Download Tear functions in patients with pterygium

Tear functions in patients
with pterygium
Sibel Çalışkan Kadayifçilar*, Mehmet Orhan & Murat İrkeç
Department of Ophthalmology, University of Hacettepe, Ankara, Turkey
ABSTRACT.
Purpose: In the etiology of pterygium abnormalities in tear functions have also
been emphasized. In this study, tear function tests are evaluated in patients with
pterygium.
Methods: Schirmer’s test 1, tear film break-up time and mucus fern patterns
were evaluated in 70 eyes with pterygium and in 70 eyes of the age matched
control group. Marginal tear films were also assessed.
Results: Tear film break-up time was significantly reduced in the pterygium
group. Mucus fern patterns and marginal tear films were found to be markedly
abnormal in the eyes with pterygium, however, there was no significant difference in Schirmer’s test 1.
Conclusion: Tear function tests disclosed disrupted tear film stability which is
more likely to be due to the altered mucin. This change may either be the
primary factor inducing pterygium formation or reflect an existing pathology
in the cells lining the ocular surface.
Key words: pterygium – Schirmer’s test 1 – tear film break-up time – mucus fern test – mucin.
Acta Ophthalmol. Scand. 1998: 76: 176–179
Copyright c Acta Ophthalmol Scand 1998. ISSN 1395-3907
A
pterygium is a degenerative corneal
limbal process which may progress
onto the cornea in the interpalpebral area
(Jaros & DeLouise 1988). Despite several
theories, its etiology has not been adequately explained. Prolonged exposure
to ultraviolet (UV) light has been implicated in the pathogenesis of pterygium
(Hill & Maske 1989; Taylor et al. 1989,
1992; Adamis et al. 1990; Mackenzie et
al. 1992; Coroneo 1993; Kwok & Coroneo 1994). One study performed in
British Columbia, northern India, Thailand and Taiwan revealed that the ageadjusted prevalence rate of pterygium in
sawmill workers – who worked indoors –
was 25.3% compared to 7.1% in controls
(Detels & Dhir 1967). This study provided evidence that the cause of the pterygium may be multifactorial. Mechanical
irritation by dust particles and/or tear
function abnormalities have also been
proposed as etiologic factors (Coroneo
1993).
Disruption of the tear film has been
suggested to be the result of either rapid
176
evaporation or microtrauma from microparticles of dust or ice (Taylor 1980).
In this study tear functions were investigated in patients with pterygium.
Material and Methods
Seventy eyes of 70 patients with pterygium were enrolled in the study. The patient group consisted of 36 women and
34 men with an age range between 21 to
75 (Mean 46.06∫13.21).
Seventy eyes of 70 age matched patients with refractive problems and without any other ophthalmologic disorder
constituted the control group. There were
34 women and 36 men in this group, with
an age range between 23 to 73 (Mean
48.11∫10.12).
There was no significant difference between the groups with regard to age
(p±0.05) or sex (p±0.05).
With slit lamp examination, patients
with blepharitis and allergic conjuncti-
vitis with significant papillary hypertrophy were excluded.
During the initial examination, Schirmer’s test 1 was performed first, then
marginal tear strip was assessed at least
15 minutes later, and tear film break-up
time was estimated. Samples for the mucus fern test were taken on a separate day.
Schirmer’s Test 1
Standard Schirmer tear test filter strip
(Clement Clarke International) was inserted in the lateral lower fornix of the
eye taking care not to touch the cornea.
Topical anesthetics were not applied. The
patient was instructed to keep the eyes
open and to blink as necessary. After 5
minutes, the filter strip was removed and
the amount of wetting from the fold was
measured (Clinch et al. 1983).
Marginal Tear Strip
One drop of 1% sodium fluorescein was instilled to the lower fornix. The patient was
asked to blink several times to distribute
the fluorescein evenly. The eye was then
examined using a slit lamp with a cobalt
blue filter, and the meniscus formed by the
tears at the lower lid margin was observed.
This marginal tear strip was then designated as intact, not intact temporally, or
not intact (Taylor & Louis 1980).
Tear film break-up time (BUT)
After the assessment of the marginal tear
strip, tear film break-up time was meas-
Table 1. Mean Schirmer’s test 1 results and tear
film break-up time in pterygium and control
groups.
Tear function
tests
Eyes with
pterygium
Controls
Schirmer-1
(mm/5 min)
BUT (sec)
17.10∫1.12
9.84∫0.40
19.86∫1.01
13.41∫0.58
Table 2. Distribution of Schirmer’s test 1 and tear film break-up time (BUT) values, mucus fern
patterns and marginal tear strip continuity in pterygium vs. control groups and statistical results.
Pterygium
Test
Number of eyes
Controls
%
Number of eyes
%
Statistical result*
Schirmer’s test-1 (mm/5 min)
0–4
5
5–9
5
10–14
15
15–19
24
Ø20
21
7.1
7.1
21.4
34.3
30
2
4
13
18
33
2.9
5.7
18.6
25.7
47.1
p±0.05
p±0.05
p±0.05
p±0.05
p±0.05
BUT (sec)
0–4
5–9
10–14
Ø15
2
34
25
9
2.9
48.6
35.7
12.9
3
18
14
35
4.3
25.7
20
50
p±0.05
p∞0.05
p±0.05
p∞0.05
Mucus Fern Pattern (Type)
I
17
II
24
III
25
IV
4
24.3
34.3
35.7
5.7
36
25
7
2
51.4
35.7
10
2.9
p∞0.05
p±0.05
p∞0.05
p±0.05
Marginal Tear Strip
Intact
Not intact temporally
Not intact
42.9
47.1
10
45
21
4
64.3
30
5.7
p∞0.05
p∞0.05
p±0.05
30
33
7
eyes (51.5%) with pterygium and in 21
(30%) control eyes. The difference was
statistically significant (p∞0.01).
In mucus fern test, type III and type
IV crystallization patterns which signify
abnormality of the tear film were observed in 41.4% of the eyes with pterygium and in 12.9% of the eyes in the
control group (Table 2). There was a statistically significant difference (p∞0.01).
Marginal tear film was intact in 42.9%
of the eyes with pterygium and in 64.3%
of the control eyes (Table 2). The difference was significant statistically (p∞0.05).
Discussion
*p∞0.05: Statistically significant, p±0.05: Not significant statistically.
ured. The patient was asked to stare directly ahead without blinking; the eyelids
were not held. The time interval between
the last blink and the development of the
first randomly distributed dry spot on the
cornea was measured with a stop-watch.
This test was repeated 3 times and the average was taken (Taylor & Louis 1980).
Eyes with a dry spot consistently localized in the same corneal area indicating
significant surface abnormality were excluded from the study.
Mucus Fern Test
2–3 microliters of tear were collected with
a capillary tube from the lower fornix
without anesthesia, with care taken not
to grasp on the conjunctival surface. The
sample was allowed to dry on a light
microscopy slide. The crystallization pattern was observed under light microscopy
(160¿ and 400¿). Mucus crystallization
patterns were classified into four groups
(Rolando 1984; Rolando et al. 1988):
Type I: Uniform and closely branching
arborization.
Type II: Single ferns are smaller and
less branching is present.
Type III: Small ferns with almost no
branches; many empty spaces.
Type IV: Ferning is absent and clusters
of mucus can be present.
Results were statistically evaluated
using t-test, chi-square test and Mc Nemar test.
Results
Schirmer’s test 1 values were as low as 3
mm and as high as 50 mm with a mean
of 17.10∫1.12 mm in the pterygium
group. In the control group the mean was
19.86∫1.01 mm with a range of 4–50 mm
(Table 1). The difference between the
groups was not significant (tΩ1.71,
p±0.05). Schirmer’s test 1 values were
less than 10 mm in 10 eyes (14.2%) with
pterygium and in 6 (9.6%) control eyes.
The difference was not significant
(p±0.05). The distribution of Schirmer’s
test 1 values and statistical evaluation are
shown in Table 2.
BUT values were between 3 to 19 seconds with a mean of 9.84∫0.40 sec. in
patients with pterygium and between 4 to
25 seconds with a mean of 13.41∫0.58
sec. in the control group (Table 1). There
was a statistically significant difference
between the groups (tΩ5.31, p∞0.05).
The distribution of BUT values according to the groups with the statistical
analysis is presented in Table 2. BUT of
less than 10 seconds was observed in 36
The most popular theory in the pathogenesis of pterygium is UV insolation
(Hill & Maske 1989; Taylor et al. 1989,
1992; Adamis et al. 1990; Mackenzie et
al. 1992; Coroneo 1993; Kwok & Coroneo 1994) and differentiation of the limbal stem cells as a result (Kwok & Coroneo 1994). It has been hypothesized that,
in susceptible individuals actinic damage
causes an alteration in the cornea; the
damaged tissue is then recognized as foreign and hypersensitivity reactions are
mounted resulting in chronic inflammation. At the beginning a focal conjunctivitis develops at the corneoscleral
limbus which later develops into a pterygium (Hill & Maske 1989). In this inflammatory process a variety of cells, soluble mediators, and complex regulatory
pathways contribute to abnormal blood
vessel formation (Sunderkotter et al.
1991). Early unknown factors from precursor cells to current specific cytokines
like Interleukin-8 have been reported to
be angiogenic (BenEzra et al. 1990). Recently, it has also been shown that inflammation induces angiogenic peptide
vascular endothelial growth factor
(VEGF) mRNA and protein to high
levels in corneal epithelium, keratocytes
and inflammatory cells (Amano et al.
1997).
Though UV light and environmental
factors play a significant role, the development of pterygium only in some
people, not in all, living under the same
conditions suggests the role of other factors in the pathogenesis. Tear function
abnormalities have been proposed as an
etiologic factor due to the observation
that a pterygium is further exacerbated
by elevation of pterygium head, dryness
and dellen formation (Coroneo 1993).
No abnormalities in Schirmer’s test, tear
177
Fig. 1. Mucus fern patterns. Upper left, Type I (400¿); Upper right, Type II (400¿); Lower left, Type III (400¿); Lower right, Type IV (400¿).
break-up time or rose bengal staining of
the cornea were found in eyes with pterygia (Biedner et al. 1979; Taylor 1980;
Jensen 1982). It has been suggested that
drying of the tear film by wind, devitalized tissues of the medial third of the palpebral aperture and this allowed actinic
radiation damage to the conjunctival and
corneal epithelium and Bowman’s membrane (Coroneo 1993).
To evaluate functions of the tear film,
we employed a combination of Schirmer’s
test 1, BUT and mucus fern test. We considered values less than 10 mm/5 minutes
for Schirmer’s test 1, shorter than 10 seconds for BUT, and type III–type IV patterns for mucus fern test, abnormal
(Lemp 1973; Shapiro & Merin 1979; Rolando 1984; Nelson 1994).
There was no significant difference in
Schirmer’s test 1, which is important in
evaluation of the aqueous phase of the
tear film. BUT was significantly shorter
in the eyes with pterygia. Taylor has reported BUT measurements shorter than
10 seconds in 6 of 26 eyes with pterygia,
however, when compared to the control
group this was not statistically significant
(Taylor 1980). Our groups differed with
regard to the mucus fern test and marginal tear strip continuity. Taylor also
stated significant discontinuity of the
marginal tear strip in the eyes with ptery-
178
gia (Taylor 1980). In our study, in the eyes
with pterygia, strong correlation between
BUT and mucus fern test, and between
BUT and marginal tear strip continuity
were found with McNemar test.
Tear film stability is ensured by compositional factors like lipid, aqueous, mucus layers and hydrodynamic factors like
corneal sensitivity and mechanical factors via eyelid blinking (Tseng 1994). In
cases with pterygium, normal lid movement may be compromised and this may
lead to secondary changes in the desiccated epithelium, resulting in less wettable areas in BUT. In this study, cases
with dry spots consistently developing at
one location have been excluded in order
to reduce the effect of this hydrodynamic
factor on tear film stability.
BUT and mucus fern test are used to
detect mucus deficiency clinically (Tabbara & Okumoto 1982). Mucin glycoproteins are the major macromolecular
components of the mucus. Mucin plays
an important role in decreasing the surface tension of tears and increasing the
wettability of the hydrophobic lipoprotein epithelial surface (Lemp et al. 1971).
It was believed that the precorneal mucus
layer is derived from goblet cells – goblet
cell-secreted mucin (GCM) –, however,
recent studies have suggested that there
are at least two types of ocular mucins
and that the tear film predominantly consists of a unique type of mucosal epithelium-associated mucin (MEM) that can
exist in membraneous and secreted forms
(Chang & Tseng 1992). These findings
have led to a new concept that nongoblet
epithelial cells of cornea and conjunctiva
play an active role in maintaining the tear
film stability. It is likely that MEM expressed by nongoblet epithelial cells can
interact with GCM secreted by conjunctival goblet cells and, through this mucin
interaction, the interfacial tension between tear fluid and epithelial cell membrane is lowered and tear film is thus stabilized. So, in addition to compositional
and hydrodynamic factors, tear film stability is also controlled by the ocular surface epithelia (Tseng 1994). Recently it
has been shown that human conjunctival
epithelium expresses human mucin genes
MUC1 and MUC4, goblet cells MUC5
and corneal epithelium MUC1 (Inatomi
et al. 1995, 1996; Gipson & Inatomi
1997).
In conclusion, our study revealed significant abnormalities in BUT, mucus
fern test and marginal tear strip in the
eyes with pterygia. The altered mucus
pattern is likely to act as a primary
change inducing pterygium formation or
reflecting an existing pathology in the
cells lining the ocular surface. Hence, as
we do not know whether BUT was lower
before the development of pterygium,unraveling the mucin genes in patients with
pterygia may help to find out the main
factor causing the tear film instability.
References
Adamis AP, Starck T & Kenyon KR (1990):
The management of pterygium. Ophthalmol
Clin North America 3: 611–623.
Amano S, Kuroki M & Adamis AP (1997): Requirement for vascular endothelial growth
factor in wound-related corneal neovascularization. Invest Ophthalmol Vis Sci 38:
701.
Biedner B, Biger Y, Rothkoff L & Sachs U
(1979): Pterygium and basic tear secretion.
Ann Ophthalmol 11: 1235–1236.
BenEzra D, Hemo I & Maftzir G (1990): In
vivo angiogenic activity of interleukins.
Arch Ophthalmol 108: 573.
Chang HA & Tseng SCG (1992): Characterization of precorneal mucus layer. Invest
Ophthalmol Vis Sci 33(S): 951.
Clinch TE, Benedetto DA, Felberg NT &
Laibson PR (1983): Schirmer’s Test: A closer
look. Arch Ophthalmol 101: 1383–1386.
Coroneo MT (1993): Pterygium as an early indicator of ultraviolet insolation: A hypothesis. Br J Ophthalmol 77: 734–739.
Detels R & Dhir SP (1967): Pterygium: A geographical study. Arch Ophthalmol 78: 485–
491.
Gipson IK & Inatomi T (1997): A major conjunctival goblet cell mucin in the human,
mouse and rat is the gel-forming mucin
MUC5AC. Invest Ophthalmol Vis Sci 38:
465.
Hill JC & Maske R (1989): Pathogenesis of
pterygium. Eye 3: 218–226.
Inatomi T, Spurr-Michaud S, Tisdale AS &
Gipson IK (1995): Human corneal and conjunctival epithelia express MUC1 mucin. Invest Ophthalmol Vis Sci 36: 1818–1827.
Inatomi T, Spurr-Michaud S, Tisdale AS, Zhan
Q, Feldman ST & Gipson IK (1996): Expression of secretory mucin genes by human
conjunctival epithelia. Invest Ophthalmol
Vis Sci 37: 1684–1692.
Jaros PA & DeLouise VP (1988): Pingueculae
and pterygia. Surv Ophthalmol 32: 41–49.
Jensen OL (1982): Pterygium, the dominant
eye and the habit of closing one eye in the
sunlight. Acta Ophthalmol (Copenh) 60:
568–574.
Kwok LS & Coroneo MT (1994): A model for
pterygium formation. Cornea 13: 219–224.
Lemp MA, Dohlman CH & Kuwabara T
(1971): Dry eye secondary to mucus deficiency. Trans Am Acad Ophthalmol Otolaryngol 75: 1223–1227.
Lemp MA & Hamill JR (1973): Factors affecting tear film break-up in normal eyes. Arch
Ophthalmol 89: 103–105.
Mackenzie FD, Hirst LW, Battistutta D &
Green A (1992): Risk analysis in the development of pterygia. Ophthalmology 99:
1056–1061.
Nelson JD (1994): Diagnosis of keratoconjunctivitis sicca. Int Ophthalmol Clin 34: 37–55.
Rolando M (1984): Tear mucus ferning test in
normal and keratoconjunctivitis sicca eyes
Chibret Int J Ophthalmol 2: 32–41.
Rolando M, Baldi F & Calabria G (1988): Tear
mucus crystallization in children with cystic
fibrosis. Ophthalmologica 197: 202–206.
Shapiro A & Merin S (1979): Schirmer test and
break-up time of tear film in normal subjects. Am J Ophthalmol 88: 752–757.
Sunderkotter C, Beil W, Roth J & Sorg C
(1991): Cellular events associated with inflammatory angiogenesis in the mouse cornea. Am J Pathol 138: 931–939.
Tabbara KF & Okumoto M (1982): Ocular
ferning test: A qualitative test for mucus deficiency. Ophthalmology 89: 712–714.
Taylor HR (1980): Studies in tear film in climatic droplet keratopathy and pterygium.
Arch Ophthalmol 98: 86–88.
Taylor HR & Louis WJ (1980): Significance of
tear function test abnormalities. Ann
Ophthalmol 12: 531–551.
Taylor HR, West SK, Munoz B, Rosenthal FS,
Bressler SB & Bressler NM (1992): The
long-term effects of visible light on the eye.
Arch Ophthalmol 110: 99–104.
Taylor HR, West SK, Rosenthal FS, Munoz B,
Newland HS & Emmett EA (1989): Corneal
changes associated with chronic UV irradiation. Arch Ophthalmol 107: 1481–
1484.
Tseng SCG (1994): Evaluation of the ocular
surface in dry-eye conditions. Int Ophthalmol Clin 34: 57–69.
Received on April 29th, 1997
Accepted on September 3rd, 1997
Corresponding author:
Sibel Çalıskan Kadayifçilar*, M.D.
6. Sokak 22/4
06500 Bahçelievler
Ankara, Turkey
Tel: 90 312 213 82 79
Fax: 90 312 223 73 33
*Currently affiliated with Department of
Ophthalmology, Baskert University, Ankara,
Turkey
179