Meibomian Gland Dysfunction: Sameera Irfan
Meibomian Gland Dysfunction: Sameera Irfan
Meibomian Gland Dysfunction: Sameera Irfan
T
he term meibomian gland dysfunction (MGD) cally made up of two lamallae, anterior and posterior,
was described for the first time by Korb and the blepharitis is also divided into an anterior and a
Henriquezin in the early 1980s3. Its prevalence posterior variety. The term “anterior blepharitis” is
appears to be much higher in Asian populations4, i.e. referred to as the inflammation of lid-margin anterior
greater than 60% while in Caucasians, it spans from to the grey line i.e. of the skin, eyelashes, and lash fol-
3.5% to 19.9%. There was no firmly established defini- licles. The term “posterior Blepharitis” means the in-
tion of MGD before 2011 when the International flammation of structures posterior to the grey line;
Workshop on MGD defined it5 as “a chronic, diffuse that includes the meibomian duct orifices, meibomian
abnormality of the meibomian glands, characterised glands, tarsal plate, and the blepharo-conjunctival
by the terminal duct obstruction and/or qualita- junction. Frequently, a mixed variety may be seen as
tive/quantitative changes in the glandular secretion. It the inflammatory process spreads from one structure
may result in an alteration of the tear film, symptoms to the next.
of ocular irritation, clinically apparent inflammation,
and ocular surface disease”.
Anatomy & Physiology of Meibomian Glands
MGD is generally considered by the clinicians as
posterior blepharitis6. The term “Blepharitis” means The meibomian glands were first described in detail
inflammation of the eyelids. As the eyelid is anatomi- by Heinrich Meibom7 in 1666. They are modified seba-
ceous glands8 with a tubulo-acinar structure. Each ing the tear film stable. After an absence of blinking,
gland consists of a cluster of 10-15 secretory acini meibum accumulates within the ducts and is delivered
opening into a long central duct via tiny ductules. in increased amounts when a person wakes up in the
There are 30-40 glands in the upper tarsal plate, each morning12. This accounts for the diurnal variation in
gland about 5.5 mm long while there are 25 glands in meibum secretion and the excess amount of oil in the
the lower tarsal plate, each being 2 mm long. They are pre corneal tear film makes the vision misty and
densely innervated by the sympathetic and parasym- blurred in the morning.
pathetic nerves (via the V nerve) as supplying the la- To summarise, the functions of healthy meibo-
crimal and accessory lacrimal glands, thereby ensuring mian lipids are:13
an optimal composition of the tear film. There is also a
strong hormonal control mediated by estrogens, an- i: To make the optical surface of the cornea smooth
drogens, progestins, retinoic acid, growth factors and at the air-lipid interface.
neurotransmitters. ii: They reduce the evaporation of the tear film.
The secretion of meibomian glands is called mei- iii: They enhance the stability of the tear film.
bum9 which is primarily made up of nonpolar lipids iv: They allow a uniform spread of the tear film over
(about 90%, comprising of wax, sterol-esters and tri- the cornea.
acylglycerols), while less than 10% are polar amphi-
philic lipids (hydroxy fatty acids), and a small amount v: They prevent the spillover of tears from the lower
of proteins and electrolytes. The tear film lipid is a meniscus over the lid margin.
multilayered structure comprising of a thin layer of vi: They prevent contamination of the tear film by
polar lipids that resides at the aqueous–lipid interface sebum.
and acts as a surfactant (essential for the uniform vii: The lipids help seal the apposing lid margins dur-
spreading and stability of the tear film). This is cov- ing sleep.
ered by a thick layer of non-polar lipids that forms the
lipid–air interface and resists the evaporation of
aqueous component of the tear film. Pathophysiology of MGD
The mode of meibum secretion is Holocrine, MGD is a complex disease that is caused by the inter-
which means that the secretions are produced in the play of hormonal, microbial, metabolic and environ-
cytoplasm of a cell; the cell membrane ruptures to re- mental factors14. It is classified according to the rate of
lease the secretion into the gland’s lumen while the gland secretion:
cell itself is destroyed in the process. The secretion
from multiple acini are poured via tiny ductules into A: Hypo-secretion of meibum occurs due to:
the central duct that opens at the grey line of the lid 1: Obstruction of meibomian duct opening by conjunc-
margin. A thin strip of orbicularis muscle fibres, called tival scarring seen in Ocular Pemphigoid, chemical
the Riolan’s muscle, surrounds the terminal part of the burns, Stevens Johnson’s Syndrome.
central duct and the few terminal acini present close to 2: Duct obstruction by desquamated epithelial cells,
the lid margin.10,11 During a blink, the pre-tarsal orbi- clumped together forming plaques, due to hyper-
cularis muscle generates a uniform compression of the keratinisation of the lid margin. This results in sta-
tarsal plate and of the enclosed meibomian glands, sis of meibum within the duct; the back pressure
thereby promoting the flow of secretion towards the produces cystic dilation of the glands, the pressure
duct opening by a milking action. Meibum is squirted compresses the acini and causes their atrophy.
out of the duct openings by the contraction of Riolan This results in further hypo-secretion. Hyper-
muscle. keratinisation is commonly the result of hormonal
Meibum is normally liquid at body temperature imbalance as a part of the ageing process, de-
and coats the lid margins thus making their movement creased expression of androgen receptors (hor-
smooth over the ocular surface and is delivered to the monal therapy), blink abnormality, contact lens
tear meniscus. From there it is picked up by the upper wear or medications.
lid margin (as it comes down during a blink and picks 3: Hypo-secretion with thick, altered meibum may be
up the tear meniscus) and is spread uniformly over the produced in seborrheic dermatitis, acne rosacea
aqueous layer of the tear-film thus preventing its thin- and as a side-effect of medications (anti-
ning and evaporation in-between the blinks, and mak-
of omega-3 fatty acids improves the quality of meibum resulting in gland atrophy.
with a decrease in the saturated fatty acid content of Also, chronic ocular surface inflammation affects
meibum. It decreases the ocular surface inflammation. the gland morphology and function, with secretion of
Foods rich in omega-3 fatty acids are flaxseed oil, and altered meibum that adds to the ocular surface in-
olive oil and oily fish like tuna and cod. flammation. All these changes worsen as the duration
6: Microbial infection: Cholesterol esters present in of contact lens wear increases.
meibum promote the growth of commensal organ- 9: Congenital anomalies of meibomian glands: A
isms on the eyelid margin, in particular Staphylo- reduction in the number or complete absence of
coccus aureus. The bacterial lipases, in turn, break meibomian glands maybe seen in Turner syn-
down the neutral fats and cholesterol esters, re- drome, ectodermal dysplasia with cleft-lip/palate
leasing glycerides and free fatty acids into the tear (ECC syndrome). Rudimentary meibomian glands
film, destroying the mucin layer and making the maybe visible as yellow streaks on the conjunctiv-
cornea hydrophobic. This makes the tear film un- al surface of the tarsal plate.
stable. The free fatty acids also stimulate hyper-
keratinisation of the lid margins, with keratin Dystichiasis (aberrant row of eyelashes) maybe
plugs adding to the blockage of meibomian ducts. present at birth in which meibomian glands are re-
placed by an extra row of eyelashes at the grey line.
7: Infestation with the Demodex mite: Demodex The misdirected eye lashes cause ocular surface trau-
mite is a microscopic ectoparasite of the humans- ma as well as meibum deficiency. Dystichiasis can also
kin and constitutes a part of the normal flora. It occur secondary to repeated rubbing of eyelids that
produces disease when its cell population increas- occurs in VKC, chronic allergic conjunctivitis or in the
es which has been detected in about 46.8% of autosomal dominant lymphoedema. Rubbing induces
MGD patients.21,22. It is of two distinct varieties: metaplasia of meibocytes to form eyelash follicles.
demodex folliculorum that infests the eyelash fol-
licles, and demodex brevis that burrows deep into
the sebaceous and meibomian glands. It causes a Clinical Presentation of MGD
direct mechanical damage to the epithelial cells of MGD, in its early stages, is asymptomatic and may
eyelash follicles (by feeding on them), and by lay- remain undiagnosed. It only becomes symptomatic
ing eggs at the base of eyelashes, causing follicular when it has worsened enough to cause tear-film insta-
distention and misdirected lashes. D. brevis me- bility or eyelid inflammation. Its symptoms and signs
chanically blocks the orifice of meibomian ducts are varied and include changes due to:
and produces a granulomatous reaction inside the
a: Altered morphology of the lid margin, altered
glands resulting in a chlazion.23 Therefore, it
meibum secretion, bacterial overgrowth and gland
should be considered in the differential diagnosis
dropout.
of every ocular surface disease.
b: Tear film instability.
Diagnosis can be made by random epilation of
nonadjacent eyelashes placed on a glass slide, c: Ocular surface inflammation
mounted with a coverslip with the addition of a drop-
let of oil, sodium fluorescein, peanut oil, or 75% alco-
hol which helps release embedded Demodex in the Symptoms & Signs
hair follicles. The most common symptom is visual fluctuation that
occurs during visual tasks associated with decreased
8: Contact Lens Wear 24: The pre-corneal tear film is
blinking, such as driving, reading, staring at a com-
approximately 3 microns thick; the average central
puter screen or watching television. This results in
thickness of a contact lens is 30 microns. When the
blurred vision, reduced focusing ability, and diplopia.
contact lens is worn, the tear film is split both
Despite the presence of a dry eye, a foreign body sen-
above and below the lens, its thickness is altered
sation and paradoxical reflex tearing may occur (as the
resulting in excessive evaporation and further
lacrimal gland function is normal and dry spots on
thinning.
cornea stimulate the reflex), particularly when patients
Contact lenses cause a direct mechanical trauma to are exposed to low environmental humidity and blow-
the lid margin by constant rubbing, desquamating the ing air.
epithelium, plugging the meibomian duct orifices
Chronic lid margin inflammation is manifested by
symptoms of lid discomfort, pain, redness and irrita- MGD is graded accordingly:29
tion. Grade 0: Normal, clear meibum is seen squirting out of
The symptoms related to ocular surface inflamma- the duct orifices with each blink and can be easily
tion are burning, itching, frequent blinking and pho- expressed by lightly touching the lid margin.
tophobia which gradually worsens to severe blepha- Grade 1 MGD: meibum looking opaque, viscous and
rospasm.25 In a study, MGD and dry eyes were the
needs pressure on the lid margin to be expressed. Pa-
most common causative factors for blepharospasm.26 tient is asymptomatic at this stage and has no corneal
The symptoms of ocular irritation tend be worse in the
staining. MGE score is more than 7.
morning because of prolonged exposure of the ocular
surface to toxic meibum and hyper-osmolar tears (due Grade 2 MGD: meibum becomes more thick, cheese
to poor clearance of the tear film) during sleep. These like, expressed with difficulty; frothing may be noted
symptoms also get worsened after the insertion of at the lid margins (indicates lipid breakdown by bac-
punctal plugs due to poor tear clearance. The most terial lipases). Patient may be asymptomatic or may
troublesome symptom is chronic burning with or have slight discomfort of lid margins, mild conjunctiv-
without associated photophobia. This is presumably al hyperaemia, mild corneal staining detected by fluo-
attributable to the presence of inflammatory mediators rescein at the inferior limbus and an MGE score of 7.
or to increased tear osmolarity in the pre-corneal tear Grade 3 MGD: plugging of ducts with thick meibum
film. Itching of eyelids is more commonly present in that cannot be expressed by pressure. MGE score is 3-
atopic patients. 7. Excessive frothing at the canthal angles or the lid
Morphological changes should be assessed on slit margins is noted. Patient is moderately symptomatic
lamp examination and documented27. with irritable lid margins, injected, watery eyes with
inferior corneal and conjunctival staining.
i: Lid margin: thickening, hyperaemia, telangiecta-
Grade 4 MGD: Meibomian gland dropout is detected
sia, keratinisation, foaminess or frothing at the
by the presence of notching at the grey line and by
canthal angles and along the lid margin. Presence
transillumination with a pen-light through everted
of scales along eyelash follicles should be noted
eyelids or by infrared photography. MGE score 0-3. At
(keeping in mind Demodex infestation).
this stage patient presents with severe dry eye symp-
ii: Meibomian duct orifice: plugging with thick toms and corneal staining.
meibum, notching (indicating lost/atrophic
iv: Ocular Surface Signs: Damage to the ocular sur-
glands), distichiasis.
face can result from avariety of closely linked factors
iii: Meibum quality is assessed by gently pressing the like increased tear-film evaporation that causes hyper-
lid margin with a finger or a cotton-tipped appli- osmolar tears and mediates the release of pro-
cator, and noting the ease with which meibum is inflammatory mediators in the tear-film like cytokines,
expressed and its texture. leukotriens, as well as decreased lubrication of the
Meibomian gland expressibility (MGE) is a clinical conjunctival surface of the eyelids prevent their
score28 that helps in assessing the severity of disease at smooth excursion over the eyeball. These result in an
initial presentation, and how it improves with treat- irritable eye and the symptoms overlap with the dry
ment. This is calculated by finding the number of eye disease. MGD is considered as themain contribu-
glands that can be expressed with mild pressure either tor to an evaporative dry eye disease, but an increased
with a cotton-tipped swab or a commercially available tear production (measured with Schirmer’s test) may
device that is specifically formulated for this purpose. be noted in patients with MGD. This is due to a com-
Five glands in the nasal, middle, and lateral thirds of pensatory reflex tearing due to ocular surface abnor-
the lower eyelid (total 15 glands) are expressed and malities and discomfort.
scored at each visit. A score of zero indicates a com-
plete blockage of ducts and total absence of meibum.
Diagnostic tests:30
A score of 15 indicates that the glands are expressible
throughout the lower eyelid. Patients with MGE score 1: Administer a symptoms questionnaire, Ocular
0-5 are always symptomatic, and those with a score of surface Disease Index (OSDI).31 This question-
7 or more, are usually asymptomatic. The quality of naire assesses symptoms of photophobia, ocular/
secretion is noted whether clear, opaque, vicid, cheesy. eyelid pain, blurring of vision, problems with
reading/driving/watching TV.
2: Measure blink rate and blink interval: Blinking a toxic meibum production.
normally occurs once every 3-4 seconds (15-20 Rose bengal and lissamine green stain dead / de-
times /minute) in most people. However, during vitalised epithelial cells and healthy cells that have lost
reading or staring at a computer/cellphone screen, their mucin coating. The conjunctiva is more intensely
the blink rate slows to 4.5 per minute, or once stained than the cornea. Therefore, early or mild cases
every 13.5 seconds. Blinking has a significant role of dry eye disease can be detected more easily with
in the secretion of meibum into the tear film, as al- these dyes.
ready explained. If the blink rate is slowed or
blinks are incomplete (the upper lid fails to close 7: Tear-film Break up time (TFBUT): It is assessed by
onto the lower lid), the lipid layer will build up at instilling a drop of fluorescein stain in the conjunc-
the lid margin and meibomian glands will be used tival sac and using a slit lamp with cobalt blue il-
less over time. This could lead to meibomian lumination. Time is noted between the last blink
gland atrophy if unidentified. and the appearance of a black island in the normal
green fluorescence of the tear film, or the first dry
3: Measure lower tear meniscus height and its clarity. spot on the cornea. The test is performed prior to
Normal lower tear meniscus is 1.00-2.00 mm. It the instillation of anaesthetic eye drops (as they
can simply be measured by narrowing the vertical are toxic to the corneal epithelium and produce
beam of a slit lamp or by Meniscometry: an in- dry spots). Normal TFBUT is 15-45 seconds. If it is
strument measures the tear meniscus height, its > 5 seconds, the patient is usually asymptomatic,
radius and cross-sectional area. but when it becomes less than 2 seconds, the pa-
4: MGE score: Expressibility of meibum, noting its tients are almost invariably symptomatic.
quality and grading the MGD. 8: Blink dynamics need to be noted: The examiner
5: Measure tear osmolarity:32 (measuring the concen- evaluates, by inspection on a slit-lamp, whether
tration of solutes/salts). As the aqueous component the upper lid closes on to the lower lid with a
of the tear-film evaporates, the concentration of blink, the frequency of partial and complete
solutes (mainly salts) increases. This test has be- blinks, the area of ocular surface (cornea and con-
come a critical part of dry eye management. It re- junctiva) that remains exposed with each complete
quires only a microlitre sample of tears (0.2 μL) blink.
collected by a micro-pen from the lateral canthal 9: Schirmer’s test:33 It is of two types: Schirmer I per-
tear meniscus. It is placed in an instrument, called formed without the topical anaesthesia and
the osmometer, which gives the reading in a Schirmer I performed after topical anaesthesia.
minute. The disadvantages are the need for an ex-
pensive equipment and its constant maintenance. S I test performed after topical anaesthesia measures
only the basal lacrimal secretion. It is highly specific and
The osmolarity of both eyes is measured; a differ- sensitive for a dry eye disease due to aqueous deficiency.
ence of 8 mOsm/L or more in the tear osmolarity be- After instilling a topical anaesthetic, a thin strip of fil-
tween the two eyes is considered abnormal. ter paper (5 x 35 mm) is placed in the inferior cul-de-
The osmolarity score of 300 mOsm/L or greater in sac in the lateral canthus. The excess tears should be
the higher scoring eye is considered abnormal. From wiped off prior to measuring the basal aqueous pro-
300-320 mOsm/L, is graded as mild; from 320-340 duction. This distinguishes a dry eye due to less
mOsm/L, is graded as moderate; and greater than 340 aqueous production from the one due to excess
mOsm/L, is graded as a severe dry eye disease. aqueous evaporation (due to MGD).
6: Ocular surface staining by Fluorescein: It stains S I test can be performed without the anaesthesia: this
the corneal stroma under the desquamated epithe- measures the basal tear secretion (which is from the
lium but does not stain a dry spot (it becomes hy- accessory lacrimal glands) as well as the reflex secre-
drophobic after losing its mucin coating), and ap- tion from the main lacrimal gland which is stimulated
pears as a blue spot in the uniform green fluores- by the irritating nature of the filter paper. Less than 10
cence of the tear film. Fluorescein pools in the mm of wetting after 5 minutes is diagnostic of ATD.
areas of epithelial erosions/thinning. The area of The test is relatively specific, but it is poorly sensitive.
ocular surface stained should be noted as an inter- Schirmer II test is performed without the anaes-
palpebral staining is due to excess evaporation of thesia. The nasal mucosa is stimulated by a cotton
aqueous while an inferior limbal staining is due to
wisp or a pungent odour and the amount of tear pro- iii: Gentle massage: after the application of heat, up-
duction (both reflex and basal) are noted. This should per eyelid should be massaged downwards with
only be performed in patients in whom Schirmer I test the fingers, while the lower lid massaged upwards
fails to demonstrate tear production (in KCS). to establish meibum flow out of the glands.
10: Meibography: Document morphology and mei- iv: Blinking exercises: they help improve meibum
bomian gland count in upper and lower lids by in- flow and tear-film spread over the ocular surface
fra-red camera, confocal microscopy, spectral- by contraction of pre-tarsal orbicularis and Riolan
domain optical coherence tomography. Normal muscle. Patients should be advised to do 10 good
meibomian glands are long, vertical, extending blinks at a time; the eyes should be fully closed for
from the lid margin to the end of tarsal plate. They 2 seconds, then squeezed for another 2 seconds.
become dilated and tortuous in early/mild dis- This should be done for every hour of digital de-
ease. In disease of intermediate duration/ mod- vice use.
erate severity, the gland dropout increases with iv: Topical lubricants: They help to relieve ocular
loss of identifiable gland architecture. In pro- surface irritation by replenishing the tear film.
longed / severe disease, all glands are markedly Preservative-free preparations should be preferred
shortened or absent. to prevent further damage to the ocular surface.
v: Topical or systemic antibiotics to control infec-
Management and Treatment of MGD34 tions: low-dose oral doxycycline (50-100 mg/day
i: Patient education: this is the most important part for 6 weeks) helps to reduce inflammation in the
of treatment in order to ensure compliance to eyelid tissue, it is anti-angiogenic and helps in res-
therapy. Patients need to be educated regarding toring healthy meibum secretion. Azithromycin
the chronic nature MGD, its prolonged therapy, 250 mg once daily is also affective in patients al-
affect of diet (flaxseed oil, fish oil, and olive oil), lergic to doxycycline.
environment dryness/humidity and the drying ef- vi: Topical Cyclosporin eyedrops (0.5%)36 or Tacro-
fects of topical or systemic medications. limus ointment / skin cream 0.03%: Cyclosporine
ii: Lid hygiene: lids should be scrubbed gently with as well as Tacrolimus are highly specific immuno-
diluted baby shampoo applied on cotton-tipped modulator drugs that primarily affects T-
applicator, and rinsed with lukewarm water. This lymphocytes. They are used as steroid-sparing
removes toxic foamy meibum and reduces micro- agents as they have all the anti-inflammatory af-
bial load. fects but without the side-effects of prolonged ste-
roid use. They increase the production of aqueous,
iii: Warm compresses or application of heat is the improve goblet cell count and reduce meibomian
mainstay of therapy. Normal meibum is liquid at gland inflammation. In addition, Tacrolimus
body temperature, but denatured meibum be- cream applied to the lid margin reduces vascular
comes thick, dry and hard. It blocks the duct open- congestion, telengiactasia, and improves the quali-
ing as well as the whole lumen of the ducts. Heat ty of meibum produced. To have these affects,
therapy dissolves the thick meibum, and to be ef- therapy has to be continued for 2-4 months. The
fective, the glands have to be consistently heated tear-film break-up time has shown to improve
to at least 45°C (113°F). This can be done with ap- with this therapy.
plication of a warm wet towel or cotton pads,
soaked in hot (not boiling) water; with the eyes vi: Treating Demodex mite infestation:37 Manage-
closed, the hot towelis held onto the eyelids for 2 ment involves reduction in the number of Demo-
minutes. It is made wet again with hot water and dex mites; total eradication is not required as it is a
the process repeated five times, so that total heat part of the normal skin flora. This can be achieved
application is for 10 minutes. This needs to be by a combination of lid scrubs (scrubbing the eye-
done daily for at least a month. It can also be done lids twice daily with baby shampoo diluted with
with commercially available heat masks, or devic- water to yield a 50% dilution and applying an an-
es (Lipi Flow Thermal Pulsation System, MiBo tibiotic ointment at night until resolution of symp-
Thermaflow)35 that helps the liquefaction of mei- toms) and removal of the eyelash collarettes with
bum and massages it upwards towards the ducts the use of a cotton-tipped applicator and lid foam.
from where it can be easily expressed. Demodex mites are resistant to a wide range of an-
tiseptic agents including 10% povidone-iodine, i: Add anti-inflammatory therapy for dry eyes (Top-
75% alcohol and erythromycin. The most effective ical Cyclosporin 0.5%, Tacrolimus 0.03%)40,41
and commonly used treatment is tea tree oil. ii: Ductal probing.
Chemically, it is Terpinen-4-oil –a terpene with an-
timicrobial, antifungal, and antiseptic properties. Grade 4: All of Grade 3 therapy.
There are many commercially available products
that contain tea tree oil like shampoo, soap, oint-
CONCLUSION
ment, skin cream. Hypochlorous acid and mercury
MGD is an extremely common clinical entity and is
oxide 1% ointment is also effective. Patients
the leading cause of an evaporative dry eye. It should
should be instructed to avoid oil-based cleansers
be specifically looked for and treated in its early stages
and greasy makeup as they can provide further
even in an asymptomatic patient; if untreated, it
"food" for the mites. They should discard the pre-
progresses to meibomian gland atrophy and drop out
viously used make-up, use hot water to wash their
which is an irreversible stage. The goal of therapy is to
clothes, and a hot dryer to dry them.
improve the flow and the quality of meibum so as to
vii: Intra-ductal Probing: it clears the obstruction of restore the stability of the tear film. Since the therapy
the ducts and allows the meibum to flow thereby has to be continued for 2-3 months, patient education
reducing the intra-ductal pressure (IDP), inflam- is mandatory to ensure compliance.
mation, lid congestion with improvement of
symptoms.
viii: Intense pulsed light (IPL): this also liquifies the Author’s Affiliation
meibum and improves its drainage by delivering Dr. Sameera Irfan
a combination of heat and gentle pressure to the FRCS, Consultant
eyelids. It is an in-office therapy and requires 1-2
sessions.
Author’s Contribution
The International Workshop on MGD recom- Dr. Sameera Irfan
mended a Staged Treatment Algorithm, depending Literature review, Manuscript writing & review.
upon the grade of MGD.
Grade 1:
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