Abstract

Intra-tissue refractive index shaping (IRIS) is a novel, non-ablative form of vision correction by which femtosecond laser pulses are tightly focused into ocular tissues to induce localized refractive index (RI) change via nonlinear absorption. Here, we examined the effects of Blue-IRIS on corneal microstructure to gain insights into underlying mechanisms. Three-layer grating patterns were inscribed with IRIS ~180 µm below the epithelial surface of ex vivo rabbit globes using a 400 nm femtosecond laser. Keeping laser power constant at 82 mW in the focal volume, multiple patterns were written at different scan speeds. The largest RI change induced in this study was + 0.011 at 20 mm/s. After measuring the phase change profile of each inscribed pattern, two-photon excited autofluorescence (TPEF) and second harmonic generation (SHG) microscopy were used to quantify changes in stromal structure. While TPEF increased significantly with induced RI change, there was a noticeable suppression of SHG signal in IRIS treated regions. We posit that enhancement of TPEF was due to the formation of new fluorophores, while decreases in SHG were most likely due to degradation of collagen triple helices. All in all, the changes observed suggest that IRIS works by inducing a localized, photochemical change in collagen structure.

© 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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2018 (1)

C. Wang, M. Fomovsky, G. X. Miao, M. Zyablitskaya, and S. Vukelic, “Femtosecond laser crosslinking of the cornea for non-invasive vision correction,” Nat. Photonics 12(7), 416–422 (2018).
[Crossref]

2017 (2)

K. T. Wozniak, N. Elkins, D. R. Brooks, D. E. Savage, S. MacRae, J. D. Ellis, W. H. Knox, and K. R. Huxlin, “Contrasting cellular damage after Blue-IRIS and Femto-LASIK in cat cornea,” Exp. Eye Res. 165, 20–28 (2017).
[Crossref] [PubMed]

G. A. Gandara-Montano, V. Stoy, M. Dudic, V. Petrak, K. Haskovcova, and W. H. Knox, “Large optical phase shifts in hydrogels written with femtosecond laser pulses: elucidating the role of localized water concentration changes,” Opt. Mater. Express 7(9), 3162–3180 (2017).
[Crossref]

2016 (1)

A. M. Calvo-Maroto, R. J. Perez-Cambrodi, S. Garcia-Lazaro, T. Ferrer-Blasco, and A. Cerviño, “Ocular autofluorescence in diabetes mellitus. A review,” J. Diabetes 8(5), 619–628 (2016).
[Crossref] [PubMed]

2015 (2)

2014 (2)

D. E. Savage, D. R. Brooks, M. DeMagistris, L. Xu, S. MacRae, J. D. Ellis, W. H. Knox, and K. R. Huxlin, “First demonstration of Ocular Refractive Change Using Blue-IRIS in Live Cats,” Invest. Ophthalmol. Vis. Sci. 55(7), 4603–4612 (2014).
[Crossref] [PubMed]

A. Manickavasagam, L. M. Hirvonen, L. N. Melita, E. Z. Chong, R. J. Cook, L. Bozec, and F. Festy, “Multimodal optical characterisation of collagen photodegradation by femtosecond infrared laser ablation,” Analyst (Lond.) 139(23), 6135–6143 (2014).
[Crossref] [PubMed]

2012 (2)

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]

X. Chen, O. Nadiarynkh, S. Plotnikov, and P. J. Campagnola, “Second harmonic generation microscopy for quantitative analysis of collagen fibrillar structure,” Nat. Protoc. 7(4), 654–669 (2012).
[Crossref] [PubMed]

2011 (3)

L. Cui, K. R. Huxlin, L. Xu, S. MacRae, and W. H. Knox, “High-resolution, noninvasive, two-photon fluorescence measurement of molecular concentrations in corneal tissue,” Invest. Ophthalmol. Vis. Sci. 52(5), 2556–2564 (2011).
[Crossref] [PubMed]

L. Xu, W. H. Knox, M. DeMagistris, N. Wang, and K. R. Huxlin, “Noninvasive Intratissue Refractive Index Shaping (IRIS) of the Cornea with Blue Femtosecond Laser Light,” Invest. Ophthalmol. Vis. Sci. 52(11), 8148–8155 (2011).
[Crossref] [PubMed]

A. E. Tuer, S. Krouglov, N. Prent, R. Cisek, D. Sandkuijl, K. Yasufuku, B. C. Wilson, and V. Barzda, “Nonlinear Optical Properties of Type I Collagen Fibers Studied by Polarization Dependent Second Harmonic Generation Microscopy,” J. Phys. Chem. B 115(44), 12759–12769 (2011).
[Crossref] [PubMed]

2010 (5)

L. J. Nagy, L. Ding, L. Xu, W. H. Knox, and K. R. Huxlin, “Potentiation of Femtosecond Laser Intratissue Refractive Index Shaping (IRIS) in the Living Cornea with Sodium Fluorescein,” Invest. Ophthalmol. Vis. Sci. 51(2), 850–856 (2010).
[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]

J. M. Dela Cruz, J. D. McMullen, R. M. Williams, and W. R. Zipfel, “Feasibility of using multiphoton excited tissue autofluorescence for in vivo human histopathology,” Biomed. Opt. Express 1(5), 1320–1330 (2010).
[Crossref] [PubMed]

X. Han and E. Brown, “Measurement of the ratio of forward-propagating to back-propagating second harmonic signal using a single objective,” Opt. Express 18(10), 10538–10550 (2010).
[Crossref] [PubMed]

V. Hovhannisyan, A. Ghazaryan, Y. F. Chen, S. J. Chen, and C. Y. Dong, “Photophysical mechanisms of collagen modification by 80 MHz femtosecond laser,” Opt. Express 18(23), 24037–24047 (2010).
[Crossref] [PubMed]

2009 (2)

2008 (3)

2007 (2)

M. Oujja, E. Rebollar, C. Abrusci, A. Del Amo, F. Catalina, and M. Castillejo, “UV, visible and IR laser interaction with gelatine,” J. Phys. Conf. Ser. 59, 571–574 (2007).
[Crossref]

M. Wisniewski, A. Sionkowska, H. Kaczmarek, S. Lazare, V. Tokarev, and C. Belin, “Spectroscopic study of a KrF excimer laser treated surface of the thin collagen films,” J Photoch Photobio A 188(2-3), 192–199 (2007).
[Crossref]

2006 (5)

S. V. Plotnikov, A. C. Millard, P. J. Campagnola, and W. A. Mohler, “Characterization of the myosin-based source for second-harmonic generation from muscle sarcomeres,” Biophys. J. 90(2), 693–703 (2006).
[Crossref] [PubMed]

Y. Sun, W. L. Chen, S. J. Lin, S. H. Jee, Y. F. Chen, L. C. Lin, P. T. C. So, and C. Y. Dong, “Investigating mechanisms of collagen thermal denaturation by high resolution second-harmonic generation imaging,” Biophys. J. 91(7), 2620–2625 (2006).
[Crossref] [PubMed]

T. A. Theodossiou, C. Thrasivoulou, C. Ekwobi, and D. L. Becker, “Second harmonic generation confocal microscopy of collagen type I from rat tendon cryosections,” Biophys. J. 91(12), 4665–4677 (2006).
[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]

L. Ding, R. Blackwell, J. F. Kunzler, and W. H. Knox, “Large refractive index change in silicone-based and non-silicone-based hydrogel polymers induced by femtosecond laser micro-machining,” Opt. Express 14(24), 11901–11909 (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]

A. Vogel, J. Noack, G. Huttman, and G. Paltauf, “Mechanisms of femtosecond laser nanosurgery of cells and tissues,” Appl. Phys. B 81(8), 1015–1047 (2005).
[Crossref]

2003 (2)

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7075–7080 (2003).
[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]

2001 (2)

J. L. Ojeda, J. A. Ventosa, and S. Piedra, “The three-dimensional microanatomy of the rabbit and human cornea. A chemical and mechanical microdissection-SEM approach,” J. Anat. 199(5), 567–576 (2001).
[Crossref] [PubMed]

M. J. Davies and R. J. W. Truscott, “Photo-oxidation of proteins and its role in cataractogenesis,” J. Photochem. Photobiol. B 63(1-3), 114–125 (2001).
[Crossref] [PubMed]

2000 (1)

S. Yamamoto, H. Hashizume, J. Hitomi, M. Shigeno, S. Sawaguchi, H. Abe, and T. Ushiki, “The subfibrillar arrangement of corneal and scleral collagen fibrils as revealed by scanning electron and atomic force microscopy,” Arch. Histol. Cytol. 63(2), 127–135 (2000).
[Crossref] [PubMed]

1999 (1)

1992 (1)

R. L. Lindstrom, H. E. Kaufman, D. L. Skelnik, R. A. Laing, J. H. Lass, D. C. Musch, M. D. Trousdale, W. J. Reinhart, T. E. Burris, A. Sugar, R. M. Davis, K. Hirokawa, T. Smith, and J. F. Gordon, “Optisol Corneal Storage Medium,” Am. J. Ophthalmol. 114(3), 345–356 (1992).
[Crossref] [PubMed]

1988 (1)

R. M. Goldstein, H. A. Zebker, and C. L. Werner, “Satellite Radar Interferometry - Two-Dimensional Phase Unwrapping,” Radio Sci. 23(4), 713–720 (1988).
[Crossref]

1982 (1)

1981 (1)

K. M. Meek, G. F. Elliott, Z. Sayers, S. B. Whitburn, and M. H. J. Koch, “Interpretation of the Meridional X-Ray Diffraction Pattern from Collagen Fibrils in Corneal Stroma,” J. Mol. Biol. 149(3), 477–488 (1981).
[Crossref] [PubMed]

1980 (1)

1975 (1)

Abe, H.

S. Yamamoto, H. Hashizume, J. Hitomi, M. Shigeno, S. Sawaguchi, H. Abe, and T. Ushiki, “The subfibrillar arrangement of corneal and scleral collagen fibrils as revealed by scanning electron and atomic force microscopy,” Arch. Histol. Cytol. 63(2), 127–135 (2000).
[Crossref] [PubMed]

Abrusci, C.

M. Oujja, E. Rebollar, C. Abrusci, A. Del Amo, F. Catalina, and M. Castillejo, “UV, visible and IR laser interaction with gelatine,” J. Phys. Conf. Ser. 59, 571–574 (2007).
[Crossref]

Anderson, N.

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]

Barzda, V.

A. E. Tuer, S. Krouglov, N. Prent, R. Cisek, D. Sandkuijl, K. Yasufuku, B. C. Wilson, and V. Barzda, “Nonlinear Optical Properties of Type I Collagen Fibers Studied by Polarization Dependent Second Harmonic Generation Microscopy,” J. Phys. Chem. B 115(44), 12759–12769 (2011).
[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]

Becker, D. L.

T. A. Theodossiou, C. Thrasivoulou, C. Ekwobi, and D. L. Becker, “Second harmonic generation confocal microscopy of collagen type I from rat tendon cryosections,” Biophys. J. 91(12), 4665–4677 (2006).
[Crossref] [PubMed]

Belin, C.

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K. T. Wozniak, N. Elkins, D. R. Brooks, D. E. Savage, S. MacRae, J. D. Ellis, W. H. Knox, and K. R. Huxlin, “Contrasting cellular damage after Blue-IRIS and Femto-LASIK in cat cornea,” Exp. Eye Res. 165, 20–28 (2017).
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D. E. Savage, D. R. Brooks, M. DeMagistris, L. Xu, S. MacRae, J. D. Ellis, W. H. Knox, and K. R. Huxlin, “First demonstration of Ocular Refractive Change Using Blue-IRIS in Live Cats,” Invest. Ophthalmol. Vis. Sci. 55(7), 4603–4612 (2014).
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A. M. Calvo-Maroto, R. J. Perez-Cambrodi, S. Garcia-Lazaro, T. Ferrer-Blasco, and A. Cerviño, “Ocular autofluorescence in diabetes mellitus. A review,” J. Diabetes 8(5), 619–628 (2016).
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X. Chen, O. Nadiarynkh, S. Plotnikov, and P. J. Campagnola, “Second harmonic generation microscopy for quantitative analysis of collagen fibrillar structure,” Nat. Protoc. 7(4), 654–669 (2012).
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V. Hovhannisyan, A. Ghazaryan, Y. F. Chen, S. J. Chen, and C. Y. Dong, “Photophysical mechanisms of collagen modification by 80 MHz femtosecond laser,” Opt. Express 18(23), 24037–24047 (2010).
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A. Manickavasagam, L. M. Hirvonen, L. N. Melita, E. Z. Chong, R. J. Cook, L. Bozec, and F. Festy, “Multimodal optical characterisation of collagen photodegradation by femtosecond infrared laser ablation,” Analyst (Lond.) 139(23), 6135–6143 (2014).
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L. Cui, K. R. Huxlin, L. Xu, S. MacRae, and W. H. Knox, “High-resolution, noninvasive, two-photon fluorescence measurement of molecular concentrations in corneal tissue,” Invest. Ophthalmol. Vis. Sci. 52(5), 2556–2564 (2011).
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M. Oujja, E. Rebollar, C. Abrusci, A. Del Amo, F. Catalina, and M. Castillejo, “UV, visible and IR laser interaction with gelatine,” J. Phys. Conf. Ser. 59, 571–574 (2007).
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DeMagistris, M.

D. E. Savage, D. R. Brooks, M. DeMagistris, L. Xu, S. MacRae, J. D. Ellis, W. H. Knox, and K. R. Huxlin, “First demonstration of Ocular Refractive Change Using Blue-IRIS in Live Cats,” Invest. Ophthalmol. Vis. Sci. 55(7), 4603–4612 (2014).
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L. Xu, W. H. Knox, M. DeMagistris, N. Wang, and K. R. Huxlin, “Noninvasive Intratissue Refractive Index Shaping (IRIS) of the Cornea with Blue Femtosecond Laser Light,” Invest. Ophthalmol. Vis. Sci. 52(11), 8148–8155 (2011).
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K. T. Wozniak, N. Elkins, D. R. Brooks, D. E. Savage, S. MacRae, J. D. Ellis, W. H. Knox, and K. R. Huxlin, “Contrasting cellular damage after Blue-IRIS and Femto-LASIK in cat cornea,” Exp. Eye Res. 165, 20–28 (2017).
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G. A. Gandara-Montano, A. Ivansky, D. E. Savage, J. D. Ellis, and W. H. Knox, “Femtosecond laser writing of freeform gradient index microlenses in hydrogel-based contact lenses,” Opt. Mater. Express 5(10), 2257–2271 (2015).
[Crossref]

D. E. Savage, D. R. Brooks, M. DeMagistris, L. Xu, S. MacRae, J. D. Ellis, W. H. Knox, and K. R. Huxlin, “First demonstration of Ocular Refractive Change Using Blue-IRIS in Live Cats,” Invest. Ophthalmol. Vis. Sci. 55(7), 4603–4612 (2014).
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A. M. Calvo-Maroto, R. J. Perez-Cambrodi, S. Garcia-Lazaro, T. Ferrer-Blasco, and A. Cerviño, “Ocular autofluorescence in diabetes mellitus. A review,” J. Diabetes 8(5), 619–628 (2016).
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A. Manickavasagam, L. M. Hirvonen, L. N. Melita, E. Z. Chong, R. J. Cook, L. Bozec, and F. Festy, “Multimodal optical characterisation of collagen photodegradation by femtosecond infrared laser ablation,” Analyst (Lond.) 139(23), 6135–6143 (2014).
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A. M. Calvo-Maroto, R. J. Perez-Cambrodi, S. Garcia-Lazaro, T. Ferrer-Blasco, and A. Cerviño, “Ocular autofluorescence in diabetes mellitus. A review,” J. Diabetes 8(5), 619–628 (2016).
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A. Manickavasagam, L. M. Hirvonen, L. N. Melita, E. Z. Chong, R. J. Cook, L. Bozec, and F. Festy, “Multimodal optical characterisation of collagen photodegradation by femtosecond infrared laser ablation,” Analyst (Lond.) 139(23), 6135–6143 (2014).
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K. T. Wozniak, N. Elkins, D. R. Brooks, D. E. Savage, S. MacRae, J. D. Ellis, W. H. Knox, and K. R. Huxlin, “Contrasting cellular damage after Blue-IRIS and Femto-LASIK in cat cornea,” Exp. Eye Res. 165, 20–28 (2017).
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D. E. Savage, D. R. Brooks, M. DeMagistris, L. Xu, S. MacRae, J. D. Ellis, W. H. Knox, and K. R. Huxlin, “First demonstration of Ocular Refractive Change Using Blue-IRIS in Live Cats,” Invest. Ophthalmol. Vis. Sci. 55(7), 4603–4612 (2014).
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L. Xu, W. H. Knox, M. DeMagistris, N. Wang, and K. R. Huxlin, “Noninvasive Intratissue Refractive Index Shaping (IRIS) of the Cornea with Blue Femtosecond Laser Light,” Invest. Ophthalmol. Vis. Sci. 52(11), 8148–8155 (2011).
[Crossref] [PubMed]

L. Cui, K. R. Huxlin, L. Xu, S. MacRae, and W. H. Knox, “High-resolution, noninvasive, two-photon fluorescence measurement of molecular concentrations in corneal tissue,” Invest. Ophthalmol. Vis. Sci. 52(5), 2556–2564 (2011).
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L. J. Nagy, L. Ding, L. Xu, W. H. Knox, and K. R. Huxlin, “Potentiation of Femtosecond Laser Intratissue Refractive Index Shaping (IRIS) in the Living Cornea with Sodium Fluorescein,” Invest. Ophthalmol. Vis. Sci. 51(2), 850–856 (2010).
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W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7075–7080 (2003).
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M. Wisniewski, A. Sionkowska, H. Kaczmarek, S. Lazare, V. Tokarev, and C. Belin, “Spectroscopic study of a KrF excimer laser treated surface of the thin collagen films,” J Photoch Photobio A 188(2-3), 192–199 (2007).
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R. L. Lindstrom, H. E. Kaufman, D. L. Skelnik, R. A. Laing, J. H. Lass, D. C. Musch, M. D. Trousdale, W. J. Reinhart, T. E. Burris, A. Sugar, R. M. Davis, K. Hirokawa, T. Smith, and J. F. Gordon, “Optisol Corneal Storage Medium,” Am. J. Ophthalmol. 114(3), 345–356 (1992).
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Kim, B. M.

Knox, W. H.

G. A. Gandara-Montano, V. Stoy, M. Dudic, V. Petrak, K. Haskovcova, and W. H. Knox, “Large optical phase shifts in hydrogels written with femtosecond laser pulses: elucidating the role of localized water concentration changes,” Opt. Mater. Express 7(9), 3162–3180 (2017).
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K. T. Wozniak, N. Elkins, D. R. Brooks, D. E. Savage, S. MacRae, J. D. Ellis, W. H. Knox, and K. R. Huxlin, “Contrasting cellular damage after Blue-IRIS and Femto-LASIK in cat cornea,” Exp. Eye Res. 165, 20–28 (2017).
[Crossref] [PubMed]

G. A. Gandara-Montano, A. Ivansky, D. E. Savage, J. D. Ellis, and W. H. Knox, “Femtosecond laser writing of freeform gradient index microlenses in hydrogel-based contact lenses,” Opt. Mater. Express 5(10), 2257–2271 (2015).
[Crossref]

D. E. Savage, D. R. Brooks, M. DeMagistris, L. Xu, S. MacRae, J. D. Ellis, W. H. Knox, and K. R. Huxlin, “First demonstration of Ocular Refractive Change Using Blue-IRIS in Live Cats,” Invest. Ophthalmol. Vis. Sci. 55(7), 4603–4612 (2014).
[Crossref] [PubMed]

L. Xu, W. H. Knox, M. DeMagistris, N. Wang, and K. R. Huxlin, “Noninvasive Intratissue Refractive Index Shaping (IRIS) of the Cornea with Blue Femtosecond Laser Light,” Invest. Ophthalmol. Vis. Sci. 52(11), 8148–8155 (2011).
[Crossref] [PubMed]

L. Cui, K. R. Huxlin, L. Xu, S. MacRae, and W. H. Knox, “High-resolution, noninvasive, two-photon fluorescence measurement of molecular concentrations in corneal tissue,” Invest. Ophthalmol. Vis. Sci. 52(5), 2556–2564 (2011).
[Crossref] [PubMed]

L. J. Nagy, L. Ding, L. Xu, W. H. Knox, and K. R. Huxlin, “Potentiation of Femtosecond Laser Intratissue Refractive Index Shaping (IRIS) in the Living Cornea with Sodium Fluorescein,” Invest. Ophthalmol. Vis. Sci. 51(2), 850–856 (2010).
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L. Ding, L. G. Cancado, L. Novotny, W. H. Knox, N. Anderson, D. Jani, J. Linhardt, R. I. Blackwell, and J. E. Kiinzler, “Micro-Raman spectroscopy of refractive index microstructures in silicone-based hydrogel polymers created by high-repetition-rate femtosecond laser micromachining,” J. Opt. Soc. Am. B 26(4), 595–602 (2009).
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L. Ding, R. Blackwell, J. F. Kunzler, and W. H. Knox, “Large refractive index change in silicone-based and non-silicone-based hydrogel polymers induced by femtosecond laser micro-machining,” Opt. Express 14(24), 11901–11909 (2006).
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Kunzler, J. F.

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).
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R. L. Lindstrom, H. E. Kaufman, D. L. Skelnik, R. A. Laing, J. H. Lass, D. C. Musch, M. D. Trousdale, W. J. Reinhart, T. E. Burris, A. Sugar, R. M. Davis, K. Hirokawa, T. Smith, and J. F. Gordon, “Optisol Corneal Storage Medium,” Am. J. Ophthalmol. 114(3), 345–356 (1992).
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R. L. Lindstrom, H. E. Kaufman, D. L. Skelnik, R. A. Laing, J. H. Lass, D. C. Musch, M. D. Trousdale, W. J. Reinhart, T. E. Burris, A. Sugar, R. M. Davis, K. Hirokawa, T. Smith, and J. F. Gordon, “Optisol Corneal Storage Medium,” Am. J. Ophthalmol. 114(3), 345–356 (1992).
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Lazare, S.

M. Wisniewski, A. Sionkowska, H. Kaczmarek, S. Lazare, V. Tokarev, and C. Belin, “Spectroscopic study of a KrF excimer laser treated surface of the thin collagen films,” J Photoch Photobio A 188(2-3), 192–199 (2007).
[Crossref]

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).
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Y. Sun, W. L. Chen, S. J. Lin, S. H. Jee, Y. F. Chen, L. C. Lin, P. T. C. So, and C. Y. Dong, “Investigating mechanisms of collagen thermal denaturation by high resolution second-harmonic generation imaging,” Biophys. J. 91(7), 2620–2625 (2006).
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Y. Sun, W. L. Chen, S. J. Lin, S. H. Jee, Y. F. Chen, L. C. Lin, P. T. C. So, and C. Y. Dong, “Investigating mechanisms of collagen thermal denaturation by high resolution second-harmonic generation imaging,” Biophys. J. 91(7), 2620–2625 (2006).
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R. L. Lindstrom, H. E. Kaufman, D. L. Skelnik, R. A. Laing, J. H. Lass, D. C. Musch, M. D. Trousdale, W. J. Reinhart, T. E. Burris, A. Sugar, R. M. Davis, K. Hirokawa, T. Smith, and J. F. Gordon, “Optisol Corneal Storage Medium,” Am. J. Ophthalmol. 114(3), 345–356 (1992).
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MacRae, S.

K. T. Wozniak, N. Elkins, D. R. Brooks, D. E. Savage, S. MacRae, J. D. Ellis, W. H. Knox, and K. R. Huxlin, “Contrasting cellular damage after Blue-IRIS and Femto-LASIK in cat cornea,” Exp. Eye Res. 165, 20–28 (2017).
[Crossref] [PubMed]

D. E. Savage, D. R. Brooks, M. DeMagistris, L. Xu, S. MacRae, J. D. Ellis, W. H. Knox, and K. R. Huxlin, “First demonstration of Ocular Refractive Change Using Blue-IRIS in Live Cats,” Invest. Ophthalmol. Vis. Sci. 55(7), 4603–4612 (2014).
[Crossref] [PubMed]

L. Cui, K. R. Huxlin, L. Xu, S. MacRae, and W. H. Knox, “High-resolution, noninvasive, two-photon fluorescence measurement of molecular concentrations in corneal tissue,” Invest. Ophthalmol. Vis. Sci. 52(5), 2556–2564 (2011).
[Crossref] [PubMed]

Manickavasagam, A.

A. Manickavasagam, L. M. Hirvonen, L. N. Melita, E. Z. Chong, R. J. Cook, L. Bozec, and F. Festy, “Multimodal optical characterisation of collagen photodegradation by femtosecond infrared laser ablation,” Analyst (Lond.) 139(23), 6135–6143 (2014).
[Crossref] [PubMed]

McMullen, J. D.

Meek, K. M.

K. M. Meek and C. Knupp, “Corneal structure and transparency,” Prog. Retin. Eye Res. 49, 1–16 (2015).
[Crossref] [PubMed]

K. M. Meek, G. F. Elliott, Z. Sayers, S. B. Whitburn, and M. H. J. Koch, “Interpretation of the Meridional X-Ray Diffraction Pattern from Collagen Fibrils in Corneal Stroma,” J. Mol. Biol. 149(3), 477–488 (1981).
[Crossref] [PubMed]

Melita, L. N.

A. Manickavasagam, L. M. Hirvonen, L. N. Melita, E. Z. Chong, R. J. Cook, L. Bozec, and F. Festy, “Multimodal optical characterisation of collagen photodegradation by femtosecond infrared laser ablation,” Analyst (Lond.) 139(23), 6135–6143 (2014).
[Crossref] [PubMed]

Miao, G. X.

C. Wang, M. Fomovsky, G. X. Miao, M. Zyablitskaya, and S. Vukelic, “Femtosecond laser crosslinking of the cornea for non-invasive vision correction,” Nat. Photonics 12(7), 416–422 (2018).
[Crossref]

Millard, A. C.

S. V. Plotnikov, A. C. Millard, P. J. Campagnola, and W. A. Mohler, “Characterization of the myosin-based source for second-harmonic generation from muscle sarcomeres,” Biophys. J. 90(2), 693–703 (2006).
[Crossref] [PubMed]

Mohler, W. A.

S. V. Plotnikov, A. C. Millard, P. J. Campagnola, and W. A. Mohler, “Characterization of the myosin-based source for second-harmonic generation from muscle sarcomeres,” Biophys. J. 90(2), 693–703 (2006).
[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]

Musch, D. C.

R. L. Lindstrom, H. E. Kaufman, D. L. Skelnik, R. A. Laing, J. H. Lass, D. C. Musch, M. D. Trousdale, W. J. Reinhart, T. E. Burris, A. Sugar, R. M. Davis, K. Hirokawa, T. Smith, and J. F. Gordon, “Optisol Corneal Storage Medium,” Am. J. Ophthalmol. 114(3), 345–356 (1992).
[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]

Nadiarynkh, O.

X. Chen, O. Nadiarynkh, S. Plotnikov, and P. J. Campagnola, “Second harmonic generation microscopy for quantitative analysis of collagen fibrillar structure,” Nat. Protoc. 7(4), 654–669 (2012).
[Crossref] [PubMed]

Nagy, L. J.

L. J. Nagy, L. Ding, L. Xu, W. H. Knox, and K. R. Huxlin, “Potentiation of Femtosecond Laser Intratissue Refractive Index Shaping (IRIS) in the Living Cornea with Sodium Fluorescein,” Invest. Ophthalmol. Vis. Sci. 51(2), 850–856 (2010).
[Crossref] [PubMed]

Nikitin, A. Y.

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7075–7080 (2003).
[Crossref] [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]

Noack, J.

A. Vogel, J. Noack, G. Huttman, and G. Paltauf, “Mechanisms of femtosecond laser nanosurgery of cells and tissues,” Appl. Phys. B 81(8), 1015–1047 (2005).
[Crossref]

Novotny, L.

Ojeda, J. L.

J. L. Ojeda, J. A. Ventosa, and S. Piedra, “The three-dimensional microanatomy of the rabbit and human cornea. A chemical and mechanical microdissection-SEM approach,” J. Anat. 199(5), 567–576 (2001).
[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]

Oujja, M.

M. Oujja, E. Rebollar, C. Abrusci, A. Del Amo, F. Catalina, and M. Castillejo, “UV, visible and IR laser interaction with gelatine,” J. Phys. Conf. Ser. 59, 571–574 (2007).
[Crossref]

Paltauf, G.

A. Vogel, J. Noack, G. Huttman, and G. Paltauf, “Mechanisms of femtosecond laser nanosurgery of cells and tissues,” Appl. Phys. B 81(8), 1015–1047 (2005).
[Crossref]

Perez-Cambrodi, R. J.

A. M. Calvo-Maroto, R. J. Perez-Cambrodi, S. Garcia-Lazaro, T. Ferrer-Blasco, and A. Cerviño, “Ocular autofluorescence in diabetes mellitus. A review,” J. Diabetes 8(5), 619–628 (2016).
[Crossref] [PubMed]

Petrak, V.

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]

Piedra, S.

J. L. Ojeda, J. A. Ventosa, and S. Piedra, “The three-dimensional microanatomy of the rabbit and human cornea. A chemical and mechanical microdissection-SEM approach,” J. Anat. 199(5), 567–576 (2001).
[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]

Plotnikov, S.

X. Chen, O. Nadiarynkh, S. Plotnikov, and P. J. Campagnola, “Second harmonic generation microscopy for quantitative analysis of collagen fibrillar structure,” Nat. Protoc. 7(4), 654–669 (2012).
[Crossref] [PubMed]

Plotnikov, S. V.

S. V. Plotnikov, A. C. Millard, P. J. Campagnola, and W. A. Mohler, “Characterization of the myosin-based source for second-harmonic generation from muscle sarcomeres,” Biophys. J. 90(2), 693–703 (2006).
[Crossref] [PubMed]

Prent, N.

A. E. Tuer, S. Krouglov, N. Prent, R. Cisek, D. Sandkuijl, K. Yasufuku, B. C. Wilson, and V. Barzda, “Nonlinear Optical Properties of Type I Collagen Fibers Studied by Polarization Dependent Second Harmonic Generation Microscopy,” J. Phys. Chem. B 115(44), 12759–12769 (2011).
[Crossref] [PubMed]

Rebollar, E.

M. Oujja, E. Rebollar, C. Abrusci, A. Del Amo, F. Catalina, and M. Castillejo, “UV, visible and IR laser interaction with gelatine,” J. Phys. Conf. Ser. 59, 571–574 (2007).
[Crossref]

Reinhart, W. J.

R. L. Lindstrom, H. E. Kaufman, D. L. Skelnik, R. A. Laing, J. H. Lass, D. C. Musch, M. D. Trousdale, W. J. Reinhart, T. E. Burris, A. Sugar, R. M. Davis, K. Hirokawa, T. Smith, and J. F. Gordon, “Optisol Corneal Storage Medium,” Am. J. Ophthalmol. 114(3), 345–356 (1992).
[Crossref] [PubMed]

Sandkuijl, D.

A. E. Tuer, S. Krouglov, N. Prent, R. Cisek, D. Sandkuijl, K. Yasufuku, B. C. Wilson, and V. Barzda, “Nonlinear Optical Properties of Type I Collagen Fibers Studied by Polarization Dependent Second Harmonic Generation Microscopy,” J. Phys. Chem. B 115(44), 12759–12769 (2011).
[Crossref] [PubMed]

Savage, D. E.

K. T. Wozniak, N. Elkins, D. R. Brooks, D. E. Savage, S. MacRae, J. D. Ellis, W. H. Knox, and K. R. Huxlin, “Contrasting cellular damage after Blue-IRIS and Femto-LASIK in cat cornea,” Exp. Eye Res. 165, 20–28 (2017).
[Crossref] [PubMed]

G. A. Gandara-Montano, A. Ivansky, D. E. Savage, J. D. Ellis, and W. H. Knox, “Femtosecond laser writing of freeform gradient index microlenses in hydrogel-based contact lenses,” Opt. Mater. Express 5(10), 2257–2271 (2015).
[Crossref]

D. E. Savage, D. R. Brooks, M. DeMagistris, L. Xu, S. MacRae, J. D. Ellis, W. H. Knox, and K. R. Huxlin, “First demonstration of Ocular Refractive Change Using Blue-IRIS in Live Cats,” Invest. Ophthalmol. Vis. Sci. 55(7), 4603–4612 (2014).
[Crossref] [PubMed]

Sawaguchi, S.

S. Yamamoto, H. Hashizume, J. Hitomi, M. Shigeno, S. Sawaguchi, H. Abe, and T. Ushiki, “The subfibrillar arrangement of corneal and scleral collagen fibrils as revealed by scanning electron and atomic force microscopy,” Arch. Histol. Cytol. 63(2), 127–135 (2000).
[Crossref] [PubMed]

Sayers, Z.

K. M. Meek, G. F. Elliott, Z. Sayers, S. B. Whitburn, and M. H. J. Koch, “Interpretation of the Meridional X-Ray Diffraction Pattern from Collagen Fibrils in Corneal Stroma,” J. Mol. Biol. 149(3), 477–488 (1981).
[Crossref] [PubMed]

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]

Scholl, M. S.

Shigeno, M.

S. Yamamoto, H. Hashizume, J. Hitomi, M. Shigeno, S. Sawaguchi, H. Abe, and T. Ushiki, “The subfibrillar arrangement of corneal and scleral collagen fibrils as revealed by scanning electron and atomic force microscopy,” Arch. Histol. Cytol. 63(2), 127–135 (2000).
[Crossref] [PubMed]

Sionkowska, A.

M. Wisniewski, A. Sionkowska, H. Kaczmarek, S. Lazare, V. Tokarev, and C. Belin, “Spectroscopic study of a KrF excimer laser treated surface of the thin collagen films,” J Photoch Photobio A 188(2-3), 192–199 (2007).
[Crossref]

Skelnik, D. L.

R. L. Lindstrom, H. E. Kaufman, D. L. Skelnik, R. A. Laing, J. H. Lass, D. C. Musch, M. D. Trousdale, W. J. Reinhart, T. E. Burris, A. Sugar, R. M. Davis, K. Hirokawa, T. Smith, and J. F. Gordon, “Optisol Corneal Storage Medium,” Am. J. Ophthalmol. 114(3), 345–356 (1992).
[Crossref] [PubMed]

Smith, T.

R. L. Lindstrom, H. E. Kaufman, D. L. Skelnik, R. A. Laing, J. H. Lass, D. C. Musch, M. D. Trousdale, W. J. Reinhart, T. E. Burris, A. Sugar, R. M. Davis, K. Hirokawa, T. Smith, and J. F. Gordon, “Optisol Corneal Storage Medium,” Am. J. Ophthalmol. 114(3), 345–356 (1992).
[Crossref] [PubMed]

So, P. T. C.

Y. Sun, W. L. Chen, S. J. Lin, S. H. Jee, Y. F. Chen, L. C. Lin, P. T. C. So, and C. Y. Dong, “Investigating mechanisms of collagen thermal denaturation by high resolution second-harmonic generation imaging,” Biophys. J. 91(7), 2620–2625 (2006).
[Crossref] [PubMed]

Stoy, V.

Sugar, A.

R. L. Lindstrom, H. E. Kaufman, D. L. Skelnik, R. A. Laing, J. H. Lass, D. C. Musch, M. D. Trousdale, W. J. Reinhart, T. E. Burris, A. Sugar, R. M. Davis, K. Hirokawa, T. Smith, and J. F. Gordon, “Optisol Corneal Storage Medium,” Am. J. Ophthalmol. 114(3), 345–356 (1992).
[Crossref] [PubMed]

Sun, Y.

Y. Sun, W. L. Chen, S. J. Lin, S. H. Jee, Y. F. Chen, L. C. Lin, P. T. C. So, and C. Y. Dong, “Investigating mechanisms of collagen thermal denaturation by high resolution second-harmonic generation imaging,” Biophys. J. 91(7), 2620–2625 (2006).
[Crossref] [PubMed]

Suzaki, Y.

Tachibana, A.

Takeda, M.

Tang, P.

Theodossiou, T. A.

T. A. Theodossiou, C. Thrasivoulou, C. Ekwobi, and D. L. Becker, “Second harmonic generation confocal microscopy of collagen type I from rat tendon cryosections,” Biophys. J. 91(12), 4665–4677 (2006).
[Crossref] [PubMed]

Thrasivoulou, C.

T. A. Theodossiou, C. Thrasivoulou, C. Ekwobi, and D. L. Becker, “Second harmonic generation confocal microscopy of collagen type I from rat tendon cryosections,” Biophys. J. 91(12), 4665–4677 (2006).
[Crossref] [PubMed]

Tokarev, V.

M. Wisniewski, A. Sionkowska, H. Kaczmarek, S. Lazare, V. Tokarev, and C. Belin, “Spectroscopic study of a KrF excimer laser treated surface of the thin collagen films,” J Photoch Photobio A 188(2-3), 192–199 (2007).
[Crossref]

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]

Trousdale, M. D.

R. L. Lindstrom, H. E. Kaufman, D. L. Skelnik, R. A. Laing, J. H. Lass, D. C. Musch, M. D. Trousdale, W. J. Reinhart, T. E. Burris, A. Sugar, R. M. Davis, K. Hirokawa, T. Smith, and J. F. Gordon, “Optisol Corneal Storage Medium,” Am. J. Ophthalmol. 114(3), 345–356 (1992).
[Crossref] [PubMed]

Truscott, R. J. W.

M. J. Davies and R. J. W. Truscott, “Photo-oxidation of proteins and its role in cataractogenesis,” J. Photochem. Photobiol. B 63(1-3), 114–125 (2001).
[Crossref] [PubMed]

Tuer, A. E.

A. E. Tuer, S. Krouglov, N. Prent, R. Cisek, D. Sandkuijl, K. Yasufuku, B. C. Wilson, and V. Barzda, “Nonlinear Optical Properties of Type I Collagen Fibers Studied by Polarization Dependent Second Harmonic Generation Microscopy,” J. Phys. Chem. B 115(44), 12759–12769 (2011).
[Crossref] [PubMed]

Ushiki, T.

S. Yamamoto, H. Hashizume, J. Hitomi, M. Shigeno, S. Sawaguchi, H. Abe, and T. Ushiki, “The subfibrillar arrangement of corneal and scleral collagen fibrils as revealed by scanning electron and atomic force microscopy,” Arch. Histol. Cytol. 63(2), 127–135 (2000).
[Crossref] [PubMed]

Ventosa, J. A.

J. L. Ojeda, J. A. Ventosa, and S. Piedra, “The three-dimensional microanatomy of the rabbit and human cornea. A chemical and mechanical microdissection-SEM approach,” J. Anat. 199(5), 567–576 (2001).
[Crossref] [PubMed]

Vogel, A.

A. Vogel, J. Noack, G. Huttman, and G. Paltauf, “Mechanisms of femtosecond laser nanosurgery of cells and tissues,” Appl. Phys. B 81(8), 1015–1047 (2005).
[Crossref]

Vukelic, S.

C. Wang, M. Fomovsky, G. X. Miao, M. Zyablitskaya, and S. Vukelic, “Femtosecond laser crosslinking of the cornea for non-invasive vision correction,” Nat. Photonics 12(7), 416–422 (2018).
[Crossref]

Wang, C.

C. Wang, M. Fomovsky, G. X. Miao, M. Zyablitskaya, and S. Vukelic, “Femtosecond laser crosslinking of the cornea for non-invasive vision correction,” Nat. Photonics 12(7), 416–422 (2018).
[Crossref]

Wang, N.

L. Xu, W. H. Knox, M. DeMagistris, N. Wang, and K. R. Huxlin, “Noninvasive Intratissue Refractive Index Shaping (IRIS) of the Cornea with Blue Femtosecond Laser Light,” Invest. Ophthalmol. Vis. Sci. 52(11), 8148–8155 (2011).
[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, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7075–7080 (2003).
[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]

Werner, C. L.

R. M. Goldstein, H. A. Zebker, and C. L. Werner, “Satellite Radar Interferometry - Two-Dimensional Phase Unwrapping,” Radio Sci. 23(4), 713–720 (1988).
[Crossref]

Whitburn, S. B.

K. M. Meek, G. F. Elliott, Z. Sayers, S. B. Whitburn, and M. H. J. Koch, “Interpretation of the Meridional X-Ray Diffraction Pattern from Collagen Fibrils in Corneal Stroma,” J. Mol. Biol. 149(3), 477–488 (1981).
[Crossref] [PubMed]

Williams, R. M.

J. M. Dela Cruz, J. D. McMullen, R. M. Williams, and W. R. Zipfel, “Feasibility of using multiphoton excited tissue autofluorescence for in vivo human histopathology,” Biomed. Opt. Express 1(5), 1320–1330 (2010).
[Crossref] [PubMed]

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]

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7075–7080 (2003).
[Crossref] [PubMed]

Wilson, B. C.

A. E. Tuer, S. Krouglov, N. Prent, R. Cisek, D. Sandkuijl, K. Yasufuku, B. C. Wilson, and V. Barzda, “Nonlinear Optical Properties of Type I Collagen Fibers Studied by Polarization Dependent Second Harmonic Generation Microscopy,” J. Phys. Chem. B 115(44), 12759–12769 (2011).
[Crossref] [PubMed]

Wisniewski, M.

M. Wisniewski, A. Sionkowska, H. Kaczmarek, S. Lazare, V. Tokarev, and C. Belin, “Spectroscopic study of a KrF excimer laser treated surface of the thin collagen films,” J Photoch Photobio A 188(2-3), 192–199 (2007).
[Crossref]

Wollensak, G.

G. Wollensak and E. Iomdina, “Long-term biomechanical properties of rabbit sclera after collagen crosslinking using riboflavin and ultraviolet A (UVA),” Acta Ophthalmol. 87(2), 193–198 (2009).
[Crossref] [PubMed]

Wozniak, K. T.

K. T. Wozniak, N. Elkins, D. R. Brooks, D. E. Savage, S. MacRae, J. D. Ellis, W. H. Knox, and K. R. Huxlin, “Contrasting cellular damage after Blue-IRIS and Femto-LASIK in cat cornea,” Exp. Eye Res. 165, 20–28 (2017).
[Crossref] [PubMed]

Xu, L.

D. E. Savage, D. R. Brooks, M. DeMagistris, L. Xu, S. MacRae, J. D. Ellis, W. H. Knox, and K. R. Huxlin, “First demonstration of Ocular Refractive Change Using Blue-IRIS in Live Cats,” Invest. Ophthalmol. Vis. Sci. 55(7), 4603–4612 (2014).
[Crossref] [PubMed]

L. Xu, W. H. Knox, M. DeMagistris, N. Wang, and K. R. Huxlin, “Noninvasive Intratissue Refractive Index Shaping (IRIS) of the Cornea with Blue Femtosecond Laser Light,” Invest. Ophthalmol. Vis. Sci. 52(11), 8148–8155 (2011).
[Crossref] [PubMed]

L. Cui, K. R. Huxlin, L. Xu, S. MacRae, and W. H. Knox, “High-resolution, noninvasive, two-photon fluorescence measurement of molecular concentrations in corneal tissue,” Invest. Ophthalmol. Vis. Sci. 52(5), 2556–2564 (2011).
[Crossref] [PubMed]

L. J. Nagy, L. Ding, L. Xu, W. H. Knox, and K. R. Huxlin, “Potentiation of Femtosecond Laser Intratissue Refractive Index Shaping (IRIS) in the Living Cornea with Sodium Fluorescein,” Invest. Ophthalmol. Vis. Sci. 51(2), 850–856 (2010).
[Crossref] [PubMed]

Yamamoto, S.

S. Yamamoto, H. Hashizume, J. Hitomi, M. Shigeno, S. Sawaguchi, H. Abe, and T. Ushiki, “The subfibrillar arrangement of corneal and scleral collagen fibrils as revealed by scanning electron and atomic force microscopy,” Arch. Histol. Cytol. 63(2), 127–135 (2000).
[Crossref] [PubMed]

Yasufuku, K.

A. E. Tuer, S. Krouglov, N. Prent, R. Cisek, D. Sandkuijl, K. Yasufuku, B. C. Wilson, and V. Barzda, “Nonlinear Optical Properties of Type I Collagen Fibers Studied by Polarization Dependent Second Harmonic Generation Microscopy,” J. Phys. Chem. B 115(44), 12759–12769 (2011).
[Crossref] [PubMed]

Zebker, H. A.

R. M. Goldstein, H. A. Zebker, and C. L. Werner, “Satellite Radar Interferometry - Two-Dimensional Phase Unwrapping,” Radio Sci. 23(4), 713–720 (1988).
[Crossref]

Zettel, M. L.

Zipfel, W. R.

J. M. Dela Cruz, J. D. McMullen, R. M. Williams, and W. R. Zipfel, “Feasibility of using multiphoton excited tissue autofluorescence for in vivo human histopathology,” Biomed. Opt. Express 1(5), 1320–1330 (2010).
[Crossref] [PubMed]

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]

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7075–7080 (2003).
[Crossref] [PubMed]

Zyablitskaya, M.

C. Wang, M. Fomovsky, G. X. Miao, M. Zyablitskaya, and S. Vukelic, “Femtosecond laser crosslinking of the cornea for non-invasive vision correction,” Nat. Photonics 12(7), 416–422 (2018).
[Crossref]

Acta Ophthalmol. (1)

G. Wollensak and E. Iomdina, “Long-term biomechanical properties of rabbit sclera after collagen crosslinking using riboflavin and ultraviolet A (UVA),” Acta Ophthalmol. 87(2), 193–198 (2009).
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Am. J. Ophthalmol. (1)

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Other (3)

V. Hovhannisyan, W. Lo, C. Hu, S.-J. Chen, and C. Y. Dong, “Non-ablative processing of biofibers by femtosecond IR laser,” in European Conferences on Biomedical Optics, (SPIE, 2009), 7.

D. E. Savage, “A non-ablative technique for femtosecond laser-based refractive correction: development, efficacy, and tissue effects,” (University of Rochester, Rochester, N.Y., 2018).

D. E. Savage, University of Rochester, Rochester, N.Y. 14627, and D. R. Brooks, Y. Li, M. Yu, J. A. Weiss, W. H. Knox and K. R. Huxlin are preparing a manuscript to be called “Blue-IRIS alters corneal refractive index by changing collagen fibrillar organization.”

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Figures (6)

Fig. 1
Fig. 1 (a) Blue-IRIS mounting scheme for intact rabbit globe. Globes were mounted on a three-axis translation system during raster scanning. (b) Custom-built MZI used for phase change measurement. The reference arm and test arm were recombined to form an interference pattern that contained the phase difference between two arms. (c) Two-photon microscopy system used for TPEF and SHG imaging. Immediately after each TPEF and F-SHG image stack was collected, the filter (525 nm, 100 nm bandwidth) for the backward channel was replaced with a 405 nm, 30 nm bandwidth emission filter and another SHG image stack was taken from exactly the same ROI.
Fig. 2
Fig. 2 (a) Histogram of one IRIS pattern written at 40 mm/s, its TPEF image is shown at the top right corner. (b) Curve fitting of the histogram.
Fig. 3
Fig. 3 Interferogram and retrieved phase map of eye 3 taken from the MZI, with scan speeds of each pattern given on the interferogram.
Fig. 4
Fig. 4 Phase change measured at 633 nm as a function of scan speed, repeated on three eyes (red, blue and green data points), with a linear fit and R2 values included in the graph. The green “damage” line indicates that at speeds below 20 mm/s, which include 10 mm/s, damage is obtained, rather than a measurable phase change.
Fig. 5
Fig. 5 TPEF (green), F-SHG (red) and B-SHG (magenta) images of the same ROIs over different IRIS patterns written at different speeds from eye 1. Note the faint green autofluorescence of the corneal epithelium on the top of all TPEF images, which contrasts with the strong TPEF signal emanating from the IRIS patterns. Note also the decreased SHG signal coincident with each IRIS pattern. Scale bar: 100 µm for all images.
Fig. 6
Fig. 6 Change in TPEF (a), F-SHG (b), B-SHG intensity (c), and F/B ratio (d) as a function of IRIS scan speed. Linear least-square fitting was performed using all the data points from three eyes, with R2 values indicated in each graph.

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f(x,y)=a1exp( ( xb1 c1 ) 2 )+a2exp( ( xb2 c2 ) 2 )
MD(%)= b2b1 b1 ×100%

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