corneal epithelium acquired at different depths and showing the cellular structure of the epithelium (E-G). White dots inside the cells correspond to reflections from the cellular nuclei. Enface UHR-OCT image of a larger area of the corneal epithelium (H) and a corresponding IVCM image (J).
Fig. 4
Fig. 4 Typical volumetric image of a healthy human anterior cornea (A). The same image showing the sub-basal corneal nerves, located in the basal cell layer of the epithelium (B). A typical cross-sectional histological image with GFAP marked corneal nerves (C, brown color). An UHR-OCT enface image of sub-basal corneal nerves, acquired in-vivo from a healthy subject (D). A typical IVCM image of sub-basal corneal nerves (E).
Fig. 5
Fig. 5 UHR-OCT volumetric images of the corneal stroma showing keratocyte cells in the anterior and middle stroma respectively (A and D). Corresponding enface UHR-OCT images with red arrows marking thin stromal nerves (B and E). IVCM images of the anterior and middle stroma respectively (C and F) showing keratocytes and thin stromal nerves (red arrows).
Fig. 6
Fig. 6 Cross-sectional UHR-OCT image of the healthy human cornea, acquired in-vivo with a 10x microscope objective with the imaging beam focused in the posterior cornea (A). Magnified view of the area in Fig. 6(A) marked with the red dashed line rectangle (B). 5X magnification was applied in axial direction to allow viewing of the corneal endothelium (END), Descemet’s membrane (DM) and the pre-Descemet’s layer (PDL). Keratocytes located at the boundary between the posterior stroma and the PDL are marked with red arrows. Typical H&E histological image of the healthy posterior human cornea (C). Enface IVCM image of the cellular structure of the corneal endothelium (D). Enface UHR-OCT image acquired in-vivo from a healthy corneal endothelium (E) from a single plane inside the endothelial layer at a depth location marked with the blue arrow in Fig. 6(B). The white hyper-reflective dots that appear arranged in a hexagonal pattern, most likely correspond to reflections from endothelial cell nuclei. FFT map of the UHR-OCT image shown in Fig. 6(E) and (F). The radius of the ring structure in the FFT map corresponds to the mean distance between the reflective white dots in the UHR-OCT image (Fig. 6(E)). The length of the radius was measured to be ~20 µm, which correlated very well with the average size of the healthy endothelial cells that was determined from the IVCM image shown in Fig. 6(D). Figure 6(G) shows a maximum intensity projection OCT image of the corneal endothelium that was acquired ex-vivo. The image clearly shows the hexagonal structure of the corneal endothelial cells.
Fig. 7
Fig. 7 Enface, maximum intensity projection image of the corneal endothelium that was acquired in-vivo from a healthy subject at the maximum camera speed of 250 kHz (A). A small region in the image (red line rectangle) shows hexagonally shaped endothelial cells. A magnified view of this area is shown in Fig. 7(B). Cross-sectional B-scans from the same 3D data set, corresponding to locations marked with the blue and orange arrows in the enface image (C and D), show loss of image contrast due to fast axial eye motion.