Abstract

A combined nonlinear optical microscopy (NLOM) and optical coherence microscopy (OCM) imaging system has been assembled in order to simultaneously capture co-registered volumetric images of corneal morphology and biochemistry. Tracking of cell nuclei visible in the OCM volume enabled the calculation of strain depth profile in response to changes in intraocular pressure for rabbit cornea stroma. Results revealed nonlinear responses with a depth dependent strain distribution, exhibiting smaller strains in the anterior and larger strains in the posterior stroma. Cross-sectional images of collagen lamellae, visible in NLOM, showed inhomogeneous collagen structure along the anterior-posterior direction that correlated well with the noted heterogeneous corneal mechanical responses.

© 2011 OSA

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    [CrossRef] [PubMed]

2009

M. Abahussin, S. Hayes, N. E. Knox Cartwright, C. S. Kamma-Lorger, Y. Khan, J. Marshall, and K. M. Meek, “3D collagen orientation study of the human cornea using X-ray diffraction and femtosecond laser technology,” Invest. Ophthalmol. Vis. Sci. 50(11), 5159–5164 (2009).
[CrossRef] [PubMed]

S. Pang, A. T. Yeh, C. Wang, and K. E. Meissner, “Beyond the 1/Tp limit: two-photon-excited fluorescence using pulses as short as sub-10-fs,” J. Biomed. Opt. 14(5), 054041 (2009).
[CrossRef] [PubMed]

2008

A. Pandolfi and G. A. Holzapfel, “Three-dimensional modeling and computational analysis of the human cornea considering distributed collagen fibril orientations,” J. Biomech. Eng. 130(6), 061006 (2008).
[CrossRef] [PubMed]

Q. Wu and A. T. Yeh, “Rabbit cornea microstructure response to changes in intraocular pressure visualized by using nonlinear optical microscopy,” Cornea 27(2), 202–208 (2008).
[CrossRef] [PubMed]

C. Kirwan and M. O’Keefe, “Measurement of intraocular pressure in LASIK and LASEK patients using the Reichert Ocular Response Analyzer and Goldmann applanation tonometry,” J. Refract. Surg. 24(4), 366–370 (2008).
[PubMed]

2007

J. S. Pepose, S. K. Feigenbaum, M. A. Qazi, J. P. Sanderson, and C. J. Roberts, “Changes in corneal biomechanics and intraocular pressure following LASIK using static, dynamic, and noncontact tonometry,” Am. J. Ophthalmol. 143(1), 39–47.e1 (2007).
[CrossRef] [PubMed]

2006

M. Kohlhaas, E. Spoerl, A. G. Boehm, and K. Pollack, “A correction formula for the real intraocular pressure after LASIK for the correction of myopic astigmatism,” J. Refract. Surg. 22(3), 263–267 (2006).
[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]

A. Labbé, H. Liang, C. Martin, F. Brignole-Baudouin, J.-M. Warnet, and C. Baudouin, “Comparative anatomy of laboratory animal corneas with a new-generation high-resolution in vivo confocal microscope,” Curr. Eye Res. 31(6), 501–509 (2006).
[CrossRef] [PubMed]

H.-Y. Tan, Y. Sun, W. Lo, S.-J. Lin, C.-H. Hsiao, Y.-F. Chen, S. C.-M. Huang, W.-C. Lin, S.-H. Jee, H.-S. Yu, and C.-Y. Dong, “Multiphoton fluorescence and second harmonic generation imaging of the structural alterations in keratoconus ex vivo,” Invest. Ophthalmol. Vis. Sci. 47(12), 5251–5259 (2006).
[CrossRef] [PubMed]

A. M. Larson and A. T. Yeh, “Ex vivo characterization of sub-10-fs pulses,” Opt. Lett. 31(11), 1681–1683 (2006).
[CrossRef] [PubMed]

2005

P. M. Pinsky, D. van der Heide, and D. Chernyak, “Computational modeling of mechanical anisotropy in the cornea and sclera,” J. Cataract Refract. Surg. 31(1), 136–145 (2005).
[CrossRef] [PubMed]

J. Liu and C. J. Roberts, “Influence of corneal biomechanical properties on intraocular pressure measurement: quantitative analysis,” J. Cataract Refract. Surg. 31(1), 146–155 (2005).
[CrossRef] [PubMed]

2004

H. Aghamohammadzadeh, R. H. Newton, and K. M. Meek, “X-ray scattering used to map the preferred collagen orientation in the human cornea and limbus,” Structure 12(2), 249–256 (2004).
[PubMed]

A. L. Clark, A. Gillenwater, R. Alizadeh-Naderi, A. K. El-Naggar, and R. Richards-Kortum, “Detection and diagnosis of oral neoplasia with an optical coherence microscope,” J. Biomed. Opt. 9(6), 1271–1280 (2004).
[CrossRef] [PubMed]

2002

2001

B. R. Masters and M. Böhnke, “Three-dimensional confocal microscopy of the human cornea in vivo,” Ophthalmic Res. 33(3), 125–135 (2001).
[CrossRef] [PubMed]

L. J. Müller, E. Pels, and G. F. J. M. Vrensen, “The specific architecture of the anterior stroma accounts for maintenance of corneal curvature,” Br. J. Ophthalmol. 85(4), 437–443 (2001).
[CrossRef] [PubMed]

2000

C. Roberts, “The cornea is not a piece of plastic,” J. Refract. Surg. 16(4), 407–413 (2000).
[PubMed]

T. Møller-Pedersen, H. D. Cavanagh, W. M. Petroll, and J. V. Jester, “Stromal wound healing explains refractive instability and haze development after photorefractive keratectomy: a 1-year confocal microscopic study,” Ophthalmology 107(7), 1235–1245 (2000).
[CrossRef] [PubMed]

1999

J. V. Jester, T. Moller-Pedersen, J. Huang, C. M. Sax, W. T. Kays, H. D. Cavangh, W. M. Petroll, and J. Piatigorsky, “The cellular basis of corneal transparency: evidence for ‘corneal crystallins’,” J. Cell Sci. 112(Pt 5), 613–622 (1999).
[PubMed]

1998

W. Radner, M. Zehetmayer, R. Aufreiter, and R. Mallinger, “Interlacing and cross-angle distribution of collagen lamellae in the human cornea,” Cornea 17(5), 537–543 (1998).
[CrossRef] [PubMed]

H. Hennighausen, S. T. Feldman, J. F. Bille, and A. D. McCulloch, “Anterior-posterior strain variation in normally hydrated and swollen rabbit cornea,” Invest. Ophthalmol. Vis. Sci. 39(2), 253–262 (1998).
[PubMed]

1997

T. J. Shin, R. P. Vito, L. W. Johnson, and B. E. McCarey, “The distribution of strain in the human cornea,” J. Biomech. 30(5), 497–503 (1997).
[CrossRef] [PubMed]

H. F. Li, W. M. Petroll, T. Møller-Pedersen, J. K. Maurer, H. D. Cavanagh, and J. V. Jester, “Epithelial and corneal thickness measurements by in vivo confocal microscopy through focusing (CMTF),” Curr. Eye Res. 16(3), 214–221 (1997).
[CrossRef] [PubMed]

1996

J. O. Hjortdal, “Regional elastic performance of the human cornea,” J. Biomech. 29(7), 931–942 (1996).
[CrossRef] [PubMed]

1995

D. W. Piston, B. R. Masters, and W. W. Webb, “Three-dimensionally resolved NAD(P)H cellular metabolic redox imaging of the in situ cornea with two-photon excitation laser scanning microscopy,” J. Microsc. 178(Pt 1), 20–27 (1995).
[PubMed]

1994

1993

W. M. Petroll, H. D. Cavanagh, and J. V. Jester, “Three-dimensional imaging of corneal cells using in vivo confocal microscopy,” J. Microsc. 170(Pt 3), 213–219 (1993).
[PubMed]

1986

B. Jue and D. M. Maurice, “The mechanical properties of the rabbit and human cornea,” J. Biomech. 19(10), 847–853 (1986).
[CrossRef] [PubMed]

1981

S. Hodson, C. Wigham, L. Williams, K. R. Mayes, and M. V. Graham, “Observation on the human cornea in vitro,” Exp. Eye Res. 32(3), 353–360 (1981).
[CrossRef] [PubMed]

Abahussin, M.

M. Abahussin, S. Hayes, N. E. Knox Cartwright, C. S. Kamma-Lorger, Y. Khan, J. Marshall, and K. M. Meek, “3D collagen orientation study of the human cornea using X-ray diffraction and femtosecond laser technology,” Invest. Ophthalmol. Vis. Sci. 50(11), 5159–5164 (2009).
[CrossRef] [PubMed]

Aghamohammadzadeh, H.

H. Aghamohammadzadeh, R. H. Newton, and K. M. Meek, “X-ray scattering used to map the preferred collagen orientation in the human cornea and limbus,” Structure 12(2), 249–256 (2004).
[PubMed]

Alizadeh-Naderi, R.

A. L. Clark, A. Gillenwater, R. Alizadeh-Naderi, A. K. El-Naggar, and R. Richards-Kortum, “Detection and diagnosis of oral neoplasia with an optical coherence microscope,” J. Biomed. Opt. 9(6), 1271–1280 (2004).
[CrossRef] [PubMed]

Aufreiter, R.

W. Radner, M. Zehetmayer, R. Aufreiter, and R. Mallinger, “Interlacing and cross-angle distribution of collagen lamellae in the human cornea,” Cornea 17(5), 537–543 (1998).
[CrossRef] [PubMed]

Baudouin, C.

A. Labbé, H. Liang, C. Martin, F. Brignole-Baudouin, J.-M. Warnet, and C. Baudouin, “Comparative anatomy of laboratory animal corneas with a new-generation high-resolution in vivo confocal microscope,” Curr. Eye Res. 31(6), 501–509 (2006).
[CrossRef] [PubMed]

Bille, J. F.

H. Hennighausen, S. T. Feldman, J. F. Bille, and A. D. McCulloch, “Anterior-posterior strain variation in normally hydrated and swollen rabbit cornea,” Invest. Ophthalmol. Vis. Sci. 39(2), 253–262 (1998).
[PubMed]

Boehm, A. G.

M. Kohlhaas, E. Spoerl, A. G. Boehm, and K. Pollack, “A correction formula for the real intraocular pressure after LASIK for the correction of myopic astigmatism,” J. Refract. Surg. 22(3), 263–267 (2006).
[PubMed]

Böhnke, M.

B. R. Masters and M. Böhnke, “Three-dimensional confocal microscopy of the human cornea in vivo,” Ophthalmic Res. 33(3), 125–135 (2001).
[CrossRef] [PubMed]

Brignole-Baudouin, F.

A. Labbé, H. Liang, C. Martin, F. Brignole-Baudouin, J.-M. Warnet, and C. Baudouin, “Comparative anatomy of laboratory animal corneas with a new-generation high-resolution in vivo confocal microscope,” Curr. Eye Res. 31(6), 501–509 (2006).
[CrossRef] [PubMed]

Cavanagh, H. D.

T. Møller-Pedersen, H. D. Cavanagh, W. M. Petroll, and J. V. Jester, “Stromal wound healing explains refractive instability and haze development after photorefractive keratectomy: a 1-year confocal microscopic study,” Ophthalmology 107(7), 1235–1245 (2000).
[CrossRef] [PubMed]

H. F. Li, W. M. Petroll, T. Møller-Pedersen, J. K. Maurer, H. D. Cavanagh, and J. V. Jester, “Epithelial and corneal thickness measurements by in vivo confocal microscopy through focusing (CMTF),” Curr. Eye Res. 16(3), 214–221 (1997).
[CrossRef] [PubMed]

W. M. Petroll, H. D. Cavanagh, and J. V. Jester, “Three-dimensional imaging of corneal cells using in vivo confocal microscopy,” J. Microsc. 170(Pt 3), 213–219 (1993).
[PubMed]

Cavangh, H. D.

J. V. Jester, T. Moller-Pedersen, J. Huang, C. M. Sax, W. T. Kays, H. D. Cavangh, W. M. Petroll, and J. Piatigorsky, “The cellular basis of corneal transparency: evidence for ‘corneal crystallins’,” J. Cell Sci. 112(Pt 5), 613–622 (1999).
[PubMed]

Chen, Y.-F.

H.-Y. Tan, Y. Sun, W. Lo, S.-J. Lin, C.-H. Hsiao, Y.-F. Chen, S. C.-M. Huang, W.-C. Lin, S.-H. Jee, H.-S. Yu, and C.-Y. Dong, “Multiphoton fluorescence and second harmonic generation imaging of the structural alterations in keratoconus ex vivo,” Invest. Ophthalmol. Vis. Sci. 47(12), 5251–5259 (2006).
[CrossRef] [PubMed]

Chernyak, D.

P. M. Pinsky, D. van der Heide, and D. Chernyak, “Computational modeling of mechanical anisotropy in the cornea and sclera,” J. Cataract Refract. Surg. 31(1), 136–145 (2005).
[CrossRef] [PubMed]

Clark, A. L.

A. L. Clark, A. Gillenwater, R. Alizadeh-Naderi, A. K. El-Naggar, and R. Richards-Kortum, “Detection and diagnosis of oral neoplasia with an optical coherence microscope,” J. Biomed. Opt. 9(6), 1271–1280 (2004).
[CrossRef] [PubMed]

Dong, C.-Y.

H.-Y. Tan, Y. Sun, W. Lo, S.-J. Lin, C.-H. Hsiao, Y.-F. Chen, S. C.-M. Huang, W.-C. Lin, S.-H. Jee, H.-S. Yu, and C.-Y. Dong, “Multiphoton fluorescence and second harmonic generation imaging of the structural alterations in keratoconus ex vivo,” Invest. Ophthalmol. Vis. Sci. 47(12), 5251–5259 (2006).
[CrossRef] [PubMed]

El-Naggar, A. K.

A. L. Clark, A. Gillenwater, R. Alizadeh-Naderi, A. K. El-Naggar, and R. Richards-Kortum, “Detection and diagnosis of oral neoplasia with an optical coherence microscope,” J. Biomed. Opt. 9(6), 1271–1280 (2004).
[CrossRef] [PubMed]

Feigenbaum, S. K.

J. S. Pepose, S. K. Feigenbaum, M. A. Qazi, J. P. Sanderson, and C. J. Roberts, “Changes in corneal biomechanics and intraocular pressure following LASIK using static, dynamic, and noncontact tonometry,” Am. J. Ophthalmol. 143(1), 39–47.e1 (2007).
[CrossRef] [PubMed]

Feldman, S. T.

H. Hennighausen, S. T. Feldman, J. F. Bille, and A. D. McCulloch, “Anterior-posterior strain variation in normally hydrated and swollen rabbit cornea,” Invest. Ophthalmol. Vis. Sci. 39(2), 253–262 (1998).
[PubMed]

Fujimoto, J. G.

Gillenwater, A.

A. L. Clark, A. Gillenwater, R. Alizadeh-Naderi, A. K. El-Naggar, and R. Richards-Kortum, “Detection and diagnosis of oral neoplasia with an optical coherence microscope,” J. Biomed. Opt. 9(6), 1271–1280 (2004).
[CrossRef] [PubMed]

Graham, M. V.

S. Hodson, C. Wigham, L. Williams, K. R. Mayes, and M. V. Graham, “Observation on the human cornea in vitro,” Exp. Eye Res. 32(3), 353–360 (1981).
[CrossRef] [PubMed]

Hayes, S.

M. Abahussin, S. Hayes, N. E. Knox Cartwright, C. S. Kamma-Lorger, Y. Khan, J. Marshall, and K. M. Meek, “3D collagen orientation study of the human cornea using X-ray diffraction and femtosecond laser technology,” Invest. Ophthalmol. Vis. Sci. 50(11), 5159–5164 (2009).
[CrossRef] [PubMed]

Hee, M. R.

Hennighausen, H.

H. Hennighausen, S. T. Feldman, J. F. Bille, and A. D. McCulloch, “Anterior-posterior strain variation in normally hydrated and swollen rabbit cornea,” Invest. Ophthalmol. Vis. Sci. 39(2), 253–262 (1998).
[PubMed]

Hjortdal, J. O.

J. O. Hjortdal, “Regional elastic performance of the human cornea,” J. Biomech. 29(7), 931–942 (1996).
[CrossRef] [PubMed]

Hodson, S.

S. Hodson, C. Wigham, L. Williams, K. R. Mayes, and M. V. Graham, “Observation on the human cornea in vitro,” Exp. Eye Res. 32(3), 353–360 (1981).
[CrossRef] [PubMed]

Holzapfel, G. A.

A. Pandolfi and G. A. Holzapfel, “Three-dimensional modeling and computational analysis of the human cornea considering distributed collagen fibril orientations,” J. Biomech. Eng. 130(6), 061006 (2008).
[CrossRef] [PubMed]

Hsiao, C.-H.

H.-Y. Tan, Y. Sun, W. Lo, S.-J. Lin, C.-H. Hsiao, Y.-F. Chen, S. C.-M. Huang, W.-C. Lin, S.-H. Jee, H.-S. Yu, and C.-Y. Dong, “Multiphoton fluorescence and second harmonic generation imaging of the structural alterations in keratoconus ex vivo,” Invest. Ophthalmol. Vis. Sci. 47(12), 5251–5259 (2006).
[CrossRef] [PubMed]

Huang, J.

J. V. Jester, T. Moller-Pedersen, J. Huang, C. M. Sax, W. T. Kays, H. D. Cavangh, W. M. Petroll, and J. Piatigorsky, “The cellular basis of corneal transparency: evidence for ‘corneal crystallins’,” J. Cell Sci. 112(Pt 5), 613–622 (1999).
[PubMed]

Huang, S. C.-M.

H.-Y. Tan, Y. Sun, W. Lo, S.-J. Lin, C.-H. Hsiao, Y.-F. Chen, S. C.-M. Huang, W.-C. Lin, S.-H. Jee, H.-S. Yu, and C.-Y. Dong, “Multiphoton fluorescence and second harmonic generation imaging of the structural alterations in keratoconus ex vivo,” Invest. Ophthalmol. Vis. Sci. 47(12), 5251–5259 (2006).
[CrossRef] [PubMed]

Izatt, J. A.

Jee, S.-H.

H.-Y. Tan, Y. Sun, W. Lo, S.-J. Lin, C.-H. Hsiao, Y.-F. Chen, S. C.-M. Huang, W.-C. Lin, S.-H. Jee, H.-S. Yu, and C.-Y. Dong, “Multiphoton fluorescence and second harmonic generation imaging of the structural alterations in keratoconus ex vivo,” Invest. Ophthalmol. Vis. Sci. 47(12), 5251–5259 (2006).
[CrossRef] [PubMed]

Jester, J. V.

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]

T. Møller-Pedersen, H. D. Cavanagh, W. M. Petroll, and J. V. Jester, “Stromal wound healing explains refractive instability and haze development after photorefractive keratectomy: a 1-year confocal microscopic study,” Ophthalmology 107(7), 1235–1245 (2000).
[CrossRef] [PubMed]

J. V. Jester, T. Moller-Pedersen, J. Huang, C. M. Sax, W. T. Kays, H. D. Cavangh, W. M. Petroll, and J. Piatigorsky, “The cellular basis of corneal transparency: evidence for ‘corneal crystallins’,” J. Cell Sci. 112(Pt 5), 613–622 (1999).
[PubMed]

H. F. Li, W. M. Petroll, T. Møller-Pedersen, J. K. Maurer, H. D. Cavanagh, and J. V. Jester, “Epithelial and corneal thickness measurements by in vivo confocal microscopy through focusing (CMTF),” Curr. Eye Res. 16(3), 214–221 (1997).
[CrossRef] [PubMed]

W. M. Petroll, H. D. Cavanagh, and J. V. Jester, “Three-dimensional imaging of corneal cells using in vivo confocal microscopy,” J. Microsc. 170(Pt 3), 213–219 (1993).
[PubMed]

Johnson, L. W.

T. J. Shin, R. P. Vito, L. W. Johnson, and B. E. McCarey, “The distribution of strain in the human cornea,” J. Biomech. 30(5), 497–503 (1997).
[CrossRef] [PubMed]

Jue, B.

B. Jue and D. M. Maurice, “The mechanical properties of the rabbit and human cornea,” J. Biomech. 19(10), 847–853 (1986).
[CrossRef] [PubMed]

Kamma-Lorger, C. S.

M. Abahussin, S. Hayes, N. E. Knox Cartwright, C. S. Kamma-Lorger, Y. Khan, J. Marshall, and K. M. Meek, “3D collagen orientation study of the human cornea using X-ray diffraction and femtosecond laser technology,” Invest. Ophthalmol. Vis. Sci. 50(11), 5159–5164 (2009).
[CrossRef] [PubMed]

Kays, W. T.

J. V. Jester, T. Moller-Pedersen, J. Huang, C. M. Sax, W. T. Kays, H. D. Cavangh, W. M. Petroll, and J. Piatigorsky, “The cellular basis of corneal transparency: evidence for ‘corneal crystallins’,” J. Cell Sci. 112(Pt 5), 613–622 (1999).
[PubMed]

Kenney, M. C.

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]

Khan, Y.

M. Abahussin, S. Hayes, N. E. Knox Cartwright, C. S. Kamma-Lorger, Y. Khan, J. Marshall, and K. M. Meek, “3D collagen orientation study of the human cornea using X-ray diffraction and femtosecond laser technology,” Invest. Ophthalmol. Vis. Sci. 50(11), 5159–5164 (2009).
[CrossRef] [PubMed]

Kirwan, C.

C. Kirwan and M. O’Keefe, “Measurement of intraocular pressure in LASIK and LASEK patients using the Reichert Ocular Response Analyzer and Goldmann applanation tonometry,” J. Refract. Surg. 24(4), 366–370 (2008).
[PubMed]

Knox Cartwright, N. E.

M. Abahussin, S. Hayes, N. E. Knox Cartwright, C. S. Kamma-Lorger, Y. Khan, J. Marshall, and K. M. Meek, “3D collagen orientation study of the human cornea using X-ray diffraction and femtosecond laser technology,” Invest. Ophthalmol. Vis. Sci. 50(11), 5159–5164 (2009).
[CrossRef] [PubMed]

Kohlhaas, M.

M. Kohlhaas, E. Spoerl, A. G. Boehm, and K. Pollack, “A correction formula for the real intraocular pressure after LASIK for the correction of myopic astigmatism,” J. Refract. Surg. 22(3), 263–267 (2006).
[PubMed]

Labbé, A.

A. Labbé, H. Liang, C. Martin, F. Brignole-Baudouin, J.-M. Warnet, and C. Baudouin, “Comparative anatomy of laboratory animal corneas with a new-generation high-resolution in vivo confocal microscope,” Curr. Eye Res. 31(6), 501–509 (2006).
[CrossRef] [PubMed]

Larson, A. M.

Li, H. F.

H. F. Li, W. M. Petroll, T. Møller-Pedersen, J. K. Maurer, H. D. Cavanagh, and J. V. Jester, “Epithelial and corneal thickness measurements by in vivo confocal microscopy through focusing (CMTF),” Curr. Eye Res. 16(3), 214–221 (1997).
[CrossRef] [PubMed]

Liang, H.

A. Labbé, H. Liang, C. Martin, F. Brignole-Baudouin, J.-M. Warnet, and C. Baudouin, “Comparative anatomy of laboratory animal corneas with a new-generation high-resolution in vivo confocal microscope,” Curr. Eye Res. 31(6), 501–509 (2006).
[CrossRef] [PubMed]

Lin, S.-J.

H.-Y. Tan, Y. Sun, W. Lo, S.-J. Lin, C.-H. Hsiao, Y.-F. Chen, S. C.-M. Huang, W.-C. Lin, S.-H. Jee, H.-S. Yu, and C.-Y. Dong, “Multiphoton fluorescence and second harmonic generation imaging of the structural alterations in keratoconus ex vivo,” Invest. Ophthalmol. Vis. Sci. 47(12), 5251–5259 (2006).
[CrossRef] [PubMed]

Lin, W.-C.

H.-Y. Tan, Y. Sun, W. Lo, S.-J. Lin, C.-H. Hsiao, Y.-F. Chen, S. C.-M. Huang, W.-C. Lin, S.-H. Jee, H.-S. Yu, and C.-Y. Dong, “Multiphoton fluorescence and second harmonic generation imaging of the structural alterations in keratoconus ex vivo,” Invest. Ophthalmol. Vis. Sci. 47(12), 5251–5259 (2006).
[CrossRef] [PubMed]

Liu, J.

J. Liu and C. J. Roberts, “Influence of corneal biomechanical properties on intraocular pressure measurement: quantitative analysis,” J. Cataract Refract. Surg. 31(1), 146–155 (2005).
[CrossRef] [PubMed]

Lo, W.

H.-Y. Tan, Y. Sun, W. Lo, S.-J. Lin, C.-H. Hsiao, Y.-F. Chen, S. C.-M. Huang, W.-C. Lin, S.-H. Jee, H.-S. Yu, and C.-Y. Dong, “Multiphoton fluorescence and second harmonic generation imaging of the structural alterations in keratoconus ex vivo,” Invest. Ophthalmol. Vis. Sci. 47(12), 5251–5259 (2006).
[CrossRef] [PubMed]

Mallinger, R.

W. Radner and R. Mallinger, “Interlacing of collagen lamellae in the midstroma of the human cornea,” Cornea 21(6), 598–601 (2002).
[CrossRef] [PubMed]

W. Radner, M. Zehetmayer, R. Aufreiter, and R. Mallinger, “Interlacing and cross-angle distribution of collagen lamellae in the human cornea,” Cornea 17(5), 537–543 (1998).
[CrossRef] [PubMed]

Marshall, J.

M. Abahussin, S. Hayes, N. E. Knox Cartwright, C. S. Kamma-Lorger, Y. Khan, J. Marshall, and K. M. Meek, “3D collagen orientation study of the human cornea using X-ray diffraction and femtosecond laser technology,” Invest. Ophthalmol. Vis. Sci. 50(11), 5159–5164 (2009).
[CrossRef] [PubMed]

Martin, C.

A. Labbé, H. Liang, C. Martin, F. Brignole-Baudouin, J.-M. Warnet, and C. Baudouin, “Comparative anatomy of laboratory animal corneas with a new-generation high-resolution in vivo confocal microscope,” Curr. Eye Res. 31(6), 501–509 (2006).
[CrossRef] [PubMed]

Masters, B. R.

B. R. Masters and M. Böhnke, “Three-dimensional confocal microscopy of the human cornea in vivo,” Ophthalmic Res. 33(3), 125–135 (2001).
[CrossRef] [PubMed]

D. W. Piston, B. R. Masters, and W. W. Webb, “Three-dimensionally resolved NAD(P)H cellular metabolic redox imaging of the in situ cornea with two-photon excitation laser scanning microscopy,” J. Microsc. 178(Pt 1), 20–27 (1995).
[PubMed]

Maurer, J. K.

H. F. Li, W. M. Petroll, T. Møller-Pedersen, J. K. Maurer, H. D. Cavanagh, and J. V. Jester, “Epithelial and corneal thickness measurements by in vivo confocal microscopy through focusing (CMTF),” Curr. Eye Res. 16(3), 214–221 (1997).
[CrossRef] [PubMed]

Maurice, D. M.

B. Jue and D. M. Maurice, “The mechanical properties of the rabbit and human cornea,” J. Biomech. 19(10), 847–853 (1986).
[CrossRef] [PubMed]

Mayes, K. R.

S. Hodson, C. Wigham, L. Williams, K. R. Mayes, and M. V. Graham, “Observation on the human cornea in vitro,” Exp. Eye Res. 32(3), 353–360 (1981).
[CrossRef] [PubMed]

McCarey, B. E.

T. J. Shin, R. P. Vito, L. W. Johnson, and B. E. McCarey, “The distribution of strain in the human cornea,” J. Biomech. 30(5), 497–503 (1997).
[CrossRef] [PubMed]

McCulloch, A. D.

H. Hennighausen, S. T. Feldman, J. F. Bille, and A. D. McCulloch, “Anterior-posterior strain variation in normally hydrated and swollen rabbit cornea,” Invest. Ophthalmol. Vis. Sci. 39(2), 253–262 (1998).
[PubMed]

Meek, K. M.

M. Abahussin, S. Hayes, N. E. Knox Cartwright, C. S. Kamma-Lorger, Y. Khan, J. Marshall, and K. M. Meek, “3D collagen orientation study of the human cornea using X-ray diffraction and femtosecond laser technology,” Invest. Ophthalmol. Vis. Sci. 50(11), 5159–5164 (2009).
[CrossRef] [PubMed]

H. Aghamohammadzadeh, R. H. Newton, and K. M. Meek, “X-ray scattering used to map the preferred collagen orientation in the human cornea and limbus,” Structure 12(2), 249–256 (2004).
[PubMed]

Meissner, K. E.

S. Pang, A. T. Yeh, C. Wang, and K. E. Meissner, “Beyond the 1/Tp limit: two-photon-excited fluorescence using pulses as short as sub-10-fs,” J. Biomed. Opt. 14(5), 054041 (2009).
[CrossRef] [PubMed]

Moller-Pedersen, T.

J. V. Jester, T. Moller-Pedersen, J. Huang, C. M. Sax, W. T. Kays, H. D. Cavangh, W. M. Petroll, and J. Piatigorsky, “The cellular basis of corneal transparency: evidence for ‘corneal crystallins’,” J. Cell Sci. 112(Pt 5), 613–622 (1999).
[PubMed]

Møller-Pedersen, T.

T. Møller-Pedersen, H. D. Cavanagh, W. M. Petroll, and J. V. Jester, “Stromal wound healing explains refractive instability and haze development after photorefractive keratectomy: a 1-year confocal microscopic study,” Ophthalmology 107(7), 1235–1245 (2000).
[CrossRef] [PubMed]

H. F. Li, W. M. Petroll, T. Møller-Pedersen, J. K. Maurer, H. D. Cavanagh, and J. V. Jester, “Epithelial and corneal thickness measurements by in vivo confocal microscopy through focusing (CMTF),” Curr. Eye Res. 16(3), 214–221 (1997).
[CrossRef] [PubMed]

Morishige, N.

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]

Müller, L. J.

L. J. Müller, E. Pels, and G. F. J. M. Vrensen, “The specific architecture of the anterior stroma accounts for maintenance of corneal curvature,” Br. J. Ophthalmol. 85(4), 437–443 (2001).
[CrossRef] [PubMed]

Nassif, N.

Newton, R. H.

H. Aghamohammadzadeh, R. H. Newton, and K. M. Meek, “X-ray scattering used to map the preferred collagen orientation in the human cornea and limbus,” Structure 12(2), 249–256 (2004).
[PubMed]

Nishida, T.

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]

O’Keefe, M.

C. Kirwan and M. O’Keefe, “Measurement of intraocular pressure in LASIK and LASEK patients using the Reichert Ocular Response Analyzer and Goldmann applanation tonometry,” J. Refract. Surg. 24(4), 366–370 (2008).
[PubMed]

Owen, G. M.

Pandolfi, A.

A. Pandolfi and G. A. Holzapfel, “Three-dimensional modeling and computational analysis of the human cornea considering distributed collagen fibril orientations,” J. Biomech. Eng. 130(6), 061006 (2008).
[CrossRef] [PubMed]

Pang, S.

S. Pang, A. T. Yeh, C. Wang, and K. E. Meissner, “Beyond the 1/Tp limit: two-photon-excited fluorescence using pulses as short as sub-10-fs,” J. Biomed. Opt. 14(5), 054041 (2009).
[CrossRef] [PubMed]

Pels, E.

L. J. Müller, E. Pels, and G. F. J. M. Vrensen, “The specific architecture of the anterior stroma accounts for maintenance of corneal curvature,” Br. J. Ophthalmol. 85(4), 437–443 (2001).
[CrossRef] [PubMed]

Pepose, J. S.

J. S. Pepose, S. K. Feigenbaum, M. A. Qazi, J. P. Sanderson, and C. J. Roberts, “Changes in corneal biomechanics and intraocular pressure following LASIK using static, dynamic, and noncontact tonometry,” Am. J. Ophthalmol. 143(1), 39–47.e1 (2007).
[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]

T. Møller-Pedersen, H. D. Cavanagh, W. M. Petroll, and J. V. Jester, “Stromal wound healing explains refractive instability and haze development after photorefractive keratectomy: a 1-year confocal microscopic study,” Ophthalmology 107(7), 1235–1245 (2000).
[CrossRef] [PubMed]

J. V. Jester, T. Moller-Pedersen, J. Huang, C. M. Sax, W. T. Kays, H. D. Cavangh, W. M. Petroll, and J. Piatigorsky, “The cellular basis of corneal transparency: evidence for ‘corneal crystallins’,” J. Cell Sci. 112(Pt 5), 613–622 (1999).
[PubMed]

H. F. Li, W. M. Petroll, T. Møller-Pedersen, J. K. Maurer, H. D. Cavanagh, and J. V. Jester, “Epithelial and corneal thickness measurements by in vivo confocal microscopy through focusing (CMTF),” Curr. Eye Res. 16(3), 214–221 (1997).
[CrossRef] [PubMed]

W. M. Petroll, H. D. Cavanagh, and J. V. Jester, “Three-dimensional imaging of corneal cells using in vivo confocal microscopy,” J. Microsc. 170(Pt 3), 213–219 (1993).
[PubMed]

Piatigorsky, J.

J. V. Jester, T. Moller-Pedersen, J. Huang, C. M. Sax, W. T. Kays, H. D. Cavangh, W. M. Petroll, and J. Piatigorsky, “The cellular basis of corneal transparency: evidence for ‘corneal crystallins’,” J. Cell Sci. 112(Pt 5), 613–622 (1999).
[PubMed]

Pinsky, P. M.

P. M. Pinsky, D. van der Heide, and D. Chernyak, “Computational modeling of mechanical anisotropy in the cornea and sclera,” J. Cataract Refract. Surg. 31(1), 136–145 (2005).
[CrossRef] [PubMed]

Piston, D. W.

D. W. Piston, B. R. Masters, and W. W. Webb, “Three-dimensionally resolved NAD(P)H cellular metabolic redox imaging of the in situ cornea with two-photon excitation laser scanning microscopy,” J. Microsc. 178(Pt 1), 20–27 (1995).
[PubMed]

Pollack, K.

M. Kohlhaas, E. Spoerl, A. G. Boehm, and K. Pollack, “A correction formula for the real intraocular pressure after LASIK for the correction of myopic astigmatism,” J. Refract. Surg. 22(3), 263–267 (2006).
[PubMed]

Qazi, M. A.

J. S. Pepose, S. K. Feigenbaum, M. A. Qazi, J. P. Sanderson, and C. J. Roberts, “Changes in corneal biomechanics and intraocular pressure following LASIK using static, dynamic, and noncontact tonometry,” Am. J. Ophthalmol. 143(1), 39–47.e1 (2007).
[CrossRef] [PubMed]

Radner, W.

W. Radner and R. Mallinger, “Interlacing of collagen lamellae in the midstroma of the human cornea,” Cornea 21(6), 598–601 (2002).
[CrossRef] [PubMed]

W. Radner, M. Zehetmayer, R. Aufreiter, and R. Mallinger, “Interlacing and cross-angle distribution of collagen lamellae in the human cornea,” Cornea 17(5), 537–543 (1998).
[CrossRef] [PubMed]

Richards-Kortum, R.

A. L. Clark, A. Gillenwater, R. Alizadeh-Naderi, A. K. El-Naggar, and R. Richards-Kortum, “Detection and diagnosis of oral neoplasia with an optical coherence microscope,” J. Biomed. Opt. 9(6), 1271–1280 (2004).
[CrossRef] [PubMed]

Roberts, C.

C. Roberts, “The cornea is not a piece of plastic,” J. Refract. Surg. 16(4), 407–413 (2000).
[PubMed]

Roberts, C. J.

J. S. Pepose, S. K. Feigenbaum, M. A. Qazi, J. P. Sanderson, and C. J. Roberts, “Changes in corneal biomechanics and intraocular pressure following LASIK using static, dynamic, and noncontact tonometry,” Am. J. Ophthalmol. 143(1), 39–47.e1 (2007).
[CrossRef] [PubMed]

J. Liu and C. J. Roberts, “Influence of corneal biomechanical properties on intraocular pressure measurement: quantitative analysis,” J. Cataract Refract. Surg. 31(1), 146–155 (2005).
[CrossRef] [PubMed]

Sanderson, J. P.

J. S. Pepose, S. K. Feigenbaum, M. A. Qazi, J. P. Sanderson, and C. J. Roberts, “Changes in corneal biomechanics and intraocular pressure following LASIK using static, dynamic, and noncontact tonometry,” Am. J. Ophthalmol. 143(1), 39–47.e1 (2007).
[CrossRef] [PubMed]

Sax, C. M.

J. V. Jester, T. Moller-Pedersen, J. Huang, C. M. Sax, W. T. Kays, H. D. Cavangh, W. M. Petroll, and J. Piatigorsky, “The cellular basis of corneal transparency: evidence for ‘corneal crystallins’,” J. Cell Sci. 112(Pt 5), 613–622 (1999).
[PubMed]

Shin, T. J.

T. J. Shin, R. P. Vito, L. W. Johnson, and B. E. McCarey, “The distribution of strain in the human cornea,” J. Biomech. 30(5), 497–503 (1997).
[CrossRef] [PubMed]

Spoerl, E.

M. Kohlhaas, E. Spoerl, A. G. Boehm, and K. Pollack, “A correction formula for the real intraocular pressure after LASIK for the correction of myopic astigmatism,” J. Refract. Surg. 22(3), 263–267 (2006).
[PubMed]

Sun, Y.

H.-Y. Tan, Y. Sun, W. Lo, S.-J. Lin, C.-H. Hsiao, Y.-F. Chen, S. C.-M. Huang, W.-C. Lin, S.-H. Jee, H.-S. Yu, and C.-Y. Dong, “Multiphoton fluorescence and second harmonic generation imaging of the structural alterations in keratoconus ex vivo,” Invest. Ophthalmol. Vis. Sci. 47(12), 5251–5259 (2006).
[CrossRef] [PubMed]

Swanson, E. A.

Tan, H.-Y.

H.-Y. Tan, Y. Sun, W. Lo, S.-J. Lin, C.-H. Hsiao, Y.-F. Chen, S. C.-M. Huang, W.-C. Lin, S.-H. Jee, H.-S. Yu, and C.-Y. Dong, “Multiphoton fluorescence and second harmonic generation imaging of the structural alterations in keratoconus ex vivo,” Invest. Ophthalmol. Vis. Sci. 47(12), 5251–5259 (2006).
[CrossRef] [PubMed]

Tromberg, B. J.

van der Heide, D.

P. M. Pinsky, D. van der Heide, and D. Chernyak, “Computational modeling of mechanical anisotropy in the cornea and sclera,” J. Cataract Refract. Surg. 31(1), 136–145 (2005).
[CrossRef] [PubMed]

Vito, R. P.

T. J. Shin, R. P. Vito, L. W. Johnson, and B. E. McCarey, “The distribution of strain in the human cornea,” J. Biomech. 30(5), 497–503 (1997).
[CrossRef] [PubMed]

Vrensen, G. F. J. M.

L. J. Müller, E. Pels, and G. F. J. M. Vrensen, “The specific architecture of the anterior stroma accounts for maintenance of corneal curvature,” Br. J. Ophthalmol. 85(4), 437–443 (2001).
[CrossRef] [PubMed]

Wang, C.

S. Pang, A. T. Yeh, C. Wang, and K. E. Meissner, “Beyond the 1/Tp limit: two-photon-excited fluorescence using pulses as short as sub-10-fs,” J. Biomed. Opt. 14(5), 054041 (2009).
[CrossRef] [PubMed]

Warnet, J.-M.

A. Labbé, H. Liang, C. Martin, F. Brignole-Baudouin, J.-M. Warnet, and C. Baudouin, “Comparative anatomy of laboratory animal corneas with a new-generation high-resolution in vivo confocal microscope,” Curr. Eye Res. 31(6), 501–509 (2006).
[CrossRef] [PubMed]

Webb, W. W.

D. W. Piston, B. R. Masters, and W. W. Webb, “Three-dimensionally resolved NAD(P)H cellular metabolic redox imaging of the in situ cornea with two-photon excitation laser scanning microscopy,” J. Microsc. 178(Pt 1), 20–27 (1995).
[PubMed]

Wigham, C.

S. Hodson, C. Wigham, L. Williams, K. R. Mayes, and M. V. Graham, “Observation on the human cornea in vitro,” Exp. Eye Res. 32(3), 353–360 (1981).
[CrossRef] [PubMed]

Williams, L.

S. Hodson, C. Wigham, L. Williams, K. R. Mayes, and M. V. Graham, “Observation on the human cornea in vitro,” Exp. Eye Res. 32(3), 353–360 (1981).
[CrossRef] [PubMed]

Wu, Q.

Q. Wu and A. T. Yeh, “Rabbit cornea microstructure response to changes in intraocular pressure visualized by using nonlinear optical microscopy,” Cornea 27(2), 202–208 (2008).
[CrossRef] [PubMed]

Yeh, A. T.

S. Pang, A. T. Yeh, C. Wang, and K. E. Meissner, “Beyond the 1/Tp limit: two-photon-excited fluorescence using pulses as short as sub-10-fs,” J. Biomed. Opt. 14(5), 054041 (2009).
[CrossRef] [PubMed]

Q. Wu and A. T. Yeh, “Rabbit cornea microstructure response to changes in intraocular pressure visualized by using nonlinear optical microscopy,” Cornea 27(2), 202–208 (2008).
[CrossRef] [PubMed]

A. M. Larson and A. T. Yeh, “Ex vivo characterization of sub-10-fs pulses,” Opt. Lett. 31(11), 1681–1683 (2006).
[CrossRef] [PubMed]

A. T. Yeh, N. Nassif, A. Zoumi, and B. J. Tromberg, “Selective corneal imaging using combined second-harmonic generation and two-photon excited fluorescence,” Opt. Lett. 27(23), 2082–2084 (2002).
[CrossRef] [PubMed]

Yu, H.-S.

H.-Y. Tan, Y. Sun, W. Lo, S.-J. Lin, C.-H. Hsiao, Y.-F. Chen, S. C.-M. Huang, W.-C. Lin, S.-H. Jee, H.-S. Yu, and C.-Y. Dong, “Multiphoton fluorescence and second harmonic generation imaging of the structural alterations in keratoconus ex vivo,” Invest. Ophthalmol. Vis. Sci. 47(12), 5251–5259 (2006).
[CrossRef] [PubMed]

Zehetmayer, M.

W. Radner, M. Zehetmayer, R. Aufreiter, and R. Mallinger, “Interlacing and cross-angle distribution of collagen lamellae in the human cornea,” Cornea 17(5), 537–543 (1998).
[CrossRef] [PubMed]

Zoumi, A.

Am. J. Ophthalmol.

J. S. Pepose, S. K. Feigenbaum, M. A. Qazi, J. P. Sanderson, and C. J. Roberts, “Changes in corneal biomechanics and intraocular pressure following LASIK using static, dynamic, and noncontact tonometry,” Am. J. Ophthalmol. 143(1), 39–47.e1 (2007).
[CrossRef] [PubMed]

Br. J. Ophthalmol.

L. J. Müller, E. Pels, and G. F. J. M. Vrensen, “The specific architecture of the anterior stroma accounts for maintenance of corneal curvature,” Br. J. Ophthalmol. 85(4), 437–443 (2001).
[CrossRef] [PubMed]

Cornea

W. Radner and R. Mallinger, “Interlacing of collagen lamellae in the midstroma of the human cornea,” Cornea 21(6), 598–601 (2002).
[CrossRef] [PubMed]

W. Radner, M. Zehetmayer, R. Aufreiter, and R. Mallinger, “Interlacing and cross-angle distribution of collagen lamellae in the human cornea,” Cornea 17(5), 537–543 (1998).
[CrossRef] [PubMed]

Q. Wu and A. T. Yeh, “Rabbit cornea microstructure response to changes in intraocular pressure visualized by using nonlinear optical microscopy,” Cornea 27(2), 202–208 (2008).
[CrossRef] [PubMed]

Curr. Eye Res.

H. F. Li, W. M. Petroll, T. Møller-Pedersen, J. K. Maurer, H. D. Cavanagh, and J. V. Jester, “Epithelial and corneal thickness measurements by in vivo confocal microscopy through focusing (CMTF),” Curr. Eye Res. 16(3), 214–221 (1997).
[CrossRef] [PubMed]

A. Labbé, H. Liang, C. Martin, F. Brignole-Baudouin, J.-M. Warnet, and C. Baudouin, “Comparative anatomy of laboratory animal corneas with a new-generation high-resolution in vivo confocal microscope,” Curr. Eye Res. 31(6), 501–509 (2006).
[CrossRef] [PubMed]

Exp. Eye Res.

S. Hodson, C. Wigham, L. Williams, K. R. Mayes, and M. V. Graham, “Observation on the human cornea in vitro,” Exp. Eye Res. 32(3), 353–360 (1981).
[CrossRef] [PubMed]

Invest. Ophthalmol. Vis. Sci.

H. Hennighausen, S. T. Feldman, J. F. Bille, and A. D. McCulloch, “Anterior-posterior strain variation in normally hydrated and swollen rabbit cornea,” Invest. Ophthalmol. Vis. Sci. 39(2), 253–262 (1998).
[PubMed]

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[CrossRef] [PubMed]

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Figures (6)

Fig. 3
Fig. 3

Keratocyte morphology changes with corneal swelling. OCM images of same keratocyte at different hydration states shown in minutes past the first image (A-D). Co-registered NLOM-OCM images (E-G). False color was applied to OCM (green, E) and SHG (red, F) images and overlaid (G) to reveal the interrelationship between keratocyte network and underlying collagen matrix. The clear morphological changes provided verification of hydration state throughout the biomechanical imaging experiments. Scale bars are 20 µm.

Fig. 1
Fig. 1

NLOM-OCM setup. BS, beam splitter; CM, chirp mirror; C, cornea sample; CCD, line scan camera; DG, diffraction grating; DM, dichroic mirror; F, filter; L, lens; M, mirror; O, objective; PMT, photomultiplier tube; SMF, single-mode fiber; XY, 2-axis scanning mirrors

Fig. 6
Fig. 6

Cross-sectional collagen structure of swollen (A,B) and normally hydrated cornea (C-F) at 5 mmHg (A and C, raw; B and D, processed) and 20 mmHg (E, raw; F, processed). Scale bar is 40 µm.

Fig. 2
Fig. 2

Representative NLOM (lower) OCM (upper) images of rabbit cornea at different depths. Epithelium (A), epithelial-stromal boundary (B), stroma (C), Descemet’s membrane by OCM (D) and endothelium (E). Stars and arrows indicate keratocyte nuclei and nerve fibers, respectively. Scale bar is 40 µm.

Fig. 5
Fig. 5

Cornea strains (A) and its correlation with structural (gap area) responses (B) layer-by-layer. The pressure-strain curves combined with collagen microstructural responses can readily be grouped by depth as anterior (40%), transitional mid (20%) and posterior (40%) which is consistent with marked differences in mechanical responses between groups.

Fig. 4
Fig. 4

Cell nuclei centroid identification and displacement calculation with changes in IOP from 5 mmHg (A) to 8 (B), 10 (C), 15 (D) and 20 mmHg (E). Scale bar is 20 µm.

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