Free
Clinical Trials  |   August 2013
Measurement of Tear Film Thickness Using Ultrahigh-Resolution Optical Coherence Tomography
Author Affiliations & Notes
  • René M. Werkmeister
    Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
  • Aneesh Alex
    Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
  • Semira Kaya
    Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
  • Angelika Unterhuber
    Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
  • Bernd Hofer
    Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
  • Jasmin Riedl
    Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
  • Michael Bronhagl
    Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
  • Martin Vietauer
    Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
  • Doreen Schmidl
    Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
  • Tilman Schmoll
    Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
  • Gerhard Garhöfer
    Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
  • Wolfgang Drexler
    Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
  • Rainer A. Leitgeb
    Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
  • Martin Groeschl
    Institute of Applied Physics, Vienna University of Technology, Vienna, Austria
  • Leopold Schmetterer
    Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
    Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
  • Correspondence: Leopold Schmetterer, Center for Medical Physics and Biomedical Engineering, Währinger Gürtel 18-20, A-1090 Vienna, Austria; leopold.schmetterer@meduniwien.ac.at
Investigative Ophthalmology & Visual Science August 2013, Vol.54, 5578-5583. doi:10.1167/iovs.13-11920
  • Views
  • PDF
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      René M. Werkmeister, Aneesh Alex, Semira Kaya, Angelika Unterhuber, Bernd Hofer, Jasmin Riedl, Michael Bronhagl, Martin Vietauer, Doreen Schmidl, Tilman Schmoll, Gerhard Garhöfer, Wolfgang Drexler, Rainer A. Leitgeb, Martin Groeschl, Leopold Schmetterer; Measurement of Tear Film Thickness Using Ultrahigh-Resolution Optical Coherence Tomography. Invest. Ophthalmol. Vis. Sci. 2013;54(8):5578-5583. doi: 10.1167/iovs.13-11920.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose.: To visualize the precorneal tear film with ultrahigh-resolution spectral domain optical coherence tomography, enabling quantification of tear film thickness in healthy subjects.

Methods.: A custom-built spectral domain optical coherence tomography system comprising a broadband titanium:sapphire laser operating at 800 nm and a high-speed charge coupled device (CCD) camera with a read-out rate of 47 kHz was used for measurement of precorneal tear film thickness. The system provides a theoretical axial resolution of 1.2 μm in tissue. The signal-to-noise ratio close to the zero delay was measured with 94 dB. A total of 26 healthy subjects were included in this study. Measurement was started immediately after blinking and averaged over a period of 1 second. In a subset of eight healthy subjects, the reproducibility of the approach was studied by measuring the tear film thickness every 10 minutes over 1 hour.

Results.: The average central tear film thickness of the measured population was 4.79 ± 0.88 μm. Reproducibility was very high, with an intraclass correlation coefficient of 0.97. A breakup of the tear film was observed in one subject after 14 seconds.

Conclusions.: Our data indicate that the human precorneal tear film can be measured with excellent reproducibility using ultrahigh-resolution optical coherence tomography. This technique may be a valuable tool in the management of dry eye syndrome. (ClinicalTrials.gov number, NCT01746602.)

Introduction
Dry eye syndrome (DES) is a highly prevalent disease affecting the ocular surface with potentially sight-threatening potential. 1 A major challenge in DES is that the association between the symptoms of the disease and the signs that can be objectively measured are weak. 2 One of the most widely used techniques is the measurement of breakup time (BUT), which is employed in clinical routine as well as in clinical trials. However, this technique provides poor reproducibility and significant intra- and interobserver variability. 
Traditional methods used for estimation of tear film thickness have an invasive character and include the application of absorbent paper to the cornea, 3 the placement of glass fibers against the cornea, 4 and the measurement of fluorescence after instilling fluorescein. 5 Studies using these methods have reported tear film thickness values between 4 μm and 8.5 μm. 3,5 Later, noninvasive approaches such as confocal microscopy and interferometry have been used to quantify the tear film thickness and have shown a large variation of results ranging from 3 μm to 46 μm. 67  
Optical coherence tomography (OCT) is a noninvasive in vivo imaging modality capable of generating images of biological tissues with high axial and transverse resolutions. To date, OCT has made its most significant impact in the field of ophthalmology. It has been successfully employed for obtaining high-resolution images of both anterior 810 and posterior segments 1113 of the human eye. In tissues such as skin, 14 OCT is mainly limited by strong scattering and absorption of incident light. By performing OCT imaging at 1300 nm, indirect measurement of tear film thickness has yielded values of 3.4 ± 2.6 μm. 1517 With the advances in broadband light sources, direct visualization of the normal tear film became possible and some effort was directed towards the measurement of tear film thickness by means of OCT. 9,16,1821  
In this paper, we report on measurement of tear film thickness using a custom-built ultrahigh-resolution OCT system, where central tear film thickness is determined in a fully automated way, and provide data on reproducibility. 
Materials and Methods
Subjects
The study protocol was approved by the Ethics Committee of the Medical University of Vienna and was carried out in accordance with the tenets of the Declaration of Helsinki. A total of 26 healthy female and male subjects aged between 19 and 35 years participated in this study. The nature of the study was explained to all subjects, and they gave written consent to participate. Each subject passed an ophthalmic screening examination including slit-lamp biomicroscopy, indirect funduscopy, and applanation tonometry. Inclusion criteria were normal ophthalmic findings and IOP <20 mm Hg. 
Spectral Domain (SD)-OCT System
The cornea was imaged by a spectrometer-based ultrahigh-resolution SD-OCT system operating at 800 nm. As light source, a broadband titanium:sapphire laser (Integral OCT; Femtolasers Produktions GmbH, Vienna, Austria) was used. The spectrum of the laser was centered at 800 nm with a full width at half maximum (FWHM) bandwidth of 170 nm, resulting in a theoretical axial resolution of 1.2 μm in the cornea. A fiber-optical coupler with an asymmetric splitting ratio of 90:10 was used to divide the light coming from the source into the sample and reference arm. The free-space pathway of the reference arm contained a variable neutral density (ND) filter and a dispersion compensator (LSM04DC; Thorlabs GmbH, Dachau/Munich, Germany) for balancing dispersion due to optic components in the sample arm. In the sample arm, light was collimated by means of a fiber collimator (f = 12 mm; Schäfter+Kirchhoff GmbH, Hamburg, Germany), passed two galvanometric mirrors (GVS002; Thorlabs GmbH) for scanning in two dimensions, and was focused onto the sample by an OCT scan lens (LSM04-BB; Thorlabs GmbH). The power of the incident light focused onto the cornea was lowered to 800 μW, which is 10 times below the maximum permissible exposure as specified by the American National Standards Institute (ANSI), 22 to ensure the safety of the eye. The light-delivery system of the sample arm was mounted on a modified slit-lamp headrest. The interference spectrum returning from the interferometer was directed onto a 50 × 50-mm transmission grating with L = 1200 lines per mm (1200 lpmm; Wasatch Photonics, Logan, UT) using a collimator with a focal length f = 100 mm (OZ Optics, Ottawa, Canada). The dispersed light emerging from the transmissive grating was imaged onto a high-speed CCD camera (e2v EM4CL 2014; Aviva, Essex, UK) by means of an objective with a focal length f = 85 mm (ZEISS PLANAR T 1,4/85 ZF-IR-I; Carl Zeiss AG, Oberkochen, Germany). The system was operated at an acquisition rate of 24.000 A-scans/s. Each OCT B-scan comprised 1024 pixels in depth and 512 or 1024 A-lines, respectively. The transverse resolution of the employed OCT system was 21 μm at the front surface of the cornea. 
Experimental Paradigm
In all subjects, the right eye was chosen for OCT imaging of the cornea and tear film. Tomograms were recorded at the center of the cornea directly above and out of the central specular reflex of the probe beam at the corneal apex (Fig. 1). The correct alignment of the probe beam onto the desired measurement location was controlled by means of a CCD video camera. The subjects were asked to look straight forward onto an internal fixation target and to avoid blinking during the recording period, but to blink normally during the alignment procedure. After a short resting period, subjects were asked to blink, and imaging started immediately after opening of the eyes. For measurements of central tear film thickness, 20 tomograms, each comprising 1024 A-lines, at the corneal apex, were recorded. This led to a measurement time of approximately 1 second. In a subgroup of eight participants, imaging of the tear film was repeated every 10 minutes over a period of 1 hour to assess reproducibility of our approach. Furthermore, in one subject, tear film thickness was recorded over 16 seconds to examine the change in thickness over time. To do so, 16 three-dimensional (3-D) volumes with a size of 4 mm × 4 mm × 1 mm (horizontal × vertical × depth), each containing 512 × 128 × 1024 pixels were acquired within 16 seconds. For measurement of central tear film thickness, in each volume, the 10 frames above the central reflex were postprocessed and gave the thickness value for a certain point in time. 
Figure 1. 
 
Sample measurement of human precorneal tear film using ultrahigh-resolution OCT. TF, tear film; EP, corneal epithelium; BL, Bowman's layer; ST, corneal stroma; DM, Descemet's membrane; ED, corneal endothelium.
Figure 1. 
 
Sample measurement of human precorneal tear film using ultrahigh-resolution OCT. TF, tear film; EP, corneal epithelium; BL, Bowman's layer; ST, corneal stroma; DM, Descemet's membrane; ED, corneal endothelium.
Data Processing and Analysis
Before segmentation of the layers at the anterior eye, the stack of 20 images was preprocessed using the freeware software ImageJ (National Institutes of Health, Bethesda, MD; available in the public domain at http://rsbweb.nih.gov/ij/). This procedure comprised the adjustment of brightness and contrast, application of a median filter for smoothing of the edges, and registration of the images by vertical and horizontal translation. 23 Thereafter, the image stack was loaded into software written in National Instruments LabView 2011 (Austin, TX) for automatic segmentation of precorneal and corneal layers. First, the front surface of the tear film (i.e., the highly reflective surface at the air-sample interface) was detected by means of the Dijkstra algorithm 24 (see Fig. 2a). Thereafter, the curvature of the tear film layer was used to flatten the corneal structures (see Fig. 2b).For each A-scan (i.e., each vertical line within the image), the intensity profile was plotted, and tear film thickness was defined as the distance between the strongest peak arising from the interface air–tear (blue arrow in Fig. 2c) and the peak caused by scattering and reflection of the incident probe beam at the interface tear–epithelium. Finally, the average tear film thickness was calculated as the mean value over the entire central cornea. All axial distance values for the tear film obtained with OCT were divided by the average group refractive index for the tear film of 1.339 in order to obtain geometrical distances (value was interpolated from the values given for 400 nm, 25 588 nm, 26 700 nm, 25 and 1300 nm 27 ). 
Figure 2. 
 
Detection scheme for tear film thickness. (a) Line-wise contrast enhancement and automatic detection of air–tear film interface by means of Dijkstra algorithm. (b) Flattening of the tear film. (c) Definition of the tear film in the linearized image. (d) Intensity profile of an A-scan and definition of the tear film thickness as the distance between tear film front surface (blue arrow) and cornea front surface (green arrow). The additional sharp peak arises from the linearization of the tear film using the Dijkstra algorithm.
Figure 2. 
 
Detection scheme for tear film thickness. (a) Line-wise contrast enhancement and automatic detection of air–tear film interface by means of Dijkstra algorithm. (b) Flattening of the tear film. (c) Definition of the tear film in the linearized image. (d) Intensity profile of an A-scan and definition of the tear film thickness as the distance between tear film front surface (blue arrow) and cornea front surface (green arrow). The additional sharp peak arises from the linearization of the tear film using the Dijkstra algorithm.
In all subjects, the tear film was evaluated as the time mean over the 1-second measurement period. If, in an OCT image, the automatic segmentation algorithm was not capable of identifying the tear film–cornea interface, the image was excluded from further analysis. 
To quantify reliability of measurements, intraclass correlation coefficients (κ) were calculated. 28 The calculation of κ is based on a repeated-measure ANOVA model using the variance among subjects (vS ), the variance among measurements (vM ), and the residual error variance (ve ) and is given by  The higher the intraclass correlation coefficient is, the better the reproducibility of the method. A κ of 1 reflects perfect reproducibility. In addition, the coefficients of variation (CVs) were calculated. For this purpose, the standard deviation (SD) was calculated for each subject individually. By dividing the SD by the individual mean of tear film thickness, a CV was calculated. As a measure of reproducibility, the mean and SD of these individual CVs are presented.  
Results
In Figure 1, an exemplary ultrahigh-resolution OCT image of the human cornea is depicted. Precorneal tear film—the topmost highly reflective layer—and all corneal layers (i.e., corneal epithelium, Bowman's layer, corneal stroma, Descemet's membrane, and corneal endothelium) can be distinguished. Central tear film thickness data as obtained in 26 healthy subjects are presented in Figure 3. The SD over the 1 second of measurement time was typically 1 μm. In one subject (subject number 16), only one image fulfilled the quality criteria, and as such no SD could be calculated. The average tear film thickness in all participating subjects was 4.79 ± 0.88 μm. The range was relatively narrow with values between 3.8 and 6.8 μm. 
Figure 3. 
 
Precorneal tear film thickness as obtained in 26 healthy subjects. The mean ± SD is shown.
Figure 3. 
 
Precorneal tear film thickness as obtained in 26 healthy subjects. The mean ± SD is shown.
The CV over the seven measurements within 1 hour was 3.8% ± 3.2% in the eight subjects that participated in the reproducibility studies. The maximum CV that was seen in a subject was 10.6%. The intraclass correlation coefficient was 0.97. 
The time course of precorneal tear film thickness in a healthy subject over 16 seconds is presented in Figure 4. A significant decrease in tear film thickness of approximately 3 μm was observed over the observation period. Furthermore, in this subject, a breakup of the tear film at the periphery of the cornea could be observed after 14 seconds. An exemplary image showing this breakup is depicted in Figure 5. As can be seen, the tear film thickness gradually decreases from the left-hand side of the apex to almost zero and then increases again towards the periphery. 
Figure 4. 
 
Time course of precorneal tear film thickness in a healthy subject, over 16 seconds. A significant decrease in tear film thickness is observed.
Figure 4. 
 
Time course of precorneal tear film thickness in a healthy subject, over 16 seconds. A significant decrease in tear film thickness is observed.
Figure 5. 
 
Tear film breakup as observed in one subject after 14 seconds. The green ellipse indicates the location of the tear film breakup.
Figure 5. 
 
Tear film breakup as observed in one subject after 14 seconds. The green ellipse indicates the location of the tear film breakup.
Discussion
The present study indicates that the precorneal tear film can be quantified in a reproducible way using ultrahigh-resolution OCT based on titanium:sapphire laser. The average thickness of the tear film was found to be 4.79 μm, which is in the same range as the values observed during previous OCT studies. 9,16 This is very similar to the thickness values (4.7 ± 1.6 μm) for one subject, obtained with an ultrahigh resolution OCT system using a supercontinuum source centered at 812.5 nm with an FWHM bandwidth of 375 nm and comprising a spectrometer based on Czerny–Turner configuration. 19,20  
In the present study, the used scanning pattern yielded tear film thickness values of a location close to the apex of the cornea. When thickness measurements were performed over a longer time, a decrease in central tear film thickness could be observed (Fig. 4). The measured decrease of 3 μm is in accordance with values detected by an interferometric method. 29,30 This decrease in tear film thickness is most likely related to tangential flow. 30 Contrary to a dry eye, where evaporation contributes by a larger extent to thinning of the tear film, in the case of a healthy subject with a normal lipid layer, this effect is negligible when considering an evaporation rate 31 of 13.57 · 10−7g · cm−2 · s−1 (resulting in a thinning rate of 135.7 nm · s−1), which is well below the resolution of the present OCT system. The evaporation rate, however, changes dramatically when the lipid layer is ruptured, which results in a fast breakup of the tear film only a few seconds after blinking. 
The approach of recording 3-D volumes over the entire cornea enables examination of tear film thickness at different locations and, thus, might allow for both detection of the tear film breakup in patients with DES and the recording of tear film thickness maps as well. Operating the system at higher acquisition speeds and recording several corneal volume data sets enable the generation of tear film thickness maps and the study of tear film dynamics within the time period between two blinks. 
Recent studies suggest that measurement of tear film thickness using OCT may be used to quantify treatment success in DES. Employing a superluminescent diode with a center wavelength of 840 nm and an FWHM bandwidth of 100 nm, Wang and coworkers achieved a resolution of approximately 3 μm and were able to show that the cyclosporine treatment increased upper and lower tear meniscus volume. 32 As such, the International Workshop on Meibomian Gland Dysfunction listed OCT as one of the promising technologies to quantify signs of DES. 33,34  
In conclusion, we presented a promising approach using ultrahigh-resolution OCT for imaging the precorneal tear film and made use of a fully automated algorithm for evaluating the tear film thickness. Furthermore, we were able to image breakup of the tear film in a healthy subject. This technique may have considerable potential in following patients with DES. 
Acknowledgments
Supported by the Christian Doppler Laboratory for Laser Development and their Application in Medicine. 
Disclosure: R.M. Werkmeister, None; A. Alex, None; S. Kaya, None; A. Unterhuber, None; B. Hofer, None; J. Riedl, None; M. Bronhagl, None; M. Vietauer, None; D. Schmidl, None; T. Schmoll, None; G. Garhöfer, None; W. Drexler, None; R.A. Leitgeb, None; M. Groeschl, None; L. Schmetterer, None 
References
Epidemiology Subcommittee of the International Dry Eye WorkShop. The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye WorkShop. Ocul Surf . 2007; 5: 93–107. [CrossRef] [PubMed]
Diagnostic Methodology Subcommittee of the International Dry Eye WorkShop. Methodologies to diagnose and monitor dry eye disease: report of the Diagnostic Methodology Subcommittee of the International Dry Eye WorkShop. Ocul Surf . 2007; 5: 108–152. [CrossRef] [PubMed]
Ehlers N. The thickness of the precorneal film. Acta Ophthalmol . 1965; 43: 92–100.
Mishima S. Some physiological aspects of the precorneal tear film. Arch Ophthalmol . 1965; 73: 233–241. [CrossRef] [PubMed]
Benedetto DA Shah DO Kaufman HE. The instilled fluid dynamics and surface chemistry of polymers in the preocular tear film. Invest Ophthalmol . 1975; 14: 887–902. [PubMed]
Fogt N King-Smith PE Tuell G. Interferometric measurement of tear film thickness by use of spectral oscillations. J Opt Soc Am A Opt Image Sci Vis . 1998; 15: 268–275. [CrossRef] [PubMed]
Prydal JI Artal P Woon H Campbell FW. Study of human precorneal tear film thickness and structure using laser interferometry. Invest Ophthalmol Vis Sci . 1992; 33: 2006–2011. [PubMed]
Muscat S McKay N Parks S Kemp E Keating D. Repeatability and reproducibility of corneal thickness measurements by optical coherence tomography. Invest Ophthalmol Vis Sci . 2002; 43: 1791–1795. [PubMed]
Schmoll T Unterhuber A Kolbitsch C Le T Stingl A Leitgeb R. Precise thickness measurements of Bowman's layer, epithelium, and tear film. Optom Vis Sci . 2012; 89: E795–E802. [CrossRef] [PubMed]
Christopoulos V Kagemann L Wollstein G In vivo corneal high-speed, ultra high-resolution optical coherence tomography. Arch Ophthalmol . 2007; 125: 1027–1035. [CrossRef] [PubMed]
Leitgeb R Drexler W Unterhuber A Ultrahigh resolution Fourier domain optical coherence tomography. Opt Express . 2004; 12: 2156–2165. [CrossRef] [PubMed]
Torzicky T Pircher M Zotter S Bonesi M Gotzinger E Hitzenberger CK. Automated measurement of choroidal thickness in the human eye by polarization sensitive optical coherence tomography. Opt Express . 2012; 20: 7564–7574. [CrossRef] [PubMed]
Nassif N Cense B Park B In vivo high-resolution video-rate spectral-domain optical coherence tomography of the human retina and optic nerve. Opt Express . 2004; 12: 367–376. [CrossRef] [PubMed]
Alex A Povazay B Hofer B Multispectral in vivo three-dimensional optical coherence tomography of human skin. J Biomed Opt . 2010; 15:026025.
Wang J Fonn D Simpson TL Jones L. Precorneal and pre- and postlens tear film thickness measured indirectly with optical coherence tomography. Invest Ophthalmol Vis Sci . 2003; 44: 2524–2528. [CrossRef] [PubMed]
Wang J Aquavella J Palakuru J Chung S Feng C. Relationships between central tear film thickness and tear menisci of the upper and lower eyelids. Invest Ophthalmol Vis Sci . 2006; 47: 4349–4355. [CrossRef] [PubMed]
Chen Q Wang J Tao A Shen M Jiao S Lu F. Ultrahigh-resolution measurement by optical coherence tomography of dynamic tear film changes on contact lenses. Invest Ophthalmol Vis Sci . 2010; 51: 1988–1993. [CrossRef] [PubMed]
Palakuru JR Wang J Aquavella JV. Effect of blinking on tear volume after instillation of midviscosity artificial tears. Am J Ophthalmol . 2008; 146: 920–924. [CrossRef] [PubMed]
Yadav R Lee KS Rolland JP Zavislan JM Aquavella JV Yoon G. Micrometer axial resolution OCT for corneal imaging. Biomed Opt Express . 2011; 2: 3037–3046. [CrossRef] [PubMed]
Kottaiyan R Yoon G Wang Q Yadav R Zavislan JM Aquavella JV. Integrated multimodal metrology for objective and noninvasive tear evaluation. Ocul Surf . 2012; 10: 43–50. [CrossRef] [PubMed]
Qiu X Gong L Lu Y Jin H Robitaille M. The diagnostic significance of Fourier-domain optical coherence tomography in Sjögren syndrome, aqueous tear deficiency and lipid tear deficiency patients. Acta Ophthalmol . 2012; 90: e359–e366. [CrossRef] [PubMed]
American National Standards Institute. American National Standard for Safe Use of Lasers . Orlando, FL: The Laser Institute of America; 2000; ANSI Z136.1-2000.
Thevenaz P Ruttimann UE Unser M. A pyramid approach to subpixel registration based on intensity. IEEE Trans Image Process . 1998; 7: 27–41. [CrossRef] [PubMed]
Dijkstra EW. A note on two problems in connexion with graphs. Numerische Mathematik . 1959; 1: 269–271. [CrossRef]
Tuchin VV. Optical Clearing of Tissue and Blood . Bellingham, WA: SPIE Publications; 2005.
Craig JP Simmons PA Patel S Tomlinson A. Refractive index and osmolality of human tears. Optom Vis Sci . 1995; 72: 718–724. [CrossRef] [PubMed]
Lin RC Shure MA Rollins AM Izatt JA Huang D. Group index of the human cornea at 1.3-microm wavelength obtained in vitro by optical coherence domain reflectometry. Opt Lett . 2004; 29: 83–85. [CrossRef] [PubMed]
Bartko JJ Carpenter WT Jr. On the methods and theory of reliability. J Nerv Ment Dis . 1976; 163: 307–317. [CrossRef] [PubMed]
Nichols JJ Mitchell GL King-Smith PE. Thinning rate of the precorneal and prelens tear films. Invest Ophthalmol Vis Sci . 2005; 46: 2353–2361. [CrossRef] [PubMed]
King-Smith PE Nichols JJ Nichols KK Fink BA Braun RJ. Contributions of evaporation and other mechanisms to tear film thinning and break-up. Optom Vis Sci . 2008; 85: 623–630. [CrossRef] [PubMed]
Graig JP Tomlinson A McCann A. Tear Film. In: Besharse J Dana R eds. Encyclopedia of the Eye . Oxford, UK: Elsevier B.V.; 2010.
Wang J Cui L Shen M Perez VL Wang MR. Ultra-high resolution optical coherence tomography for monitoring tear meniscus volume in dry eye after topical cyclosporine treatment. Clin Ophthalmol . 2012; 6: 933–938. [CrossRef] [PubMed]
Tomlinson A Bron AJ Korb DR The international workshop on meibomian gland dysfunction: report of the diagnosis subcommittee. Invest Ophthalmol Vis Sci . 2011; 52: 2006–2049. [CrossRef] [PubMed]
Nichols KK Foulks GN Bron AJ The international workshop on meibomian gland dysfunction: executive summary. Invest Ophthalmol Vis Sci . 2011; 52: 1922–1929. [CrossRef] [PubMed]
Figure 1. 
 
Sample measurement of human precorneal tear film using ultrahigh-resolution OCT. TF, tear film; EP, corneal epithelium; BL, Bowman's layer; ST, corneal stroma; DM, Descemet's membrane; ED, corneal endothelium.
Figure 1. 
 
Sample measurement of human precorneal tear film using ultrahigh-resolution OCT. TF, tear film; EP, corneal epithelium; BL, Bowman's layer; ST, corneal stroma; DM, Descemet's membrane; ED, corneal endothelium.
Figure 2. 
 
Detection scheme for tear film thickness. (a) Line-wise contrast enhancement and automatic detection of air–tear film interface by means of Dijkstra algorithm. (b) Flattening of the tear film. (c) Definition of the tear film in the linearized image. (d) Intensity profile of an A-scan and definition of the tear film thickness as the distance between tear film front surface (blue arrow) and cornea front surface (green arrow). The additional sharp peak arises from the linearization of the tear film using the Dijkstra algorithm.
Figure 2. 
 
Detection scheme for tear film thickness. (a) Line-wise contrast enhancement and automatic detection of air–tear film interface by means of Dijkstra algorithm. (b) Flattening of the tear film. (c) Definition of the tear film in the linearized image. (d) Intensity profile of an A-scan and definition of the tear film thickness as the distance between tear film front surface (blue arrow) and cornea front surface (green arrow). The additional sharp peak arises from the linearization of the tear film using the Dijkstra algorithm.
Figure 3. 
 
Precorneal tear film thickness as obtained in 26 healthy subjects. The mean ± SD is shown.
Figure 3. 
 
Precorneal tear film thickness as obtained in 26 healthy subjects. The mean ± SD is shown.
Figure 4. 
 
Time course of precorneal tear film thickness in a healthy subject, over 16 seconds. A significant decrease in tear film thickness is observed.
Figure 4. 
 
Time course of precorneal tear film thickness in a healthy subject, over 16 seconds. A significant decrease in tear film thickness is observed.
Figure 5. 
 
Tear film breakup as observed in one subject after 14 seconds. The green ellipse indicates the location of the tear film breakup.
Figure 5. 
 
Tear film breakup as observed in one subject after 14 seconds. The green ellipse indicates the location of the tear film breakup.
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×