Abstract

Dry eye syndrome is a highly prevalent disease of the ocular surface characterized by an instability of the tear film. Traditional methods used for the evaluation of tear film stability are invasive or show limited repeatability. Here we propose a new non-invasive fully automated approach to measure tear film thickness based on spectral domain optical coherence tomography and on an efficient delay estimator. Silicon wafer phantom were used to validate the thickness measurement. The technique was applied in vivo in healthy subjects. Series of tear film thickness maps were generated, allowing for the visualization of tear film dynamics. Our results show that the in vivo central tear film thickness measurements are precise and repeatable with a coefficient of variation of about 0.65% and that repeatable tear film dynamics can be observed. The presented approach could be used in clinical setting to study patients with dry eye disease and monitor their treatments.

© 2015 Optical Society of America

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References

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2015 (2)

D. Schmidl, L. Schmetterer, K. J. Witkowska, A. Unterhuber, V. Aranha dos Santos, S. Kaya, J. Nepp, C. Baar, P. Rosner, R. M. Werkmeister, and G. Garhofer, “Tear film thickness after treatment with artificial tears in patients with moderate dry eye disease,” Cornea 34(4), 421–426 (2015).
[Crossref] [PubMed]

R. J. Braun, P. E. King-Smith, C. G. Begley, L. Li, and N. R. Gewecke, “Dynamics and function of the tear film in relation to the blink cycle,” Prog. Retin. Eye Res. 45, 132–164 (2015).
[Crossref] [PubMed]

2014 (4)

H. Lu, M. R. Wang, J. Wang, and M. Shen, “Tear film measurement by optical reflectometry technique,” J. Biomed. Opt. 19(2), 027001 (2014).
[Crossref] [PubMed]

J. Vehof, D. Kozareva, P. G. Hysi, and C. J. Hammond, “Prevalence and risk factors of dry eye disease in a British female cohort,” Br. J. Ophthalmol. 98(12), 1712–1717 (2014).
[Crossref] [PubMed]

L. Li, R. J. Braun, K. L. Maki, W. D. Henshaw, and P. E. King-Smith, “Tear film dynamics with evaporation, wetting, and time-dependent flux boundary condition on an eye-shaped domain,” Phys Fluids (1994) 26(5), 052101 (2014).
[Crossref] [PubMed]

J. Huang, Q. Yuan, B. Zhang, K. Xu, P. Tankam, E. Clarkson, M. A. Kupinski, H. B. Hindman, J. V. Aquavella, T. J. Suleski, and J. P. Rolland, “Measurement of a multi-layered tear film phantom using optical coherence tomography and statistical decision theory,” Biomed. Opt. Express 5(12), 4374–4386 (2014).
[Crossref] [PubMed]

2013 (3)

J. Huang, K. S. Lee, E. Clarkson, M. Kupinski, K. L. Maki, D. S. Ross, J. V. Aquavella, and J. P. Rolland, “Phantom study of tear film dynamics with optical coherence tomography and maximum-likelihood estimation,” Opt. Lett. 38(10), 1721–1723 (2013).
[Crossref] [PubMed]

R. M. Werkmeister, A. Alex, S. Kaya, A. Unterhuber, B. Hofer, J. Riedl, M. Bronhagl, M. Vietauer, D. Schmidl, T. Schmoll, G. Garhöfer, W. Drexler, R. A. Leitgeb, M. Groeschl, and L. Schmetterer, “Measurement of tear film thickness using ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 54(8), 5578–5583 (2013).
[Crossref] [PubMed]

D. F. Sweeney, T. J. Millar, and S. R. Raju, “Tear film stability: a review,” Exp. Eye Res. 117, 28–38 (2013).
[Crossref] [PubMed]

2012 (3)

T. Schmoll, A. Unterhuber, C. Kolbitsch, T. Le, A. Stingl, and R. Leitgeb, “Precise thickness measurements of Bowman’s layer, epithelium, and tear film,” Optom. Vis. Sci. 89(5), E795–E802 (2012).
[Crossref] [PubMed]

R. Kottaiyan, G. Yoon, Q. Wang, R. Yadav, J. M. Zavislan, and J. V. Aquavella, “Integrated multimodal metrology for objective and noninvasive tear evaluation,” Ocul. Surf. 10(1), 43–50 (2012).
[Crossref] [PubMed]

M. K. J. Klamann, A.-K. B. Maier, J. Gonnermann, J. P. Klein, and U. Pleyer, “Measurement of dynamic ocular surface temperature in healthy subjects using a new thermography device,” Curr. Eye Res. 37(8), 678–683 (2012).
[Crossref] [PubMed]

2011 (2)

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

K. Gumus, C. H. Crockett, K. Rao, E. Yeu, M. P. Weikert, M. Shirayama, S. Hada, and S. C. Pflugfelder, “Noninvasive assessment of tear stability with the tear stability analysis system in tear dysfunction patients,” Invest. Ophthalmol. Vis. Sci. 52(1), 456–461 (2011).
[Crossref] [PubMed]

2010 (1)

Q. Chen, J. Wang, A. Tao, M. Shen, S. Jiao, and F. Lu, “Ultrahigh-resolution measurement by optical coherence tomography of dynamic tear film changes on contact lenses,” Invest. Ophthalmol. Vis. Sci. 51(4), 1988–1993 (2010).
[Crossref] [PubMed]

2009 (1)

J. L. Gayton, “Etiology, prevalence, and treatment of dry eye disease,” Clin. Ophthalmol. 3, 405–412 (2009).
[Crossref] [PubMed]

2008 (1)

G. Savini, P. Prabhawasat, T. Kojima, M. Grueterich, E. Espana, and E. Goto, “The challenge of dry eye diagnosis,” Clin. Ophthalmol. 2(1), 31–55 (2008).
[Crossref] [PubMed]

2007 (2)

G. Foulks, M. Lemp, J. Jester, J. Sutphin, J. Murube, and G. Novack, “Report of the international dry eye workshop,” Ocul. Surf. 5, 65–203 (2007).
[Crossref]

M. A. Lemp and G. N. Foulks, “The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007),” Ocul. Surf. 5(2), 75–92 (2007).
[Crossref] [PubMed]

2006 (2)

D. H. Szczȩsna, J. Jaroński, H. T. Kasprzak, and U. Stenevi, “Interferometric measurements of dynamic changes of tear film,” J. Biomed. Opt. 11(3), 034028 (2006).
[Crossref] [PubMed]

P. E. King-Smith, B. A. Fink, J. J. Nichols, K. K. Nichols, and R. M. Hill, “Interferometric imaging of the full thickness of the precorneal tear film,” J. Opt. Soc. Am. A 23(9), 2097–2104 (2006).
[Crossref] [PubMed]

2004 (4)

N. Yokoi and A. Komuro, “Non-invasive methods of assessing the tear film,” Exp. Eye Res. 78(3), 399–407 (2004).
[Crossref] [PubMed]

M. E. Johnson and P. J. Murphy, “Changes in the tear film and ocular surface from dry eye syndrome,” Prog. Retin. Eye Res. 23(4), 449–474 (2004).
[Crossref] [PubMed]

P. E. King-Smith, B. A. Fink, R. M. Hill, K. W. Koelling, and J. M. Tiffany, “The thickness of the tear film,” Curr. Eye Res. 29(4-5), 357–368 (2004).
[Crossref] [PubMed]

I. K. Gipson, “Distribution of mucins at the ocular surface,” Exp. Eye Res. 78(3), 379–388 (2004).
[Crossref] [PubMed]

2003 (3)

J. Wang, D. Fonn, T. L. Simpson, and L. Jones, “Precorneal and pre- and postlens tear film thickness measured indirectly with optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 44(6), 2524–2528 (2003).
[Crossref] [PubMed]

R. Leitgeb, C. Hitzenberger, and A. Fercher, “Performance of fourier domain vs. time domain optical coherence tomography,” Opt. Express 11(8), 889–894 (2003).
[Crossref] [PubMed]

E. Goto and S. C. Tseng, “Differentiation of lipid tear deficiency dry eye by kinetic analysis of tear interference images,” Arch. Ophthalmol. 121(2), 173–180 (2003).
[Crossref] [PubMed]

2002 (1)

M. L. Fowler, “Phase-based frequency estimation: a review,” Digit. Signal Process. 12(4), 590–615 (2002).
[Crossref]

2000 (1)

P. E. King-Smith, B. A. Fink, N. Fogt, K. K. Nichols, R. M. Hill, and G. S. Wilson, “The thickness of the human precorneal tear film: evidence from reflection spectra,” Invest. Ophthalmol. Vis. Sci. 41(11), 3348–3359 (2000).
[PubMed]

1999 (2)

P. E. King-Smith, B. A. Fink, and N. Fogt, “Three interferometric methods for measuring the thickness of layers of the tear film,” Optom. Vis. Sci. 76(1), 19–32 (1999).
[Crossref] [PubMed]

P. B. Morgan, M. P. Soh, and N. Efron, “Corneal surface temperature decreases with age,” Cont. Lens Anterior Eye 22(1), 11–13 (1999).
[Crossref] [PubMed]

1998 (1)

J. L. Creech, L. T. Do, I. Fatt, and C. J. Radke, “In vivo tear-film thickness determination and implications for tear-film stability,” Curr. Eye Res. 17(11), 1058–1066 (1998).
[Crossref] [PubMed]

1997 (1)

1995 (2)

J. P. Craig, P. A. Simmons, S. Patel, and A. Tomlinson, “Refractive index and osmolality of human tears,” Optom. Vis. Sci. 72(10), 718–724 (1995).
[Crossref] [PubMed]

J. M. Tiffany, “Physiological functions of the meibomian glands,” Prog. Retin. Eye Res. 14(1), 47–74 (1995).
[Crossref]

1992 (2)

R. P. Feenstra and S. C. Tseng, “What is actually stained by rose bengal?” Arch. Ophthalmol. 110(7), 984–993 (1992).
[Crossref] [PubMed]

J. I. Prydal and F. W. Campbell, “Study of precorneal tear film thickness and structure by interferometry and confocal microscopy,” Invest. Ophthalmol. Vis. Sci. 33(6), 1996–2005 (1992).
[PubMed]

1989 (2)

M. G. Doane, “An instrument for in vivo tear film interferometry,” Optom. Vis. Sci. 66(6), 383–388 (1989).
[Crossref] [PubMed]

S. Kay, “A fast and accurate single frequency estimator,” IEEE Trans. Acoust. Speech Signal Process. 37(12), 1987–1990 (1989).
[Crossref]

1986 (1)

J. M. Tiffany, “Refractive index of meibomian and other lipids,” Curr. Eye Res. 5(11), 887–889 (1986).
[Crossref] [PubMed]

1985 (1)

T. Olsen, “Reflectometry of the precorneal film,” Acta Ophthalmol. (Copenh.) 63(4), 432–438 (1985).
[Crossref] [PubMed]

1983 (1)

T. E. Clinch, D. A. Benedetto, N. T. Felberg, and P. R. Laibson, “Schirmer’s test. a closer look,” Arch. Ophthalmol. 101(9), 1383–1386 (1983).
[Crossref] [PubMed]

1974 (1)

D. W. Scherz, M. G. Doane, and C. H. Dohlman, “Tear volume in normal eyes and keratoconjunctivitis sicca,” Graefes Arch. Für Klin, Exp. Ophthalmol. 192, 141–150 (1974).

1973 (1)

M. A. Lemp, “Breakup of the tear film,” Int. Ophthalmol. Clin. 13(1), 97–102 (1973).
[Crossref] [PubMed]

1969 (1)

M. S. Norn, “Desiccation of the precorneal film. I. Corneal wetting-time,” Acta Ophthalmol. 47(4), 865–880 (1969).
[Crossref] [PubMed]

1968 (1)

R. Mapstone, “Measurement of corneal temperature,” Exp. Eye Res. 7(2), 237–242 (1968).
[Crossref] [PubMed]

1965 (2)

S. Mishima, “Some physiological aspects of the precorneal tear film,” Arch. Ophthalmol. 73(2), 233–241 (1965).
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N. Ehlers, “The thickness of the precorneal tear film,” Acta Ophthalmol. (Copenh.) 81, 92–100 (1965).

1962 (1)

M. S. Norn, “Vital staining of cornea and conjunctiva,” Acta Ophthalmol. (Copenh.) 40(4), 389–401 (1962).
[Crossref] [PubMed]

1961 (1)

S. Mishima and D. M. Maurice, “The effect of normal evaporation on the eye,” Exp. Eye Res. 1(1), 46–52 (1961).
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1903 (1)

P. O. Schirmer, “Studien zur Physiologie und Pathologie der Tränenabsonderung und Tränenabfuhr,” Graefes, Arch. Ophthalmol. 56, 197–291 (1903).

Alex, A.

R. M. Werkmeister, A. Alex, S. Kaya, A. Unterhuber, B. Hofer, J. Riedl, M. Bronhagl, M. Vietauer, D. Schmidl, T. Schmoll, G. Garhöfer, W. Drexler, R. A. Leitgeb, M. Groeschl, and L. Schmetterer, “Measurement of tear film thickness using ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 54(8), 5578–5583 (2013).
[Crossref] [PubMed]

Aquavella, J. V.

Aranha dos Santos, V.

D. Schmidl, L. Schmetterer, K. J. Witkowska, A. Unterhuber, V. Aranha dos Santos, S. Kaya, J. Nepp, C. Baar, P. Rosner, R. M. Werkmeister, and G. Garhofer, “Tear film thickness after treatment with artificial tears in patients with moderate dry eye disease,” Cornea 34(4), 421–426 (2015).
[Crossref] [PubMed]

S. Kaya, D. Schmidl, L. Schmetterer, K. Napora, A. Unterhuber, V. Aranha dos Santos, C. Baar, G. Garhofer, and R. M. Werkmeister, “Effects of hyaluronic acid on tear film thickness as assesed with high-resolution optical coherence tomography (OCT),” Acta Ophthalmol. (Copenh.). in press.

Baar, C.

D. Schmidl, L. Schmetterer, K. J. Witkowska, A. Unterhuber, V. Aranha dos Santos, S. Kaya, J. Nepp, C. Baar, P. Rosner, R. M. Werkmeister, and G. Garhofer, “Tear film thickness after treatment with artificial tears in patients with moderate dry eye disease,” Cornea 34(4), 421–426 (2015).
[Crossref] [PubMed]

S. Kaya, D. Schmidl, L. Schmetterer, K. Napora, A. Unterhuber, V. Aranha dos Santos, C. Baar, G. Garhofer, and R. M. Werkmeister, “Effects of hyaluronic acid on tear film thickness as assesed with high-resolution optical coherence tomography (OCT),” Acta Ophthalmol. (Copenh.). in press.

Begley, C. G.

R. J. Braun, P. E. King-Smith, C. G. Begley, L. Li, and N. R. Gewecke, “Dynamics and function of the tear film in relation to the blink cycle,” Prog. Retin. Eye Res. 45, 132–164 (2015).
[Crossref] [PubMed]

Benedetto, D. A.

T. E. Clinch, D. A. Benedetto, N. T. Felberg, and P. R. Laibson, “Schirmer’s test. a closer look,” Arch. Ophthalmol. 101(9), 1383–1386 (1983).
[Crossref] [PubMed]

Braun, R. J.

R. J. Braun, P. E. King-Smith, C. G. Begley, L. Li, and N. R. Gewecke, “Dynamics and function of the tear film in relation to the blink cycle,” Prog. Retin. Eye Res. 45, 132–164 (2015).
[Crossref] [PubMed]

L. Li, R. J. Braun, K. L. Maki, W. D. Henshaw, and P. E. King-Smith, “Tear film dynamics with evaporation, wetting, and time-dependent flux boundary condition on an eye-shaped domain,” Phys Fluids (1994) 26(5), 052101 (2014).
[Crossref] [PubMed]

Bronhagl, M.

R. M. Werkmeister, A. Alex, S. Kaya, A. Unterhuber, B. Hofer, J. Riedl, M. Bronhagl, M. Vietauer, D. Schmidl, T. Schmoll, G. Garhöfer, W. Drexler, R. A. Leitgeb, M. Groeschl, and L. Schmetterer, “Measurement of tear film thickness using ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 54(8), 5578–5583 (2013).
[Crossref] [PubMed]

Campbell, F. W.

J. I. Prydal and F. W. Campbell, “Study of precorneal tear film thickness and structure by interferometry and confocal microscopy,” Invest. Ophthalmol. Vis. Sci. 33(6), 1996–2005 (1992).
[PubMed]

Chen, Q.

Q. Chen, J. Wang, A. Tao, M. Shen, S. Jiao, and F. Lu, “Ultrahigh-resolution measurement by optical coherence tomography of dynamic tear film changes on contact lenses,” Invest. Ophthalmol. Vis. Sci. 51(4), 1988–1993 (2010).
[Crossref] [PubMed]

Clarkson, E.

Clinch, T. E.

T. E. Clinch, D. A. Benedetto, N. T. Felberg, and P. R. Laibson, “Schirmer’s test. a closer look,” Arch. Ophthalmol. 101(9), 1383–1386 (1983).
[Crossref] [PubMed]

Craig, J. P.

J. P. Craig, P. A. Simmons, S. Patel, and A. Tomlinson, “Refractive index and osmolality of human tears,” Optom. Vis. Sci. 72(10), 718–724 (1995).
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Creech, J. L.

J. L. Creech, L. T. Do, I. Fatt, and C. J. Radke, “In vivo tear-film thickness determination and implications for tear-film stability,” Curr. Eye Res. 17(11), 1058–1066 (1998).
[Crossref] [PubMed]

Crockett, C. H.

K. Gumus, C. H. Crockett, K. Rao, E. Yeu, M. P. Weikert, M. Shirayama, S. Hada, and S. C. Pflugfelder, “Noninvasive assessment of tear stability with the tear stability analysis system in tear dysfunction patients,” Invest. Ophthalmol. Vis. Sci. 52(1), 456–461 (2011).
[Crossref] [PubMed]

Do, L. T.

J. L. Creech, L. T. Do, I. Fatt, and C. J. Radke, “In vivo tear-film thickness determination and implications for tear-film stability,” Curr. Eye Res. 17(11), 1058–1066 (1998).
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Doane, M. G.

M. G. Doane, “An instrument for in vivo tear film interferometry,” Optom. Vis. Sci. 66(6), 383–388 (1989).
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D. W. Scherz, M. G. Doane, and C. H. Dohlman, “Tear volume in normal eyes and keratoconjunctivitis sicca,” Graefes Arch. Für Klin, Exp. Ophthalmol. 192, 141–150 (1974).

Dohlman, C. H.

D. W. Scherz, M. G. Doane, and C. H. Dohlman, “Tear volume in normal eyes and keratoconjunctivitis sicca,” Graefes Arch. Für Klin, Exp. Ophthalmol. 192, 141–150 (1974).

Drexler, W.

R. M. Werkmeister, A. Alex, S. Kaya, A. Unterhuber, B. Hofer, J. Riedl, M. Bronhagl, M. Vietauer, D. Schmidl, T. Schmoll, G. Garhöfer, W. Drexler, R. A. Leitgeb, M. Groeschl, and L. Schmetterer, “Measurement of tear film thickness using ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 54(8), 5578–5583 (2013).
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Efron, N.

P. B. Morgan, M. P. Soh, and N. Efron, “Corneal surface temperature decreases with age,” Cont. Lens Anterior Eye 22(1), 11–13 (1999).
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Ehlers, N.

N. Ehlers, “The thickness of the precorneal tear film,” Acta Ophthalmol. (Copenh.) 81, 92–100 (1965).

Espana, E.

G. Savini, P. Prabhawasat, T. Kojima, M. Grueterich, E. Espana, and E. Goto, “The challenge of dry eye diagnosis,” Clin. Ophthalmol. 2(1), 31–55 (2008).
[Crossref] [PubMed]

Fatt, I.

J. L. Creech, L. T. Do, I. Fatt, and C. J. Radke, “In vivo tear-film thickness determination and implications for tear-film stability,” Curr. Eye Res. 17(11), 1058–1066 (1998).
[Crossref] [PubMed]

Feenstra, R. P.

R. P. Feenstra and S. C. Tseng, “What is actually stained by rose bengal?” Arch. Ophthalmol. 110(7), 984–993 (1992).
[Crossref] [PubMed]

Felberg, N. T.

T. E. Clinch, D. A. Benedetto, N. T. Felberg, and P. R. Laibson, “Schirmer’s test. a closer look,” Arch. Ophthalmol. 101(9), 1383–1386 (1983).
[Crossref] [PubMed]

Fercher, A.

Fink, B. A.

P. E. King-Smith, B. A. Fink, J. J. Nichols, K. K. Nichols, and R. M. Hill, “Interferometric imaging of the full thickness of the precorneal tear film,” J. Opt. Soc. Am. A 23(9), 2097–2104 (2006).
[Crossref] [PubMed]

P. E. King-Smith, B. A. Fink, R. M. Hill, K. W. Koelling, and J. M. Tiffany, “The thickness of the tear film,” Curr. Eye Res. 29(4-5), 357–368 (2004).
[Crossref] [PubMed]

P. E. King-Smith, B. A. Fink, N. Fogt, K. K. Nichols, R. M. Hill, and G. S. Wilson, “The thickness of the human precorneal tear film: evidence from reflection spectra,” Invest. Ophthalmol. Vis. Sci. 41(11), 3348–3359 (2000).
[PubMed]

P. E. King-Smith, B. A. Fink, and N. Fogt, “Three interferometric methods for measuring the thickness of layers of the tear film,” Optom. Vis. Sci. 76(1), 19–32 (1999).
[Crossref] [PubMed]

Fogt, N.

P. E. King-Smith, B. A. Fink, N. Fogt, K. K. Nichols, R. M. Hill, and G. S. Wilson, “The thickness of the human precorneal tear film: evidence from reflection spectra,” Invest. Ophthalmol. Vis. Sci. 41(11), 3348–3359 (2000).
[PubMed]

P. E. King-Smith, B. A. Fink, and N. Fogt, “Three interferometric methods for measuring the thickness of layers of the tear film,” Optom. Vis. Sci. 76(1), 19–32 (1999).
[Crossref] [PubMed]

Fonn, D.

J. Wang, D. Fonn, T. L. Simpson, and L. Jones, “Precorneal and pre- and postlens tear film thickness measured indirectly with optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 44(6), 2524–2528 (2003).
[Crossref] [PubMed]

Foulks, G.

G. Foulks, M. Lemp, J. Jester, J. Sutphin, J. Murube, and G. Novack, “Report of the international dry eye workshop,” Ocul. Surf. 5, 65–203 (2007).
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Foulks, G. N.

M. A. Lemp and G. N. Foulks, “The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007),” Ocul. Surf. 5(2), 75–92 (2007).
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Fowler, M. L.

M. L. Fowler, “Phase-based frequency estimation: a review,” Digit. Signal Process. 12(4), 590–615 (2002).
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Garhofer, G.

D. Schmidl, L. Schmetterer, K. J. Witkowska, A. Unterhuber, V. Aranha dos Santos, S. Kaya, J. Nepp, C. Baar, P. Rosner, R. M. Werkmeister, and G. Garhofer, “Tear film thickness after treatment with artificial tears in patients with moderate dry eye disease,” Cornea 34(4), 421–426 (2015).
[Crossref] [PubMed]

S. Kaya, D. Schmidl, L. Schmetterer, K. Napora, A. Unterhuber, V. Aranha dos Santos, C. Baar, G. Garhofer, and R. M. Werkmeister, “Effects of hyaluronic acid on tear film thickness as assesed with high-resolution optical coherence tomography (OCT),” Acta Ophthalmol. (Copenh.). in press.

Garhöfer, G.

R. M. Werkmeister, A. Alex, S. Kaya, A. Unterhuber, B. Hofer, J. Riedl, M. Bronhagl, M. Vietauer, D. Schmidl, T. Schmoll, G. Garhöfer, W. Drexler, R. A. Leitgeb, M. Groeschl, and L. Schmetterer, “Measurement of tear film thickness using ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 54(8), 5578–5583 (2013).
[Crossref] [PubMed]

Gayton, J. L.

J. L. Gayton, “Etiology, prevalence, and treatment of dry eye disease,” Clin. Ophthalmol. 3, 405–412 (2009).
[Crossref] [PubMed]

Gewecke, N. R.

R. J. Braun, P. E. King-Smith, C. G. Begley, L. Li, and N. R. Gewecke, “Dynamics and function of the tear film in relation to the blink cycle,” Prog. Retin. Eye Res. 45, 132–164 (2015).
[Crossref] [PubMed]

Gipson, I. K.

I. K. Gipson, “Distribution of mucins at the ocular surface,” Exp. Eye Res. 78(3), 379–388 (2004).
[Crossref] [PubMed]

Gonnermann, J.

M. K. J. Klamann, A.-K. B. Maier, J. Gonnermann, J. P. Klein, and U. Pleyer, “Measurement of dynamic ocular surface temperature in healthy subjects using a new thermography device,” Curr. Eye Res. 37(8), 678–683 (2012).
[Crossref] [PubMed]

Goto, E.

G. Savini, P. Prabhawasat, T. Kojima, M. Grueterich, E. Espana, and E. Goto, “The challenge of dry eye diagnosis,” Clin. Ophthalmol. 2(1), 31–55 (2008).
[Crossref] [PubMed]

E. Goto and S. C. Tseng, “Differentiation of lipid tear deficiency dry eye by kinetic analysis of tear interference images,” Arch. Ophthalmol. 121(2), 173–180 (2003).
[Crossref] [PubMed]

Groeschl, M.

R. M. Werkmeister, A. Alex, S. Kaya, A. Unterhuber, B. Hofer, J. Riedl, M. Bronhagl, M. Vietauer, D. Schmidl, T. Schmoll, G. Garhöfer, W. Drexler, R. A. Leitgeb, M. Groeschl, and L. Schmetterer, “Measurement of tear film thickness using ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 54(8), 5578–5583 (2013).
[Crossref] [PubMed]

Grueterich, M.

G. Savini, P. Prabhawasat, T. Kojima, M. Grueterich, E. Espana, and E. Goto, “The challenge of dry eye diagnosis,” Clin. Ophthalmol. 2(1), 31–55 (2008).
[Crossref] [PubMed]

Gumus, K.

K. Gumus, C. H. Crockett, K. Rao, E. Yeu, M. P. Weikert, M. Shirayama, S. Hada, and S. C. Pflugfelder, “Noninvasive assessment of tear stability with the tear stability analysis system in tear dysfunction patients,” Invest. Ophthalmol. Vis. Sci. 52(1), 456–461 (2011).
[Crossref] [PubMed]

Hada, S.

K. Gumus, C. H. Crockett, K. Rao, E. Yeu, M. P. Weikert, M. Shirayama, S. Hada, and S. C. Pflugfelder, “Noninvasive assessment of tear stability with the tear stability analysis system in tear dysfunction patients,” Invest. Ophthalmol. Vis. Sci. 52(1), 456–461 (2011).
[Crossref] [PubMed]

Hammond, C. J.

J. Vehof, D. Kozareva, P. G. Hysi, and C. J. Hammond, “Prevalence and risk factors of dry eye disease in a British female cohort,” Br. J. Ophthalmol. 98(12), 1712–1717 (2014).
[Crossref] [PubMed]

Henshaw, W. D.

L. Li, R. J. Braun, K. L. Maki, W. D. Henshaw, and P. E. King-Smith, “Tear film dynamics with evaporation, wetting, and time-dependent flux boundary condition on an eye-shaped domain,” Phys Fluids (1994) 26(5), 052101 (2014).
[Crossref] [PubMed]

Hill, R. M.

P. E. King-Smith, B. A. Fink, J. J. Nichols, K. K. Nichols, and R. M. Hill, “Interferometric imaging of the full thickness of the precorneal tear film,” J. Opt. Soc. Am. A 23(9), 2097–2104 (2006).
[Crossref] [PubMed]

P. E. King-Smith, B. A. Fink, R. M. Hill, K. W. Koelling, and J. M. Tiffany, “The thickness of the tear film,” Curr. Eye Res. 29(4-5), 357–368 (2004).
[Crossref] [PubMed]

P. E. King-Smith, B. A. Fink, N. Fogt, K. K. Nichols, R. M. Hill, and G. S. Wilson, “The thickness of the human precorneal tear film: evidence from reflection spectra,” Invest. Ophthalmol. Vis. Sci. 41(11), 3348–3359 (2000).
[PubMed]

Hindman, H. B.

Hitzenberger, C.

Hofer, B.

R. M. Werkmeister, A. Alex, S. Kaya, A. Unterhuber, B. Hofer, J. Riedl, M. Bronhagl, M. Vietauer, D. Schmidl, T. Schmoll, G. Garhöfer, W. Drexler, R. A. Leitgeb, M. Groeschl, and L. Schmetterer, “Measurement of tear film thickness using ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 54(8), 5578–5583 (2013).
[Crossref] [PubMed]

Huang, J.

Huibers, P. D.

Hysi, P. G.

J. Vehof, D. Kozareva, P. G. Hysi, and C. J. Hammond, “Prevalence and risk factors of dry eye disease in a British female cohort,” Br. J. Ophthalmol. 98(12), 1712–1717 (2014).
[Crossref] [PubMed]

Jaronski, J.

D. H. Szczȩsna, J. Jaroński, H. T. Kasprzak, and U. Stenevi, “Interferometric measurements of dynamic changes of tear film,” J. Biomed. Opt. 11(3), 034028 (2006).
[Crossref] [PubMed]

Jester, J.

G. Foulks, M. Lemp, J. Jester, J. Sutphin, J. Murube, and G. Novack, “Report of the international dry eye workshop,” Ocul. Surf. 5, 65–203 (2007).
[Crossref]

Jiao, S.

Q. Chen, J. Wang, A. Tao, M. Shen, S. Jiao, and F. Lu, “Ultrahigh-resolution measurement by optical coherence tomography of dynamic tear film changes on contact lenses,” Invest. Ophthalmol. Vis. Sci. 51(4), 1988–1993 (2010).
[Crossref] [PubMed]

Johnson, M. E.

M. E. Johnson and P. J. Murphy, “Changes in the tear film and ocular surface from dry eye syndrome,” Prog. Retin. Eye Res. 23(4), 449–474 (2004).
[Crossref] [PubMed]

Jones, L.

J. Wang, D. Fonn, T. L. Simpson, and L. Jones, “Precorneal and pre- and postlens tear film thickness measured indirectly with optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 44(6), 2524–2528 (2003).
[Crossref] [PubMed]

Kasprzak, H. T.

D. H. Szczȩsna, J. Jaroński, H. T. Kasprzak, and U. Stenevi, “Interferometric measurements of dynamic changes of tear film,” J. Biomed. Opt. 11(3), 034028 (2006).
[Crossref] [PubMed]

Kay, S.

S. Kay, “A fast and accurate single frequency estimator,” IEEE Trans. Acoust. Speech Signal Process. 37(12), 1987–1990 (1989).
[Crossref]

Kaya, S.

D. Schmidl, L. Schmetterer, K. J. Witkowska, A. Unterhuber, V. Aranha dos Santos, S. Kaya, J. Nepp, C. Baar, P. Rosner, R. M. Werkmeister, and G. Garhofer, “Tear film thickness after treatment with artificial tears in patients with moderate dry eye disease,” Cornea 34(4), 421–426 (2015).
[Crossref] [PubMed]

R. M. Werkmeister, A. Alex, S. Kaya, A. Unterhuber, B. Hofer, J. Riedl, M. Bronhagl, M. Vietauer, D. Schmidl, T. Schmoll, G. Garhöfer, W. Drexler, R. A. Leitgeb, M. Groeschl, and L. Schmetterer, “Measurement of tear film thickness using ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 54(8), 5578–5583 (2013).
[Crossref] [PubMed]

S. Kaya, D. Schmidl, L. Schmetterer, K. Napora, A. Unterhuber, V. Aranha dos Santos, C. Baar, G. Garhofer, and R. M. Werkmeister, “Effects of hyaluronic acid on tear film thickness as assesed with high-resolution optical coherence tomography (OCT),” Acta Ophthalmol. (Copenh.). in press.

King-Smith, P. E.

R. J. Braun, P. E. King-Smith, C. G. Begley, L. Li, and N. R. Gewecke, “Dynamics and function of the tear film in relation to the blink cycle,” Prog. Retin. Eye Res. 45, 132–164 (2015).
[Crossref] [PubMed]

L. Li, R. J. Braun, K. L. Maki, W. D. Henshaw, and P. E. King-Smith, “Tear film dynamics with evaporation, wetting, and time-dependent flux boundary condition on an eye-shaped domain,” Phys Fluids (1994) 26(5), 052101 (2014).
[Crossref] [PubMed]

P. E. King-Smith, B. A. Fink, J. J. Nichols, K. K. Nichols, and R. M. Hill, “Interferometric imaging of the full thickness of the precorneal tear film,” J. Opt. Soc. Am. A 23(9), 2097–2104 (2006).
[Crossref] [PubMed]

P. E. King-Smith, B. A. Fink, R. M. Hill, K. W. Koelling, and J. M. Tiffany, “The thickness of the tear film,” Curr. Eye Res. 29(4-5), 357–368 (2004).
[Crossref] [PubMed]

P. E. King-Smith, B. A. Fink, N. Fogt, K. K. Nichols, R. M. Hill, and G. S. Wilson, “The thickness of the human precorneal tear film: evidence from reflection spectra,” Invest. Ophthalmol. Vis. Sci. 41(11), 3348–3359 (2000).
[PubMed]

P. E. King-Smith, B. A. Fink, and N. Fogt, “Three interferometric methods for measuring the thickness of layers of the tear film,” Optom. Vis. Sci. 76(1), 19–32 (1999).
[Crossref] [PubMed]

Klamann, M. K. J.

M. K. J. Klamann, A.-K. B. Maier, J. Gonnermann, J. P. Klein, and U. Pleyer, “Measurement of dynamic ocular surface temperature in healthy subjects using a new thermography device,” Curr. Eye Res. 37(8), 678–683 (2012).
[Crossref] [PubMed]

Klein, J. P.

M. K. J. Klamann, A.-K. B. Maier, J. Gonnermann, J. P. Klein, and U. Pleyer, “Measurement of dynamic ocular surface temperature in healthy subjects using a new thermography device,” Curr. Eye Res. 37(8), 678–683 (2012).
[Crossref] [PubMed]

Koelling, K. W.

P. E. King-Smith, B. A. Fink, R. M. Hill, K. W. Koelling, and J. M. Tiffany, “The thickness of the tear film,” Curr. Eye Res. 29(4-5), 357–368 (2004).
[Crossref] [PubMed]

Kojima, T.

G. Savini, P. Prabhawasat, T. Kojima, M. Grueterich, E. Espana, and E. Goto, “The challenge of dry eye diagnosis,” Clin. Ophthalmol. 2(1), 31–55 (2008).
[Crossref] [PubMed]

Kolbitsch, C.

T. Schmoll, A. Unterhuber, C. Kolbitsch, T. Le, A. Stingl, and R. Leitgeb, “Precise thickness measurements of Bowman’s layer, epithelium, and tear film,” Optom. Vis. Sci. 89(5), E795–E802 (2012).
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Komuro, A.

N. Yokoi and A. Komuro, “Non-invasive methods of assessing the tear film,” Exp. Eye Res. 78(3), 399–407 (2004).
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Kottaiyan, R.

R. Kottaiyan, G. Yoon, Q. Wang, R. Yadav, J. M. Zavislan, and J. V. Aquavella, “Integrated multimodal metrology for objective and noninvasive tear evaluation,” Ocul. Surf. 10(1), 43–50 (2012).
[Crossref] [PubMed]

Kozareva, D.

J. Vehof, D. Kozareva, P. G. Hysi, and C. J. Hammond, “Prevalence and risk factors of dry eye disease in a British female cohort,” Br. J. Ophthalmol. 98(12), 1712–1717 (2014).
[Crossref] [PubMed]

Kupinski, M.

Kupinski, M. A.

Laibson, P. R.

T. E. Clinch, D. A. Benedetto, N. T. Felberg, and P. R. Laibson, “Schirmer’s test. a closer look,” Arch. Ophthalmol. 101(9), 1383–1386 (1983).
[Crossref] [PubMed]

Le, T.

T. Schmoll, A. Unterhuber, C. Kolbitsch, T. Le, A. Stingl, and R. Leitgeb, “Precise thickness measurements of Bowman’s layer, epithelium, and tear film,” Optom. Vis. Sci. 89(5), E795–E802 (2012).
[Crossref] [PubMed]

Lee, K. S.

Lee, K.-S.

Leitgeb, R.

T. Schmoll, A. Unterhuber, C. Kolbitsch, T. Le, A. Stingl, and R. Leitgeb, “Precise thickness measurements of Bowman’s layer, epithelium, and tear film,” Optom. Vis. Sci. 89(5), E795–E802 (2012).
[Crossref] [PubMed]

R. Leitgeb, C. Hitzenberger, and A. Fercher, “Performance of fourier domain vs. time domain optical coherence tomography,” Opt. Express 11(8), 889–894 (2003).
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Leitgeb, R. A.

R. M. Werkmeister, A. Alex, S. Kaya, A. Unterhuber, B. Hofer, J. Riedl, M. Bronhagl, M. Vietauer, D. Schmidl, T. Schmoll, G. Garhöfer, W. Drexler, R. A. Leitgeb, M. Groeschl, and L. Schmetterer, “Measurement of tear film thickness using ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 54(8), 5578–5583 (2013).
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Lemp, M.

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D. Schmidl, L. Schmetterer, K. J. Witkowska, A. Unterhuber, V. Aranha dos Santos, S. Kaya, J. Nepp, C. Baar, P. Rosner, R. M. Werkmeister, and G. Garhofer, “Tear film thickness after treatment with artificial tears in patients with moderate dry eye disease,” Cornea 34(4), 421–426 (2015).
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Nichols, K. K.

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M. S. Norn, “Desiccation of the precorneal film. I. Corneal wetting-time,” Acta Ophthalmol. 47(4), 865–880 (1969).
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M. S. Norn, “Vital staining of cornea and conjunctiva,” Acta Ophthalmol. (Copenh.) 40(4), 389–401 (1962).
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Novack, G.

G. Foulks, M. Lemp, J. Jester, J. Sutphin, J. Murube, and G. Novack, “Report of the international dry eye workshop,” Ocul. Surf. 5, 65–203 (2007).
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J. P. Craig, P. A. Simmons, S. Patel, and A. Tomlinson, “Refractive index and osmolality of human tears,” Optom. Vis. Sci. 72(10), 718–724 (1995).
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K. Gumus, C. H. Crockett, K. Rao, E. Yeu, M. P. Weikert, M. Shirayama, S. Hada, and S. C. Pflugfelder, “Noninvasive assessment of tear stability with the tear stability analysis system in tear dysfunction patients,” Invest. Ophthalmol. Vis. Sci. 52(1), 456–461 (2011).
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M. K. J. Klamann, A.-K. B. Maier, J. Gonnermann, J. P. Klein, and U. Pleyer, “Measurement of dynamic ocular surface temperature in healthy subjects using a new thermography device,” Curr. Eye Res. 37(8), 678–683 (2012).
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D. F. Sweeney, T. J. Millar, and S. R. Raju, “Tear film stability: a review,” Exp. Eye Res. 117, 28–38 (2013).
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K. Gumus, C. H. Crockett, K. Rao, E. Yeu, M. P. Weikert, M. Shirayama, S. Hada, and S. C. Pflugfelder, “Noninvasive assessment of tear stability with the tear stability analysis system in tear dysfunction patients,” Invest. Ophthalmol. Vis. Sci. 52(1), 456–461 (2011).
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Rosner, P.

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Schmetterer, L.

D. Schmidl, L. Schmetterer, K. J. Witkowska, A. Unterhuber, V. Aranha dos Santos, S. Kaya, J. Nepp, C. Baar, P. Rosner, R. M. Werkmeister, and G. Garhofer, “Tear film thickness after treatment with artificial tears in patients with moderate dry eye disease,” Cornea 34(4), 421–426 (2015).
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R. M. Werkmeister, A. Alex, S. Kaya, A. Unterhuber, B. Hofer, J. Riedl, M. Bronhagl, M. Vietauer, D. Schmidl, T. Schmoll, G. Garhöfer, W. Drexler, R. A. Leitgeb, M. Groeschl, and L. Schmetterer, “Measurement of tear film thickness using ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 54(8), 5578–5583 (2013).
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S. Kaya, D. Schmidl, L. Schmetterer, K. Napora, A. Unterhuber, V. Aranha dos Santos, C. Baar, G. Garhofer, and R. M. Werkmeister, “Effects of hyaluronic acid on tear film thickness as assesed with high-resolution optical coherence tomography (OCT),” Acta Ophthalmol. (Copenh.). in press.

Schmidl, D.

D. Schmidl, L. Schmetterer, K. J. Witkowska, A. Unterhuber, V. Aranha dos Santos, S. Kaya, J. Nepp, C. Baar, P. Rosner, R. M. Werkmeister, and G. Garhofer, “Tear film thickness after treatment with artificial tears in patients with moderate dry eye disease,” Cornea 34(4), 421–426 (2015).
[Crossref] [PubMed]

R. M. Werkmeister, A. Alex, S. Kaya, A. Unterhuber, B. Hofer, J. Riedl, M. Bronhagl, M. Vietauer, D. Schmidl, T. Schmoll, G. Garhöfer, W. Drexler, R. A. Leitgeb, M. Groeschl, and L. Schmetterer, “Measurement of tear film thickness using ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 54(8), 5578–5583 (2013).
[Crossref] [PubMed]

S. Kaya, D. Schmidl, L. Schmetterer, K. Napora, A. Unterhuber, V. Aranha dos Santos, C. Baar, G. Garhofer, and R. M. Werkmeister, “Effects of hyaluronic acid on tear film thickness as assesed with high-resolution optical coherence tomography (OCT),” Acta Ophthalmol. (Copenh.). in press.

Schmoll, T.

R. M. Werkmeister, A. Alex, S. Kaya, A. Unterhuber, B. Hofer, J. Riedl, M. Bronhagl, M. Vietauer, D. Schmidl, T. Schmoll, G. Garhöfer, W. Drexler, R. A. Leitgeb, M. Groeschl, and L. Schmetterer, “Measurement of tear film thickness using ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 54(8), 5578–5583 (2013).
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T. Schmoll, A. Unterhuber, C. Kolbitsch, T. Le, A. Stingl, and R. Leitgeb, “Precise thickness measurements of Bowman’s layer, epithelium, and tear film,” Optom. Vis. Sci. 89(5), E795–E802 (2012).
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Shen, M.

H. Lu, M. R. Wang, J. Wang, and M. Shen, “Tear film measurement by optical reflectometry technique,” J. Biomed. Opt. 19(2), 027001 (2014).
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Q. Chen, J. Wang, A. Tao, M. Shen, S. Jiao, and F. Lu, “Ultrahigh-resolution measurement by optical coherence tomography of dynamic tear film changes on contact lenses,” Invest. Ophthalmol. Vis. Sci. 51(4), 1988–1993 (2010).
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Shirayama, M.

K. Gumus, C. H. Crockett, K. Rao, E. Yeu, M. P. Weikert, M. Shirayama, S. Hada, and S. C. Pflugfelder, “Noninvasive assessment of tear stability with the tear stability analysis system in tear dysfunction patients,” Invest. Ophthalmol. Vis. Sci. 52(1), 456–461 (2011).
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Simmons, P. A.

J. P. Craig, P. A. Simmons, S. Patel, and A. Tomlinson, “Refractive index and osmolality of human tears,” Optom. Vis. Sci. 72(10), 718–724 (1995).
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Simpson, T. L.

J. Wang, D. Fonn, T. L. Simpson, and L. Jones, “Precorneal and pre- and postlens tear film thickness measured indirectly with optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 44(6), 2524–2528 (2003).
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Soh, M. P.

P. B. Morgan, M. P. Soh, and N. Efron, “Corneal surface temperature decreases with age,” Cont. Lens Anterior Eye 22(1), 11–13 (1999).
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Stenevi, U.

D. H. Szczȩsna, J. Jaroński, H. T. Kasprzak, and U. Stenevi, “Interferometric measurements of dynamic changes of tear film,” J. Biomed. Opt. 11(3), 034028 (2006).
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Stingl, A.

T. Schmoll, A. Unterhuber, C. Kolbitsch, T. Le, A. Stingl, and R. Leitgeb, “Precise thickness measurements of Bowman’s layer, epithelium, and tear film,” Optom. Vis. Sci. 89(5), E795–E802 (2012).
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Suleski, T. J.

Sutphin, J.

G. Foulks, M. Lemp, J. Jester, J. Sutphin, J. Murube, and G. Novack, “Report of the international dry eye workshop,” Ocul. Surf. 5, 65–203 (2007).
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Sweeney, D. F.

D. F. Sweeney, T. J. Millar, and S. R. Raju, “Tear film stability: a review,” Exp. Eye Res. 117, 28–38 (2013).
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Szcz?sna, D. H.

D. H. Szczȩsna, J. Jaroński, H. T. Kasprzak, and U. Stenevi, “Interferometric measurements of dynamic changes of tear film,” J. Biomed. Opt. 11(3), 034028 (2006).
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Tankam, P.

Tao, A.

Q. Chen, J. Wang, A. Tao, M. Shen, S. Jiao, and F. Lu, “Ultrahigh-resolution measurement by optical coherence tomography of dynamic tear film changes on contact lenses,” Invest. Ophthalmol. Vis. Sci. 51(4), 1988–1993 (2010).
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P. E. King-Smith, B. A. Fink, R. M. Hill, K. W. Koelling, and J. M. Tiffany, “The thickness of the tear film,” Curr. Eye Res. 29(4-5), 357–368 (2004).
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Tomlinson, A.

J. P. Craig, P. A. Simmons, S. Patel, and A. Tomlinson, “Refractive index and osmolality of human tears,” Optom. Vis. Sci. 72(10), 718–724 (1995).
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E. Goto and S. C. Tseng, “Differentiation of lipid tear deficiency dry eye by kinetic analysis of tear interference images,” Arch. Ophthalmol. 121(2), 173–180 (2003).
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Unterhuber, A.

D. Schmidl, L. Schmetterer, K. J. Witkowska, A. Unterhuber, V. Aranha dos Santos, S. Kaya, J. Nepp, C. Baar, P. Rosner, R. M. Werkmeister, and G. Garhofer, “Tear film thickness after treatment with artificial tears in patients with moderate dry eye disease,” Cornea 34(4), 421–426 (2015).
[Crossref] [PubMed]

R. M. Werkmeister, A. Alex, S. Kaya, A. Unterhuber, B. Hofer, J. Riedl, M. Bronhagl, M. Vietauer, D. Schmidl, T. Schmoll, G. Garhöfer, W. Drexler, R. A. Leitgeb, M. Groeschl, and L. Schmetterer, “Measurement of tear film thickness using ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 54(8), 5578–5583 (2013).
[Crossref] [PubMed]

T. Schmoll, A. Unterhuber, C. Kolbitsch, T. Le, A. Stingl, and R. Leitgeb, “Precise thickness measurements of Bowman’s layer, epithelium, and tear film,” Optom. Vis. Sci. 89(5), E795–E802 (2012).
[Crossref] [PubMed]

S. Kaya, D. Schmidl, L. Schmetterer, K. Napora, A. Unterhuber, V. Aranha dos Santos, C. Baar, G. Garhofer, and R. M. Werkmeister, “Effects of hyaluronic acid on tear film thickness as assesed with high-resolution optical coherence tomography (OCT),” Acta Ophthalmol. (Copenh.). in press.

Vehof, J.

J. Vehof, D. Kozareva, P. G. Hysi, and C. J. Hammond, “Prevalence and risk factors of dry eye disease in a British female cohort,” Br. J. Ophthalmol. 98(12), 1712–1717 (2014).
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Vietauer, M.

R. M. Werkmeister, A. Alex, S. Kaya, A. Unterhuber, B. Hofer, J. Riedl, M. Bronhagl, M. Vietauer, D. Schmidl, T. Schmoll, G. Garhöfer, W. Drexler, R. A. Leitgeb, M. Groeschl, and L. Schmetterer, “Measurement of tear film thickness using ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 54(8), 5578–5583 (2013).
[Crossref] [PubMed]

Wang, J.

H. Lu, M. R. Wang, J. Wang, and M. Shen, “Tear film measurement by optical reflectometry technique,” J. Biomed. Opt. 19(2), 027001 (2014).
[Crossref] [PubMed]

Q. Chen, J. Wang, A. Tao, M. Shen, S. Jiao, and F. Lu, “Ultrahigh-resolution measurement by optical coherence tomography of dynamic tear film changes on contact lenses,” Invest. Ophthalmol. Vis. Sci. 51(4), 1988–1993 (2010).
[Crossref] [PubMed]

J. Wang, D. Fonn, T. L. Simpson, and L. Jones, “Precorneal and pre- and postlens tear film thickness measured indirectly with optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 44(6), 2524–2528 (2003).
[Crossref] [PubMed]

Wang, M. R.

H. Lu, M. R. Wang, J. Wang, and M. Shen, “Tear film measurement by optical reflectometry technique,” J. Biomed. Opt. 19(2), 027001 (2014).
[Crossref] [PubMed]

Wang, Q.

R. Kottaiyan, G. Yoon, Q. Wang, R. Yadav, J. M. Zavislan, and J. V. Aquavella, “Integrated multimodal metrology for objective and noninvasive tear evaluation,” Ocul. Surf. 10(1), 43–50 (2012).
[Crossref] [PubMed]

Weikert, M. P.

K. Gumus, C. H. Crockett, K. Rao, E. Yeu, M. P. Weikert, M. Shirayama, S. Hada, and S. C. Pflugfelder, “Noninvasive assessment of tear stability with the tear stability analysis system in tear dysfunction patients,” Invest. Ophthalmol. Vis. Sci. 52(1), 456–461 (2011).
[Crossref] [PubMed]

Werkmeister, R. M.

D. Schmidl, L. Schmetterer, K. J. Witkowska, A. Unterhuber, V. Aranha dos Santos, S. Kaya, J. Nepp, C. Baar, P. Rosner, R. M. Werkmeister, and G. Garhofer, “Tear film thickness after treatment with artificial tears in patients with moderate dry eye disease,” Cornea 34(4), 421–426 (2015).
[Crossref] [PubMed]

R. M. Werkmeister, A. Alex, S. Kaya, A. Unterhuber, B. Hofer, J. Riedl, M. Bronhagl, M. Vietauer, D. Schmidl, T. Schmoll, G. Garhöfer, W. Drexler, R. A. Leitgeb, M. Groeschl, and L. Schmetterer, “Measurement of tear film thickness using ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 54(8), 5578–5583 (2013).
[Crossref] [PubMed]

S. Kaya, D. Schmidl, L. Schmetterer, K. Napora, A. Unterhuber, V. Aranha dos Santos, C. Baar, G. Garhofer, and R. M. Werkmeister, “Effects of hyaluronic acid on tear film thickness as assesed with high-resolution optical coherence tomography (OCT),” Acta Ophthalmol. (Copenh.). in press.

Wilson, G. S.

P. E. King-Smith, B. A. Fink, N. Fogt, K. K. Nichols, R. M. Hill, and G. S. Wilson, “The thickness of the human precorneal tear film: evidence from reflection spectra,” Invest. Ophthalmol. Vis. Sci. 41(11), 3348–3359 (2000).
[PubMed]

Witkowska, K. J.

D. Schmidl, L. Schmetterer, K. J. Witkowska, A. Unterhuber, V. Aranha dos Santos, S. Kaya, J. Nepp, C. Baar, P. Rosner, R. M. Werkmeister, and G. Garhofer, “Tear film thickness after treatment with artificial tears in patients with moderate dry eye disease,” Cornea 34(4), 421–426 (2015).
[Crossref] [PubMed]

Xu, K.

Yadav, R.

R. Kottaiyan, G. Yoon, Q. Wang, R. Yadav, J. M. Zavislan, and J. V. Aquavella, “Integrated multimodal metrology for objective and noninvasive tear evaluation,” Ocul. Surf. 10(1), 43–50 (2012).
[Crossref] [PubMed]

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

Yeu, E.

K. Gumus, C. H. Crockett, K. Rao, E. Yeu, M. P. Weikert, M. Shirayama, S. Hada, and S. C. Pflugfelder, “Noninvasive assessment of tear stability with the tear stability analysis system in tear dysfunction patients,” Invest. Ophthalmol. Vis. Sci. 52(1), 456–461 (2011).
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Yokoi, N.

N. Yokoi and A. Komuro, “Non-invasive methods of assessing the tear film,” Exp. Eye Res. 78(3), 399–407 (2004).
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Yoon, G.

R. Kottaiyan, G. Yoon, Q. Wang, R. Yadav, J. M. Zavislan, and J. V. Aquavella, “Integrated multimodal metrology for objective and noninvasive tear evaluation,” Ocul. Surf. 10(1), 43–50 (2012).
[Crossref] [PubMed]

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

Yuan, Q.

Zavislan, J. M.

R. Kottaiyan, G. Yoon, Q. Wang, R. Yadav, J. M. Zavislan, and J. V. Aquavella, “Integrated multimodal metrology for objective and noninvasive tear evaluation,” Ocul. Surf. 10(1), 43–50 (2012).
[Crossref] [PubMed]

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

Zhang, B.

Acta Ophthalmol. (1)

M. S. Norn, “Desiccation of the precorneal film. I. Corneal wetting-time,” Acta Ophthalmol. 47(4), 865–880 (1969).
[Crossref] [PubMed]

Acta Ophthalmol. (Copenh.) (3)

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Figures (9)

Fig. 1
Fig. 1 Optical setup of the ultra-high resolution SD-OCT system used for in vivo imaging of human tear film and in vitro imaging of the silicon wafer. PR: prism pair for dispersion compensation; M: mirror; L: Titanium:sapphire broad bandwidth laser; C: collimators; F: neutral density filters; P: beam splitter plate; S: two-axis galvanometric scanner; Cam: line camera; O: objectives; G: diffraction grating.
Fig. 2
Fig. 2 Schematic diagram of the simplified model of the tear film OCT signal. Due to the axial resolution value of the system, the lipid and mucous layers of the tear film cannot be resolved and the tear film is seen as a single layer bounded by the front surface of the tear film (air-tear interface) and the front surface of the cornea (tear-epithelium interface).
Fig. 3
Fig. 3 Validation of the signal model and delay estimation technique. The sample was composed of a layer of photoresist on a silicon (Si) substrate. (a) Diagram of the simplified interferometer. The optical propagation paths are represented as colored curve with corresponding delay values. (b) OCT M-scan of the sample in linear scale. Colored curves: position of the periodogram maxima associated with each propagation path. (c) One OCT A-scan of the selected from the M-scan of Fig. 3(b). Three main peaks associated with each propagation path are observed.
Fig. 4
Fig. 4 (a) Tomogram of the cornea measured in vivo by the ultrahigh resolution OCT system. (b) Close-up view on the tear film around the cornea apex, corresponding to the area delimited by the white rectangle in Fig. 4(a). Periodogram local maxima (points) and polynomial robust fitting (curve) associated with each of the tear film interfaces (blue color for air-tear interface and green color for tear-epithelium interface). The central TFT is indicated as a red vertical line segment. (c) OCT periodogram corresponding to the location indicated by the white rectangle in Fig. 4(b). The local maxima associated with each tear film interface are shown (blue points and vertical segments for air-tear interface and green points and vertical segments for tear-epithelium interface respectively). The line directly above the white asterisk symbol in Fig. 4(a) denotes an artifact originating from the internal fixation target. The axial scale bars and depth axis correspond to a distance in tear film.
Fig. 5
Fig. 5 TFT measurement with a thinner tear film approaching the system’s resolution limit. When comparing with Fig. 4, a decrease of the TFT can clearly be observed. (a) Tomogram of the cornea measured in vivo by the ultrahigh resolution OCT system. (b) Close-up view on the tear film around the cornea apex, corresponding to the area delimited by the white rectangle in Fig. 5(a). Periodogram local maxima (points) and polynomial robust fitting (curve) associated with each of the tear film interfaces (blue color for air-tear interface and green color for tear-epithelium interface). The central TFT is indicated as a red vertical line segment. (c) OCT periodogram corresponding to the location indicated by the white rectangle in Fig. 5(b). The local maxima associated with each tear film interface are shown (blue points and vertical segments for air-tear interface and green points and vertical segments for tear-epithelium interface respectively). The line directly above the white asterisk symbol in Fig. 5(a) denotes an artifact originating from the internal fixation target. The axial scale bars and depth axis correspond to a distance in tear film.
Fig. 6
Fig. 6 Histogram of measured values of the central TFT in vivo on a healthy subject. Mean central TFT: 5.122 µm. Standard deviation: 0.034 µm. Coefficient of variation: 0.65%.
Fig. 7
Fig. 7 Observation of tear film dynamics using en face TFT maps (2.5 mm x 2.5 mm). A thinning of the tear film from about 5 µm to about 2.5 µm in 15 s is observed in each measurement. (a) Slit lamp image of the front surface depicting the imaged area. (b) En face TFT maps measured directly after blink in a healthy subject. (c) Repetition of the measurement in the same condition as in (b). A similar tear film dynamics is observed in each series.
Fig. 8
Fig. 8 (a) Schematic drawing of the beam scanning geometry at the corneal front surface for the TFT measurement in the case of our nearly telecentric scanning configuration. (b) Ratio t'/t as a function of the distance to the apex h for several corneal front surface radii of curvature R. The ratio between the observed TFT t' and the true TFTt increases as the distance to apex increase.
Fig. 9
Fig. 9 Refractive index of tears [53] (blue asterisk), refractive indexn(dashed lines) and group index N g (continuous lines) of water in different conditions of salinity s and temperature T.

Equations (30)

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S out (ω)= S in (ω)|H(ω) | 2 ,
H(ω)=a(1+ r 1 exp(i τ 1 ω+ ϕ 1 )+ r 2 exp(i τ 2 ω+ ϕ 2 )) ,
|H(ω) | 2 =|a | 2 ( 1+2 r 1 cos(i τ 1 ω+ ϕ 1 )+2 r 2 cos(i τ 2 ω+ ϕ 2 ) ) .
z= v g Δτ 2 .
X[n]=Acos(θn+ ϕ 0 )+W[n] ,
V[ τ ^ ]=E[ ( τ ^ τ) 2 ]CRLB{τ}.
CRLB{τ}= c 1 (δ τ FWHM ) 2 SN R peak .
σ τ ^ c 2 δ τ FWHM SN R peak .
I(θ)=| n x [n]exp(iθn) | 2 .
θ ^ =arg max θ I(θ) .
A( τ d )=| n s [n]exp(i τ d n) | 2 ,
τ ^ d =arg max τ d A( τ d ) .
t' t = 1 cos( a ) ,
N g =1.341±0.01 .
GV D λ = λ c d 2 n d λ 2 .
E(z,t)=E(0,t τ g ) e i ϕ 0 ,
ϕ 0 = 2πc λ c ( τ g τ φ ) ,
N g ( λ c )=n( λ c ) λ c dn dλ | λ c .
H z (ω)=exp(i(ω τ g + ϕ 0 )) .
E(ω,z)=E(ω,0) H z (ω).
X[n]=Acos(θn+ ϕ 0 )+W[n] ,
CRLB{θ}= 6 N 3 SN R 1 ,
X[n]=Acos(τ ω n + ϕ 1 )+W[n] ,
τ= θ dω .
CRLB{bΠ}= b 2 CRLB{Π},
CRLB{τ}= 1 d ω 2 6 N 3 SN R 1 .
Δω=Ndω ,
δ τ FWHM 1.207 Δω .
SN R peak A k m ¯ 2 V[ Y k m ] ,
CRLB{τ}= c 1 (δ τ FWHM ) 2 SN R peak ,

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