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Original Article

Study of Meibomian Gland Dysfunction and

Hypercholesterolemia
Ashwin Segi, Kirti Nath Jha, Krishnagopal Srikanth
Department of Ophthalmology, Mahatma Gandhi Medical College and Research Institute, Sri Balaji Vidyapeeth, Puducherry, India

Abstract
Background: Hypercholesterolemia is a risk factor for ischemic heart disease and cerebrovascular disease. Increased cholesterol in the
meibomian gland secretion has been considered necessary for development of meibomian gland dysfunction (MGD). Aim: To study the
association of MGD with hypercholesterolemia in adults aged 20-60 years age. Setting and Design: Observational case-control study.
Methods and Materials: We studied one hundred and twenty individuals aged 20-60 years divided into two groups; sixty cases of MGD
and no known hypercholesterolemia; sixty controls with neither MGD nor hypercholesterolemia. Examination included anterior segment
examination, tear film break-up time (TBUT), Schirmer’s test and assessment of meibomian gland function. MGD was graded based on quality
of meibum secretion and meibomian gland function (expressibility). Other investigations included lipid profile, random blood sugar, serum
creatinine and body mass index (BMI). Statistical Analysis: We calculated proportion, mean, standard deviation, 95% confidence interval (CI),
Z- test, and paired t-test for comparison between groups. Results: Hypercholesterolemia (i.e. serum cholesterol ≥ 200 mg/dl) was found in 39
(65%) and 31 (51.67%) among cases and control respectively. Hypercholesterolemia was found in 17 (44.7%) cases with grade 2 meibomian
gland function (i.e. expressibility) (p=0.038) and 26 (68.4%) cases with grade 2 meibomian gland secretion (p = 0.037), these associations
were statistically significant. Conclusions: Moderate MGD (i.e. grade 2 expressibility and secretion) is associated with elevated level of total
cholesterol (i.e. serum cholesterol level ≥ 200 mg/dl).

Keywords: Dry eye, hypercholesterolemia, meibomian gland dysfunction

Introduction This study aimed to investigate the association between MGD

Meibomian gland dysfunction  (MGD) is a chronic, diffuse
abnormality of the meibomian glands, commonly characterized
by terminal duct obstruction and/or qualitative/quantitative
changes in the glandular secretion. [1] It may result in
alteration of the tear film, symptoms of eye irritation,
clinically apparent inflammation, and ocular surface disease.
Hypercholesterolemia  (total cholesterol  >200  mg/dl) is an
important risk factor for cerebrovascular disease, ischemic
heart disease, and peripheral vascular disease.[2]
Recent studies indicate that patients with moderate‑to‑severe MGD
have a high incidence of total blood cholesterol than the general
population. Furthermore, the young‑ and middle‑aged patients with
MGD with no history of hypercholesterolemia may have higher
blood cholesterol levels than the general population.[3,4]
Received: 10-02-2019      Revised: 04-03-2019
Accepted: 07-03-2019      Published: 11-11-2019
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and hypercholesterolemia in young‑ and middle‑aged adults
aged 20–60 years. MGD may prove a marker for unknown
hypercholesterolemia in case such an association between
hypercholesterolemia and MGD exists.
Material and Methods
This observational case–control study was conducted at a
rural tertiary care hospital from January 2015 to June 2016
with prior approval from the institutional human ethics
committee. Individuals aged 20–60 years with MGD and no
known hypercholesterolemia formed the cases; individuals
Address for correspondence: Dr. Kirti Nath Jha,
Mahatma Gandhi Medical College and Research Institute, Sri Balaji
Vidyapeeth, Pondy‑Cuddalore Main Road, Puducherry ‑ 607 402, India.
E‑mail: kirtinath.jha@gmail.com
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remix, tweak, and build upon the work non‑commercially, as long as appropriate credit
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For reprints contact: reprints@medknow.com

DOI: How to cite this article: Segi A, Jha KN, Srikanth K. Study of meibomian
10.4103/tjosr.tjosr_17_19 gland dysfunction and hypercholesterolemia. TNOA J Ophthalmic Sci Res
2019;57:208-12.

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Segi, et al.: Study of meibomian gland dysfunction and hypercholesterolemia

without MGD and no hypercholesterolemia formed the
controls.
Individuals aged below 20 and above 60  years were
excluded. Individuals with infectious keratoconjunctivitis
or inflammatory ocular surface diseases unrelated to MGD,
history of recent ocular surgery, presence of corneal arcus
and alterations of the lacrimal drainage system, concomitant
topical ophthalmic medications, and those with history of
topical ophthalmic steroids administration during 4  weeks
preceding the study, treatment with systemic drugs affecting
tearing, pregnancy, history of hypercholesterolemia or intake of
lipid‑lowering drugs, diabetes mellitus or any other systemic,
neurologic, rheumatologic, or dermatologic disorder affecting
the health of the ocular surface were also excluded from the
study.
Examination included height in meters and body weight in
kilograms and calculation of body mass index (BMI = weight
in kg/height in m2). Biochemical parameters included lipid
profile, random blood sugar, and serum creatinine. Eye
examination included anterior segment examination and
dilated fundus examination. MGD was diagnosed on the basis
of meibomian gland expression and the quality of meibum;
the meibomian gland secretion and function was noted by
expressing the glands under the slit lamp with the index finger.
The meibomian gland expression was done by applying digital
pressure through the substance of the lid. The procedure
involved digital expression of secretion from the central
glands with a force that does not require the application of
a rigid surface on the conjunctival aspect of the eyelid. As
such, when the eyelids are normal, light expression sufficed.
Heavy pressure was avoided as it may express presecretory
lipids from the acini. The process involved assessment of all
Table 1: Age‑sex distribution of cases and controls
Age (years) Cases Control
Male Female Male Female
20-40 ‑ 4 1 3
41-60 23 33 27 29
Total 23 37 28 32
three portions (lateral, middle, and the medial) of the lower
eyelid margin.[5]
Meibomian gland function was graded as follows: 0
(no obstruction ‑  meibum easily expressed), 1  (mild
obstruction ‑  meibum expressible with mild pressure),
2 (moderate obstruction ‑ meibum expressible with moderate
pressure), and 3 (complete obstruction ‑ no glands expressible,
even with hard pressure).[6‑8] The quality of expressed meibum
was graded as follows: 0  (clear fluid), 1  (cloudy fluid),
2  (cloudy particulate fluid), and 3  (toothpaste‑like).[8,9] Tear
film break‑up time  (TBUT) and Schirmer’s test were also
recorded. TBUT is the interval in seconds between a complete
blink and the appearance of the first randomly distributed dry
spot on the fluorescein sodium‑stained precorneal tear film
seen under the cobalt blue filter of the slit lamp.
Schirmer’s test is employed for quantitative assessment of
aqueous tear. It was performed by placing Whatman filter
paper 41 (5 mm × 35 mm) in the lower conjunctival fornix,
at the junction of outer one‑third and inner two‑third for
5 min. The measurement of wetting (in mm) after 5 min was
taken as a measure of aqueous tear secretion. We did not use
topical anesthetic during the procedure. Each eye was tested
separately.
Statistical analysis
The analysis of the data was carried out using Microsoft Office
Excel 2007 and IBM SPSS Statistics version 20 (IBM Corp,
Armonk, NY, USA). We calculated proportion, mean, standard
deviation, 95% confidence interval  (CI), Z‑test, and paired
t‑test for comparison between groups. P ≤ 0.05 was considered
as statistically significant.
Results
The study population included 120 individuals; 60 cases of
MGD and 60 controls without MGD. There were 51 males
and 69 females; M: F ratio 0.74. Among the cases, there were
23 (38.3%) males and 37 (61.67%) females. Controls included
28  (46.67%) males and 32  (53.3%) females [Table 1]. The
average age of the cases was 54.8 ± 5.6 years. The average
age of the controls was 52.3 ± 6.4 years. The difference of
age among cases and controls was not statistically significant.

Table 2: Average biochemical parameters of cases and controls

Patients with MGD (n=60) Controls (n=60) P (cases vs. controls)
BMI, mean±SD 23.5±1.9 23.4±1.8 0.78
Triglyceride (mg/dl), mean±SD 141.4±36.2 145.5±29.1 0.49
Total cholesterol (mg/dl), mean±SD 204.7±20.7 198.03±23.7 0.11
LDL (mg/dl), mean±SD 136.2±21.5 130.77±21.1 0.16
HDL (mg/dl), mean±SD 35.7±8.3 38.7±7.6 0.04
FBS (mg/dl), mean±SD 92.8±16.3 96.3±27.7 0.39
Creatinine (mg/dl), mean±SD 0.85±0.14 0.89±0.16 0.104
Hypertriglyceridemia, triglycerides ≥150 (mg/dl), n (%) 31 (51.7) 28 (46.7) 0.58
BMI: Body mass index, HDL: High‑density lipoprotein, LDL: Low‑density lipoprotein, FBS: Fasting blood sugar, MGD: Meibomian gland dysfunction,
SD: Standard deviation

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Segi, et al.: Study of meibomian gland dysfunction and hypercholesterolemia

Table 3: Comparison of total cholesterol levels among Table 6: Meibomian gland function (expressibility) and
cases and controls cholesterol levels
Age Mean±SD P Cholesterol (mg/dl) Function Total
(years)
Patients with MGD total Controls total 0 1 2 3
cholesterol (mg/dl) cholesterol (mg/dl) <200 3 15 4 ‑ 22
≤40 193.3±11.79 169.75±46.31 0.397 ≥200 3 16 17 2 38
41-50 192.62±19.98 204.72±29.98 0.216
51-60 209.09±20.15 197.84±14.79 0.006
MGD: Meibomian gland dysfunction, SD: Standard deviation Table 7: Meibomian gland secretion and cholesterol
levels

Table 4: Distribution of meibomian gland function among Cholesterol (mg/dl) Secretion Total

cases 0 1 2 3
<200 2 8 8 2 20
31
≥200 ‑ 10 26 2 38

21 level among the cases and controls in the age groups ≤40 and
41–50 years. In the age group, 51–60 years, the cases and the
controls had serum cholesterol values of 209.09 ± 20.15 mg/dl
and 197.84 ± 14.79 mg/dl, respectively. This difference was
6
found to be statistically significant (P = 0.006) [Table 3].
2 On the basis of expressibility, 6  (10%) cases had Grade  0
meibomian gland function, 31  (51.67%) cases Grade  1
Grade 0 Grade 1 Grade 2 Grade 3
meibomian gland function, 21  (35%) cases had Grade  2
meibomian gland function, and 2 (3.33%) cases had Grade 3
meibomian gland function [Table 4].
Table 5: Distribution of meibomian gland secretion among On the basis of quality of secretion, 2 (3.33%) cases showed
cases Grade 0 meibomian gland secretions, 19  (31.67%) cases
showed Grade 1 secretion, 33 (56.6%) cases showed Grade 2
33
meibomian gland secretions, and Grade 3 secretion was seen
in 4  (6.67%) cases [Table 5]. In two patients, those with
obstructive MGD, secretion quality could not be graded.
We noticed that only 4  (18.18%) individuals with serum
19
cholesterol <200 mg/dl needed moderate pressure to express
meibomian secretion  (i.e., Grade  2). Among those with
serum cholesterol, ≥200 mg/dl 17 (44.73%) fell into Grade
2 meibomian gland function (Z score = 2.0782, P = 0.038)
4
2 [Table 6]. This association was found statistically significant.

Grade 0 Grade1 Grade 2 Grade 3

Average BMI of the cases was 23.5 ± 1.9 kg/m2 and the controls
was 23.4 ± 1.8 kg/m2, respectively, (P = 0.78). Average serum
cholesterol among the cases was 204.7 ± 20.7 mg/dl, among
the controls was 198.03  ±  23.7  mg/dl,  (P  =  0.11). Average
triglyceride level among the cases was 141.4  ±  36.2  mg/dl
and among the controls was 145.5 ± 29.1 mg/dl, (P = 0.49).
Mean biochemical parameters of the cases and the controls
are shown in Table 2.
The age‑wise stratification of cases and controls into three
groups and comparison of serum cholesterol between these
subgroups did not reveal any statistical difference in cholesterol
We noticed only 8  (40%) individuals with serum
cholesterol  <200  mg/dl had cloudy white secretion with
particulate material (i.e. Grade 2), among those with serum
cholesterol ≥200 mg/dl 26 (68.4%) fell into Grade 2 meibomian
gland secretion (Z score = 2.0889, P = 0.037) [Table 7].
This association was found statistically significant.
(Odd ratio  =  3.25, 95% CI  =  0.39–26.92). The odds ratio
was compared between Grade  2 and Grade  3  secretions.
To find differences of their association with cases of
MGD and controls, we carried out stepwise logistic
regression analysis including age, sex, BMI, triglyceride,
total cholesterol, high‑density lipoprotein (HDL), low‑density
lipoprotein  (LDL), very‑LDL  (VLDL), and glucose as
covariates. MGD showed negative association with increased
blood HDL (P = 0.047, 95%   CI, 0.874–0.999). Increase in age

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Segi, et al.: Study of meibomian gland dysfunction and hypercholesterolemia
showed positive correlation with MGD (P = 0.035, 95% CI,
1.005–1.161). Sex, BMI, total cholesterol, LDL, VLDL, and
blood glucose did not show statistically significant association
with MGD.
Discussion
The prevalence of MGD, a common cause of chronic ocular
irritation varies from 3.5% to 70% in various series.[10]
MGD occurs due to change in composition of meibum or an
obstruction of the meibomian glands which occurs secondary
to hyperkeratinization of the duct epithelium and plugging
with a solidified secretion.[11] The resulting changes in tear film
lipid layer lead to increased evaporation and tear osmolarity,
and signs and symptoms of dry eye.[12] The composition of
meibum is mainly of wax and neutral sterol esters (~60%),
with lesser quantities of polar lipids, triglycerides, free fatty
acids, and free sterols.[13] Cholesterol esters are present in
patients with MGD.[14] Studies have also hypothesized that
increased cholesterol in the glandular secretion might have a
role in the pathogenesis of MGD.[11,15] Increase in cholesterol
concentration in meibum results in increase in its melting point,
and viscosity. These changes in meibum result in meibomian
gland plugging and development of MGD.[13]
Hypercholesterolemia is a risk factor for ischemic heart
disease, cerebrovascular disease, and peripheral vascular
disease.[2] There are three main types of lipoproteins in
total cholesterol: LDL, HDL, and VLDL. Raised levels
of LDL or decreased levels of HDL have been reported
to increase the risk of cardiovascular disease. [16] MGD
Grade  2 and above were seen more frequently among
individuals with hypercholesterolemia  (i.e., ≥200  mg/dl)
in this study. Since MGD Grade  2 and above alone are
symptomatic, it may be stated that symptomatic MGD is
associated with hypercholesterolemia. Results of this study
thus find support from an earlier study that noted similar
association. [2,3] We also found the association between
meibomian gland function  (expressibility) and cholesterol
levels; majority of the cases with Grade  2 expressibility
had hypercholesterolemia  (i.e., ≥200  mg/dl)  (P  =  0.038).
Hypercholesterolemia (i.e., ≥200 mg/dl) was found associated
with alterations in meibomian gland secretions also. Most
cases (68%) with Grade 2 secretion had higher than normal
cholesterol levels. These observations support our premise of
association between hypercholesterolemia and MGD. Due
to the limited sample size, it is not possible to comment on
the association between hypercholesterolemia and severe
MGD (Grade 3 meibomian gland secretion and meibomian
gland expressibility). We did not take into consideration
among cases Grade 0 and Grade 1 meibomian gland secretion
and function since they are rarely associated with dry eye
syndrome.
Other workers also have noted a higher incidence of
hypercholesterolemia in patients with moderate‑to‑severe
MGD in comparison to the general population.[3] Increase in
TNOA Journal of Ophthalmic Science and Research  ¦  Volume 57  ¦  Issue 3  ¦  July-September 2019
cholesterol level occurred from increased HDL level. However,
in our study, MGD showed a negative association with increased
blood HDL (P = 0.047, 95% CI, 0.874–0.999). Pinna et al. also
noted that young‑ and middle‑aged patients with symptomatic
MGD and with no history of hypercholesterolemia may have
higher blood cholesterol level than controls of similar age
without MGD. However, study by Pinna et al., is limited by its
small sample size restricted to people from Italian ancestry.[3]
Cholesterol levels among different age groups within cases
and controls in our study reveal higher mean cholesterol
level among the individuals aged 51–60 years. Increasing age
correlates also with increase in the total cholesterol levels and
MGD. In view of a few subjects (total: three) between 20 and
40 years, we are not in a position to opine on the association
between MGD and hypercholesterolemia in young adults.
Relatively small sample size remains the only limitation of this
study. Therefore, this study may be considered a pilot study
that needs validation on a larger population. Our findings, if
validated on a larger population, open the possibility of MGD
diagnosed during ophthalmic consultation being the first
indication of undiagnosed hypercholesterolemia.
Conclusion
Among young and middleaged adults aged 20–60 years,
individuals with moderate MGD have a higher incidence of
hypercholesterolemia than the healthy controls.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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