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RESEARCH REPORT
ABSTRACT
Aims: The main purpose of this study was to investigate the relationship between Meibomian gland atrophy
(meiboscore) and Meibomian gland expressibility. In addition, the local distribution of Meibomian gland loss
was analyzed.
Methods: A retrospective analysis of 128 patients (92 women and 36 men, 57 ± 17 years) from our dry eye clinic
was performed. Infrared meibography was performed using the Keratograph 5 M (Oculus, Wetzlar, Germany)
For personal use only.
1
2 D. Finis et al.
ocular surface disease’’.3,4 A lot of different tests have and expressible Meibomian glands as a test of
been proposed for the diagnosis of MGD; however, no meibomian gland function. In addition, an analysis
clear diagnostic criteria have been defined yet. The of the local distribution of Meibomian gland loss was
most common diagnostic tools are the assessment of performed to determine, whether Meibomian gland
lid margin changes and diagnostic expression of the atrophy follows a certain pattern and if the examin-
Meibomian glands. If the diagnostic expression is ation of only the lower eyelid is sufficient for the
performed with the fingers, less than 10 Meibomian diagnosis of MGD.
glands of the lower eyelid yielding secretion indicate
the diagnosis of obstructive MGD.5 As the force
applied to the eye lid by this method is very variable, MATERIALS AND METHODS
Korb et al.5,6 developed a hand-held device, with
which a defined pressure can be applied to the eyelid. A retrospective analysis of data from 128 patients
For this standardized expression, 4 expressible (252 eyes, age 57 ± 17 years, 92 women and 36 men)
glands of the lower eyelid suggest a high likelihood from the dry eye clinic of the Department of
of obstructive MGD. Ophthalmology of the University of Duesseldorf
The obstruction of Meibomian glands is mainly was performed between April 2012 and March 2013.
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caused by an increased keratinization of the epider- All examinations were part of the routine diagnostic
mal epithelium in the excretory ducts.7,8 In addition, and were analyzed anonymously. This study followed
a change in lipid composition of Meibomian gland the tenets of the declaration of Helsinki.
secretion causes increased viscosity and thus further Inclusion criteria were as follows: (a) at least
reduced discharge of Meibum.9–11 This can be 18 years of age and (b) an evaluable meibography of
exacerbated by an increased number of commensal the upper and lower eyelid.
bacteria on the lid margin which influence the lipid Exclusion criteria were as follows: (a) Ocular
composition by production of lipases and ester- surgery or trauma within three months before exam-
ases.7,12 As a consequence, the tear film lipid layer ination, (b) any eyelid abnormalities, and (c) systemic
becomes thinner and destabilizes, resulting in an diseases resulting in dry eye.
For personal use only.
evaporative dry eye. Second, the ongoing production Before clinical examination, patients were
of secretions causes an elevated intraglandular pres- required to complete a symptom questionnaire
sure resulting in atrophy of the secretory acini.2,8 [Ocular-surface-disease-index (OSDI)]. This question-
Atrophy of Meibomian glands can be visualized naire gives a range of 0 (no symptoms) till 100 (severe
using meibography. Initially, a light source applied to symptoms).
either the palpebral or the conjunctival side of the eye Meibography was performed using the
lid was used to for Meibomian gland visualization by Keratograph 5 M Õ (Oculus, Wetzlar, Germany). The
trans illumination. Recently, infrared cameras were evaluation was based on the criteria proposed by Arita
introduced to detect a Meibomian gland loss non- et al.15 First, the Meibomian glands of the upper eyelid
invasively.5,13,14 Several scoring systems have been were visualized and graded. No atrophy corresponds
developed to quantify Meibomian gland loss.5 Some to 0 point, less than one-third to one point, more than
of them are based on the examination of the lower one-third to two points, and more than two-thirds to
eyelid only whereas some scoring systems evaluate three points. After that the glands of the lower eyelid
both the upper and the lower eyelid. However, up to were visualized and graded in the same way. The
now, there are no data concerning the local distribu- values for the upper (MS UEL) and lower eyelid (MS
tion of Meibomian gland loss. Therefore, it is not LEL) are then added to the total meiboscore (MS total)
certain, whether it is sufficient to examine just the with a range from 0 to 6 (Figure 1).
lower eyelid or if it is necessary to examine the upper In addition, a separate analysis of the nasal third of
tarsus, as well. In addition, it is still unclear what the lower eyelid (MS LEL nasal), the middle third of
diagnostic information a loss of Meibomian glands the lower eyelid (MS LEL middle), and the temporal
provides and what impact a loss of part of the third of the lower eyelid (MS LEL temporal) was
Meibomian glands has on the function of the remain- performed. No atrophy in an individual in nasal third
ing glands. So far it has been shown that meibography corresponded to 0 point, a partial degree of atrophy to
scores as an expression of loss of functional one point, and total atrophy to two points. The same
Meibomian glands are correlated with age and inverse analysis was performed for the nasal third of the upper
correlated with tear break-up-time (BUT)15 but there eyelid (MS UEL nasal), the middle third of the upper
are no data on the correlation of meibography and eyelid (MS UEL middle), and the temporal third of the
diagnostic Meibomian gland expression as an import- upper eyelid (MS UEL temporal) (Figure 2). To get the
ant test for obstructive MGD.5 most objective results, all meibography images were
Therefore, the main purpose of this study was to analyzed by two different investigators.
investigate the relationship between Meibomian The number of expressible Meibomian glands was
gland atrophy measured by infrared meibography quantified using the Meibomian-gland-evaluatorÕ
Current Eye Research
Non-contact Meibography in the Diagnosis of MGD 3
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FIGURE 1 Grading of meibography according to Arita et al. (A: lower eyelid; B: upper eyelid): 1, no loss of Meibomian glands (0
point); 2, less than one-third loss of Meibomian glands (one point); 3, less than two-thirds loss of Meibomian glands (two points); 4,
more than two-thirds loss of Meibomian glands (three points).
For personal use only.
the height of a normal tear meniscus was graded as TABLE 1 Characteristics of the study collective.
3 and a large fold which extends over the inner lid
25% 75% p-value
margin was graded as 4. Percentile Median Percentile KS
Statistical analysis was performed using Microsoft
Excel 2010 and GraphPad Prism version 6 (GraphPad Age 47 58 70 0.0033
Inc., San Diego, CA). For normally distributed values LLT (nm) 47 64 89 50.0001
Tear meniscus 0.2 0.3 0.4 50.0001
and for non-normally distributed values, the linear height (mm)
Pearson’s correlation coefficient and the linear correl- TBUT (s) 3 6 13.5 50.0001
ation coefficient by Spearman were calculated, Schirmer 5 10 17.5 50.0001
respectively. A p-value of 50.05 was considered LIPCOF 2 3 3 50.0001
statistically significant. The testing for normal distri- Staining 0 3 4.5 50.0001
Expr. glands 2 4 7 50.0001
bution was performed by using the Kolmogorov– OSDI 32.1 45.8 61.4 0.035
Smirnov test. A p-value40.05 was considered as not MS UEL temporal 1 1 1 50.0001
statistically significantly different to the normal MS UEL middle 1 1 1 50.0001
distribution. For analysis of the local distribution of MS UEL nasal 1 1 1 50.0001
the meiboscore and comparison between individual MS UEL 1 1 2 50.0001
MS LEL temporal 0 1 1 50.0001
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!
TABLE 2 Correlations between the total meiboscore and partial meiboscores of the eyelids.
MS total versus MS total versus MS total versus MS total versus MS total versus MS total versus MS total versus MS total versus
Spearman r MS UEL temporal MS UEL middle MS UEL nasal MS UEL MS LEL temporal MS LEL middle MS LEL nasal MS LEL
MS total, meiboscore according to Arita et al.; MS UEL, meiboscore of the upper eyelid; MS LEL, meiboscore of the lower eyelid; nasal, middle, and temporal refer to the individual third
0.2122–0.4392
TABLE 4 Sensitivity and specificity for different cut-off values
0.06431
0.03271
MS total
of the meiboscore to detect MGD Meiboscore as defined by
0.3222 to
0.2851 to
Arita et al., MGD defined as 4 expressible Meibomian glands.
0.3304
50.0001
0.1966
0.0029
0.1615
0.0117
Sensitivity Specificity
0.1866–0.4183 Meiboscore 1 0.963 0.108
Meiboscore 2 0.836 0.247
Meiboscore 3 0.493 0.645
0.04709
0.001405
MS LEL
0.3077 to
0.2545 to
Meiboscore 4 0.284 0.796
50.0001
0.1806
0.0066
0.1287
Meiboscore 5 0.164 0.903
0.307
0.046
0.2595–0.4803
MS LEL nasal
0.01044
0.1713 to
0.2471 to
Korb et al.6
0.03691
0.3752
50.0001
0.5835
0.0633
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DISCUSSION
MS LEL middle
0.2328–0.4577
0.2804 to
50.0001
0.2633
0.1558
0.0157
0.1302–0.3703
0.07420
0.1862 to
0.05695
For personal use only.
0.2542
50.0001
0.1921
0.3807
0.07609
MS UEL
0.3255 to
50.0001
0.2102
0.0015
0.2041
0.0014
0.01039
0.2461 to
50.0001
0.1902
0.0042
0.0633
0.1198
0.1706–0.4046
0.2538 to
50.0001
0.2632
50.0001
0.0472
0.128
0.007695
0.2486 to
0.3205
50.0001
0.1893
0.0044
0.1225
0.0576
versus
Although Meibomian gland lost was not constant Table 4, there is no cut-off value with a satisfactory
over the tarsal surface in this study, there was a strong sensitivity and specificity for the detection of MGD as
correlation between meiboscores of the upper and the defined by 4 expressible Meibomian glands. For
lower eyelid and the total meiboscore, indicating that comparison, determination of tear-osmolarity with a
the examination of the lower eyelid might be suffi- cut-off value of 316 mOsm/L was found to yield a
cient for screening purposes in the clinical routine. For sensitivity of 59%, a specificity of 94%, and a overall
the meiboscore of the middle third of the lower eyelid, predictive accuracy of 89% for the diagnosis of dry
we could still find a strong connection with the total eye syndrome.5 Also other tests like, for example,
meiboscore as well as with functional parameters like thermography might be better single test for the
TBUT or expressible glands. However, the correlation diagnosis of dry eye.22,23 In our study, collectively
coefficient was lower (r = 0.71) compared with the 33.3% (5 of 15) of the eyes without Meibomian gland
complete lower eyelid (r = 0.89), indicating the neces- atrophy (meiboscore 0) showed less than four express-
sity to examine the complete lower eyelid. ible glands, which underlines that MGD can occur
Nonetheless, in unclear cases of MGD, the complete without atrophy of the Meibomian glands, and
examination of both the upper and the lower eyelid that this group of patients would be overlooked, if
should always be performed. Although there was a only meibography would be used for the diagnosis
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handheld instrument to apply a certain pressure on atrophy is not constantly distributed over the tarsal
the eyelid. The main advantage of this instrument is plate but the examination of the lower tarsus seems to
that the high variability of diagnostic expression be sufficient for the evaluation of Meibomian gland
between different investigators caused by variance atrophy. The correlation of the meiboscore with
of the applied force to the eyelid is minimized.5,6 expressible Meibomian glands and TBUT suggest
Obstructive MGD is the main reason for an evapora- that in patients with detectable Meibomian gland
tive dry eye but clinical signs like obvious blepharitis atrophy there is also an impaired Meibomian gland
are often absent. Therefore, the diagnostic expression function. However, due to its limited sensitivity and
can be considered to be the most important functional specificity, meibography alone seems not to be suffi-
test in the diagnosis of obstructive MGD.5 The cient as a single test, but has to be interpreted in the
negative correlation between expressible Meibomian context of other clinical parameters such as express-
glands and Meibomian gland atrophy found by ible glands and TBUT for the diagnosis of MGD. In
meibography strongly indicates that meibography is the future, larger, prospective studies are needed to
a useful test in the diagnosis of MGD and underlines further evaluate the potential of meibography in the
that Meibomian gland loss is associated with an diagnosis of MGD.
impaired Meibomian gland function.
The inverse correlation between meibography and
TBUT as another functional parameter was already
described by Arita et al. and Ban et al.15,19 Our data DECLARATION OF INTEREST
show similar results using non-invasive and auto-
mated TBUT measurements. However, non-invasive The Keratograph 5 M used in this study was provided
TBUT usually shows higher values than fluorescein- by the company Oculus. David Finis has received
TBUT because of the destabilizing effect of fluorescein travel reimbursement from the company Oculus.
applied on the tear film. While it has also been Otherwise there are no conflicts of interest related to
suggested that non-invasive and fluorescein-TBUT the present work for any of the authors.
might measure different phenomena,5 our data are in
accordance with the results of Arita and Ban et al.
However, our data also shows that for TBUT values
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