OSA's Digital Library

Biomedical Optics Express

Biomedical Optics Express

  • Editor: Joseph A. Izatt
  • Vol. 1, Iss. 4 — Nov. 1, 2010
  • pp: 1127–1137

Non-invasive in vivo measurement of the tear film using spatial autocorrelation in a live mammal model

Kaveh Azartash, Chyong-jy Nein Shy, Kevin Flynn, James V. Jester, and Enrico Gratton  »View Author Affiliations

Biomedical Optics Express, Vol. 1, Issue 4, pp. 1127-1137 (2010)

View Full Text Article

Enhanced HTML    Acrobat PDF (1117 KB)

Browse Journals / Lookup Meetings

Browse by Journal and Year


Lookup Conference Papers

Close Browse Journals / Lookup Meetings

Article Tools



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

OCIS Codes
(170.4460) Medical optics and biotechnology : Ophthalmic optics and devices
(170.4470) Medical optics and biotechnology : Ophthalmology

ToC Category:
Ophthalmology Applications

Original Manuscript: July 19, 2010
Revised Manuscript: October 3, 2010
Manuscript Accepted: October 7, 2010
Published: October 8, 2010

Kaveh Azartash, Chyong-jy Nein Shy, Kevin Flynn, James V. Jester, and Enrico Gratton, "Non-invasive in vivo measurement of the tear film using spatial autocorrelation in a live mammal model," Biomed. Opt. Express 1, 1127-1137 (2010)

Sort:  Author  |  Year  |  Journal  |  Reset  


  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]
  2. 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.
  3. 2007 report of the International Dry Eye Workshop (DEWS),Ocul. Surf. 5(2), 1–204 (2007). [PubMed]
  4. 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]
  5. H. D. Perry, “Dry eye disease: pathophysiology, classification, and diagnosis,” Am. J. Manag. Care 14(3Suppl), S79–S87 (2008). [PubMed]
  6. 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]
  7. 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]
  8. 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).
  9. M. A. Lemp, “Advances in understanding and managing dry eye disease,” Am. J. Ophthalmol. 146(3), 350–356, e1 (2008). [CrossRef] [PubMed]
  10. M. Ozdemir and H. Temizdemir, “Age- and gender-related tear function changes in normal population,” Eye (Lond.) 24(1), 79–83 (2010). [CrossRef]
  11. 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]
  12. 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]
  13. 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]
  14. 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.
  15. 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]
  16. 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]
  17. 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]
  18. 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]
  19. 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]
  20. 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]
  21. K. Y. Li and G. Yoon, “Changes in aberrations and retinal image quality due to tear film dynamics,” Opt. Express 14(25), 12552–12559 (2006). [CrossRef] [PubMed]
  22. 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]
  23. 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]
  24. ANSI Z136, 1–2007, A.N.S.f.S.U.o. Lasers, editor (Laser Institute of America, 2007).
  25. N. O. Petersen, “Scanning fluorescence correlation spectroscopy. I. Theory and simulation of aggregation measurements,” Biophys. J. 49(4), 809–815 (1986). [CrossRef] [PubMed]
  26. 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]
  27. 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]
  28. 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]
  29. 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]
  30. M. A. Digman and E. Gratton, “Imaging barriers to diffusion by pair correlation functions,” Biophys. J. 97(2), 665–673 (2009). [CrossRef] [PubMed]
  31. N. O. Petersen, “Scanning fluorescence correlation spectroscopy. I. Theory and simulation of aggregation measurements,” Biophys. J. 49(4), 809–815 (1986). [CrossRef] [PubMed]
  32. 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]
  33. 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]
  34. 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]
  35. 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]
  36. 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]
  37. 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]
  38. 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]
  39. 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]
  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]

Cited By

Alert me when this paper is cited

OSA is able to provide readers links to articles that cite this paper by participating in CrossRef's Cited-By Linking service. CrossRef includes content from more than 3000 publishers and societies. In addition to listing OSA journal articles that cite this paper, citing articles from other participating publishers will also be listed.


Fig. 1 Fig. 2 Fig. 3
Fig. 4 Fig. 5

« Previous Article  |  Next Article »

OSA is a member of CrossRef.

CrossCheck Deposited