Abstract

We present a multimodal imaging system which combines multiphoton microscopy and optical coherence tomography to visualize the morphological structures, and to quantify the refractive index (RI) and thickness of cornea. The morphological similarities and differences at different corneal layers across various species are identified. In the piscine and human corneas, the stromata exhibit thin fibers that indicate an overall collagen direction. Human corneas display collagen micro-folds which cause increased light attenuation. In the murine, porcine and bovine corneas, the stromata show interwoven collagen patterns. The Bowman’s layer and the Descemet’s membrane are also distinguished in some species. The RI and thicknesses are quantified for the epithelium and the stromal layers respectively, where the epithelium is found to have slightly higher RI than the stroma. The average epithelial and stromal RI are, respectively, 1.371 ± 0.016 and 1.360 ± 0.008 for the murine corneas; 1.502 ± 0.057 and 1.335 ± 0.011 for the piscine corneas; 1.433 ± 0.023 and 1.357 ± 0.013 for the human corneas; 1.476 ± 0.091 and 1.343 ± 0.013 for the porcine corneas; and 1.400 ± 0.007 and 1.376 ± 0.003 for the bovine corneas. The multimodal system can potentially provide a comprehensive characterization of the cornea.

© 2014 Optical Society of America

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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
  5. Y. L. Kim, J. T. Walsh, T. K. Goldstick, and M. R. Glucksberg, “Variation of corneal refractive index with hydration,” Phys. Med. Biol. 49(5), 859–868 (2004).
    [Crossref] [PubMed]
  6. F. Aptel, N. Olivier, A. Deniset-Besseau, J. M. Legeais, K. Plamann, M. C. Schanne-Klein, and E. Beaurepaire, “Multimodal nonlinear imaging of the human cornea,” Invest. Ophthalmol. Vis. Sci. 51(5), 2459–2465 (2010).
    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
  30. S. Patel, J. Marshall, and F. W. Fitzke, “Refractive index of the human corneal epithelium and stroma,” J. Refract. Surg. 11(2), 100–105 (1995).
    [PubMed]
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  32. S. Patel, J. L. Alió, and J. J. Pérez-Santonja, “Refractive index change in bovine and human corneal stroma before and after LASIK: a study of untreated and re-treated corneas implicating stromal hydration,” Invest. Ophthalmol. Vis. Sci. 45(10), 3523–3530 (2004).
    [Crossref] [PubMed]

2013 (1)

2012 (1)

2011 (3)

J. M. Bueno, E. J. Gualda, and P. Artal, “Analysis of corneal stroma organization with wavefront optimized nonlinear microscopy,” Cornea 30(6), 692–701 (2011).
[Crossref] [PubMed]

S. Tang, Y. Zhou, K. K. H. Chan, and T. Lai, “Multiscale multimodal imaging with multiphoton microscopy and optical coherence tomography,” Opt. Lett. 36(24), 4800–4802 (2011).
[Crossref] [PubMed]

D. W. DelMonte and T. Kim, “Anatomy and physiology of the cornea,” J. Cataract Refract. Surg. 37(3), 588–598 (2011).
[Crossref] [PubMed]

2010 (1)

F. Aptel, N. Olivier, A. Deniset-Besseau, J. M. Legeais, K. Plamann, M. C. Schanne-Klein, and E. Beaurepaire, “Multimodal nonlinear imaging of the human cornea,” Invest. Ophthalmol. Vis. Sci. 51(5), 2459–2465 (2010).
[Crossref] [PubMed]

2009 (2)

B. R. Masters, “Correlation of histology and linear and nonlinear microscopy of the living human cornea,” J. Biophotonics 2(3), 127–139 (2009).
[Crossref] [PubMed]

R. F. Guthoff, A. Zhivov, and O. Stachs, “In vivo confocal microscopy, an inner vision of the cornea - a major review,” Clin. Experiment. Ophthalmol. 37(1), 100–117 (2009).
[Crossref] [PubMed]

2008 (3)

R. LaComb, O. Nadiarnykh, S. S. Townsend, and P. J. Campagnola, “Phase matching considerations in second harmonic generation from tissues: effects on emission directionality, conversion efficiency and observed morphology,” Opt. Commun. 281(7), 1823–1832 (2008).
[Crossref] [PubMed]

A. Faramarzi and H. Ziai, “Central corneal thickness measurement by ultrasound versus Orbscan II,” J Ophthalmic Vis Res 3(2), 83–86 (2008).
[PubMed]

B. Vasudevan, T. L. Simpson, and J. G. Sivak, “Regional variation in the refractive-index of the bovine and human cornea,” Optom. Vis. Sci. 85(10), 977–981 (2008).
[Crossref] [PubMed]

2007 (1)

N. Morishige, A. J. Wahlert, M. C. Kenney, D. J. Brown, K. Kawamoto, T. Chikama, T. Nishida, and J. V. Jester, “Second-harmonic imaging microscopy of normal human and keratoconus cornea,” Invest. Ophthalmol. Vis. Sci. 48(3), 1087–1094 (2007).
[Crossref] [PubMed]

2006 (3)

N. Morishige, W. M. Petroll, T. Nishida, M. C. Kenney, and J. V. Jester, “Noninvasive corneal stromal collagen imaging using two-photon-generated second-harmonic signals,” J. Cataract Refract. Surg. 32(11), 1784–1791 (2006).
[Crossref] [PubMed]

K. D. Rao, Y. Verma, H. S. Patel, and P. K. Gupta, “Non-invasive ophthalmic imaging of adult zebrafish eye using optical coherence tomography,” Curr. Sci. 90(11), 1506–1510 (2006).

B. J. Kaluzny, J. J. Kałuzny, A. Szkulmowska, I. Gorczyńska, M. Szkulmowski, T. Bajraszewski, M. Wojtkowski, and P. Targowski, “Spectral optical coherence tomography: a novel technique for cornea imaging,” Cornea 25(8), 960–965 (2006).
[Crossref] [PubMed]

2005 (2)

R. M. Williams, W. R. Zipfel, and W. W. Webb, “Interpreting second-harmonic generation images of collagen I fibrils,” Biophys. J. 88(2), 1377–1386 (2005).
[Crossref] [PubMed]

Y. Barkana, Y. Gerber, U. Elbaz, S. Schwartz, G. Ken-Dror, I. Avni, and D. Zadok, “Central corneal thickness measurement with the pentacam Scheimpflug system, optical low-coherence reflectometry pachymeter, and ultrasound pachymetry,” J. Cataract Refract. Surg. 31(9), 1729–1735 (2005).
[Crossref] [PubMed]

2004 (4)

C. Wirbelauer and D. T. Pham, “Continuous monitoring of corneal thickness changes during LASIK with online optical coherence pachymetry,” J. Cataract Refract. Surg. 30(12), 2559–2568 (2004).
[Crossref] [PubMed]

S. Patel, J. L. Alió, and J. J. Pérez-Santonja, “Refractive index change in bovine and human corneal stroma before and after LASIK: a study of untreated and re-treated corneas implicating stromal hydration,” Invest. Ophthalmol. Vis. Sci. 45(10), 3523–3530 (2004).
[Crossref] [PubMed]

J. W. McLaren, C. B. Nau, J. C. Erie, and W. M. Bourne, “Corneal thickness measurement by confocal microscopy, ultrasound, and scanning slit methods,” Am. J. Ophthalmol. 137(6), 1011–1020 (2004).
[Crossref] [PubMed]

Y. L. Kim, J. T. Walsh, T. K. Goldstick, and M. R. Glucksberg, “Variation of corneal refractive index with hydration,” Phys. Med. Biol. 49(5), 859–868 (2004).
[Crossref] [PubMed]

2003 (2)

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
[Crossref] [PubMed]

S. R. Uhlhorn, F. Manns, H. Tahi, P. Rol, and J. M. Parel, “Corneal group refractive index measurement using low-coherence interferometry,” Proc. SPIE 3246, 14–21 (2003).
[Crossref]

2002 (2)

M. D. Merindano, J. Costa, M. Canals, J. M. Potau, and D. Ruano, “A comparative study of Bowman’s layer in some mammals: relationships with other constituent corneal structures,” Eur. J. Anat. 6(3), 133–139 (2002).

S. Hayashi, T. Osawa, and K. Tohyama, “Comparative observations on corneas, with special reference to Bowman’s layer and Descemet’s membrane in mammals and amphibians,” J. Morphol. 254(3), 247–258 (2002).
[Crossref] [PubMed]

2001 (3)

K. M. Meek and A. J. Quantock, “The use of x-ray scattering techniques to determine corneal ultrastructure,” Prog. Retin. Eye Res. 20(1), 95–137 (2001).
[Crossref] [PubMed]

N. Efron, I. Perez-Gomez, H. A. Mutalib, and J. Hollingsworth, “Confocal microscopy of the normal human cornea,” Cont. Lens Anterior Eye 24(1), 16–24 (2001).
[Crossref] [PubMed]

M. Bechmann, M. J. Thiel, A. S. Neubauer, S. Ullrich, K. Ludwig, K. R. Kenyon, and M. W. Ulbig, “Central corneal thickness measurement with a retinal optical coherence tomography device versus standard ultrasonic pachymetry,” Cornea 20(1), 50–54 (2001).
[Crossref] [PubMed]

2000 (1)

L. R. Nelson, D. O. Hodge, and W. M. Bourne, “In vitro comparison of Chen medium and Optisol-GS medium for human corneal storage,” Cornea 19(6), 782–787 (2000).
[Crossref] [PubMed]

1999 (1)

S. Shah, A. Chatterjee, M. Mathai, S. P. Kelly, J. Kwartz, D. Henson, and D. McLeod, “Relationship between corneal thickness and measured intraocular pressure in a general ophthalmology clinic,” Ophthalmology 106(11), 2154–2160 (1999).
[Crossref] [PubMed]

1995 (2)

Alió, J. L.

S. Patel, J. L. Alió, and J. J. Pérez-Santonja, “Refractive index change in bovine and human corneal stroma before and after LASIK: a study of untreated and re-treated corneas implicating stromal hydration,” Invest. Ophthalmol. Vis. Sci. 45(10), 3523–3530 (2004).
[Crossref] [PubMed]

Aptel, F.

F. Aptel, N. Olivier, A. Deniset-Besseau, J. M. Legeais, K. Plamann, M. C. Schanne-Klein, and E. Beaurepaire, “Multimodal nonlinear imaging of the human cornea,” Invest. Ophthalmol. Vis. Sci. 51(5), 2459–2465 (2010).
[Crossref] [PubMed]

Artal, P.

J. M. Bueno, E. J. Gualda, and P. Artal, “Analysis of corneal stroma organization with wavefront optimized nonlinear microscopy,” Cornea 30(6), 692–701 (2011).
[Crossref] [PubMed]

Avni, I.

Y. Barkana, Y. Gerber, U. Elbaz, S. Schwartz, G. Ken-Dror, I. Avni, and D. Zadok, “Central corneal thickness measurement with the pentacam Scheimpflug system, optical low-coherence reflectometry pachymeter, and ultrasound pachymetry,” J. Cataract Refract. Surg. 31(9), 1729–1735 (2005).
[Crossref] [PubMed]

Bajraszewski, T.

B. J. Kaluzny, J. J. Kałuzny, A. Szkulmowska, I. Gorczyńska, M. Szkulmowski, T. Bajraszewski, M. Wojtkowski, and P. Targowski, “Spectral optical coherence tomography: a novel technique for cornea imaging,” Cornea 25(8), 960–965 (2006).
[Crossref] [PubMed]

Barkana, Y.

Y. Barkana, Y. Gerber, U. Elbaz, S. Schwartz, G. Ken-Dror, I. Avni, and D. Zadok, “Central corneal thickness measurement with the pentacam Scheimpflug system, optical low-coherence reflectometry pachymeter, and ultrasound pachymetry,” J. Cataract Refract. Surg. 31(9), 1729–1735 (2005).
[Crossref] [PubMed]

Beaurepaire, E.

F. Aptel, N. Olivier, A. Deniset-Besseau, J. M. Legeais, K. Plamann, M. C. Schanne-Klein, and E. Beaurepaire, “Multimodal nonlinear imaging of the human cornea,” Invest. Ophthalmol. Vis. Sci. 51(5), 2459–2465 (2010).
[Crossref] [PubMed]

Bechmann, M.

M. Bechmann, M. J. Thiel, A. S. Neubauer, S. Ullrich, K. Ludwig, K. R. Kenyon, and M. W. Ulbig, “Central corneal thickness measurement with a retinal optical coherence tomography device versus standard ultrasonic pachymetry,” Cornea 20(1), 50–54 (2001).
[Crossref] [PubMed]

Bouma, B. E.

Bourne, W. M.

J. W. McLaren, C. B. Nau, J. C. Erie, and W. M. Bourne, “Corneal thickness measurement by confocal microscopy, ultrasound, and scanning slit methods,” Am. J. Ophthalmol. 137(6), 1011–1020 (2004).
[Crossref] [PubMed]

L. R. Nelson, D. O. Hodge, and W. M. Bourne, “In vitro comparison of Chen medium and Optisol-GS medium for human corneal storage,” Cornea 19(6), 782–787 (2000).
[Crossref] [PubMed]

Brezinski, M. E.

Brown, D. J.

N. Morishige, A. J. Wahlert, M. C. Kenney, D. J. Brown, K. Kawamoto, T. Chikama, T. Nishida, and J. V. Jester, “Second-harmonic imaging microscopy of normal human and keratoconus cornea,” Invest. Ophthalmol. Vis. Sci. 48(3), 1087–1094 (2007).
[Crossref] [PubMed]

Bueno, J. M.

J. M. Bueno, E. J. Gualda, and P. Artal, “Analysis of corneal stroma organization with wavefront optimized nonlinear microscopy,” Cornea 30(6), 692–701 (2011).
[Crossref] [PubMed]

Campagnola, P. J.

R. LaComb, O. Nadiarnykh, S. S. Townsend, and P. J. Campagnola, “Phase matching considerations in second harmonic generation from tissues: effects on emission directionality, conversion efficiency and observed morphology,” Opt. Commun. 281(7), 1823–1832 (2008).
[Crossref] [PubMed]

Canals, M.

M. D. Merindano, J. Costa, M. Canals, J. M. Potau, and D. Ruano, “A comparative study of Bowman’s layer in some mammals: relationships with other constituent corneal structures,” Eur. J. Anat. 6(3), 133–139 (2002).

Chan, K. K. H.

Chatterjee, A.

S. Shah, A. Chatterjee, M. Mathai, S. P. Kelly, J. Kwartz, D. Henson, and D. McLeod, “Relationship between corneal thickness and measured intraocular pressure in a general ophthalmology clinic,” Ophthalmology 106(11), 2154–2160 (1999).
[Crossref] [PubMed]

Chikama, T.

N. Morishige, A. J. Wahlert, M. C. Kenney, D. J. Brown, K. Kawamoto, T. Chikama, T. Nishida, and J. V. Jester, “Second-harmonic imaging microscopy of normal human and keratoconus cornea,” Invest. Ophthalmol. Vis. Sci. 48(3), 1087–1094 (2007).
[Crossref] [PubMed]

Costa, J.

M. D. Merindano, J. Costa, M. Canals, J. M. Potau, and D. Ruano, “A comparative study of Bowman’s layer in some mammals: relationships with other constituent corneal structures,” Eur. J. Anat. 6(3), 133–139 (2002).

DelMonte, D. W.

D. W. DelMonte and T. Kim, “Anatomy and physiology of the cornea,” J. Cataract Refract. Surg. 37(3), 588–598 (2011).
[Crossref] [PubMed]

Deniset-Besseau, A.

F. Aptel, N. Olivier, A. Deniset-Besseau, J. M. Legeais, K. Plamann, M. C. Schanne-Klein, and E. Beaurepaire, “Multimodal nonlinear imaging of the human cornea,” Invest. Ophthalmol. Vis. Sci. 51(5), 2459–2465 (2010).
[Crossref] [PubMed]

Efron, N.

N. Efron, I. Perez-Gomez, H. A. Mutalib, and J. Hollingsworth, “Confocal microscopy of the normal human cornea,” Cont. Lens Anterior Eye 24(1), 16–24 (2001).
[Crossref] [PubMed]

Elbaz, U.

Y. Barkana, Y. Gerber, U. Elbaz, S. Schwartz, G. Ken-Dror, I. Avni, and D. Zadok, “Central corneal thickness measurement with the pentacam Scheimpflug system, optical low-coherence reflectometry pachymeter, and ultrasound pachymetry,” J. Cataract Refract. Surg. 31(9), 1729–1735 (2005).
[Crossref] [PubMed]

Erie, J. C.

J. W. McLaren, C. B. Nau, J. C. Erie, and W. M. Bourne, “Corneal thickness measurement by confocal microscopy, ultrasound, and scanning slit methods,” Am. J. Ophthalmol. 137(6), 1011–1020 (2004).
[Crossref] [PubMed]

Faramarzi, A.

A. Faramarzi and H. Ziai, “Central corneal thickness measurement by ultrasound versus Orbscan II,” J Ophthalmic Vis Res 3(2), 83–86 (2008).
[PubMed]

Fitzke, F. W.

S. Patel, J. Marshall, and F. W. Fitzke, “Refractive index of the human corneal epithelium and stroma,” J. Refract. Surg. 11(2), 100–105 (1995).
[PubMed]

Fujimoto, J. G.

Gerber, Y.

Y. Barkana, Y. Gerber, U. Elbaz, S. Schwartz, G. Ken-Dror, I. Avni, and D. Zadok, “Central corneal thickness measurement with the pentacam Scheimpflug system, optical low-coherence reflectometry pachymeter, and ultrasound pachymetry,” J. Cataract Refract. Surg. 31(9), 1729–1735 (2005).
[Crossref] [PubMed]

Glucksberg, M. R.

Y. L. Kim, J. T. Walsh, T. K. Goldstick, and M. R. Glucksberg, “Variation of corneal refractive index with hydration,” Phys. Med. Biol. 49(5), 859–868 (2004).
[Crossref] [PubMed]

Goldstick, T. K.

Y. L. Kim, J. T. Walsh, T. K. Goldstick, and M. R. Glucksberg, “Variation of corneal refractive index with hydration,” Phys. Med. Biol. 49(5), 859–868 (2004).
[Crossref] [PubMed]

Gorczynska, I.

B. J. Kaluzny, J. J. Kałuzny, A. Szkulmowska, I. Gorczyńska, M. Szkulmowski, T. Bajraszewski, M. Wojtkowski, and P. Targowski, “Spectral optical coherence tomography: a novel technique for cornea imaging,” Cornea 25(8), 960–965 (2006).
[Crossref] [PubMed]

Gualda, E. J.

J. M. Bueno, E. J. Gualda, and P. Artal, “Analysis of corneal stroma organization with wavefront optimized nonlinear microscopy,” Cornea 30(6), 692–701 (2011).
[Crossref] [PubMed]

Gupta, P. K.

K. D. Rao, Y. Verma, H. S. Patel, and P. K. Gupta, “Non-invasive ophthalmic imaging of adult zebrafish eye using optical coherence tomography,” Curr. Sci. 90(11), 1506–1510 (2006).

Gusachenko, I.

Guthoff, R. F.

R. F. Guthoff, A. Zhivov, and O. Stachs, “In vivo confocal microscopy, an inner vision of the cornea - a major review,” Clin. Experiment. Ophthalmol. 37(1), 100–117 (2009).
[Crossref] [PubMed]

Hayashi, S.

S. Hayashi, T. Osawa, and K. Tohyama, “Comparative observations on corneas, with special reference to Bowman’s layer and Descemet’s membrane in mammals and amphibians,” J. Morphol. 254(3), 247–258 (2002).
[Crossref] [PubMed]

Hee, M. R.

Henson, D.

S. Shah, A. Chatterjee, M. Mathai, S. P. Kelly, J. Kwartz, D. Henson, and D. McLeod, “Relationship between corneal thickness and measured intraocular pressure in a general ophthalmology clinic,” Ophthalmology 106(11), 2154–2160 (1999).
[Crossref] [PubMed]

Hodge, D. O.

L. R. Nelson, D. O. Hodge, and W. M. Bourne, “In vitro comparison of Chen medium and Optisol-GS medium for human corneal storage,” Cornea 19(6), 782–787 (2000).
[Crossref] [PubMed]

Hollingsworth, J.

N. Efron, I. Perez-Gomez, H. A. Mutalib, and J. Hollingsworth, “Confocal microscopy of the normal human cornea,” Cont. Lens Anterior Eye 24(1), 16–24 (2001).
[Crossref] [PubMed]

Jester, J. V.

N. Morishige, A. J. Wahlert, M. C. Kenney, D. J. Brown, K. Kawamoto, T. Chikama, T. Nishida, and J. V. Jester, “Second-harmonic imaging microscopy of normal human and keratoconus cornea,” Invest. Ophthalmol. Vis. Sci. 48(3), 1087–1094 (2007).
[Crossref] [PubMed]

N. Morishige, W. M. Petroll, T. Nishida, M. C. Kenney, and J. V. Jester, “Noninvasive corneal stromal collagen imaging using two-photon-generated second-harmonic signals,” J. Cataract Refract. Surg. 32(11), 1784–1791 (2006).
[Crossref] [PubMed]

Kaluzny, B. J.

B. J. Kaluzny, J. J. Kałuzny, A. Szkulmowska, I. Gorczyńska, M. Szkulmowski, T. Bajraszewski, M. Wojtkowski, and P. Targowski, “Spectral optical coherence tomography: a novel technique for cornea imaging,” Cornea 25(8), 960–965 (2006).
[Crossref] [PubMed]

Kaluzny, J. J.

B. J. Kaluzny, J. J. Kałuzny, A. Szkulmowska, I. Gorczyńska, M. Szkulmowski, T. Bajraszewski, M. Wojtkowski, and P. Targowski, “Spectral optical coherence tomography: a novel technique for cornea imaging,” Cornea 25(8), 960–965 (2006).
[Crossref] [PubMed]

Kawamoto, K.

N. Morishige, A. J. Wahlert, M. C. Kenney, D. J. Brown, K. Kawamoto, T. Chikama, T. Nishida, and J. V. Jester, “Second-harmonic imaging microscopy of normal human and keratoconus cornea,” Invest. Ophthalmol. Vis. Sci. 48(3), 1087–1094 (2007).
[Crossref] [PubMed]

Kelly, S. P.

S. Shah, A. Chatterjee, M. Mathai, S. P. Kelly, J. Kwartz, D. Henson, and D. McLeod, “Relationship between corneal thickness and measured intraocular pressure in a general ophthalmology clinic,” Ophthalmology 106(11), 2154–2160 (1999).
[Crossref] [PubMed]

Ken-Dror, G.

Y. Barkana, Y. Gerber, U. Elbaz, S. Schwartz, G. Ken-Dror, I. Avni, and D. Zadok, “Central corneal thickness measurement with the pentacam Scheimpflug system, optical low-coherence reflectometry pachymeter, and ultrasound pachymetry,” J. Cataract Refract. Surg. 31(9), 1729–1735 (2005).
[Crossref] [PubMed]

Kenney, M. C.

N. Morishige, A. J. Wahlert, M. C. Kenney, D. J. Brown, K. Kawamoto, T. Chikama, T. Nishida, and J. V. Jester, “Second-harmonic imaging microscopy of normal human and keratoconus cornea,” Invest. Ophthalmol. Vis. Sci. 48(3), 1087–1094 (2007).
[Crossref] [PubMed]

N. Morishige, W. M. Petroll, T. Nishida, M. C. Kenney, and J. V. Jester, “Noninvasive corneal stromal collagen imaging using two-photon-generated second-harmonic signals,” J. Cataract Refract. Surg. 32(11), 1784–1791 (2006).
[Crossref] [PubMed]

Kenyon, K. R.

M. Bechmann, M. J. Thiel, A. S. Neubauer, S. Ullrich, K. Ludwig, K. R. Kenyon, and M. W. Ulbig, “Central corneal thickness measurement with a retinal optical coherence tomography device versus standard ultrasonic pachymetry,” Cornea 20(1), 50–54 (2001).
[Crossref] [PubMed]

Kim, T.

D. W. DelMonte and T. Kim, “Anatomy and physiology of the cornea,” J. Cataract Refract. Surg. 37(3), 588–598 (2011).
[Crossref] [PubMed]

Kim, Y. L.

Y. L. Kim, J. T. Walsh, T. K. Goldstick, and M. R. Glucksberg, “Variation of corneal refractive index with hydration,” Phys. Med. Biol. 49(5), 859–868 (2004).
[Crossref] [PubMed]

Kowalczuk, L.

Kwartz, J.

S. Shah, A. Chatterjee, M. Mathai, S. P. Kelly, J. Kwartz, D. Henson, and D. McLeod, “Relationship between corneal thickness and measured intraocular pressure in a general ophthalmology clinic,” Ophthalmology 106(11), 2154–2160 (1999).
[Crossref] [PubMed]

LaComb, R.

R. LaComb, O. Nadiarnykh, S. S. Townsend, and P. J. Campagnola, “Phase matching considerations in second harmonic generation from tissues: effects on emission directionality, conversion efficiency and observed morphology,” Opt. Commun. 281(7), 1823–1832 (2008).
[Crossref] [PubMed]

Lai, T.

Lamarre, I.

Latour, G.

Legeais, J. M.

F. Aptel, N. Olivier, A. Deniset-Besseau, J. M. Legeais, K. Plamann, M. C. Schanne-Klein, and E. Beaurepaire, “Multimodal nonlinear imaging of the human cornea,” Invest. Ophthalmol. Vis. Sci. 51(5), 2459–2465 (2010).
[Crossref] [PubMed]

Ludwig, K.

M. Bechmann, M. J. Thiel, A. S. Neubauer, S. Ullrich, K. Ludwig, K. R. Kenyon, and M. W. Ulbig, “Central corneal thickness measurement with a retinal optical coherence tomography device versus standard ultrasonic pachymetry,” Cornea 20(1), 50–54 (2001).
[Crossref] [PubMed]

Manns, F.

S. R. Uhlhorn, F. Manns, H. Tahi, P. Rol, and J. M. Parel, “Corneal group refractive index measurement using low-coherence interferometry,” Proc. SPIE 3246, 14–21 (2003).
[Crossref]

Marshall, J.

S. Patel, J. Marshall, and F. W. Fitzke, “Refractive index of the human corneal epithelium and stroma,” J. Refract. Surg. 11(2), 100–105 (1995).
[PubMed]

Masters, B. R.

B. R. Masters, “Correlation of histology and linear and nonlinear microscopy of the living human cornea,” J. Biophotonics 2(3), 127–139 (2009).
[Crossref] [PubMed]

Mathai, M.

S. Shah, A. Chatterjee, M. Mathai, S. P. Kelly, J. Kwartz, D. Henson, and D. McLeod, “Relationship between corneal thickness and measured intraocular pressure in a general ophthalmology clinic,” Ophthalmology 106(11), 2154–2160 (1999).
[Crossref] [PubMed]

McLaren, J. W.

J. W. McLaren, C. B. Nau, J. C. Erie, and W. M. Bourne, “Corneal thickness measurement by confocal microscopy, ultrasound, and scanning slit methods,” Am. J. Ophthalmol. 137(6), 1011–1020 (2004).
[Crossref] [PubMed]

McLeod, D.

S. Shah, A. Chatterjee, M. Mathai, S. P. Kelly, J. Kwartz, D. Henson, and D. McLeod, “Relationship between corneal thickness and measured intraocular pressure in a general ophthalmology clinic,” Ophthalmology 106(11), 2154–2160 (1999).
[Crossref] [PubMed]

Meek, K. M.

K. M. Meek and A. J. Quantock, “The use of x-ray scattering techniques to determine corneal ultrastructure,” Prog. Retin. Eye Res. 20(1), 95–137 (2001).
[Crossref] [PubMed]

Merindano, M. D.

M. D. Merindano, J. Costa, M. Canals, J. M. Potau, and D. Ruano, “A comparative study of Bowman’s layer in some mammals: relationships with other constituent corneal structures,” Eur. J. Anat. 6(3), 133–139 (2002).

Morishige, N.

N. Morishige, A. J. Wahlert, M. C. Kenney, D. J. Brown, K. Kawamoto, T. Chikama, T. Nishida, and J. V. Jester, “Second-harmonic imaging microscopy of normal human and keratoconus cornea,” Invest. Ophthalmol. Vis. Sci. 48(3), 1087–1094 (2007).
[Crossref] [PubMed]

N. Morishige, W. M. Petroll, T. Nishida, M. C. Kenney, and J. V. Jester, “Noninvasive corneal stromal collagen imaging using two-photon-generated second-harmonic signals,” J. Cataract Refract. Surg. 32(11), 1784–1791 (2006).
[Crossref] [PubMed]

Mutalib, H. A.

N. Efron, I. Perez-Gomez, H. A. Mutalib, and J. Hollingsworth, “Confocal microscopy of the normal human cornea,” Cont. Lens Anterior Eye 24(1), 16–24 (2001).
[Crossref] [PubMed]

Nadiarnykh, O.

R. LaComb, O. Nadiarnykh, S. S. Townsend, and P. J. Campagnola, “Phase matching considerations in second harmonic generation from tissues: effects on emission directionality, conversion efficiency and observed morphology,” Opt. Commun. 281(7), 1823–1832 (2008).
[Crossref] [PubMed]

Nau, C. B.

J. W. McLaren, C. B. Nau, J. C. Erie, and W. M. Bourne, “Corneal thickness measurement by confocal microscopy, ultrasound, and scanning slit methods,” Am. J. Ophthalmol. 137(6), 1011–1020 (2004).
[Crossref] [PubMed]

Nelson, L. R.

L. R. Nelson, D. O. Hodge, and W. M. Bourne, “In vitro comparison of Chen medium and Optisol-GS medium for human corneal storage,” Cornea 19(6), 782–787 (2000).
[Crossref] [PubMed]

Neubauer, A. S.

M. Bechmann, M. J. Thiel, A. S. Neubauer, S. Ullrich, K. Ludwig, K. R. Kenyon, and M. W. Ulbig, “Central corneal thickness measurement with a retinal optical coherence tomography device versus standard ultrasonic pachymetry,” Cornea 20(1), 50–54 (2001).
[Crossref] [PubMed]

Nishida, T.

N. Morishige, A. J. Wahlert, M. C. Kenney, D. J. Brown, K. Kawamoto, T. Chikama, T. Nishida, and J. V. Jester, “Second-harmonic imaging microscopy of normal human and keratoconus cornea,” Invest. Ophthalmol. Vis. Sci. 48(3), 1087–1094 (2007).
[Crossref] [PubMed]

N. Morishige, W. M. Petroll, T. Nishida, M. C. Kenney, and J. V. Jester, “Noninvasive corneal stromal collagen imaging using two-photon-generated second-harmonic signals,” J. Cataract Refract. Surg. 32(11), 1784–1791 (2006).
[Crossref] [PubMed]

Olivier, N.

F. Aptel, N. Olivier, A. Deniset-Besseau, J. M. Legeais, K. Plamann, M. C. Schanne-Klein, and E. Beaurepaire, “Multimodal nonlinear imaging of the human cornea,” Invest. Ophthalmol. Vis. Sci. 51(5), 2459–2465 (2010).
[Crossref] [PubMed]

Osawa, T.

S. Hayashi, T. Osawa, and K. Tohyama, “Comparative observations on corneas, with special reference to Bowman’s layer and Descemet’s membrane in mammals and amphibians,” J. Morphol. 254(3), 247–258 (2002).
[Crossref] [PubMed]

Parel, J. M.

S. R. Uhlhorn, F. Manns, H. Tahi, P. Rol, and J. M. Parel, “Corneal group refractive index measurement using low-coherence interferometry,” Proc. SPIE 3246, 14–21 (2003).
[Crossref]

Patel, H. S.

K. D. Rao, Y. Verma, H. S. Patel, and P. K. Gupta, “Non-invasive ophthalmic imaging of adult zebrafish eye using optical coherence tomography,” Curr. Sci. 90(11), 1506–1510 (2006).

Patel, S.

S. Patel, J. L. Alió, and J. J. Pérez-Santonja, “Refractive index change in bovine and human corneal stroma before and after LASIK: a study of untreated and re-treated corneas implicating stromal hydration,” Invest. Ophthalmol. Vis. Sci. 45(10), 3523–3530 (2004).
[Crossref] [PubMed]

S. Patel, J. Marshall, and F. W. Fitzke, “Refractive index of the human corneal epithelium and stroma,” J. Refract. Surg. 11(2), 100–105 (1995).
[PubMed]

Perez-Gomez, I.

N. Efron, I. Perez-Gomez, H. A. Mutalib, and J. Hollingsworth, “Confocal microscopy of the normal human cornea,” Cont. Lens Anterior Eye 24(1), 16–24 (2001).
[Crossref] [PubMed]

Pérez-Santonja, J. J.

S. Patel, J. L. Alió, and J. J. Pérez-Santonja, “Refractive index change in bovine and human corneal stroma before and after LASIK: a study of untreated and re-treated corneas implicating stromal hydration,” Invest. Ophthalmol. Vis. Sci. 45(10), 3523–3530 (2004).
[Crossref] [PubMed]

Petroll, W. M.

N. Morishige, W. M. Petroll, T. Nishida, M. C. Kenney, and J. V. Jester, “Noninvasive corneal stromal collagen imaging using two-photon-generated second-harmonic signals,” J. Cataract Refract. Surg. 32(11), 1784–1791 (2006).
[Crossref] [PubMed]

Pham, D. T.

C. Wirbelauer and D. T. Pham, “Continuous monitoring of corneal thickness changes during LASIK with online optical coherence pachymetry,” J. Cataract Refract. Surg. 30(12), 2559–2568 (2004).
[Crossref] [PubMed]

Plamann, K.

F. Aptel, N. Olivier, A. Deniset-Besseau, J. M. Legeais, K. Plamann, M. C. Schanne-Klein, and E. Beaurepaire, “Multimodal nonlinear imaging of the human cornea,” Invest. Ophthalmol. Vis. Sci. 51(5), 2459–2465 (2010).
[Crossref] [PubMed]

Potau, J. M.

M. D. Merindano, J. Costa, M. Canals, J. M. Potau, and D. Ruano, “A comparative study of Bowman’s layer in some mammals: relationships with other constituent corneal structures,” Eur. J. Anat. 6(3), 133–139 (2002).

Quantock, A. J.

K. M. Meek and A. J. Quantock, “The use of x-ray scattering techniques to determine corneal ultrastructure,” Prog. Retin. Eye Res. 20(1), 95–137 (2001).
[Crossref] [PubMed]

Rao, K. D.

K. D. Rao, Y. Verma, H. S. Patel, and P. K. Gupta, “Non-invasive ophthalmic imaging of adult zebrafish eye using optical coherence tomography,” Curr. Sci. 90(11), 1506–1510 (2006).

Rol, P.

S. R. Uhlhorn, F. Manns, H. Tahi, P. Rol, and J. M. Parel, “Corneal group refractive index measurement using low-coherence interferometry,” Proc. SPIE 3246, 14–21 (2003).
[Crossref]

Ruano, D.

M. D. Merindano, J. Costa, M. Canals, J. M. Potau, and D. Ruano, “A comparative study of Bowman’s layer in some mammals: relationships with other constituent corneal structures,” Eur. J. Anat. 6(3), 133–139 (2002).

Schanne-Klein, M. C.

G. Latour, I. Gusachenko, L. Kowalczuk, I. Lamarre, and M. C. Schanne-Klein, “In vivo structural imaging of the cornea by polarization-resolved second harmonic microscopy,” Biomed. Opt. Express 3(1), 1–15 (2012).
[Crossref] [PubMed]

F. Aptel, N. Olivier, A. Deniset-Besseau, J. M. Legeais, K. Plamann, M. C. Schanne-Klein, and E. Beaurepaire, “Multimodal nonlinear imaging of the human cornea,” Invest. Ophthalmol. Vis. Sci. 51(5), 2459–2465 (2010).
[Crossref] [PubMed]

Schwartz, S.

Y. Barkana, Y. Gerber, U. Elbaz, S. Schwartz, G. Ken-Dror, I. Avni, and D. Zadok, “Central corneal thickness measurement with the pentacam Scheimpflug system, optical low-coherence reflectometry pachymeter, and ultrasound pachymetry,” J. Cataract Refract. Surg. 31(9), 1729–1735 (2005).
[Crossref] [PubMed]

Shah, S.

S. Shah, A. Chatterjee, M. Mathai, S. P. Kelly, J. Kwartz, D. Henson, and D. McLeod, “Relationship between corneal thickness and measured intraocular pressure in a general ophthalmology clinic,” Ophthalmology 106(11), 2154–2160 (1999).
[Crossref] [PubMed]

Simpson, T. L.

B. Vasudevan, T. L. Simpson, and J. G. Sivak, “Regional variation in the refractive-index of the bovine and human cornea,” Optom. Vis. Sci. 85(10), 977–981 (2008).
[Crossref] [PubMed]

Sivak, J. G.

B. Vasudevan, T. L. Simpson, and J. G. Sivak, “Regional variation in the refractive-index of the bovine and human cornea,” Optom. Vis. Sci. 85(10), 977–981 (2008).
[Crossref] [PubMed]

Southern, J. F.

Stachs, O.

R. F. Guthoff, A. Zhivov, and O. Stachs, “In vivo confocal microscopy, an inner vision of the cornea - a major review,” Clin. Experiment. Ophthalmol. 37(1), 100–117 (2009).
[Crossref] [PubMed]

Szkulmowska, A.

B. J. Kaluzny, J. J. Kałuzny, A. Szkulmowska, I. Gorczyńska, M. Szkulmowski, T. Bajraszewski, M. Wojtkowski, and P. Targowski, “Spectral optical coherence tomography: a novel technique for cornea imaging,” Cornea 25(8), 960–965 (2006).
[Crossref] [PubMed]

Szkulmowski, M.

B. J. Kaluzny, J. J. Kałuzny, A. Szkulmowska, I. Gorczyńska, M. Szkulmowski, T. Bajraszewski, M. Wojtkowski, and P. Targowski, “Spectral optical coherence tomography: a novel technique for cornea imaging,” Cornea 25(8), 960–965 (2006).
[Crossref] [PubMed]

Tahi, H.

S. R. Uhlhorn, F. Manns, H. Tahi, P. Rol, and J. M. Parel, “Corneal group refractive index measurement using low-coherence interferometry,” Proc. SPIE 3246, 14–21 (2003).
[Crossref]

Tang, S.

Targowski, P.

B. J. Kaluzny, J. J. Kałuzny, A. Szkulmowska, I. Gorczyńska, M. Szkulmowski, T. Bajraszewski, M. Wojtkowski, and P. Targowski, “Spectral optical coherence tomography: a novel technique for cornea imaging,” Cornea 25(8), 960–965 (2006).
[Crossref] [PubMed]

Tearney, G. J.

Thiel, M. J.

M. Bechmann, M. J. Thiel, A. S. Neubauer, S. Ullrich, K. Ludwig, K. R. Kenyon, and M. W. Ulbig, “Central corneal thickness measurement with a retinal optical coherence tomography device versus standard ultrasonic pachymetry,” Cornea 20(1), 50–54 (2001).
[Crossref] [PubMed]

Tohyama, K.

S. Hayashi, T. Osawa, and K. Tohyama, “Comparative observations on corneas, with special reference to Bowman’s layer and Descemet’s membrane in mammals and amphibians,” J. Morphol. 254(3), 247–258 (2002).
[Crossref] [PubMed]

Townsend, S. S.

R. LaComb, O. Nadiarnykh, S. S. Townsend, and P. J. Campagnola, “Phase matching considerations in second harmonic generation from tissues: effects on emission directionality, conversion efficiency and observed morphology,” Opt. Commun. 281(7), 1823–1832 (2008).
[Crossref] [PubMed]

Uhlhorn, S. R.

S. R. Uhlhorn, F. Manns, H. Tahi, P. Rol, and J. M. Parel, “Corneal group refractive index measurement using low-coherence interferometry,” Proc. SPIE 3246, 14–21 (2003).
[Crossref]

Ulbig, M. W.

M. Bechmann, M. J. Thiel, A. S. Neubauer, S. Ullrich, K. Ludwig, K. R. Kenyon, and M. W. Ulbig, “Central corneal thickness measurement with a retinal optical coherence tomography device versus standard ultrasonic pachymetry,” Cornea 20(1), 50–54 (2001).
[Crossref] [PubMed]

Ullrich, S.

M. Bechmann, M. J. Thiel, A. S. Neubauer, S. Ullrich, K. Ludwig, K. R. Kenyon, and M. W. Ulbig, “Central corneal thickness measurement with a retinal optical coherence tomography device versus standard ultrasonic pachymetry,” Cornea 20(1), 50–54 (2001).
[Crossref] [PubMed]

Vasudevan, B.

B. Vasudevan, T. L. Simpson, and J. G. Sivak, “Regional variation in the refractive-index of the bovine and human cornea,” Optom. Vis. Sci. 85(10), 977–981 (2008).
[Crossref] [PubMed]

Verma, Y.

K. D. Rao, Y. Verma, H. S. Patel, and P. K. Gupta, “Non-invasive ophthalmic imaging of adult zebrafish eye using optical coherence tomography,” Curr. Sci. 90(11), 1506–1510 (2006).

Wahlert, A. J.

N. Morishige, A. J. Wahlert, M. C. Kenney, D. J. Brown, K. Kawamoto, T. Chikama, T. Nishida, and J. V. Jester, “Second-harmonic imaging microscopy of normal human and keratoconus cornea,” Invest. Ophthalmol. Vis. Sci. 48(3), 1087–1094 (2007).
[Crossref] [PubMed]

Walsh, J. T.

Y. L. Kim, J. T. Walsh, T. K. Goldstick, and M. R. Glucksberg, “Variation of corneal refractive index with hydration,” Phys. Med. Biol. 49(5), 859–868 (2004).
[Crossref] [PubMed]

Webb, W. W.

R. M. Williams, W. R. Zipfel, and W. W. Webb, “Interpreting second-harmonic generation images of collagen I fibrils,” Biophys. J. 88(2), 1377–1386 (2005).
[Crossref] [PubMed]

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
[Crossref] [PubMed]

Williams, R. M.

R. M. Williams, W. R. Zipfel, and W. W. Webb, “Interpreting second-harmonic generation images of collagen I fibrils,” Biophys. J. 88(2), 1377–1386 (2005).
[Crossref] [PubMed]

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
[Crossref] [PubMed]

Wirbelauer, C.

C. Wirbelauer and D. T. Pham, “Continuous monitoring of corneal thickness changes during LASIK with online optical coherence pachymetry,” J. Cataract Refract. Surg. 30(12), 2559–2568 (2004).
[Crossref] [PubMed]

Wojtkowski, M.

B. J. Kaluzny, J. J. Kałuzny, A. Szkulmowska, I. Gorczyńska, M. Szkulmowski, T. Bajraszewski, M. Wojtkowski, and P. Targowski, “Spectral optical coherence tomography: a novel technique for cornea imaging,” Cornea 25(8), 960–965 (2006).
[Crossref] [PubMed]

Zadok, D.

Y. Barkana, Y. Gerber, U. Elbaz, S. Schwartz, G. Ken-Dror, I. Avni, and D. Zadok, “Central corneal thickness measurement with the pentacam Scheimpflug system, optical low-coherence reflectometry pachymeter, and ultrasound pachymetry,” J. Cataract Refract. Surg. 31(9), 1729–1735 (2005).
[Crossref] [PubMed]

Zhivov, A.

R. F. Guthoff, A. Zhivov, and O. Stachs, “In vivo confocal microscopy, an inner vision of the cornea - a major review,” Clin. Experiment. Ophthalmol. 37(1), 100–117 (2009).
[Crossref] [PubMed]

Zhou, Y.

Ziai, H.

A. Faramarzi and H. Ziai, “Central corneal thickness measurement by ultrasound versus Orbscan II,” J Ophthalmic Vis Res 3(2), 83–86 (2008).
[PubMed]

Zipfel, W. R.

R. M. Williams, W. R. Zipfel, and W. W. Webb, “Interpreting second-harmonic generation images of collagen I fibrils,” Biophys. J. 88(2), 1377–1386 (2005).
[Crossref] [PubMed]

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
[Crossref] [PubMed]

Am. J. Ophthalmol. (1)

J. W. McLaren, C. B. Nau, J. C. Erie, and W. M. Bourne, “Corneal thickness measurement by confocal microscopy, ultrasound, and scanning slit methods,” Am. J. Ophthalmol. 137(6), 1011–1020 (2004).
[Crossref] [PubMed]

Biomed. Opt. Express (2)

Biophys. J. (1)

R. M. Williams, W. R. Zipfel, and W. W. Webb, “Interpreting second-harmonic generation images of collagen I fibrils,” Biophys. J. 88(2), 1377–1386 (2005).
[Crossref] [PubMed]

Clin. Experiment. Ophthalmol. (1)

R. F. Guthoff, A. Zhivov, and O. Stachs, “In vivo confocal microscopy, an inner vision of the cornea - a major review,” Clin. Experiment. Ophthalmol. 37(1), 100–117 (2009).
[Crossref] [PubMed]

Cont. Lens Anterior Eye (1)

N. Efron, I. Perez-Gomez, H. A. Mutalib, and J. Hollingsworth, “Confocal microscopy of the normal human cornea,” Cont. Lens Anterior Eye 24(1), 16–24 (2001).
[Crossref] [PubMed]

Cornea (4)

J. M. Bueno, E. J. Gualda, and P. Artal, “Analysis of corneal stroma organization with wavefront optimized nonlinear microscopy,” Cornea 30(6), 692–701 (2011).
[Crossref] [PubMed]

B. J. Kaluzny, J. J. Kałuzny, A. Szkulmowska, I. Gorczyńska, M. Szkulmowski, T. Bajraszewski, M. Wojtkowski, and P. Targowski, “Spectral optical coherence tomography: a novel technique for cornea imaging,” Cornea 25(8), 960–965 (2006).
[Crossref] [PubMed]

M. Bechmann, M. J. Thiel, A. S. Neubauer, S. Ullrich, K. Ludwig, K. R. Kenyon, and M. W. Ulbig, “Central corneal thickness measurement with a retinal optical coherence tomography device versus standard ultrasonic pachymetry,” Cornea 20(1), 50–54 (2001).
[Crossref] [PubMed]

L. R. Nelson, D. O. Hodge, and W. M. Bourne, “In vitro comparison of Chen medium and Optisol-GS medium for human corneal storage,” Cornea 19(6), 782–787 (2000).
[Crossref] [PubMed]

Curr. Sci. (1)

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Figures (10)

Fig. 1
Fig. 1

Experimental setup of the combined MPM/OCT imaging system. L: lens; DG: diffraction grating; BS: beam splitter; PMT: photomultiplier tube; F: filter; DM: dichroic mirror.

Fig. 2
Fig. 2

OCT and MPM images of a murine cornea. (a) OCT cross-sectional image. (b) MPM cross-sectional image. L1 is the epithelium layer. L2 is the Bowman’s layer, stroma, Descemet’s membrane, and endothelium layers. (c) – (h) MPM en face images. (c) Anterior epithelium. (d) Posterior epithelium. (e) Junction between the epithelium and the stroma. (f) Anterior stroma. (g) Posterior stroma. (h) Descemet’s membrane and Endothelium. Arrowheads point to the Descemet’s membrane. (c) – (h) are 12 µm, 28 µm, 42 µm, 92 µm, 146 µm, and 160 µm below the surface of the cornea, respectively. TPEF signals are in red. SHG signals are in green. Scale bars are 50 µm. The red dashed rectangle in the OCT image marks the co-registered MPM imaging area.

Fig. 3
Fig. 3

OCT and MPM images of a piscine cornea. (a) OCT cross-sectional image. (b) MPM cross-sectional image. S1 and S2 are the first and second stromal layers. (c) – (h) MPM en face images. (c) Anterior epithelium. (d) Posterior epithelium. (e) Junction between the epithelium and the stroma. (f) Stroma in S1. (g) Stroma in S2. (h) Descemet’s membrane and endothelium. (c) – (h) are 4 µm, 28 µm, 44 µm, 69 µm, 253 µm, and 282 µm below the surface of the cornea, respectively. Double arrow marks the direction of the collagen fiber bundles. Scale bars are 50 µm. The red dashed rectangle in the OCT image marks the co-registered MPM imaging area.

Fig. 4
Fig. 4

OCT and MPM images of a human cornea. (a) OCT cross-sectional image. (b) MPM cross-sectional image. (c) – (h) MPM en face images. (c) Epithelium. (d) Bowman’s layer. (e) – (g) Anterior to posterior stroma. (h) Descemet’s membrane and endothelium. Yellow arrowheads point to regions of weaker SHG signal in the anterior stroma. Red arrowheads point to collagen micro-folds. Black arrowheads point to the Descemet’s membrane. (c) – (h) are 42 µm, 68 µm, 110 µm, 340 µm, 680 µm, and 870 µm below the surface of the cornea, respectively. Scale bars are 50 μm. The red dashed rectangle in the OCT image marks the co-registered MPM imaging area.

Fig. 5
Fig. 5

MPM en face images identifying the human Bowman’s Layer. (a) Epithelium. (b) Posterior epithelium. (c) Bowman’s layer. (d) – (e) Anterior stroma. (f) A typical stromal region. (a) – (f) are 26 µm, 34 µm, 42 µm, 50 µm, 60 µm, and 220 µm below the surface of the cornea, respectively. Scale bar is 50 μm.

Fig. 6
Fig. 6

OCT and MPM images of a porcine cornea. (a) OCT cross-sectional image. (b) MPM cross-sectional image. (c) – (h) MPM en face images. (c) Anterior epithelium. (d) – (e) Junction between the posterior epithelium and the stroma. The Bowman’s membrane is estimated as the region between the two arrowheads. (f) – (g) Anterior to posterior stroma. (h) Descemet’s membrane and endothelium. (c) – (h) are 12 µm, 72 µm, 96 µm, 234 µm, 534 µm, and 772 µm below the surface of the cornea, respectively. Scale bars are 50 μm. The red dashed rectangle in the OCT image marks the co-registered MPM imaging area.

Fig. 7
Fig. 7

MPM en face images showing collagen structural comparison between the Bowman’s layer (a) – (b) and a typical stromal region (c) of a porcine cornea. (a) – (c) are 60 µm, 68 µm, and 190 µm below the surface of the cornea, respectively. Scale bar is 50 μm. The Bowman’s membrane is highlighted by the arrowheads.

Fig. 8
Fig. 8

OCT and MPM images of a bovine cornea. (a) OCT cross-sectional image. (b) MPM cross-sectional image. (c) – (k) MPM en face images. (c) Anterior epithelium. (d) Posterior epithelium. (e) Bowman’s layer. (f) – (g) Transition from the Bowman’s layer to the stroma. (h) Anterior stroma. (i) Posterior stroma. (j) Descemet’s membrane. (k) Endothelium. (c) – (k) are 36 µm, 136 µm, 154 µm, 164 µm, 174 µm, 478 µm, 898 µm, 934 µm, and 958 µm below the surface of the cornea, respectively. Scale bars are 50 μm. The red dashed rectangle in the OCT image marks the co-registered MPM imaging area.

Fig. 9
Fig. 9

RI results for 6 murine samples (a), 6 piscine samples (b), 8 human samples (c), 3 porcine samples (d), and 5 bovine samples (e). L1 is epithelium, L2 is the remaining corneal layers, and overall is the entire cornea thickness.

Fig. 10
Fig. 10

Comparison between the OCT and SHG signals of a human cornea and a bovine cornea. (a) – (d) OCT image, OCT intensity profile, SHG intensity profile, MPM cross-sectional image of a human cornea, respectively. (e) – (h) OCT image, OCT intensity profile, SHG intensity profile, and MPM cross-sectional image of a bovine cornea, respectively. L1 is the epithelium layer. L2 is the Bowman’s layer, stroma, Descemet’s membrane, and endothelium layers. Scale bars are 50 μm.

Tables (1)

Tables Icon

Table 1 Refractive index and thickness results for murine, piscine, human, porcine and bovine corneas

Equations (4)

Equations on this page are rendered with MathJax. Learn more.

L p =t×n
L o =t× n o 2 ( NA ) 2 n 2 ( NA ) 2
n= ( NA ) 2 + ( NA ) 4 +4[ n o 2 ( NA ) 2 ] L p 2 / L o 2 2
t= 2 L p ( NA ) 2 + ( NA ) 4 +4[ n o 2 ( NA ) 2 ] L p 2 / L o 2

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