Abstract

Tear film stability and its interaction with the corneal surface play an important role in maintaining ocular surface integrity and quality of vision. We present a non-invasive technique to quantify the pre-corneal tear film thickness. A cMOS camera is used to record the interference pattern produced by the reflections from multiple layers of the tear film Principles of spatial autocorrelation are applied to extract the frequency of the periodic patterns in the images. A mathematical model is developed to obtain the thickness of the tear film from the spatial autocorrelation image. The technique is validated using micro-fabricated thin parylene films. We obtained repeatable and precise measurement on a live rabbit model (N = 6). We obtained an average value of 10.2µm and standard deviation of, SD = 0.3 (N = 4). We measured one rabbit infected with HSV-1 virus that had a baseline tear film thickness of 4.7µm.

© 2010 OSA

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  40. D. Dursun, D. Monroy, R. Knighton, T. Tervo, M. Vesaluoma, K. Carraway, W. Feuer, and S. C. Pflugfelder, “The effects of experimental tear film removal on corneal surface regularity and barrier function,” Ophthalmology 107(9), 1754–1760 (2000).
    [CrossRef] [PubMed]

2010 (1)

M. Ozdemir and H. Temizdemir, “Age- and gender-related tear function changes in normal population,” Eye (Lond.) 24(1), 79–83 (2010).
[CrossRef]

2009 (4)

D. H. Szczesna and H. T. Kasprzak, “Numerical analysis of interferograms for evaluation of tear film build-up time,” Ophthalmic Physiol. Opt. 29(3), 211–218 (2009).
[CrossRef] [PubMed]

E. Gielen, N. Smisdom, M. vandeVen, B. De Clercq, E. Gratton, M. Digman, J. M. Rigo, J. Hofkens, Y. Engelborghs, and M. Ameloot, “Measuring diffusion of lipid-like probes in artificial and natural membranes by raster image correlation spectroscopy (RICS): use of a commercial laser-scanning microscope with analog detection,” Langmuir 25(9), 5209–5218 (2009).
[CrossRef] [PubMed]

M. A. Digman and E. Gratton, “Analysis of diffusion and binding in cells using the RICS approach,” Microsc. Res. Tech. 72(4), 323–332 (2009).
[CrossRef] [PubMed]

M. A. Digman and E. Gratton, “Imaging barriers to diffusion by pair correlation functions,” Biophys. J. 97(2), 665–673 (2009).
[CrossRef] [PubMed]

2008 (5)

S. Kukreti, A. Cerussi, B. Tromberg, and E. Gratton, “Intrinsic near-infrared spectroscopic markers of breast tumors,” Dis. Markers 25(6), 281–290 (2008).
[PubMed]

M. Vendelin and R. Birkedal, “Anisotropic diffusion of fluorescently labeled ATP in rat cardiomyocytes determined by raster image correlation spectroscopy,” Am. J. Physiol. Cell Physiol. 295(5), C1302–C1315 (2008).
[CrossRef] [PubMed]

E. Gielen, N. Smisdom, B. De Clercq, M. vandeVen, R. Gijsbers, Z. Debyser, J.-M. Rigo, J. Hofkens, Y. Engelborghs, and M. Ameloot, “Diffusion of myelin oligodendrocyte glycoprotein in living OLN-93 cells investigated by raster-scanning image correlation spectroscopy (RICS),” J. Fluoresc. 18(5), 813–819 (2008).
[CrossRef] [PubMed]

M. A. Lemp, “Advances in understanding and managing dry eye disease,” Am. J. Ophthalmol. 146(3), 350–356, e1 (2008).
[CrossRef] [PubMed]

H. D. Perry, “Dry eye disease: pathophysiology, classification, and diagnosis,” Am. J. Manag. Care 14(3Suppl), S79–S87 (2008).
[PubMed]

2007 (3)

2007 report of the International Dry Eye Workshop (DEWS),Ocul. Surf. 5(2), 1–204 (2007).
[PubMed]

D. H. Szczesna, H. T. Kasprzak, J. Jaronski, A. Rydz, and U. Stenevi, “An interferometric method for the dynamic evaluation of the tear film,” Acta Ophthalmol. Scand. 85(2), 202–208 (2007).
[CrossRef] [PubMed]

D. L. Kolin and P. W. Wiseman, “Advances in image correlation spectroscopy: measuring number densities, aggregation states, and dynamics of fluorescently labeled macromolecules in cells,” Cell Biochem. Biophys. 49(3), 141–164 (2007).
[CrossRef] [PubMed]

2006 (1)

2005 (2)

M. A. Digman, C. M. Brown, P. Sengupta, P. W. Wiseman, A. R. Horwitz, and E. Gratton, “Measuring fast dynamics in solutions and cells with a laser scanning microscope,” Biophys. J. 89(2), 1317–1327 (2005).
[CrossRef] [PubMed]

R. Montés-Micó, J. L. Alió, and W. N. Charman, “Dynamic changes in the tear film in dry eyes,” Invest. Ophthalmol. Vis. Sci. 46(5), 1615–1619 (2005).
[CrossRef] [PubMed]

2004 (2)

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]

A. J. Bron, J. M. Tiffany, S. M. Gouveia, N. Yokoi, and L. W. Voon, “Functional aspects of the tear film lipid layer,” Exp. Eye Res. 78(3), 347–360 (2004).
[CrossRef] [PubMed]

2003 (2)

J. J. Nichols and P. E. King-Smith, “Thickness of the pre- and post-contact lens tear film measured in vivo by interferometry,” Invest. Ophthalmol. Vis. Sci. 44(1), 68–77 (2003).
[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]

2002 (3)

C. G. Begley, B. Caffery, K. Nichols, G. L. Mitchell, R. Chalmers, and DREI study group, “Results of a dry eye questionnaire from optometric practices in North America,” Adv. Exp. Med. Biol. 506(Pt B), 1009–1016 (2002).
[PubMed]

G. U. Kallarackal, E. A. Ansari, N. Amos, J. C. Martin, C. Lane, and J. P. Camilleri, “A comparative study to assess the clinical use of Fluorescein Meniscus Time (FMT) with Tear Break up Time (TBUT) and Schirmer’s tests (ST) in the diagnosis of dry eyes,” Eye (Lond.) 16(5), 594–600 (2002).
[CrossRef] [PubMed]

J. Németh, B. Erdélyi, B. Csákány, P. Gáspár, A. Soumelidis, F. Kahlesz, and Z. Lang, “High-speed videotopographic measurement of tear film build-up time,” Invest. Ophthalmol. Vis. Sci. 43(6), 1783–1790 (2002).
[PubMed]

2000 (2)

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]

D. Dursun, D. Monroy, R. Knighton, T. Tervo, M. Vesaluoma, K. Carraway, W. Feuer, and S. C. Pflugfelder, “The effects of experimental tear film removal on corneal surface regularity and barrier function,” Ophthalmology 107(9), 1754–1760 (2000).
[CrossRef] [PubMed]

1999 (2)

P. W. Wiseman and N. O. Petersen, “Image correlation spectroscopy. II. Optimization for ultrasensitive detection of preexisting platelet-derived growth factor-beta receptor oligomers on intact cells,” Biophys. J. 76(2), 963–977 (1999).
[CrossRef] [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]

1998 (1)

T. J. Licznerski, H. T. Kasprzak, and W. Kowalik, “Analysis of Shearing Interferograms of Tear Film Using Fast Fourier Transforms,” J. Biomed. Opt. 3(1), 32–37 (1998).
[CrossRef]

1996 (1)

A. Joshi, D. Maurice, and J. R. Paugh, “A new method for determining corneal epithelial barrier to fluorescein in humans,” Invest. Ophthalmol. Vis. Sci. 37(6), 1008–1016 (1996).
[PubMed]

1995 (1)

K. M. Berland, P. T. C. So, and E. Gratton, “Two-photon fluorescence correlation spectroscopy: method and application to the intracellular environment,” Biophys. J. 68(2), 694–701 (1995).
[CrossRef] [PubMed]

1993 (1)

M. Covindjee, J. Van de Ven, C. Cao, Roye, and E. Gratton, “Multifrequency cross-correlation phase fluorometry of chlorophyll a fluorescence in thylakoid and PSII-enriched membranes,” Photochem. Photobiol. 58(3), 438–445 (1993).
[CrossRef] [PubMed]

1991 (3)

A. Arduini, M. J. vande Ven, S. B. Shohet, G. Mancinelli, and E. Gratton, “Measurement and analysis of triplet-state lifetimes by multifrequency cross-correlation phase and modulation phosphorimetry,” Anal. Biochem. 195(2), 327–329 (1991).
[CrossRef] [PubMed]

R. Machorro, L. E. Regalado, and J. M. Siqueiros, “Optical properties of parylene and its use as substrate in beam splitters,” Appl. Opt. 30(19), 2778–2781 (1991).
[CrossRef] [PubMed]

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

1986 (2)

N. O. Petersen, “Scanning fluorescence correlation spectroscopy. I. Theory and simulation of aggregation measurements,” Biophys. J. 49(4), 809–815 (1986).
[CrossRef] [PubMed]

N. O. Petersen, “Scanning fluorescence correlation spectroscopy. I. Theory and simulation of aggregation measurements,” Biophys. J. 49(4), 809–815 (1986).
[CrossRef] [PubMed]

Alió, J. L.

R. Montés-Micó, J. L. Alió, and W. N. Charman, “Dynamic changes in the tear film in dry eyes,” Invest. Ophthalmol. Vis. Sci. 46(5), 1615–1619 (2005).
[CrossRef] [PubMed]

Ameloot, M.

E. Gielen, N. Smisdom, M. vandeVen, B. De Clercq, E. Gratton, M. Digman, J. M. Rigo, J. Hofkens, Y. Engelborghs, and M. Ameloot, “Measuring diffusion of lipid-like probes in artificial and natural membranes by raster image correlation spectroscopy (RICS): use of a commercial laser-scanning microscope with analog detection,” Langmuir 25(9), 5209–5218 (2009).
[CrossRef] [PubMed]

E. Gielen, N. Smisdom, B. De Clercq, M. vandeVen, R. Gijsbers, Z. Debyser, J.-M. Rigo, J. Hofkens, Y. Engelborghs, and M. Ameloot, “Diffusion of myelin oligodendrocyte glycoprotein in living OLN-93 cells investigated by raster-scanning image correlation spectroscopy (RICS),” J. Fluoresc. 18(5), 813–819 (2008).
[CrossRef] [PubMed]

Amos, N.

G. U. Kallarackal, E. A. Ansari, N. Amos, J. C. Martin, C. Lane, and J. P. Camilleri, “A comparative study to assess the clinical use of Fluorescein Meniscus Time (FMT) with Tear Break up Time (TBUT) and Schirmer’s tests (ST) in the diagnosis of dry eyes,” Eye (Lond.) 16(5), 594–600 (2002).
[CrossRef] [PubMed]

Ansari, E. A.

G. U. Kallarackal, E. A. Ansari, N. Amos, J. C. Martin, C. Lane, and J. P. Camilleri, “A comparative study to assess the clinical use of Fluorescein Meniscus Time (FMT) with Tear Break up Time (TBUT) and Schirmer’s tests (ST) in the diagnosis of dry eyes,” Eye (Lond.) 16(5), 594–600 (2002).
[CrossRef] [PubMed]

Arduini, A.

A. Arduini, M. J. vande Ven, S. B. Shohet, G. Mancinelli, and E. Gratton, “Measurement and analysis of triplet-state lifetimes by multifrequency cross-correlation phase and modulation phosphorimetry,” Anal. Biochem. 195(2), 327–329 (1991).
[CrossRef] [PubMed]

Begley, C. G.

C. G. Begley, B. Caffery, K. Nichols, G. L. Mitchell, R. Chalmers, and DREI study group, “Results of a dry eye questionnaire from optometric practices in North America,” Adv. Exp. Med. Biol. 506(Pt B), 1009–1016 (2002).
[PubMed]

Berland, K. M.

K. M. Berland, P. T. C. So, and E. Gratton, “Two-photon fluorescence correlation spectroscopy: method and application to the intracellular environment,” Biophys. J. 68(2), 694–701 (1995).
[CrossRef] [PubMed]

Birkedal, R.

M. Vendelin and R. Birkedal, “Anisotropic diffusion of fluorescently labeled ATP in rat cardiomyocytes determined by raster image correlation spectroscopy,” Am. J. Physiol. Cell Physiol. 295(5), C1302–C1315 (2008).
[CrossRef] [PubMed]

Bron, A. J.

A. J. Bron, J. M. Tiffany, S. M. Gouveia, N. Yokoi, and L. W. Voon, “Functional aspects of the tear film lipid layer,” Exp. Eye Res. 78(3), 347–360 (2004).
[CrossRef] [PubMed]

Brown, C. M.

M. A. Digman, C. M. Brown, P. Sengupta, P. W. Wiseman, A. R. Horwitz, and E. Gratton, “Measuring fast dynamics in solutions and cells with a laser scanning microscope,” Biophys. J. 89(2), 1317–1327 (2005).
[CrossRef] [PubMed]

Caffery, B.

C. G. Begley, B. Caffery, K. Nichols, G. L. Mitchell, R. Chalmers, and DREI study group, “Results of a dry eye questionnaire from optometric practices in North America,” Adv. Exp. Med. Biol. 506(Pt B), 1009–1016 (2002).
[PubMed]

Camilleri, J. P.

G. U. Kallarackal, E. A. Ansari, N. Amos, J. C. Martin, C. Lane, and J. P. Camilleri, “A comparative study to assess the clinical use of Fluorescein Meniscus Time (FMT) with Tear Break up Time (TBUT) and Schirmer’s tests (ST) in the diagnosis of dry eyes,” Eye (Lond.) 16(5), 594–600 (2002).
[CrossRef] [PubMed]

Cao, C.

M. Covindjee, J. Van de Ven, C. Cao, Roye, and E. Gratton, “Multifrequency cross-correlation phase fluorometry of chlorophyll a fluorescence in thylakoid and PSII-enriched membranes,” Photochem. Photobiol. 58(3), 438–445 (1993).
[CrossRef] [PubMed]

Carraway, K.

D. Dursun, D. Monroy, R. Knighton, T. Tervo, M. Vesaluoma, K. Carraway, W. Feuer, and S. C. Pflugfelder, “The effects of experimental tear film removal on corneal surface regularity and barrier function,” Ophthalmology 107(9), 1754–1760 (2000).
[CrossRef] [PubMed]

Cerussi, A.

S. Kukreti, A. Cerussi, B. Tromberg, and E. Gratton, “Intrinsic near-infrared spectroscopic markers of breast tumors,” Dis. Markers 25(6), 281–290 (2008).
[PubMed]

Chalmers, R.

C. G. Begley, B. Caffery, K. Nichols, G. L. Mitchell, R. Chalmers, and DREI study group, “Results of a dry eye questionnaire from optometric practices in North America,” Adv. Exp. Med. Biol. 506(Pt B), 1009–1016 (2002).
[PubMed]

Chang, W.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Charman, W. N.

R. Montés-Micó, J. L. Alió, and W. N. Charman, “Dynamic changes in the tear film in dry eyes,” Invest. Ophthalmol. Vis. Sci. 46(5), 1615–1619 (2005).
[CrossRef] [PubMed]

Covindjee, M.

M. Covindjee, J. Van de Ven, C. Cao, Roye, and E. Gratton, “Multifrequency cross-correlation phase fluorometry of chlorophyll a fluorescence in thylakoid and PSII-enriched membranes,” Photochem. Photobiol. 58(3), 438–445 (1993).
[CrossRef] [PubMed]

Csákány, B.

J. Németh, B. Erdélyi, B. Csákány, P. Gáspár, A. Soumelidis, F. Kahlesz, and Z. Lang, “High-speed videotopographic measurement of tear film build-up time,” Invest. Ophthalmol. Vis. Sci. 43(6), 1783–1790 (2002).
[PubMed]

De Clercq, B.

E. Gielen, N. Smisdom, M. vandeVen, B. De Clercq, E. Gratton, M. Digman, J. M. Rigo, J. Hofkens, Y. Engelborghs, and M. Ameloot, “Measuring diffusion of lipid-like probes in artificial and natural membranes by raster image correlation spectroscopy (RICS): use of a commercial laser-scanning microscope with analog detection,” Langmuir 25(9), 5209–5218 (2009).
[CrossRef] [PubMed]

E. Gielen, N. Smisdom, B. De Clercq, M. vandeVen, R. Gijsbers, Z. Debyser, J.-M. Rigo, J. Hofkens, Y. Engelborghs, and M. Ameloot, “Diffusion of myelin oligodendrocyte glycoprotein in living OLN-93 cells investigated by raster-scanning image correlation spectroscopy (RICS),” J. Fluoresc. 18(5), 813–819 (2008).
[CrossRef] [PubMed]

Debyser, Z.

E. Gielen, N. Smisdom, B. De Clercq, M. vandeVen, R. Gijsbers, Z. Debyser, J.-M. Rigo, J. Hofkens, Y. Engelborghs, and M. Ameloot, “Diffusion of myelin oligodendrocyte glycoprotein in living OLN-93 cells investigated by raster-scanning image correlation spectroscopy (RICS),” J. Fluoresc. 18(5), 813–819 (2008).
[CrossRef] [PubMed]

Digman, M.

E. Gielen, N. Smisdom, M. vandeVen, B. De Clercq, E. Gratton, M. Digman, J. M. Rigo, J. Hofkens, Y. Engelborghs, and M. Ameloot, “Measuring diffusion of lipid-like probes in artificial and natural membranes by raster image correlation spectroscopy (RICS): use of a commercial laser-scanning microscope with analog detection,” Langmuir 25(9), 5209–5218 (2009).
[CrossRef] [PubMed]

Digman, M. A.

M. A. Digman and E. Gratton, “Imaging barriers to diffusion by pair correlation functions,” Biophys. J. 97(2), 665–673 (2009).
[CrossRef] [PubMed]

M. A. Digman and E. Gratton, “Analysis of diffusion and binding in cells using the RICS approach,” Microsc. Res. Tech. 72(4), 323–332 (2009).
[CrossRef] [PubMed]

M. A. Digman, C. M. Brown, P. Sengupta, P. W. Wiseman, A. R. Horwitz, and E. Gratton, “Measuring fast dynamics in solutions and cells with a laser scanning microscope,” Biophys. J. 89(2), 1317–1327 (2005).
[CrossRef] [PubMed]

Dursun, D.

D. Dursun, D. Monroy, R. Knighton, T. Tervo, M. Vesaluoma, K. Carraway, W. Feuer, and S. C. Pflugfelder, “The effects of experimental tear film removal on corneal surface regularity and barrier function,” Ophthalmology 107(9), 1754–1760 (2000).
[CrossRef] [PubMed]

Engelborghs, Y.

E. Gielen, N. Smisdom, M. vandeVen, B. De Clercq, E. Gratton, M. Digman, J. M. Rigo, J. Hofkens, Y. Engelborghs, and M. Ameloot, “Measuring diffusion of lipid-like probes in artificial and natural membranes by raster image correlation spectroscopy (RICS): use of a commercial laser-scanning microscope with analog detection,” Langmuir 25(9), 5209–5218 (2009).
[CrossRef] [PubMed]

E. Gielen, N. Smisdom, B. De Clercq, M. vandeVen, R. Gijsbers, Z. Debyser, J.-M. Rigo, J. Hofkens, Y. Engelborghs, and M. Ameloot, “Diffusion of myelin oligodendrocyte glycoprotein in living OLN-93 cells investigated by raster-scanning image correlation spectroscopy (RICS),” J. Fluoresc. 18(5), 813–819 (2008).
[CrossRef] [PubMed]

Erdélyi, B.

J. Németh, B. Erdélyi, B. Csákány, P. Gáspár, A. Soumelidis, F. Kahlesz, and Z. Lang, “High-speed videotopographic measurement of tear film build-up time,” Invest. Ophthalmol. Vis. Sci. 43(6), 1783–1790 (2002).
[PubMed]

et,

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Feuer, W.

D. Dursun, D. Monroy, R. Knighton, T. Tervo, M. Vesaluoma, K. Carraway, W. Feuer, and S. C. Pflugfelder, “The effects of experimental tear film removal on corneal surface regularity and barrier function,” Ophthalmology 107(9), 1754–1760 (2000).
[CrossRef] [PubMed]

Fink, B. A.

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]

Flotte, T.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[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]

Gáspár, P.

J. Németh, B. Erdélyi, B. Csákány, P. Gáspár, A. Soumelidis, F. Kahlesz, and Z. Lang, “High-speed videotopographic measurement of tear film build-up time,” Invest. Ophthalmol. Vis. Sci. 43(6), 1783–1790 (2002).
[PubMed]

Gielen, E.

E. Gielen, N. Smisdom, M. vandeVen, B. De Clercq, E. Gratton, M. Digman, J. M. Rigo, J. Hofkens, Y. Engelborghs, and M. Ameloot, “Measuring diffusion of lipid-like probes in artificial and natural membranes by raster image correlation spectroscopy (RICS): use of a commercial laser-scanning microscope with analog detection,” Langmuir 25(9), 5209–5218 (2009).
[CrossRef] [PubMed]

E. Gielen, N. Smisdom, B. De Clercq, M. vandeVen, R. Gijsbers, Z. Debyser, J.-M. Rigo, J. Hofkens, Y. Engelborghs, and M. Ameloot, “Diffusion of myelin oligodendrocyte glycoprotein in living OLN-93 cells investigated by raster-scanning image correlation spectroscopy (RICS),” J. Fluoresc. 18(5), 813–819 (2008).
[CrossRef] [PubMed]

Gijsbers, R.

E. Gielen, N. Smisdom, B. De Clercq, M. vandeVen, R. Gijsbers, Z. Debyser, J.-M. Rigo, J. Hofkens, Y. Engelborghs, and M. Ameloot, “Diffusion of myelin oligodendrocyte glycoprotein in living OLN-93 cells investigated by raster-scanning image correlation spectroscopy (RICS),” J. Fluoresc. 18(5), 813–819 (2008).
[CrossRef] [PubMed]

Gouveia, S. M.

A. J. Bron, J. M. Tiffany, S. M. Gouveia, N. Yokoi, and L. W. Voon, “Functional aspects of the tear film lipid layer,” Exp. Eye Res. 78(3), 347–360 (2004).
[CrossRef] [PubMed]

Gratton, E.

E. Gielen, N. Smisdom, M. vandeVen, B. De Clercq, E. Gratton, M. Digman, J. M. Rigo, J. Hofkens, Y. Engelborghs, and M. Ameloot, “Measuring diffusion of lipid-like probes in artificial and natural membranes by raster image correlation spectroscopy (RICS): use of a commercial laser-scanning microscope with analog detection,” Langmuir 25(9), 5209–5218 (2009).
[CrossRef] [PubMed]

M. A. Digman and E. Gratton, “Imaging barriers to diffusion by pair correlation functions,” Biophys. J. 97(2), 665–673 (2009).
[CrossRef] [PubMed]

M. A. Digman and E. Gratton, “Analysis of diffusion and binding in cells using the RICS approach,” Microsc. Res. Tech. 72(4), 323–332 (2009).
[CrossRef] [PubMed]

S. Kukreti, A. Cerussi, B. Tromberg, and E. Gratton, “Intrinsic near-infrared spectroscopic markers of breast tumors,” Dis. Markers 25(6), 281–290 (2008).
[PubMed]

M. A. Digman, C. M. Brown, P. Sengupta, P. W. Wiseman, A. R. Horwitz, and E. Gratton, “Measuring fast dynamics in solutions and cells with a laser scanning microscope,” Biophys. J. 89(2), 1317–1327 (2005).
[CrossRef] [PubMed]

K. M. Berland, P. T. C. So, and E. Gratton, “Two-photon fluorescence correlation spectroscopy: method and application to the intracellular environment,” Biophys. J. 68(2), 694–701 (1995).
[CrossRef] [PubMed]

M. Covindjee, J. Van de Ven, C. Cao, Roye, and E. Gratton, “Multifrequency cross-correlation phase fluorometry of chlorophyll a fluorescence in thylakoid and PSII-enriched membranes,” Photochem. Photobiol. 58(3), 438–445 (1993).
[CrossRef] [PubMed]

A. Arduini, M. J. vande Ven, S. B. Shohet, G. Mancinelli, and E. Gratton, “Measurement and analysis of triplet-state lifetimes by multifrequency cross-correlation phase and modulation phosphorimetry,” Anal. Biochem. 195(2), 327–329 (1991).
[CrossRef] [PubMed]

Gregory, K.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Hee, M. R.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Hill, R. M.

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]

Hofkens, J.

E. Gielen, N. Smisdom, M. vandeVen, B. De Clercq, E. Gratton, M. Digman, J. M. Rigo, J. Hofkens, Y. Engelborghs, and M. Ameloot, “Measuring diffusion of lipid-like probes in artificial and natural membranes by raster image correlation spectroscopy (RICS): use of a commercial laser-scanning microscope with analog detection,” Langmuir 25(9), 5209–5218 (2009).
[CrossRef] [PubMed]

E. Gielen, N. Smisdom, B. De Clercq, M. vandeVen, R. Gijsbers, Z. Debyser, J.-M. Rigo, J. Hofkens, Y. Engelborghs, and M. Ameloot, “Diffusion of myelin oligodendrocyte glycoprotein in living OLN-93 cells investigated by raster-scanning image correlation spectroscopy (RICS),” J. Fluoresc. 18(5), 813–819 (2008).
[CrossRef] [PubMed]

Horwitz, A. R.

M. A. Digman, C. M. Brown, P. Sengupta, P. W. Wiseman, A. R. Horwitz, and E. Gratton, “Measuring fast dynamics in solutions and cells with a laser scanning microscope,” Biophys. J. 89(2), 1317–1327 (2005).
[CrossRef] [PubMed]

Huang, D.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Jaronski, J.

D. H. Szczesna, H. T. Kasprzak, J. Jaronski, A. Rydz, and U. Stenevi, “An interferometric method for the dynamic evaluation of the tear film,” Acta Ophthalmol. Scand. 85(2), 202–208 (2007).
[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]

Joshi, A.

A. Joshi, D. Maurice, and J. R. Paugh, “A new method for determining corneal epithelial barrier to fluorescein in humans,” Invest. Ophthalmol. Vis. Sci. 37(6), 1008–1016 (1996).
[PubMed]

Kahlesz, F.

J. Németh, B. Erdélyi, B. Csákány, P. Gáspár, A. Soumelidis, F. Kahlesz, and Z. Lang, “High-speed videotopographic measurement of tear film build-up time,” Invest. Ophthalmol. Vis. Sci. 43(6), 1783–1790 (2002).
[PubMed]

Kallarackal, G. U.

G. U. Kallarackal, E. A. Ansari, N. Amos, J. C. Martin, C. Lane, and J. P. Camilleri, “A comparative study to assess the clinical use of Fluorescein Meniscus Time (FMT) with Tear Break up Time (TBUT) and Schirmer’s tests (ST) in the diagnosis of dry eyes,” Eye (Lond.) 16(5), 594–600 (2002).
[CrossRef] [PubMed]

Kasprzak, H. T.

D. H. Szczesna and H. T. Kasprzak, “Numerical analysis of interferograms for evaluation of tear film build-up time,” Ophthalmic Physiol. Opt. 29(3), 211–218 (2009).
[CrossRef] [PubMed]

D. H. Szczesna, H. T. Kasprzak, J. Jaronski, A. Rydz, and U. Stenevi, “An interferometric method for the dynamic evaluation of the tear film,” Acta Ophthalmol. Scand. 85(2), 202–208 (2007).
[CrossRef] [PubMed]

T. J. Licznerski, H. T. Kasprzak, and W. Kowalik, “Analysis of Shearing Interferograms of Tear Film Using Fast Fourier Transforms,” J. Biomed. Opt. 3(1), 32–37 (1998).
[CrossRef]

King-Smith, P. E.

J. J. Nichols and P. E. King-Smith, “Thickness of the pre- and post-contact lens tear film measured in vivo by interferometry,” Invest. Ophthalmol. Vis. Sci. 44(1), 68–77 (2003).
[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]

Knighton, R.

D. Dursun, D. Monroy, R. Knighton, T. Tervo, M. Vesaluoma, K. Carraway, W. Feuer, and S. C. Pflugfelder, “The effects of experimental tear film removal on corneal surface regularity and barrier function,” Ophthalmology 107(9), 1754–1760 (2000).
[CrossRef] [PubMed]

Kolin, D. L.

D. L. Kolin and P. W. Wiseman, “Advances in image correlation spectroscopy: measuring number densities, aggregation states, and dynamics of fluorescently labeled macromolecules in cells,” Cell Biochem. Biophys. 49(3), 141–164 (2007).
[CrossRef] [PubMed]

Kowalik, W.

T. J. Licznerski, H. T. Kasprzak, and W. Kowalik, “Analysis of Shearing Interferograms of Tear Film Using Fast Fourier Transforms,” J. Biomed. Opt. 3(1), 32–37 (1998).
[CrossRef]

Kukreti, S.

S. Kukreti, A. Cerussi, B. Tromberg, and E. Gratton, “Intrinsic near-infrared spectroscopic markers of breast tumors,” Dis. Markers 25(6), 281–290 (2008).
[PubMed]

Lane, C.

G. U. Kallarackal, E. A. Ansari, N. Amos, J. C. Martin, C. Lane, and J. P. Camilleri, “A comparative study to assess the clinical use of Fluorescein Meniscus Time (FMT) with Tear Break up Time (TBUT) and Schirmer’s tests (ST) in the diagnosis of dry eyes,” Eye (Lond.) 16(5), 594–600 (2002).
[CrossRef] [PubMed]

Lang, Z.

J. Németh, B. Erdélyi, B. Csákány, P. Gáspár, A. Soumelidis, F. Kahlesz, and Z. Lang, “High-speed videotopographic measurement of tear film build-up time,” Invest. Ophthalmol. Vis. Sci. 43(6), 1783–1790 (2002).
[PubMed]

Lemp, M. A.

M. A. Lemp, “Advances in understanding and managing dry eye disease,” Am. J. Ophthalmol. 146(3), 350–356, e1 (2008).
[CrossRef] [PubMed]

Li, K. Y.

Licznerski, T. J.

T. J. Licznerski, H. T. Kasprzak, and W. Kowalik, “Analysis of Shearing Interferograms of Tear Film Using Fast Fourier Transforms,” J. Biomed. Opt. 3(1), 32–37 (1998).
[CrossRef]

Lin, C. P.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Machorro, R.

Mancinelli, G.

A. Arduini, M. J. vande Ven, S. B. Shohet, G. Mancinelli, and E. Gratton, “Measurement and analysis of triplet-state lifetimes by multifrequency cross-correlation phase and modulation phosphorimetry,” Anal. Biochem. 195(2), 327–329 (1991).
[CrossRef] [PubMed]

Martin, J. C.

G. U. Kallarackal, E. A. Ansari, N. Amos, J. C. Martin, C. Lane, and J. P. Camilleri, “A comparative study to assess the clinical use of Fluorescein Meniscus Time (FMT) with Tear Break up Time (TBUT) and Schirmer’s tests (ST) in the diagnosis of dry eyes,” Eye (Lond.) 16(5), 594–600 (2002).
[CrossRef] [PubMed]

Maurice, D.

A. Joshi, D. Maurice, and J. R. Paugh, “A new method for determining corneal epithelial barrier to fluorescein in humans,” Invest. Ophthalmol. Vis. Sci. 37(6), 1008–1016 (1996).
[PubMed]

Mitchell, G. L.

C. G. Begley, B. Caffery, K. Nichols, G. L. Mitchell, R. Chalmers, and DREI study group, “Results of a dry eye questionnaire from optometric practices in North America,” Adv. Exp. Med. Biol. 506(Pt B), 1009–1016 (2002).
[PubMed]

Monroy, D.

D. Dursun, D. Monroy, R. Knighton, T. Tervo, M. Vesaluoma, K. Carraway, W. Feuer, and S. C. Pflugfelder, “The effects of experimental tear film removal on corneal surface regularity and barrier function,” Ophthalmology 107(9), 1754–1760 (2000).
[CrossRef] [PubMed]

Montés-Micó, R.

R. Montés-Micó, J. L. Alió, and W. N. Charman, “Dynamic changes in the tear film in dry eyes,” Invest. Ophthalmol. Vis. Sci. 46(5), 1615–1619 (2005).
[CrossRef] [PubMed]

Murphy, P. J.

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]

Németh, J.

J. Németh, B. Erdélyi, B. Csákány, P. Gáspár, A. Soumelidis, F. Kahlesz, and Z. Lang, “High-speed videotopographic measurement of tear film build-up time,” Invest. Ophthalmol. Vis. Sci. 43(6), 1783–1790 (2002).
[PubMed]

Nichols, J. J.

J. J. Nichols and P. E. King-Smith, “Thickness of the pre- and post-contact lens tear film measured in vivo by interferometry,” Invest. Ophthalmol. Vis. Sci. 44(1), 68–77 (2003).
[CrossRef] [PubMed]

Nichols, K.

C. G. Begley, B. Caffery, K. Nichols, G. L. Mitchell, R. Chalmers, and DREI study group, “Results of a dry eye questionnaire from optometric practices in North America,” Adv. Exp. Med. Biol. 506(Pt B), 1009–1016 (2002).
[PubMed]

Nichols, K. K.

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]

Ozdemir, M.

M. Ozdemir and H. Temizdemir, “Age- and gender-related tear function changes in normal population,” Eye (Lond.) 24(1), 79–83 (2010).
[CrossRef]

Paugh, J. R.

A. Joshi, D. Maurice, and J. R. Paugh, “A new method for determining corneal epithelial barrier to fluorescein in humans,” Invest. Ophthalmol. Vis. Sci. 37(6), 1008–1016 (1996).
[PubMed]

Perry, H. D.

H. D. Perry, “Dry eye disease: pathophysiology, classification, and diagnosis,” Am. J. Manag. Care 14(3Suppl), S79–S87 (2008).
[PubMed]

Petersen, N. O.

P. W. Wiseman and N. O. Petersen, “Image correlation spectroscopy. II. Optimization for ultrasensitive detection of preexisting platelet-derived growth factor-beta receptor oligomers on intact cells,” Biophys. J. 76(2), 963–977 (1999).
[CrossRef] [PubMed]

N. O. Petersen, “Scanning fluorescence correlation spectroscopy. I. Theory and simulation of aggregation measurements,” Biophys. J. 49(4), 809–815 (1986).
[CrossRef] [PubMed]

N. O. Petersen, “Scanning fluorescence correlation spectroscopy. I. Theory and simulation of aggregation measurements,” Biophys. J. 49(4), 809–815 (1986).
[CrossRef] [PubMed]

Pflugfelder, S. C.

D. Dursun, D. Monroy, R. Knighton, T. Tervo, M. Vesaluoma, K. Carraway, W. Feuer, and S. C. Pflugfelder, “The effects of experimental tear film removal on corneal surface regularity and barrier function,” Ophthalmology 107(9), 1754–1760 (2000).
[CrossRef] [PubMed]

Puliafito, C. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Regalado, L. E.

Rigo, J. M.

E. Gielen, N. Smisdom, M. vandeVen, B. De Clercq, E. Gratton, M. Digman, J. M. Rigo, J. Hofkens, Y. Engelborghs, and M. Ameloot, “Measuring diffusion of lipid-like probes in artificial and natural membranes by raster image correlation spectroscopy (RICS): use of a commercial laser-scanning microscope with analog detection,” Langmuir 25(9), 5209–5218 (2009).
[CrossRef] [PubMed]

Rigo, J.-M.

E. Gielen, N. Smisdom, B. De Clercq, M. vandeVen, R. Gijsbers, Z. Debyser, J.-M. Rigo, J. Hofkens, Y. Engelborghs, and M. Ameloot, “Diffusion of myelin oligodendrocyte glycoprotein in living OLN-93 cells investigated by raster-scanning image correlation spectroscopy (RICS),” J. Fluoresc. 18(5), 813–819 (2008).
[CrossRef] [PubMed]

Roye,

M. Covindjee, J. Van de Ven, C. Cao, Roye, and E. Gratton, “Multifrequency cross-correlation phase fluorometry of chlorophyll a fluorescence in thylakoid and PSII-enriched membranes,” Photochem. Photobiol. 58(3), 438–445 (1993).
[CrossRef] [PubMed]

Rydz, A.

D. H. Szczesna, H. T. Kasprzak, J. Jaronski, A. Rydz, and U. Stenevi, “An interferometric method for the dynamic evaluation of the tear film,” Acta Ophthalmol. Scand. 85(2), 202–208 (2007).
[CrossRef] [PubMed]

Schuman, J. S.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Sengupta, P.

M. A. Digman, C. M. Brown, P. Sengupta, P. W. Wiseman, A. R. Horwitz, and E. Gratton, “Measuring fast dynamics in solutions and cells with a laser scanning microscope,” Biophys. J. 89(2), 1317–1327 (2005).
[CrossRef] [PubMed]

Shohet, S. B.

A. Arduini, M. J. vande Ven, S. B. Shohet, G. Mancinelli, and E. Gratton, “Measurement and analysis of triplet-state lifetimes by multifrequency cross-correlation phase and modulation phosphorimetry,” Anal. Biochem. 195(2), 327–329 (1991).
[CrossRef] [PubMed]

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).
[CrossRef] [PubMed]

Siqueiros, J. M.

Smisdom, N.

E. Gielen, N. Smisdom, M. vandeVen, B. De Clercq, E. Gratton, M. Digman, J. M. Rigo, J. Hofkens, Y. Engelborghs, and M. Ameloot, “Measuring diffusion of lipid-like probes in artificial and natural membranes by raster image correlation spectroscopy (RICS): use of a commercial laser-scanning microscope with analog detection,” Langmuir 25(9), 5209–5218 (2009).
[CrossRef] [PubMed]

E. Gielen, N. Smisdom, B. De Clercq, M. vandeVen, R. Gijsbers, Z. Debyser, J.-M. Rigo, J. Hofkens, Y. Engelborghs, and M. Ameloot, “Diffusion of myelin oligodendrocyte glycoprotein in living OLN-93 cells investigated by raster-scanning image correlation spectroscopy (RICS),” J. Fluoresc. 18(5), 813–819 (2008).
[CrossRef] [PubMed]

So, P. T. C.

K. M. Berland, P. T. C. So, and E. Gratton, “Two-photon fluorescence correlation spectroscopy: method and application to the intracellular environment,” Biophys. J. 68(2), 694–701 (1995).
[CrossRef] [PubMed]

Soumelidis, A.

J. Németh, B. Erdélyi, B. Csákány, P. Gáspár, A. Soumelidis, F. Kahlesz, and Z. Lang, “High-speed videotopographic measurement of tear film build-up time,” Invest. Ophthalmol. Vis. Sci. 43(6), 1783–1790 (2002).
[PubMed]

Stenevi, U.

D. H. Szczesna, H. T. Kasprzak, J. Jaronski, A. Rydz, and U. Stenevi, “An interferometric method for the dynamic evaluation of the tear film,” Acta Ophthalmol. Scand. 85(2), 202–208 (2007).
[CrossRef] [PubMed]

Stinson, W. G.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Swanson, E. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Szczesna, D. H.

D. H. Szczesna and H. T. Kasprzak, “Numerical analysis of interferograms for evaluation of tear film build-up time,” Ophthalmic Physiol. Opt. 29(3), 211–218 (2009).
[CrossRef] [PubMed]

D. H. Szczesna, H. T. Kasprzak, J. Jaronski, A. Rydz, and U. Stenevi, “An interferometric method for the dynamic evaluation of the tear film,” Acta Ophthalmol. Scand. 85(2), 202–208 (2007).
[CrossRef] [PubMed]

Temizdemir, H.

M. Ozdemir and H. Temizdemir, “Age- and gender-related tear function changes in normal population,” Eye (Lond.) 24(1), 79–83 (2010).
[CrossRef]

Tervo, T.

D. Dursun, D. Monroy, R. Knighton, T. Tervo, M. Vesaluoma, K. Carraway, W. Feuer, and S. C. Pflugfelder, “The effects of experimental tear film removal on corneal surface regularity and barrier function,” Ophthalmology 107(9), 1754–1760 (2000).
[CrossRef] [PubMed]

Tiffany, J. M.

A. J. Bron, J. M. Tiffany, S. M. Gouveia, N. Yokoi, and L. W. Voon, “Functional aspects of the tear film lipid layer,” Exp. Eye Res. 78(3), 347–360 (2004).
[CrossRef] [PubMed]

Tromberg, B.

S. Kukreti, A. Cerussi, B. Tromberg, and E. Gratton, “Intrinsic near-infrared spectroscopic markers of breast tumors,” Dis. Markers 25(6), 281–290 (2008).
[PubMed]

Van de Ven, J.

M. Covindjee, J. Van de Ven, C. Cao, Roye, and E. Gratton, “Multifrequency cross-correlation phase fluorometry of chlorophyll a fluorescence in thylakoid and PSII-enriched membranes,” Photochem. Photobiol. 58(3), 438–445 (1993).
[CrossRef] [PubMed]

vande Ven, M. J.

A. Arduini, M. J. vande Ven, S. B. Shohet, G. Mancinelli, and E. Gratton, “Measurement and analysis of triplet-state lifetimes by multifrequency cross-correlation phase and modulation phosphorimetry,” Anal. Biochem. 195(2), 327–329 (1991).
[CrossRef] [PubMed]

vandeVen, M.

E. Gielen, N. Smisdom, M. vandeVen, B. De Clercq, E. Gratton, M. Digman, J. M. Rigo, J. Hofkens, Y. Engelborghs, and M. Ameloot, “Measuring diffusion of lipid-like probes in artificial and natural membranes by raster image correlation spectroscopy (RICS): use of a commercial laser-scanning microscope with analog detection,” Langmuir 25(9), 5209–5218 (2009).
[CrossRef] [PubMed]

E. Gielen, N. Smisdom, B. De Clercq, M. vandeVen, R. Gijsbers, Z. Debyser, J.-M. Rigo, J. Hofkens, Y. Engelborghs, and M. Ameloot, “Diffusion of myelin oligodendrocyte glycoprotein in living OLN-93 cells investigated by raster-scanning image correlation spectroscopy (RICS),” J. Fluoresc. 18(5), 813–819 (2008).
[CrossRef] [PubMed]

Vendelin, M.

M. Vendelin and R. Birkedal, “Anisotropic diffusion of fluorescently labeled ATP in rat cardiomyocytes determined by raster image correlation spectroscopy,” Am. J. Physiol. Cell Physiol. 295(5), C1302–C1315 (2008).
[CrossRef] [PubMed]

Vesaluoma, M.

D. Dursun, D. Monroy, R. Knighton, T. Tervo, M. Vesaluoma, K. Carraway, W. Feuer, and S. C. Pflugfelder, “The effects of experimental tear film removal on corneal surface regularity and barrier function,” Ophthalmology 107(9), 1754–1760 (2000).
[CrossRef] [PubMed]

Voon, L. W.

A. J. Bron, J. M. Tiffany, S. M. Gouveia, N. Yokoi, and L. W. Voon, “Functional aspects of the tear film lipid layer,” Exp. Eye Res. 78(3), 347–360 (2004).
[CrossRef] [PubMed]

Wang, J.

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]

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]

Wiseman, P. W.

D. L. Kolin and P. W. Wiseman, “Advances in image correlation spectroscopy: measuring number densities, aggregation states, and dynamics of fluorescently labeled macromolecules in cells,” Cell Biochem. Biophys. 49(3), 141–164 (2007).
[CrossRef] [PubMed]

M. A. Digman, C. M. Brown, P. Sengupta, P. W. Wiseman, A. R. Horwitz, and E. Gratton, “Measuring fast dynamics in solutions and cells with a laser scanning microscope,” Biophys. J. 89(2), 1317–1327 (2005).
[CrossRef] [PubMed]

P. W. Wiseman and N. O. Petersen, “Image correlation spectroscopy. II. Optimization for ultrasensitive detection of preexisting platelet-derived growth factor-beta receptor oligomers on intact cells,” Biophys. J. 76(2), 963–977 (1999).
[CrossRef] [PubMed]

Yokoi, N.

A. J. Bron, J. M. Tiffany, S. M. Gouveia, N. Yokoi, and L. W. Voon, “Functional aspects of the tear film lipid layer,” Exp. Eye Res. 78(3), 347–360 (2004).
[CrossRef] [PubMed]

Yoon, G.

Acta Ophthalmol. Scand. (1)

D. H. Szczesna, H. T. Kasprzak, J. Jaronski, A. Rydz, and U. Stenevi, “An interferometric method for the dynamic evaluation of the tear film,” Acta Ophthalmol. Scand. 85(2), 202–208 (2007).
[CrossRef] [PubMed]

Adv. Exp. Med. Biol. (1)

C. G. Begley, B. Caffery, K. Nichols, G. L. Mitchell, R. Chalmers, and DREI study group, “Results of a dry eye questionnaire from optometric practices in North America,” Adv. Exp. Med. Biol. 506(Pt B), 1009–1016 (2002).
[PubMed]

Am. J. Manag. Care (1)

H. D. Perry, “Dry eye disease: pathophysiology, classification, and diagnosis,” Am. J. Manag. Care 14(3Suppl), S79–S87 (2008).
[PubMed]

Am. J. Ophthalmol. (1)

M. A. Lemp, “Advances in understanding and managing dry eye disease,” Am. J. Ophthalmol. 146(3), 350–356, e1 (2008).
[CrossRef] [PubMed]

Am. J. Physiol. Cell Physiol. (1)

M. Vendelin and R. Birkedal, “Anisotropic diffusion of fluorescently labeled ATP in rat cardiomyocytes determined by raster image correlation spectroscopy,” Am. J. Physiol. Cell Physiol. 295(5), C1302–C1315 (2008).
[CrossRef] [PubMed]

Anal. Biochem. (1)

A. Arduini, M. J. vande Ven, S. B. Shohet, G. Mancinelli, and E. Gratton, “Measurement and analysis of triplet-state lifetimes by multifrequency cross-correlation phase and modulation phosphorimetry,” Anal. Biochem. 195(2), 327–329 (1991).
[CrossRef] [PubMed]

Appl. Opt. (1)

Biophys. J. (6)

K. M. Berland, P. T. C. So, and E. Gratton, “Two-photon fluorescence correlation spectroscopy: method and application to the intracellular environment,” Biophys. J. 68(2), 694–701 (1995).
[CrossRef] [PubMed]

M. A. Digman and E. Gratton, “Imaging barriers to diffusion by pair correlation functions,” Biophys. J. 97(2), 665–673 (2009).
[CrossRef] [PubMed]

N. O. Petersen, “Scanning fluorescence correlation spectroscopy. I. Theory and simulation of aggregation measurements,” Biophys. J. 49(4), 809–815 (1986).
[CrossRef] [PubMed]

M. A. Digman, C. M. Brown, P. Sengupta, P. W. Wiseman, A. R. Horwitz, and E. Gratton, “Measuring fast dynamics in solutions and cells with a laser scanning microscope,” Biophys. J. 89(2), 1317–1327 (2005).
[CrossRef] [PubMed]

N. O. Petersen, “Scanning fluorescence correlation spectroscopy. I. Theory and simulation of aggregation measurements,” Biophys. J. 49(4), 809–815 (1986).
[CrossRef] [PubMed]

P. W. Wiseman and N. O. Petersen, “Image correlation spectroscopy. II. Optimization for ultrasensitive detection of preexisting platelet-derived growth factor-beta receptor oligomers on intact cells,” Biophys. J. 76(2), 963–977 (1999).
[CrossRef] [PubMed]

Cell Biochem. Biophys. (1)

D. L. Kolin and P. W. Wiseman, “Advances in image correlation spectroscopy: measuring number densities, aggregation states, and dynamics of fluorescently labeled macromolecules in cells,” Cell Biochem. Biophys. 49(3), 141–164 (2007).
[CrossRef] [PubMed]

Dis. Markers (1)

S. Kukreti, A. Cerussi, B. Tromberg, and E. Gratton, “Intrinsic near-infrared spectroscopic markers of breast tumors,” Dis. Markers 25(6), 281–290 (2008).
[PubMed]

Exp. Eye Res. (1)

A. J. Bron, J. M. Tiffany, S. M. Gouveia, N. Yokoi, and L. W. Voon, “Functional aspects of the tear film lipid layer,” Exp. Eye Res. 78(3), 347–360 (2004).
[CrossRef] [PubMed]

Eye (Lond.) (2)

M. Ozdemir and H. Temizdemir, “Age- and gender-related tear function changes in normal population,” Eye (Lond.) 24(1), 79–83 (2010).
[CrossRef]

G. U. Kallarackal, E. A. Ansari, N. Amos, J. C. Martin, C. Lane, and J. P. Camilleri, “A comparative study to assess the clinical use of Fluorescein Meniscus Time (FMT) with Tear Break up Time (TBUT) and Schirmer’s tests (ST) in the diagnosis of dry eyes,” Eye (Lond.) 16(5), 594–600 (2002).
[CrossRef] [PubMed]

Invest. Ophthalmol. Vis. Sci. (6)

J. Németh, B. Erdélyi, B. Csákány, P. Gáspár, A. Soumelidis, F. Kahlesz, and Z. Lang, “High-speed videotopographic measurement of tear film build-up time,” Invest. Ophthalmol. Vis. Sci. 43(6), 1783–1790 (2002).
[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]

J. J. Nichols and P. E. King-Smith, “Thickness of the pre- and post-contact lens tear film measured in vivo by interferometry,” Invest. Ophthalmol. Vis. Sci. 44(1), 68–77 (2003).
[CrossRef] [PubMed]

A. Joshi, D. Maurice, and J. R. Paugh, “A new method for determining corneal epithelial barrier to fluorescein in humans,” Invest. Ophthalmol. Vis. Sci. 37(6), 1008–1016 (1996).
[PubMed]

R. Montés-Micó, J. L. Alió, and W. N. Charman, “Dynamic changes in the tear film in dry eyes,” Invest. Ophthalmol. Vis. Sci. 46(5), 1615–1619 (2005).
[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]

J. Biomed. Opt. (1)

T. J. Licznerski, H. T. Kasprzak, and W. Kowalik, “Analysis of Shearing Interferograms of Tear Film Using Fast Fourier Transforms,” J. Biomed. Opt. 3(1), 32–37 (1998).
[CrossRef]

J. Fluoresc. (1)

E. Gielen, N. Smisdom, B. De Clercq, M. vandeVen, R. Gijsbers, Z. Debyser, J.-M. Rigo, J. Hofkens, Y. Engelborghs, and M. Ameloot, “Diffusion of myelin oligodendrocyte glycoprotein in living OLN-93 cells investigated by raster-scanning image correlation spectroscopy (RICS),” J. Fluoresc. 18(5), 813–819 (2008).
[CrossRef] [PubMed]

Langmuir (1)

E. Gielen, N. Smisdom, M. vandeVen, B. De Clercq, E. Gratton, M. Digman, J. M. Rigo, J. Hofkens, Y. Engelborghs, and M. Ameloot, “Measuring diffusion of lipid-like probes in artificial and natural membranes by raster image correlation spectroscopy (RICS): use of a commercial laser-scanning microscope with analog detection,” Langmuir 25(9), 5209–5218 (2009).
[CrossRef] [PubMed]

Microsc. Res. Tech. (1)

M. A. Digman and E. Gratton, “Analysis of diffusion and binding in cells using the RICS approach,” Microsc. Res. Tech. 72(4), 323–332 (2009).
[CrossRef] [PubMed]

Ocul. Surf. (1)

2007 report of the International Dry Eye Workshop (DEWS),Ocul. Surf. 5(2), 1–204 (2007).
[PubMed]

Ophthalmic Physiol. Opt. (1)

D. H. Szczesna and H. T. Kasprzak, “Numerical analysis of interferograms for evaluation of tear film build-up time,” Ophthalmic Physiol. Opt. 29(3), 211–218 (2009).
[CrossRef] [PubMed]

Ophthalmology (1)

D. Dursun, D. Monroy, R. Knighton, T. Tervo, M. Vesaluoma, K. Carraway, W. Feuer, and S. C. Pflugfelder, “The effects of experimental tear film removal on corneal surface regularity and barrier function,” Ophthalmology 107(9), 1754–1760 (2000).
[CrossRef] [PubMed]

Opt. Express (1)

Optom. Vis. Sci. (1)

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]

Photochem. Photobiol. (1)

M. Covindjee, J. Van de Ven, C. Cao, Roye, and E. Gratton, “Multifrequency cross-correlation phase fluorometry of chlorophyll a fluorescence in thylakoid and PSII-enriched membranes,” Photochem. Photobiol. 58(3), 438–445 (1993).
[CrossRef] [PubMed]

Prog. Retin. Eye Res. (1)

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]

Science (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

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ANSI Z136, 1–2007, A.N.S.f.S.U.o. Lasers, editor (Laser Institute of America, 2007).

M. A. Lemp, chairman, Report of the National Eye Institute/Industry Workshop on Clinical Trials in Dry Eyes, CLAO J. 21(4), 221–232(1995).

V. J. Forrester, A. D. Dick, P. G. McMenamin, and W. R. Lee, The Eye: Basic Science in Practice (W.B. Saunders, London, 2002), pp. 447.

P. E. King-Smith, B. A. Fink, R. M. Hill, K. W. Koelling, and J. M. Tiffany, “The thickness of the tear film,” in Current Eye Research (Informa Healthcare: London, 2004), pp. 357–368.

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Figures (5)

Fig. 1
Fig. 1

The schematic of the FASIC setup is shown here. A 635nm low power (<1mw) laser is illuminated onto the cornea in order to measure the pre-corneal tear film thickness. The reflecting and scattering light is captured by a cMOS camera that is positioned in an angle with respect to the incoming light. A stack of 256X256 pixel images are streamed to a computer through a firewire cable for further analysis.

Fig. 2
Fig. 2

(a): Raw camera Image. This image displays the raw camera image from a rabbit’s eye. This image displays the circular interference pattern caused by tear film layers along with other features such as: small and large dots with different orientations. This image is one of 1000 time-integrated frames that are captured by the cMOS camera to analyze the spatial fluctuations. (b): SCI.This image displays the calculated spatial correlation image (SCI) on a single frame. The SCI has a central peak and a sinusoidal background. The sinusoidal residues that are located around the peak of the SCI are later used to obtain the quantitative tear film thickness information. (c). Vertical and horizontal projection of the SCI. This image is displaying the SCI in terms of number of pixels vs. the correlation value. This image contains the Gaussian terms along with the residues for both vertical and horizontal axis of two-dimensional image. The width of the pixels is illustrated on the x-axis while the correlation value (e.g., number of dots/average intensity of image) is on the y-axis. (d): Preliminary Gaussian fits in SCI. The SCI undergoes a preliminary fit to remove the primary Gaussian components. (e): Vertical and Horizontal Fitting. After removal of the Gaussian components, the sinusoidal residues are fitted both vertically and horizontally for all the frames. This process provides the period of the interference pattern due to the tear film. After the period of the interference is obtained, it gets calibrated based on the magnification and true pixel size and is later used to obtain the true thickness value of the tear film.

Fig. 3
Fig. 3

Thickness values of the pre-corneal tear films of four rabbits is shown here. Rabbits were measured at different days and each rabbit has undergone 3 consecutive measurements with 30 seconds interval at the day of the measurement. Thinning out phenomena is clearly observed in all animals. Three healthy rabbits have normal tear film thickness of 10.1μm on average. The one rabbit with ocular herpes had a tear film thickness of 4.7µm and 4.3µm and 4.1µm in the three measurements, respectively.

Fig. 4
Fig. 4

Real time analysis of tear film dynamics in response to instillation of Refresh Tears ® (Allergan, Irvine,CA). The camera acquired images at 300 frames/s. Changes of the thickness of tear film over approximately 7 seconds are displayed here. The experiment starts out with a dried eye. A few seconds into the data acquisition, a drop of Refresh Tear Plus® is instilled into the rabbit eye. The thickness of the tear film increases approximately 10 fold. After another two seconds (when the bulk of the drop is out of the imaging plane), the tear film starts finding a stability in thickness. At this point, the thickness stays at approximately 18µm, and holds this thickness throughout the data acquisition.

Fig. 5
Fig. 5

In this figure, the retention time of Refresh Tears® (Allergan, Irvine,CA) was analyzed using a live rabbit model. The baseline showed a value of 9.6 µm. After the eye drop was instilled onto the eye, the tear film thickness increased and had a value of 17.4 µm We obtained a peak value of 17.4μm in the first measurement (time = 0). 10 minutes into the measurement, the thickness maintained values of above 16μm. Sixteen minutes after the instillation of the eye drop, we started observing a more aggressive decline in the value of the tear film thickness as the tear film thickness decreased to 14.7µm. From the 10th measurement through the 15th measurement, the pre-corneal tear film thickness undergoes a more steady decrease as it goes from 13.8μm to 11.5μm. At measurement 16; 32 minutes after the instillation of the drop the tear film thickness the sharpest decline the tear film thickness was observed as the value came back to 9.8μm. In the last two measurements, the thickness was similar to the baseline value of 9.6μm. We estimated the retention time to be about 36 minutes.

Equations (7)

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G s ( ξ , ψ ) = I ( x , y ) I ( x + ξ , y + ψ ) x , y I ( x , y ) x , y 2 1
H = B + G 1 x e ( x c ) 2 2 σ 1 x 2 + G 2 x e ( x c ) 2 2 σ 2 x 2
V = B + G 1 y e ( y c ) 2 2 σ 1 y 2 + G 2 y e ( y c ) 2 2 σ 2 y 2
I = A ( 1 cos ( k x x ) cos ( k y y ) )
k x = ( 1 / P ) cos ( ϕ )
k y = ( 1 / P ) sin ( ϕ )
t = K n P sin ( θ )

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