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Biomedical Optics Express

Biomedical Optics Express

  • Editor: Joseph A. Izatt
  • Vol. 5, Iss. 8 — Aug. 1, 2014
  • pp: 2614–2619
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Direct observation and validation of fluorescein tear film break-up patterns by using a dual thermal-fluorescent imaging system

Tai-Yuan Su, Shu-Wen Chang, Chiao-Ju Yang, and Huihua Kenny Chiang  »View Author Affiliations


Biomedical Optics Express, Vol. 5, Issue 8, pp. 2614-2619 (2014)
http://dx.doi.org/10.1364/BOE.5.002614


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Abstract

The fluorescein tear film break-up test is a common tear film stability test for dry eye diagnosis. This test requires applying fluorescein sodium drops to a tear film to observe the tear film break-up. However, this test is limited by using the fluorescein sodium drops, which can induce reflex tearing and reduce the reliability of the diagnosis results. This paper proposes that tear film evaporation accelerates on the fluorescein tear film break-up area (FTBA), resulting in a lower temperature area (LTA) on the tear film. A dual modality system was established to capture the thermal and fluorescent image of fluorescein-stain tear films for 48 participants. Observations showed that the LTA and FTBA were highly correlated in their location (r = 0.82) and size (r = 0.91). This is first study to show that the FTBA and LTA are essentially the same region. This study demonstrated the feasibility of using the noncontact thermograph method to evaluate tear film stability without using a fluorescein sodium drop.

© 2014 Optical Society of America

1. Introduction

Dry eye syndrome is one of the most common eye diseases affecting functional visual acuity [1

1. E. Goto, Y. Yagi, Y. Matsumoto, and K. Tsubota, “Impaired functional visual acuity of dry eye patients,” Am. J. Ophthalmol. 133(2), 181–186 (2002). [CrossRef] [PubMed]

] and reducing the quality of a patient’s life [2

2. B. Miljanović, R. Dana, D. A. Sullivan, and D. A. Schaumberg, “Impact of dry eye syndrome on vision-related quality of life,” Am. J. Ophthalmol. 143(3), 409–415 (2007). [CrossRef] [PubMed]

]. Dry eye syndrome is caused by a poor quality tear film and inflammation of the eyelid [3

3. K. K. Nichols, G. N. Foulks, A. J. Bron, B. J. Glasgow, M. Dogru, K. Tsubota, M. A. Lemp, and D. A. Sullivan, “The international workshop on meibomian gland dysfunction: executive summary,” Invest. Ophthalmol. Vis. Sci. 52(4), 1922–1929 (2011). [CrossRef] [PubMed]

] resulting from a lower tear production rate and / or a short tear film stable time. The ocular surface becomes dry and lacks lubrication, eventually damaging the ocular surface [4

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

].

The fluorescein tear film break-up time (FTBUT) test is one of the most common tests for dry eye syndrome. This test evaluates the tear film stability. In clinics, one of the main measures for determining dry eye is defined as a FTBUT shorter than 5 s. The FTBUT test first involves application of fluorescein sodium drops to the ocular surface and subsequent measurement of the time required for the first random dark spot to appear.

The dark spot is an area of increased concentration of fluorescein caused by tear film evaporation. This area shows a greater reduction in fluorescent intensity because of self-quenching at high concentration, and appears as a dark color under cobalt light excitation [5

5. J. J. Nichols, P. E. King-Smith, E. A. Hinel, M. Thangavelu, and K. K. Nichols, “The use of fluorescent quenching in studying the contribution of evaporation to tear thinning,” Invest. Ophthalmol. Vis. Sci. 53(9), 5426–5432 (2012). [CrossRef] [PubMed]

7

7. P. E. King-Smith, P. Ramamoorthy, R. J. Braun, and J. J. Nichols, “Tear film images and breakup analyzed using fluorescent quenching,” Invest. Ophthalmol. Vis. Sci. 54(9), 6003–6011 (2013). [CrossRef] [PubMed]

]. The dark area is the fluorescein tear film break-up area (FTBA). The FTBA is commonly caused by a poor quality tear film, and is a sign of an unstable tear film structure.

The FTBUT test is a well-established test for evaluating dry eye syndrome [8

8. A. J. Bron, “Diagnosis of dry eye,” Surv. Ophthalmol. 45(Suppl 2), S221–S226 (2001). [CrossRef] [PubMed]

, 9

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

]; however, it has several limitations. The test requires instilling fluorescein sodium drops, which is not a fully noncontact procedure. The other problem relates to the standardized fluorescein sodium concentration. Instilling liquid fluorescein sodium drops changes the total tear amount, which can affect the actual tear film break-up time [10

10. M. E. Johnson and P. J. Murphy, “The effect of instilled fluorescein solution volume on the values and repeatability of TBUT measurements,” Cornea 24(7), 811–817 (2005). [CrossRef] [PubMed]

]. The fluorescein sodium drops can also cause reflex tear secretion, which might not be acceptable for all patients because of fluorescein allergies. These drawbacks reduce the repeatability and the accuracy of the FTBUT [11

11. L. S. Mengher, A. J. Bron, S. R. Tonge, and D. J. Gilbert, “A non-invasive instrument for clinical assessment of the pre-corneal tear film stability,” Curr. Eye Res. 4(1), 1–7 (1985). [CrossRef] [PubMed]

]. A fully noninvasive measurement method for tear film break-up is required.

The lower temperature area (LTA) is the cool region on the ocular surface caused by tear film evaporation. LTA might be associated with the unstable region of the tear film or the tear film break-up area, but evidence for this explanation is limited. This paper proposes that the evaporation typically causes tear film breakup, resulting in the LTA on the tear film. Therefore, a dual modality noninvasive tear-imaging system was developed to assess objectively the characteristics of the tear film in real time. This dual modality system simultaneously observes fluorescein tear film break-up by using thermographic and fluorescent cameras to identify the relationship between the LTA and FTBA.

2. Method

2.1 Measurement procedure

2.2 Equipment

A dual modality system (Fig. 1
Fig. 1 Dual modality measurement system was established to capture the thermal image and fluorescent image of fluorescein-stain tear films. A. Thermography camera. B. Fluorescent camera. C. Fluorescein-stain tear film. D. Long-pass filter (500 nm). E. Cobalt light source. F. Germanium filter.
) was established to observe the fluorescein tear film break-up, which included a custom made thermograph (Fig. 1(A)) and a conventional fluorescent camera. (Fig. 1(B)) The dual modality system simultaneously observed the dynamics of the thermal and fluorescent characteristics of the fluorescent-stain ocular surface (Fig. 1(C)).

Ocular surface thermography (IT-85, United Integrated Services Co., Taiwan) was used to capture the thermogram; this system was designed to capture the ocular surface thermogram. The system recorded 30 frames per second at a resolution of 320 (H) x 240 (V) pixels. The difference in noise equivalent temperature was 0.07 C° and the Germanium lens transmitted an infrared spectrum of 8 to 12 μm.

A fluorescent camera (PowerShot G12, Canon Inc., Japan) with a cobalt light filter (500 long-pass filter) was attached to the side of the thermograph. Cobalt light excited the fluorescein-stain tear film. A Germanium filter transmitted the infrared light to the thermography camera and reflected the fluorescence to the fluorescent camera. The camera system adjusted the images by correcting the position of the fluorescent camera and the Germanium filter. The system measured a standard target for calculating the pixel length to the millimeter, after adjusting the thermal and fluorescent images in the same unit.

2.3 Image processing

Image processing enhanced the LTA of the thermographic image and the FTBA of the fluorescent image. The image processing steps are shown in Fig. 2
Fig. 2 The image processing steps for enhance the FTBA of the fluorescein images (a-d) and the LTA of the thermograms (e-h). The fluorescent image captured right after blinking (a.). The fluorescent image obtained at 5 s after blinking (b.). The subtraction of (a) and (b) is shown in (c). The binary image of (c.) is (d). The same processing steps for the thermograms (e-h).
. The initial fluorescent and thermal images were obtained immediately after blinking (a, e), and at 5 s after blinking (b, f). The images were subtracted between the initial and 5 s after the blinking for both the fluorescent image (c) and the thermogram (g). The images were transferred to binary images; the black area was the FTBA (d), and the black area was the LTA (h) before the center position of each LTA and FTBA was calculated, respectively.

After the image processing steps, the first appearance of the FTBA and LTA was selected on the images obtained at 5 s after blinking, then the distance between the inner canthus and the FTBA and LTA was measured in the center, in the horizontal-center-distance, in the vertical-center-distance, and in the total-center-distances. The size of the FTBA and LTA was also recorded for further analysis, as shown in Fig. 3
Fig. 3 The red circles indicate the first appearance of the LTA (a.), the FTBA (b.), respectively. O is the position of inner canthus. X and Y are the horizontal-center-distance, vertical-center-distance.
.

2.4 Statistical analysis

The data analysis was performed using SPSS version 20 (IBM, Chicago, IL, USA). Data were presented as the mean ± standard deviation. Pearson’s correlation coefficient was calculated to test the correlations among the horizontal-center-distance, vertical-center-distance, total-center-distances, and area of LTA and FTBA. The level of statistical significance was set at p < 0.001.

3. Results

The correlations of distances and areas between the LTA and FTBA are presented in Table 1

Table 1. The correlation relation of the horizontal-center-distance (Horizontal), vertical-center-distance (Vertical), total-center-distances (Distances), and area between the LTA and FTBA (Area).

table-icon
View This Table
. The position correlations between the LTA and FTBA were 0.82 in the horizontal-center-distance, 0.88 in the vertical-center-distance, 0.84 in the total-center-distances, and the area correlations between LTA and FTBA was 0.91. The scatter plot is shown in Fig. 4
Fig. 4 The scatter plots of the FTBA (fluorescein tear film break-up area) and LTA (lower temperature area), in the vertical-center-distance (a.), in horizontal-center-distance (b.), total-center-distances (c.), and the area (d.).
.

Figure 5
Fig. 5 A fluorescent-stain tear film is measured by the dual modality imaging system. (A) FTBA images (B) LTA images. The time interval between each image is 1 second. The FTBA is fully developed at 3 s; while the LTA can be observed at 2 s. Red circles represent the FTBA and LTA, respectively.
shows a typical dual modality system measurement result. The dual modality system measured the fluorescent-stain tear film at the same time that the fluorescent camera recorded a series of FTBA images and the thermographic camera recorded the corresponding series LTA images. The FTBA and LTA exhibited relevant development.

4. Discussion

In this study, a dual modality imaging system was established for observing the dynamics of fluorescein tear film break-up. The system includes thermographic and fluorescent cameras. The dual modality imaging system continually monitors the fluorescein tear film break-up in real time.

The location and area of the LTA and FTBA were highly correlated. The correlation of the center to the inner canthus distance was compared between the LTA and FTBA, which revealed a strong correlation. The result suggested that the LTA and FTBA were matched in their locations. In addition, the sizes of the LTA and FTBA were strongly correlated, and we also observed that LTA and FTBA both increased in size over time.

In this study we observed that the physical phenomenon of FTBA and LTA was similar although they were measured according to distinct image modalities in this study. The FTBA and LTA were caused by lower tear film stability. In clinics, the FTBUT test is used to test tear film stability; during this test, the tear film evaporates, becomes thinner, and eventually breaks up. During this evaporation and thinning process, the tear film is unstable, leading to tear film break-up which results in an LTA on the tear film. This can explain why the FTBA and LTA were observed in the same region in this study.

The measurement results of the tear film stability when using the fluorescent method and the thermograph method were also compared. In 22 of 48 cases, the FTBUT > 5 s, (8.8 ± 2.9 s) and exhibited a stable tear film; the LTA did not appear on the tear film until 5 s after blinking. However, in the other 26 cases, the FTBUT < 5 s, (2.8 ± 2.1 s) and exhibited an unstable tear film and the LTA appeared within 5 s after blinking. The results suggested that the appearance of the LTA is associated with low tear film stability.

This study had limitations. The ocular surface thermogram might have been blocked by an eyelash, which might have reduced the observation area of the ocular surface. In addition, the experiment was sensitive to air drifts, heat sources, eye movements, and the camera focus setting. Because of the relatively small sample size in this study, the results should be confirmed in a large clinical trial before they can be used with confidence to evaluate tear film stability.

5. Conclusions

The FTBA was demonstrated to be strongly correlated to the LTA in location and size, and also the appearance of the LTA is associated with tear film stability. These results supported that the LTA can be used to evaluate tear film break-up. Thermography can be used to implement a tear film stability test without using fluorescein sodium drops. This approach can alleviate the discomfort and inconvenience of the traditional tear film break-up test.

Acknowledgments

The authors thank the National Science Council, Taiwan for funding (101-2622-E-010-001-CC2), and the staff of Far Eastern Memorial Hospital and National Yang Ming University, as well as the research participants. The authors thank to Yu-Han, Ou for her assistance. The authors thank to Dr. Wei-Ting, Ho for his untiring support and advice.

References and links

1.

E. Goto, Y. Yagi, Y. Matsumoto, and K. Tsubota, “Impaired functional visual acuity of dry eye patients,” Am. J. Ophthalmol. 133(2), 181–186 (2002). [CrossRef] [PubMed]

2.

B. Miljanović, R. Dana, D. A. Sullivan, and D. A. Schaumberg, “Impact of dry eye syndrome on vision-related quality of life,” Am. J. Ophthalmol. 143(3), 409–415 (2007). [CrossRef] [PubMed]

3.

K. K. Nichols, G. N. Foulks, A. J. Bron, B. J. Glasgow, M. Dogru, K. Tsubota, M. A. Lemp, and D. A. Sullivan, “The international workshop on meibomian gland dysfunction: executive summary,” Invest. Ophthalmol. Vis. Sci. 52(4), 1922–1929 (2011). [CrossRef] [PubMed]

4.

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

5.

J. J. Nichols, P. E. King-Smith, E. A. Hinel, M. Thangavelu, and K. K. Nichols, “The use of fluorescent quenching in studying the contribution of evaporation to tear thinning,” Invest. Ophthalmol. Vis. Sci. 53(9), 5426–5432 (2012). [CrossRef] [PubMed]

6.

C. Begley, T. Simpson, H. Liu, E. Salvo, Z. Wu, A. Bradley, and P. Situ, “Quantitative analysis of tear film fluorescence and discomfort during tear film instability and thinning,” Invest. Ophthalmol. Vis. Sci. 54(4), 2645–2653 (2013). [CrossRef] [PubMed]

7.

P. E. King-Smith, P. Ramamoorthy, R. J. Braun, and J. J. Nichols, “Tear film images and breakup analyzed using fluorescent quenching,” Invest. Ophthalmol. Vis. Sci. 54(9), 6003–6011 (2013). [CrossRef] [PubMed]

8.

A. J. Bron, “Diagnosis of dry eye,” Surv. Ophthalmol. 45(Suppl 2), S221–S226 (2001). [CrossRef] [PubMed]

9.

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

10.

M. E. Johnson and P. J. Murphy, “The effect of instilled fluorescein solution volume on the values and repeatability of TBUT measurements,” Cornea 24(7), 811–817 (2005). [CrossRef] [PubMed]

11.

L. S. Mengher, A. J. Bron, S. R. Tonge, and D. J. Gilbert, “A non-invasive instrument for clinical assessment of the pre-corneal tear film stability,” Curr. Eye Res. 4(1), 1–7 (1985). [CrossRef] [PubMed]

12.

R. Mapstone, “Measurement of corneal temperature,” Exp. Eye Res. 7(2), 237–243 (1968). [CrossRef] [PubMed]

13.

P. B. Morgan, A. B. Tullo, and N. Efron, “Ocular surface cooling in dry eye a pilot study,” Journal of the British Contact Lens Association 19(1), 7–10 (1996). [CrossRef]

14.

A. Mori, Y. Oguchi, Y. Okusawa, M. Ono, H. Fujishima, and K. Tsubota, “Use of high-speed, high-resolution thermography to evaluate the tear film layer,” Am. J. Ophthalmol. 124(6), 729–735 (1997). [PubMed]

15.

U. R. Acharya, E. Y. Ng, G. C. Yee, T. J. Hua, and M. Kagathi, “Analysis of normal human eye with different age groups using infrared images,” J. Med. Syst. 33(3), 207–213 (2009). [CrossRef] [PubMed]

16.

J. H. Tan, E. Ng, U. Rajendra Acharya, and C. Chee, “Infrared thermography on ocular surface temperature: a review,” Infrared Phys. Technol. 52(4), 97–108 (2009). [CrossRef]

17.

T. Kamao, M. Yamaguchi, S. Kawasaki, S. Mizoue, A. Shiraishi, and Y. Ohashi, “Screening for dry eye with newly developed ocular surface thermographer,” Am. J. Ophthalmol. 151(5), 782–791 (2011). [CrossRef] [PubMed]

18.

T. Y. Su, K. H. Chen, P. H. Liu, M. H. Wu, D. O. Chang, P. F. Su, S. W. Chang, and H. K. Chiang, “Noncontact detection of dry eye using a custom designed infrared thermal image system,” J. Biomed. Opt. 16, 046009 (2011).

19.

W. Mathers, “Evaporation from the ocular surface,” Exp. Eye Res. 78(3), 389–394 (2004). [CrossRef] [PubMed]

20.

A. J. Bron, J. A. Smith, and M. Calonge, “Methodologies to diagnose and monitor dry eye disease: report of the Diagnostic Methodology Subcommittee of the International Dry Eye WorkShop (2007),” Ocul. Surf. 5(2), 108–152 (2007). [CrossRef] [PubMed]

OCIS Codes
(110.6820) Imaging systems : Thermal imaging
(170.3880) Medical optics and biotechnology : Medical and biological imaging
(170.4470) Medical optics and biotechnology : Ophthalmology

ToC Category:
Ophthalmology Applications

History
Original Manuscript: May 9, 2014
Revised Manuscript: July 5, 2014
Manuscript Accepted: July 8, 2014
Published: July 14, 2014

Citation
Tai-Yuan Su, Shu-Wen Chang, Chiao-Ju Yang, and Huihua Kenny Chiang, "Direct observation and validation of fluorescein tear film break-up patterns by using a dual thermal-fluorescent imaging system," Biomed. Opt. Express 5, 2614-2619 (2014)
http://www.opticsinfobase.org/boe/abstract.cfm?URI=boe-5-8-2614


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References

  1. E.  Goto, Y.  Yagi, Y.  Matsumoto, K.  Tsubota, “Impaired functional visual acuity of dry eye patients,” Am. J. Ophthalmol. 133(2), 181–186 (2002). [CrossRef] [PubMed]
  2. B.  Miljanović, R.  Dana, D. A.  Sullivan, D. A.  Schaumberg, “Impact of dry eye syndrome on vision-related quality of life,” Am. J. Ophthalmol. 143(3), 409–415 (2007). [CrossRef] [PubMed]
  3. K. K.  Nichols, G. N.  Foulks, A. J.  Bron, B. J.  Glasgow, M.  Dogru, K.  Tsubota, M. A.  Lemp, D. A.  Sullivan, “The international workshop on meibomian gland dysfunction: executive summary,” Invest. Ophthalmol. Vis. Sci. 52(4), 1922–1929 (2011). [CrossRef] [PubMed]
  4. M. A.  Lemp, “The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007),” Ocul. Surf. 5(2), 75–92 (2007). [CrossRef] [PubMed]
  5. J. J.  Nichols, P. E.  King-Smith, E. A.  Hinel, M.  Thangavelu, K. K.  Nichols, “The use of fluorescent quenching in studying the contribution of evaporation to tear thinning,” Invest. Ophthalmol. Vis. Sci. 53(9), 5426–5432 (2012). [CrossRef] [PubMed]
  6. C.  Begley, T.  Simpson, H.  Liu, E.  Salvo, Z.  Wu, A.  Bradley, P.  Situ, “Quantitative analysis of tear film fluorescence and discomfort during tear film instability and thinning,” Invest. Ophthalmol. Vis. Sci. 54(4), 2645–2653 (2013). [CrossRef] [PubMed]
  7. P. E.  King-Smith, P.  Ramamoorthy, R. J.  Braun, J. J.  Nichols, “Tear film images and breakup analyzed using fluorescent quenching,” Invest. Ophthalmol. Vis. Sci. 54(9), 6003–6011 (2013). [CrossRef] [PubMed]
  8. A. J.  Bron, “Diagnosis of dry eye,” Surv. Ophthalmol. 45(Suppl 2), S221–S226 (2001). [CrossRef] [PubMed]
  9. M. S.  Norn, “Desiccation of the precorneal film. I. Corneal wetting-time,” Acta Ophthalmol. (Copenh.) 47(4), 865–880 (1969). [CrossRef] [PubMed]
  10. M. E.  Johnson, P. J.  Murphy, “The effect of instilled fluorescein solution volume on the values and repeatability of TBUT measurements,” Cornea 24(7), 811–817 (2005). [CrossRef] [PubMed]
  11. L. S.  Mengher, A. J.  Bron, S. R.  Tonge, D. J.  Gilbert, “A non-invasive instrument for clinical assessment of the pre-corneal tear film stability,” Curr. Eye Res. 4(1), 1–7 (1985). [CrossRef] [PubMed]
  12. R.  Mapstone, “Measurement of corneal temperature,” Exp. Eye Res. 7(2), 237–243 (1968). [CrossRef] [PubMed]
  13. P. B.  Morgan, A. B.  Tullo, N.  Efron, “Ocular surface cooling in dry eye a pilot study,” Journal of the British Contact Lens Association 19(1), 7–10 (1996). [CrossRef]
  14. A.  Mori, Y.  Oguchi, Y.  Okusawa, M.  Ono, H.  Fujishima, K.  Tsubota, “Use of high-speed, high-resolution thermography to evaluate the tear film layer,” Am. J. Ophthalmol. 124(6), 729–735 (1997). [PubMed]
  15. U. R.  Acharya, E. Y.  Ng, G. C.  Yee, T. J.  Hua, M.  Kagathi, “Analysis of normal human eye with different age groups using infrared images,” J. Med. Syst. 33(3), 207–213 (2009). [CrossRef] [PubMed]
  16. J. H.  Tan, E.  Ng, U.  Rajendra Acharya, C.  Chee, “Infrared thermography on ocular surface temperature: a review,” Infrared Phys. Technol. 52(4), 97–108 (2009). [CrossRef]
  17. T.  Kamao, M.  Yamaguchi, S.  Kawasaki, S.  Mizoue, A.  Shiraishi, Y.  Ohashi, “Screening for dry eye with newly developed ocular surface thermographer,” Am. J. Ophthalmol. 151(5), 782–791 (2011). [CrossRef] [PubMed]
  18. T. Y.  Su, K. H.  Chen, P. H.  Liu, M. H.  Wu, D. O.  Chang, P. F.  Su, S. W.  Chang, H. K.  Chiang, “Noncontact detection of dry eye using a custom designed infrared thermal image system,” J. Biomed. Opt. 16, 046009 (2011).
  19. W.  Mathers, “Evaporation from the ocular surface,” Exp. Eye Res. 78(3), 389–394 (2004). [CrossRef] [PubMed]
  20. A. J.  Bron, J. A.  Smith, M.  Calonge, “Methodologies to diagnose and monitor dry eye disease: report of the Diagnostic Methodology Subcommittee of the International Dry Eye WorkShop (2007),” Ocul. Surf. 5(2), 108–152 (2007). [CrossRef] [PubMed]

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