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1 From the Department of Ophthalmology, Kyoto Prefectural University of Medicine, Japan; and the 2 Nuffield Laboratory of Ophthalmology, University of Oxford, United Kingdom.
| Abstract |
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METHODS. The radii (R) of the central lower tear menisci were measured by a newly developed video meniscometer in 11 eyes of 11 normal volunteers (6 men, 5 women; mean age, 27.7 ± 3.6 years [SD]) and 9 eyes of 9 patients with tear deficiency and severe dry eye in whom the puncta had been therapeutically occluded (9 women; mean age, 50.6 ± 10.4 years). In this dry eye group, the absence of reflex tearing, coupled with the absence of lacrimal drainage due to punctal occlusion allowed more precise observation of the removal of tears from the meniscus. A 1-minute CT-T was performed, followed after an interval of 10 minutes by a 1-minute S-T. Tear meniscus curvature was documented before (R0) and during the tests at 30 seconds (R30) and 60 seconds (R60).
RESULTS. In the normal group, respective R values (CT-T; S-T; mean ± SD mm) were R0 (0.26 ± 0.11; 0.26 ± 0.07), R30 (0.27 ± 0.16; 0.20 ± 0.13), and R60 (0.29 ± 0.15; 0.23 ± 0.21); and in the dry eye group, respective R values (CT-T; S-T) were R0 (0.59 ± 0.23; 0.51 ± 0.19), R30 (0.52 ± 0.25; 0.22 ± 0.09), and R60 (0.51 ± 0.19; 0.21 ± 0.08). It was demonstrated in the dry eye group that R was diminished more by the S-T than by the CT-T in the time course of the measurement (P = 0.01). In the dry eye group alteration of R occurred within the first 30 seconds, and in this group significant correlation was found between R0 and the S-T result (r = 0.67; P = 0.05), and between R60 R0 and the S-T result (r = -0.81; P = 0.01). Also, there was a significant correlation between R60 R0 and the S-T result in the normal group (r = 0.71; P = 0.02). There were no significant correlations between R0 or R60 R0 and the CT-T results in either group.
CONCLUSIONS. These studies afford some insight into the dynamics of the Schirmer test, suggesting that wetting is influenced by the negative hydrostatic pressure within the tear meniscus. With the protocol used, no conclusion could be drawn about the relation between meniscus radius and wetting of the cotton thread.
| Introduction |
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The CT-T, incorporating phenol red as an indicator,6 8 9 10 11 is commercially available in Japan. It is minimally invasive and stimulates little reflex tearing. Wetting length is measured at 15 seconds. A value of 10-mm wetting or less supports the diagnosis of dry eye. The CT-T largely reflects the basal tear volume in the inferior conjunctival sac.10 11 12 To perform the test, the cotton thread is applied at a point between the lateral and middle one third of the lower lid margin for 15 seconds. The wetted part of the thread, indicated by the red color, is measured from the upper end. Several reports indicate the usefulness of this test.6 8 11
The S-T is believed to measure reflex tearing in response to irritation of the conjunctival surface by the inserted Schirmer strip. The Schirmer I test1 2 3 4 13 14 measures tear secretion over 5 minutes while allowing natural blinking. The modified Schirmer I test,14 15 16 which incorporates a drop of anesthetic, can be used to measure basal tear secretion but is less reliable, and the technique is less well standardized. The Schirmer I test with nasal stimulation17 can be usefully applied in the more severe forms of dry eye. In Sjögrens syndrome, the reflex response to nasal stimulation is greatly diminished compared with patients with non-Sjögrens aqueous deficiency.
Reflective meniscometry18 is a newly described test that provides the opportunity to measure tear meniscus curvature on-line. Because meniscus curvature is related to meniscus volume, it provides a tool with which to examine the dynamic features of the tear reservoir during the performance of the CT-T and S-T. In the present study, a new quantitative technique, reflective meniscometry, was applied to elucidate the effect of the CT-T and S-T on the tear reservoir by evaluating the radius of tear meniscus curvature.
| Subjects and Methods |
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In the control group, only the left eye was used for the study. The dry eye group comprised nine patients with dry eye (five left eyes of five women, four right eyes of four women), aged 38 to 66 years (mean age, 50.6 ± 10.4 years [SD]). There were six patients with Sjögrens syndrome and three without Sjögrens but with tear deficiency and dry eye. Sjögrens syndrome was diagnosed on the basis of the criteria of Fox et al.19 All subjects enrolled in the dry eye group had successfully received punctal plugs (seven eyes; Ready-Set Punctum Plug-Small; FCI Ophthalmics, Issy-les-Moulineaux, France) or punctal surgery, including cauterization and upper and lower punctal suturing (two eyes). This group of patients with dry eye was specially selected to provide a model system in which the effects of uptake of tear into either the cotton thread or Schirmer strip could be tested with a minimal influence of reflex tearing and lacrimal drainage.
Before the punctal occlusion, the dry eye group showed the severest form of dry eye, with a diminished value in the Schirmer I test (0.67 ± 1.7 mm/5 min [SD]) and severe corneal fluorescein staining scores20 21 (eight eyes, area [A]3:density [D]3 and one eye, A3D2, scored from 0 to 3, depending on the severity) and a rose bengal staining score13 of 10 (8.2 ± 1.7 [SD]). Before the punctal occlusion, the patients had been treated with a combination of preservative-free artificial tears containing 0.1% KCl and 0.4% NaCl (Softsantear; Santen Pharmaceutical, Osaka, Japan) and hyaluronan ophthalmic solution (HyaleinMini; Santen) with little improvement. However, after the occlusion therapy, fluorescein staining scores improved to A0:D0 in all subjects, and all were treated with the same preservative-free artificial solution (Softsantear) four to six times per day. The dry eye group was assumed to have a low level of tear drainage and reflex tearing, so that the artificial tears provided a major proportion of the tear reservoir in the conjunctival sac, meniscus, and preocular film. On the day of the study, subjects in the dry eye group were requested not to use the artificial solution within 1 hour of the examination.
This research conformed to the tenets of the Declaration of Helsinki, and before the beginning of the study the procedures were fully explained to all subjects, and informed consent was obtained.
Video Meniscometry
Reflective meniscometry was first established by our group to
observe tear meniscus behavior and to quantify the radius of tear
meniscus curvature in a noninvasive manner.18
In the
original instrument a specular image of an illuminated target is
photographed with the tear meniscus acting as a concave mirror. An
additional instrument, the video meniscometer, was developed to capture
such images using a video-recording system. In this study, a new video
meniscometer was developed that differs from the old version because of
the introduction of a half-silvered mirror that permits coaxial viewing
of the meniscus. The coaxial alignment of the new video meniscometer
permits the meniscus of either eye to be readily accessed. To obtain an
image from the meniscus, the target with a series of black and white
stripes (four black and five white; each 4 mm wide) is set in front of
the objective lens. For the purpose of calculating the radius of tear
meniscus curvature, selected meniscus images were printed out using a
video printer (print magnification, x70).
Measurement of Tear Meniscus Curvature during CT-T and S-T
For the CT-T and S-T, commercially available strips
(Zone-Quick; Showa Yakuhin Kako, Tokyo, Japan; sterilized tear
production measuring strips [scaled], Showa Yakuhin Kako) were used.
In the present study, the tests were performed in a nonstandard manner
for a period of 1 minute only. This is longer than the standard CT-T,
and shorter than the standard S-T. Because the result obtained from a
preliminary study showed that the CT-T had far less effect on tear
meniscus curvature than had the S-T, the CT-T was performed first,
followed by the S-T, after an interval of 10 minutes.
For both tests, images of the tear meniscus were captured in the region of the central part of the lower eyelid and were videotaped for periods of 10 seconds at baseline and at 30 seconds and 60 seconds. The subjects were allowed to blink naturally during the study. Adjustment of focus took approximately 10 seconds after the insertion of a strip, and a timer was started at the moment of the cotton thread insertion. During observation, images appeared very stable, although transient changes were seen at the time of blinking. Images at the selected time points were printed out using a video printer. The radius of tear meniscus curvature was calculated as described earlier at the center of each image at the three time points by an independent observer not involved in either meniscometry or tear testing.
In both CT-T and S-T, after the meniscometry, the wetted part of the strips were measured in millimeters in the normal way: For the CT-T, the wetting length was measured from the top of the thread and for the S-T, from the notch fold in the strip.
Statistical Analysis
The results were expressed as means ± SD. Meniscus radii
between CT-T and S-T were compared using repeated-measures analysis of
variance (ANOVA) separately for each subject group after confirming the
normality of the data by plotting them on normal probability paper
(Japanese Standards Association, Tokyo, Japan). A sphericity
test was also used. In cases of significant sphericity, the
GreenhouseGeisser test and HuynhFeldt test were used for
further analysis by repeated-measures ANOVA. The meniscus radii before
CT-T (R0) were compared using an
unpaired t-test between normal subjects and those with and
dry eye. Pearsons correlation coefficient was used to compare the
experimental and actual radius in the calibration of the meniscometer
and to compare R0 or
(R60
R0) with the CT-T or S-T result.
P
0.05 was considered to be significant.
| Results |
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2 = 9.29,
df = 2; P = 0.01). In view of this, the
GreenhouseGeisser test and HuynhFeldt test were used for analysis
by repeated-measures ANOVA. However, the result was the same as that
without adjustment. We compared meniscus radii between CT-T and S-T,
and we found no statistical difference in two-way interaction
(test x time) by repeated-measures ANOVA (P =
0.39). Examples of an image of the meniscus in a normal subject exposed
to the CT-T and S-T are shown in Figure 2 .
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2 = 2.36, df = 2;
P = 0.31) in the radii data. We compared meniscus radii
between CT-T and S-T, and we found a significant difference for two-way
interaction (test x time) by repeated-measures ANOVA
(P = 0.01), demonstrating that R was
diminished by the S-T more than the C-T, during the time course of the
measurement. R0 before CT-T in the dry
eye group was significantly larger than that in the normal group
(P = 0.00). Images of the meniscus in a subject with
dry eye exposed to the CT-T and S-T are shown in Figure 2
.
Relation between R0 and the Wetting
Length for CT-T or S-T
The relation between R0 for CT-T
or S-T and respective wetting-length for CT-T or S-T was determined in
both the normal and the dry eye groups. There was no significant
correlation between R0 for CT-T and
the CT-T result (r = 0.50; P = 0.12) or
between R0 for S-T and the S-T result
(r = 0.13; P = 0.71) in the normal group.
Also, there was no correlation in the dry eye group between
R0 for CT-T and the CT-T result
(r = -0.07; P = 0.86; Fig. 3
); however, in the dry eye group, there was a significant correlation
between R0 for S-T and the S-T result
(r = 0.67; P = 0.05; Fig. 3
).
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| Discussion |
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In this study, the results of neither the CT-T nor the S-T had a marked effect on the radius of curvature of the tear meniscus in normal subjects, presumably because the amount absorbed into the strip was balanced by the addition of reflex tears to the tear pool. Lacrimal drainage may also have siphoned off excess tears. However, occasionally, when reflex tearing was sizable, an increase in the radius of curvature was noted, implying that tear absorption by the strip and increased lacrimal drainage were insufficient to deal with the increase in secretion. The dry eye group had a paradoxically larger baseline meniscus curvature than the normal group, probably because the patients with dry eye were receiving tear substitutes on a regular basis, so that meniscus volume reflected chiefly the persistence of the most recently instilled drop. Because the dry eye group was specially selected to provide a model system in which to observe the transfer of fluid from the tear reservoir into the test materials, this did not influence the interpretation of our results. It is not possible, however, to state whether differences in tear substitute constituents may have had a differential effect on the uptake of fluid into the test materials.
In patients with dry eye and occluded puncta, it was demonstrated that the uptake of tears into the Schirmer strip significantly reduced meniscus curvature. The meniscus radius had become significantly smaller by 30 seconds after the beginning of the test, indicating the greater absorbing power of the Schirmer strip. However, no additional effect on meniscus curvature was observed during the ensuing 30 seconds. We assume that wetting of the test strips continues until the suction effect of the strips is balanced by the negative hydrostatic effect of the tear meniscus.24 Based on the capillary equation P = 2T/r, where P is the suction pressure of the fluid within the capillary, T is the surface tension of the fluid, and r is the radius of the capillary, it would be anticipated that the larger the radius of the tear meniscus, the lower the suction effect, so that a larger amount of tears would be absorbed by the strip. This hypothesis supports the findings in the dry eye group, where significant correlation was seen between the S-T result and the baseline meniscus radius (R0), as well as with the total change in meniscus radius (R60 R0). This was not the case with the CT-T, in which there was no significant relation between either the wetting length and the baseline meniscus radius (R0), or the wetting length and the change in radius (R60 R0). In fact, the CT-T result did not reduce the radius of the tear meniscus curvature in the dry eye group, which implies that the amount absorbed by the thread was insufficient to produce a detectable change in meniscus volume (and therefore meniscus curvature) even when the meniscus radius was large.
The difference in effect of the two tests on meniscus curvature over time is presumed to be due mainly to the greater mass of the Schirmer strip material and thus to its greater absorptive capacity. However, differences in the capillarity of the two materials may also have played a part, because under scanning electron microscopy it was found that the cotton thread was composed of a collection of longitudinally aligned threads, whereas the Schirmer strip exhibited a meshwork structure (Fig. 5) . We surmise that the capillarity of the cotton thread may be lost as it absorbs water, because of swelling, whereas that of the Schirmer strip, with its more rigid meshlike structure, is more stable. We had expected, because the CT-T is regarded as an indicator of tear volume, that the wetting length would correlate with baseline meniscus radius. The reason that it did not do so in the present study is probably because, for technical reasons, we were obliged to make measurements at 30 and 60 seconds, whereas the CT-T is normally read at 15 seconds. It may be, that the suction effect of the meniscus is lost by 30 seconds so that the effect is not seen. In future studies we plan to re-examine this relationship by comparing baseline meniscus radius in a similar group of patients with dry eye with the wetting length at 15 seconds. Also, to exclude an effect of tear substitutes on uptake, a washout period with unpreserved saline will be used.
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| Acknowledgements |
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| Footnotes |
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Supported in part by a research grant from the Kyoto Foundation for the Promotion of Medical Science, the Intramural Research Fund of the Kyoto Prefectural University of Medicine, and the research fund from the Kowa Life Science Foundation.
Submitted for publication July 1, 1999; revised January 13, and June 20, 2000; accepted July 11, 2000.
Commercial relationships policy: N.
Corresponding author: Norihiko Yokoi, Department of Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Hirokoji-agaru, Kawaramachi-dori, Kamigyo-ku, Kyoto 602-0841, Japan. nyokoi{at}ophth.kpu-m.ac.jp
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