Relationship Between Precorneal Relationship Between Precorneal

Tear-Film Lipid Layer Spread Tear-Film Lipid Layer Spread

and Precorneal Tear-Film Stabilityand Precorneal Tear-Film Stability

Norihiko Yokoi, Aoi Komuro, and Shigeru KinoshitaNorihiko Yokoi, Aoi Komuro, and Shigeru Kinoshita

Department of Ophthalmology Department of Ophthalmology

Kyoto Prefectural University of MedicineKyoto Prefectural University of Medicine

The authors have no financial interest in the subject matter of this posterThe authors have no financial interest in the subject matter of this poster

Dynamics of the Tear-Film Lipid Layer (TFLL) spread after Dynamics of the Tear-Film Lipid Layer (TFLL) spread after

opening the eye follows a rheological Voigt model (Yokoi N, opening the eye follows a rheological Voigt model (Yokoi N,

et al. IOVS 2008;49), and the initial velocity of the TFLL et al. IOVS 2008;49), and the initial velocity of the TFLL

spread [spread [H´(0)H´(0), mm/sec.] provides the quantitative value for , mm/sec.] provides the quantitative value for

the tear volume, both in theory and in practice.the tear volume, both in theory and in practice.

The elapsed amount of time from the opening of the eye The elapsed amount of time from the opening of the eye

until the breakup (Non-invasive breakup time:until the breakup (Non-invasive breakup time: NIBUT NIBUT, sec.) , sec.)

of the precorneal tear filmof the precorneal tear film is an indication of tear film is an indication of tear film

stability (Ishibashi T, Yokoi N, et al. J Glaucoma 2003;12). stability (Ishibashi T, Yokoi N, et al. J Glaucoma 2003;12).

Therefore, we investigated the relationship between Therefore, we investigated the relationship between H´(0)H´(0)

and and NIBUTNIBUT..

Purpose Purpose

Males:Males: 3 eyes3 eyes from 3 cases; from 3 cases; Females:Females: 36 eyes36 eyes from 36 cases from 36 cases

Normal eyes :Normal eyes :

Subjects (39 eyes fromSubjects (39 eyes from 39 cases) 39 cases)

No meibomian gland dysfunctionNo meibomian gland dysfunction

Mean AgeMean Age: 52.1±14.8 (SD) yrs.: 52.1±14.8 (SD) yrs.

Definite dry eye :Definite dry eye :

Post punctal occlusion :Post punctal occlusion :

Suspected dry eye:Suspected dry eye:

4 eyes from 4 cases4 eyes from 4 cases

20 eyes from 20 cases20 eyes from 20 cases

12 eyes from 12 cases12 eyes from 12 cases

３ ３ eyes from eyes from ３ ３ casescases

(diagnoses based on 2006 dry eye diagnostic criteria in Japan)(diagnoses based on 2006 dry eye diagnostic criteria in Japan)

( )( )( )( )( )( )( )( )

In cases of severe tear deficiency where the TFLL cannot be seenIn cases of severe tear deficiency where the TFLL cannot be seen

⇒⇒ H’(0)=0mm/sec. and NIBUT=0 sec.H’(0)=0mm/sec. and NIBUT=0 sec.

In cases of severe tear deficiency where the TFLL cannot be seenIn cases of severe tear deficiency where the TFLL cannot be seen

⇒⇒ H’(0)=0mm/sec. and NIBUT=0 sec.H’(0)=0mm/sec. and NIBUT=0 sec.

MethodsMethods

① Measurement of RR (Radius of the central lower tear meniscus)(Radius of the central lower tear meniscus)① Measurement of RR (Radius of the central lower tear meniscus)(Radius of the central lower tear meniscus)

② Measurement ofMeasurement of H’(0)H’(0) (Initial velocity of the TFLL spread)(Initial velocity of the TFLL spread)② Measurement ofMeasurement of H’(0)H’(0) (Initial velocity of the TFLL spread)(Initial velocity of the TFLL spread)

③ Measurement ofMeasurement of NIBUTNIBUT (Non-invasive breakup time) of the (Non-invasive breakup time) of the precorneal tear filmprecorneal tear film

③ Measurement ofMeasurement of NIBUTNIBUT (Non-invasive breakup time) of the (Non-invasive breakup time) of the precorneal tear filmprecorneal tear film

Note:Note:Note:Note:

In cases of stable tear film where no NIBU is seen at 10 seconds In cases of stable tear film where no NIBU is seen at 10 seconds

⇒ ⇒ NIBUT=10 sec.NIBUT=10 sec.

In cases of stable tear film where no NIBU is seen at 10 seconds In cases of stable tear film where no NIBU is seen at 10 seconds

⇒ ⇒ NIBUT=10 sec.NIBUT=10 sec.

Video-MeniscometryVideo-MeniscometryVideo-MeniscometryVideo-Meniscometry

①,,①,, ②,,②,, ③ ③

Investigation Investigation of the of the correlation correlation between:between:

Investigation Investigation of the of the correlation correlation between:between:

Video-InterferometryVideo-InterferometryVideo-InterferometryVideo-Interferometry

①① ②② ③③

(B)

dydy

(A)

Automatic analysis of the spreading TFLL Automatic analysis of the spreading TFLL using the Voigt model and the cross-correlation methodusing the Voigt model and the cross-correlation method

1)1) A certain rectangular area isA certain rectangular area is determined on a captured image of the determined on a captured image of the 　 　 spreading lipid layer [Image (A)].spreading lipid layer [Image (A)].

2)2) A rectangular area of the same size and having the closest total A rectangular area of the same size and having the closest total brightness to that in Image (A) is automatically searched for in Image (B) brightness to that in Image (A) is automatically searched for in Image (B) 0.05 seconds after Image (A) based on the cross-correlation method 0.05 seconds after Image (A) based on the cross-correlation method using a custom made computer program. using a custom made computer program.

3) The transitional shift along the y-axis3) The transitional shift along the y-axis (dy) of the rectangular area (dy) of the rectangular area between (A) and (B) is then calculated; between (A) and (B) is then calculated; dydy is subsequently summed over is subsequently summed over time and adopted to the Voigt model.time and adopted to the Voigt model.

Analysis of the TFLL spread along the y-axis Analysis of the TFLL spread along the y-axis

using the Voigt-model equationusing the Voigt-model equation

　　 H　=　ρ　[H　=　ρ　[ １－１－ e　e　(-t　/λ)　(-t　/λ)　]]

H: summed shift of the rectangular area along the y-H: summed shift of the rectangular area along the y-

directiondirection

ρ: constant, t: time, λ: retardation time=ρ(1ρ: constant, t: time, λ: retardation time=ρ(1 －－ 1/e)1/e)

H’(0)H’(0) (initial velocity of the TFLL spread along the y-axis) (initial velocity of the TFLL spread along the y-axis)

was used was used as a parameter for evaluating the TFLL spreadas a parameter for evaluating the TFLL spread

Voigt-model equation:Voigt-model equation:Voigt-model equation:Voigt-model equation:

NIBUTNIBUT=5.8 sec=5.8 sec

Representative measurement of Representative measurement of H’(0) H’(0) (Left figure) and (Left figure) and

NIBUT NIBUT (Right figure)(Right figure) of the precorneal tear filmof the precorneal tear film

Sum of the upward spread of Sum of the upward spread of

the TFLL along the Y-axis (mm) the TFLL along the Y-axis (mm)

0.00.0

1.01.0

2.02.0

3.03.0

4.04.0

0.20.2 0.40.4 0.60.6 0.80.8 1.01.0 1.21.2 1.41.4 1.61.6 1.81.8 2.02.0

Actual valueActual value

Voigt modelVoigt model

H´(0)H´(0)=10.8 mm/sec.=10.8 mm/sec.

Time (sec.)Time (sec.)

NIBUNIBU

t=5.8 sec.t=5.8 sec.

t=10 sec.t=10 sec.

t=1 sec.t=1 sec.

t=3 sec.t=3 sec. t=4 sec.t=4 sec.

t=5 sec.t=5 sec. t=7 sec.t=7 sec.

t=9 sec.t=9 sec.t=8 sec.t=8 sec.

t=1.6 sec.t=1.6 sec.

BeforeBeforeopening ofopening of

the eyethe eyeOpening ofOpening of

the eyethe eye

t=0 sec.t=0 sec.

-2-2

00

22

44

66

88

1010

00 .1.1 .2.2 .3.3 .4.4 .5.5 .6.6 .7.7 .8.8 1.01.0

1212

H’(

0)

H’(

0)

(mm

/sec.)

(m

m/s

ec.)

RR (mm) (mm)

rrss=0.6751=0.6751

n=39n=39

Relationship between Relationship between RR and and H’(0)H’(0)

Results (1)Results (1)

P<0.0001P<0.0001

(Spearman)(Spearman)

-2-2

00

22

44

66

88

1010

-2-2 00 22 44 66 88 1010 1212

1212

H’(0)H’(0) (mm/sec.) (mm/sec.)

NIB

UT

NIB

UT (

sec.)

(sec.) rrss=0.9039=0.9039

P<0.0001P<0.0001

n=39n=39

Relationship between Relationship between H’(0)H’(0) and and NIBUTNIBUT

Results (2)Results (2)

(Spearman)(Spearman)

00

22

44

66

88

1010

1212

H’(0)H’(0)≧3.3≧3.3H’(0)H’(0)<3.3<3.3

NIB

UT

NIB

UT (

sec.)

(sec.)

*P<0.0001*P<0.0001

mean±SDmean±SDmean±SDmean±SD

Comparison of the NIBUT using the average (=3.3mm/sec.) of Comparison of the NIBUT using the average (=3.3mm/sec.) of

H’(0) as the cut-off valueH’(0) as the cut-off value

Results (3)Results (3)

(Student’s t-test) (Student’s t-test) **

(19)(19)

(20)(20)

Using a custom made computer program for cross-correlation Using a custom made computer program for cross-correlation

in combination with the Voigt model, the initial velocity of the in combination with the Voigt model, the initial velocity of the

TFLL spread along the y-axis [TFLL spread along the y-axis [H’(0)H’(0)] was measured. ] was measured.

A significant positive relationship was seen between the radius A significant positive relationship was seen between the radius

of tear meniscus (of tear meniscus (RR) and ) and H’(0) H’(0) (r (rss=0.6751; P<0.0001).=0.6751; P<0.0001).

Using the average (=3.3mm/sec.) of the initial velocity of the Using the average (=3.3mm/sec.) of the initial velocity of the

TFLL spread in 39 subject eyes as the cut-off value, TFLL spread in 39 subject eyes as the cut-off value, NIBUTNIBUT in the in the

H’(0) H’(0) < 3.3< 3.3 group was significantly shortergroup was significantly shorter than in the than in the H’(0) H’(0) ≧ ≧

3.3 group (P<0.0001).3.3 group (P<0.0001).

There was a significant positive relationship between There was a significant positive relationship between H’(0)H’(0) and and

the non-invasive breakup timethe non-invasive breakup time ((NIBUTNIBUT) of the precorneal tear ) of the precorneal tear

film (rfilm (rss=0.9039; P<0.0001).=0.9039; P<0.0001).

Summary of the ResultsSummary of the ResultsSummary of the ResultsSummary of the Results

1) 1) 1) 1)

2) 2) 2) 2)

3) 3) 3) 3)

ConclusionConclusion

Based on the findings of Berger & Corrsin (J Biomech Based on the findings of Berger & Corrsin (J Biomech

1974;7) regarding the significant correlation between the 1974;7) regarding the significant correlation between the

velocity of the TFLL spread and the precorneal tear-film velocity of the TFLL spread and the precorneal tear-film

aqueous-layer thickness, as well as the findings of the aqueous-layer thickness, as well as the findings of the

present study showing a significant correlation between present study showing a significant correlation between

the velocity of the TFLL and the radius of the tear the velocity of the TFLL and the radius of the tear

meniscus, it may be concluded that the precornealmeniscus, it may be concluded that the precorneal tear-tear-

film aqueous-layer thickness contributes to the stability film aqueous-layer thickness contributes to the stability

of the precorneal tear film.of the precorneal tear film.