Ophthalmol Ther (2020) 9:797–807

https://doi.org/10.1007/s40123-020-00304-3

REVIEW

Therapeutic Instruments Targeting Meibomian Gland

Dysfunction
Laura Valencia-Nieto . Andrea Novo-Diez . Marta Blanco-Vázquez .
Alberto López-Miguel

Received: July 16, 2020 / Accepted: September 11, 2020 / Published online: September 24, 2020
Ó The Author(s) 2020

ABSTRACT symptoms in MGD patients. Likewise, eyelid

massaging and cleaning devices are also ben-
The most prevalent type of meibomian gland eficial for ocular signs and symptoms; how-
dysfunction (MGD), which is obstructive, is ever, patients usually need more than one
the main cause of evaporative dry eye and is session to maintain the therapeutic effect.
characterized by changes in the meibum Thermal pulsation has been reported to be
composition and duct obstruction. Eyelid more efficient than other strategies, and the
hygiene has usually been the most common effects can last up to 12 months. Moreover,
clinical approach. However, alternative thera- intense pulsed light therapy has been
pies for MGD are emerging on the market. demonstrated to improve ocular signs and
Some warming and humidity devices have led symptoms alone and in combination with
to an improvement in the signs and other therapies. Proper counseling of clini-
cians considering MGD status and patient
compliance will help patients to undergo the
adequate technique that best suits their
condition.
Laura Valencia-Nieto, Andrea Novo-Diez, and Marta
Blanco-Vázquez have contributed equally to this
manuscript.
Keywords: Eyelid hygiene; Intense pulsed
Digital Features To view digital features for this article light; Meibomian gland dysfunction; Thermal
go to https://doi.org/10.6084/m9.figshare.12937559. pulsation

L. Valencia-Nieto
A. Novo-Diez

M. Blanco-Vázquez
A. López-Miguel
Instituto Universitario de Oftalmobiologı́a Aplicada
(IOBA), Universidad de Valladolid, Valladolid, Spain

A. Novo-Diez
Departamento de Fı́sica Teórica, Atómica y Óptica,
Universidad de Valladolid, Valladolid, Spain

A. López-Miguel (&)
Redes temáticas de investigación cooperativa en
salud (Oftared), Instituto de Salud Carlos III,
Madrid, Spain
e-mail: [email protected]
798 Ophthalmol Ther (2020) 9:797–807

classified into two categories based on the mei-

Key Summary Points bum: low-delivery and high-delivery states.
Low-delivery states are further divided into
Most of the existing commercial devices hyposecretory and obstructive conditions, the
are useful for managing MGD if performed obstructive being the most prevalent type.
correctly. Obstructive MGD is characterized by chemical
changes in the meibum or terminal duct
Regular therapeutic sessions of eyelid obstruction. Hyposecretory MGD is defined by a
hygiene are required to maintain the reduced release of meibum without MG
improvement in MGD after the initial obstruction. A high-delivery state or hyper-
one. secretory MGD is characterized by the presence
Several studies have showed that thermal of a large volume of lipids on the lid margin [1].
pulsation and intense pulsed light can be MGD is the main cause of evaporative dry
the most efficient therapies in the eye disease (DED), the most prevalent type of
medium and long term. DED. Additionally, MGD is present in some
cases of aqueous-deficiency DED [2]. DED is an
Clinicians should counsel patients based ocular surface anomaly whose prevalence ran-
on MGD severity and treatment ges from 5 to 50% worldwide, and it is associ-
compliance. ated with limitations in performing activities of
daily life and even sometimes with depression
[6, 7]. Therefore, it is important to properly
manage MGD.
DIGITAL FEATURES Some therapies for MGD include improving
the environmental humidity, increasing dietary
This article is published with digital features to omega-3 fatty acid intake, using artificial tears,
facilitate understanding of the article. To view or anti-inflammatory therapy for DED. Never-
digital features for this article go to https://doi. theless, since the final goal of the treatment is to
org/10.6084/m9.figshare.12937559. improve the flow of MG secretions [8], eyelid
hygiene is the most common clinical treatment.
It consists of the application of heat and a
INTRODUCTION mechanical massage of the eyelids to increase
meibum secretion [1]. However, traditional
Meibomian gland dysfunction (MGD) is a warm compresses need to be reheated approxi-
chronic, diffuse abnormality of the meibomian mately every 2 min to maintain the heat for a
glands (MG), characterized by terminal duct sufficient period of time (usually 10 min). This
obstruction and changes in the glandular limitation makes it a time-consuming therapy
secretion. This anomaly may result in alter- and hampers compliance, which result in a lack
ations of the tear film, symptoms of eye irrita- of effectiveness [9, 10]. Considering that there is
tion, clinical inflammation, and ocular surface no standard recommendation for eyelid warm-
disease [1]. Its prevalence varies between 3.5% ing and it must be easily performed to increase
and 19.9% in the Caucasian population, while compliance, new therapies designed for MGD
it reaches [ 60% in the Asian population [2]. management are emerging on the market.
MGs are sebaceous glands located in the This review aims to detail the latest com-
tarsal plates of the eyelids, and their function is mercial medical devices available for MGD
to release lipids and proteins to the tear film [3]. management and their clinical effectiveness. In
The crucial role of the MG secretion, also called addition, each study included in this review
meibum, is the stabilization of the tear film and addressing the effectiveness of any therapy has
the protection of the ocular surface [4, 5]. been classified in terms of level of evidence
According to the ‘International Workshop following the Scottish Intercollegiate Guideline
on Meibomian Gland Dysfunction’ [1], MGD is Network (SIGN) [11]. This article is based on
Ophthalmol Ther (2020) 9:797–807 799

previously conducted studies and does not system, which provides constant but
contain any studies with human participants or adjustable heat to the anterior surface of both
animals performed by any of the authors. eyelids. It can be applied for 15 min in the
required number of sessions [21].
The TearCareÒ System (Sight Sciences, USA)
WARMING EYELID DEVICES is an electrothermal controller that heats both
eyelids to 41–45 °C by adjusting them with a
Warming Devices flexible, single-use material called iLidTM. The
system encourages meibum expression through
Warming masks help to release the meibum normal blinking during the treatment and
secretion through their application on the through the subsequent manual MG expres-
closed eyelids. The physiological melting point sion—the set includes a disposable EXPRESSTM
of the meibum is 32 °C, but in patients with Forceps to perform the manoeuvre. Badawi et al.
MGD, it is reported to increase up to 45 °C [22, 23] performed a clinical trial (I) evaluating
because of the alteration of its chemical com- the effectiveness of the TearCareÒ System and
position [12]. Due to the increased melting the MGDRx EyeBagÒ in two different groups of
point, temperatures close to 45 °C have been MGD patients. While one group underwent the
advocated for warm compress therapy [10]. Skin TearCareÒ for 12 min and subsequent MG
burns have been reported to occur after 35 min expression, the other group self-applied 5 min
of continuous exposure to thermal contact of of daily therapy with EyeBagÒ for 4 weeks. The
45 °C [13, 14]. Therefore, eye care practitioners TearCareÒ group showed a higher improvement
usually recommend using warming devices for in signs, including MG scores, and symptoms.
5–10 min, preventing adverse effects [15]. Additionally, the effects lasted for 6 months,
The MGDRx EyeBagÒ (The Eyebag Company, and no adverse events were reported.
Halifax, UK) is a reusable silk and cotton mask The MiBo ThermofloÒ (Mibo Medical Group,
that can be heated in a microwave for 40 s. Peak USA) consists of a tactile power console and a
temperatures (37.6 °C) may be reached after wired metal eye pad. The eye pad is heated
2 min of its application on the external upper (temperature not reported) and applied on the
eyelids. After 12 min of treatment, temperatures closed eyelids along with an ultrasound gel.
may slightly decrease (36.8 °C) [16, 17]. There is only one case report (III) indicating
Bilkhu et al. [17] (level of evidence: II) that an increase in the temperature of the inner
observed that 5 min of the MGDRx EyeBagÒ surface of the eyelids was not found after
application twice a day for 2 weeks was an 12 min of the MiBoFlo eye pad application [24].
effective and safe treatment for MGD. More- Therefore, further studies to prove the effec-
over, the benefits could last for 6 months when tiveness of this device are required.
subjects continued the therapy occasionally. The EyeGieneÒ Insta-Warmth SystemTM
Murphy et al. [18] (I) showed that increasing the (Eyedetec Medical, USA) works by placing the
treatment time to 10 min seemed to be equally Warming Wafers inside the mask, without
effective. However, Ngo et al. [19] (I) found no heating them in the microwave. It produces
significant changes in clinical signs after 1 heat from a chemical reaction in each wafer.
month using the MGDRx EyeBagÒ twice a day Some studies compared this device with the
for 10 min. MGDRx EyeBagÒ. Wang et al. [25] (I) showed
The EyeBagÒ Instant (The Eyebag Company, that clinical signs improved after the applica-
Halifax, UK) is a single-use, disposable warm tion of both therapies. Both treatments trans-
compress. It is activated by air; therefore, it ferred their peak temperatures to the eyelids in
starts to heat 2–3 min after the mask is removed 3 min, although they were slightly lower in the
from the sachet, and it can be placed on the EyeGieneÒ than in the EyeBagÒ. Furthermore,
eyelids for 10 min [20]. Wang et al. [26] (III) found that the warming
The eyeXpressTM Eye Hydration System effect of the EyeBagÒ was more prolonged.
(Holbar Medical Products, USA) is a goggle
800 Ophthalmol Ther (2020) 9:797–807

Therefore, the EyeBagÒ would be more effective end of the treatment, while in the lower ones
for severe cases of MGD. they were between 37.8 °C and 38.4 °C [27, 29].
Two studies (III) suggested that Ble-
Warming and Humidity Devices phasteamÒ might be a safe and effective therapy
for MGD because DED symptoms and MG
These devices also soften the meibum to function improved after 21 days of treatment
increase its release by applying moist heat to the [30, 31]. Ocular symptoms and clinical signs,
eyelids. Although it remains unclear, it was except the conjunctival redness score, may
hypothesized that moist warming devices might achieve a higher improvement after Ble-
be less effective than dry warming devices phasteamÒ than after warm compresses (III)
because of the cooling that follows the rapid [32]. However, in another study (I), signs
heat evaporation in the case of moist devices improved equally in both therapies [33].
[27]. Nonetheless, BlephasteamÒ may be useful for
The BRUDER Moist Heat Eye Compress subjects who find warm compresses ineffective
(Bruder Healthcare, USA) is a reusable mask that (III) [34].
absorbs water molecules from the air and
releases them as moist heat. The device might Warming and Massaging Devices
maintain 54 °C during the first 3 min, and this
temperature may slowly decrease, reaching These devices apply heat to the eyelids to liq-
45 °C after 12 min. The contact of this high uefy the meibum and then apply a mechanical
temperature mask with the eyelid skin could pressure to deliver the meibum to the ocular
burn it. Therefore, clinicians and patients must surface.
proceed with caution [15]. The upper outer The LipiFlowÒ system (Johnson & Johnson
eyelids may reach the peak temperature Vision, USA) applies heat (42.5 °C) and simul-
(40.1 °C) after 2 min of treatment. Then, the taneous pulsated pressure to the inner upper
heat may remain stable and decrease to 37.9 °C and lower eyelids for 12 min. The device con-
after 12 min [16] Tichenor et al. [28] (I) com- sists of an eyelid warmer that applies the heat
pared the application of the BRUDER Compress and an eye cup that applies the pressure
once versus twice a day. Although an improve- through an inflatable air bladder [35].
ment in MG scores and symptoms was observed Regarding its effectiveness, a retrospective
for both treatment regimens, DED symptoms case series study (III) showed that symptoms,
decreased more when applying the compress MG function, lipid layer thickness (LLT), partial
once a day. Nonetheless, these results were blink rate, and tear break-up time (BUT)
attributed to the higher compliance observed in improved 4 and 12 weeks after the treatment
the once-a-day group. [36].
The Eye-ssentialÒ Mask (Thera Pearl, USA) Some studies compared LipiFlowÒ with other
produces warmth when the pearls inside the MGD management strategies. Almost all of the
mask absorb, hold and deliver the heat acquired studies comparing the LipiFlowÒ with tradi-
in the microwave. The mask reaches its peak tional eyelid hygiene (I and III) found an
temperature (38.7 °C) after 3 min and decreases improvement in symptoms in the LipiFlowÒ
to 37.9 °C after 12 min [16]. group [37–40]. Only two studies (III) found an
The BlephasteamÒ (Théa Laboratories, improvement in signs, such as MG secretion
France) is a goggle system that produces moist and BUT [39, 41]. Other authors compared
warm air and heats the eyelids through the LipiFlowÒ with other medical devices, such as
condensation of water vapor. The melted mei- Tauber et al. [42] (I), who compared LipiFlowÒ
bum secretion is favoured by the normal with iLuxÒ and did not find differences between
blinking of the patients during the treatment. the two treatments. Another study (II) reported
Temperatures recorded in the outer upper eye- that one single LipiFlowÒ session was more
lids were between 37.4 °C and 40.0 °C at the effective in decreasing DED symptoms
Ophthalmol Ther (2020) 9:797–807 801

compared to 3 months of oral doxycycline [43]. this device with manual eyelid massage [54].
Finally, Yeo et al. [44] (I) showed a significant After 2 weeks of treatment, the increase in LLT
reduction in the tear evaporation rate after 4 was greater in the eyes treated with the
and 12 weeks of LipiFlowÒ treatment, in con- Eyepeace.
trast to EyeGieneÒ and BlephasteamÒ.
It was also reported that the LipiFlowÒ sys-
tem produced successful results in patients with CLEANING DEVICES
other conditions such as Sjögren syndrome (III)
[45], dry eye after laser correction surgery (III) These devices remove the bacterial biofilm,
[41], and symptomatic contact lens wearers debris, and scurf present in the MG ducts,
(I) [46]. which could occlude them and therefore pre-
Concerning the treatment duration, Greiner vent meibum delivery.
et al. [47, 48] conducted a study (III) with dif- The MG probing consists of the insertion of
ferent follow-up periods. While the MG score, probes of different sizes in the MG ducts to
BUT, and symptoms improved at 9 and dilate them and permit the subsequent meibum
12 months compared to baseline, the improve- expression. It requires the eye to be anes-
ment was only sustained in the MG score and thetized [55]. MG probing has been found to
symptoms after 3 years [49]. The improvement decrease DED symptoms 1 and 6 months after
in MG score and symptoms after 12 months the treatment (III) [56]. Sik Sarman et al. [57]
agreed with the results of Blackie et al. [50] (I). (III) treated patients using a modified cannula
In addition, Finis et al. [51] (III) also reported an to reduce pain and bleeding. After the proce-
improvement in ocular signs 6 months after dure, patients were prescribed antibiotics, cor-
treatment, such as LLT, the number of lid-par- ticosteroids, artificial tears, and eyelid massage.
allel conjunctival folds, and bulbar conjunctival Most of the patients had severe MGD and
redness. required more than one session. After 3 months,
Several authors have tried to predict the BUT, conjunctival hyperaemia, eyelid margin
success of the LipiFlowÒ treatment based on vascularity, and DED symptoms decreased.
different parameters. Satjawatcharaphong et al. The NuLids (NuSight Medical, USA) is a
[52] (III) suggested that it depended on gender, home-use device that has a disposable silicone
DED symptoms, and non-invasive tear break-up tip that massages the eyelids to remove biofilm
time (NIBUT). However, another study (III) and scurf [58].
proposed that patients with lower tear produc- The BlephEx (Blephex LLC, USA) is a hand-
tion and higher ocular surface staining and held device for removing bacterial biofilm and
osmolarity could also respond positively to the debris from the eyelid [59, 60]. Murphy et al.
LipiFlowÒ treatment [53]. The discrepancies [59] (III) studied the effectiveness of one session
between both studies could result from the dif- of BlephEx and the subsequent nightly appli-
ferent follow-up times. In the first study, it cation of OcuSoft Lid Scrub Plus foam on
ranged between 21 and 84 days, while in the patients with Demodex folliculorum blepharitis.
second one, it ranged between 30 and 40 days. They showed that the symptomatology and the
quantity of Demodex folliculorum decreased 2
and 4 weeks after the treatment. Epstein et al.
MASSAGING EYELID DEVICES [60] (I) evaluated the effectiveness of the Ble-
phex at the beginning of the study and after 1
These devices facilitate the mechanical release month in patients with Demodex blepharitis. In
of meibum, which has to be performed manu- addition, some of the patients used terpinen-4-
ally in conventional eyelid hygiene. ol eyelid scrubs twice daily for 2 months, while
The Eyepeace eyelid massage device (Eye- others used sham scrubs. The Demodex level
peace, UK) is a self-administered silicone device decreased after 2 months in patients who used
for massaging the eyelids to improve meibum terpinen-4-ol, while it decreased after 1 and
expression. A study (I) compared the efficacy of 2 months in patients who used sham scrubs.
802 Ophthalmol Ther (2020) 9:797–807

However, no changes in ocular symptoms were studies by Liu et al. [69] and Piyacomn et al. [70]
found. Regarding the ocular signs, patients who (I), this process would reduce some inflamma-
used sham scrubs worsened tear production and tory mediators such as interleukin (IL)-17A, IL-
improved blepharitis signs and the ease of MG 6, or IL-1Ra.
expression after 1 and 2 months. Two commercial IPL devices are widely used
for MGD treatment: the E [ Eye system (E-
SWIN, France), also called Intense Regulated
LIGHT-BASED DEVICES Pulsed Light (IRPL), and the M22 system (Lu-
menis, Israel), also called Optimal Pulse Tech-
These devices apply light directly on the skin nology (OPTTM). There are some differences
near the eyelids to treat MGD. between both devices such as the treatment
The intense pulsed light (IPL) devices are schedule. The E [ Eye system is usually applied
high-intensity, non-coherent, and non-laser in three or four sessions, performed on days 1,
light sources ranging from 500 to 1200 nm [61]. 15, 45, and 75 [63, 70, 71], while the M22 sys-
Patients are fitted with safety goggles covering tem is usually applied in three sessions, sepa-
both eyes during the treatment. The skin treat- rated by 3 or 4 weeks [62, 71, 72]. The spot size
ment area requires an ultrasound gel. Light is 15 9 40 mm in E [ Eye and 15 9 35 mm in
pulses are applied into the cheek skin, near the the M22, and the cooling system is Airflow in
lower eyelids. However, one study (I) evaluated the E [ Eye and ChillTipTM Contact in the M22.
the technique applying pulses directly into the These differences might be the reason why Wu
upper eyelids [62]. A higher improvement in et al. [71] (I) found discrepant results when
MG secretion function was found in the lower comparing both devices. They found that the
eyelids than in the upper eyelids. This was MG secretion function and tear film quality
attributed to the smaller tear meniscus present improved more after the M22 than after the
in the upper eyelids, which contains fewer E [ Eye treatment.
inflammatory proteins. Regarding the efficacy, some studies assessed
The number of light pulses required to IPL treatment alone. Jiang et al. [73] (III)
improve MGD has been addressed in the clinical observed an improvement in symptoms, BUT,
trial of Xue et al. [63] (I). They reported that conjunctival injection, and MG score from
applying five light pulses instead of four seemed baseline to day 45. However, no differences
to achieve higher and earlier improvements in were found between days 75 and 45, suggesting
clinical signs and DED symptoms. that two sessions were enough to reduce the
One of the proposed mechanisms of IPL to signs and symptoms of MGD. Vigo et al. [74]
improve MGD is the reduction of the bacterial (III) also performed follow-up visits on day 1,
load of the eyelid margin that could alter mei- 15, and 45. They found an improvement in
bum secretion or obstruct MG ducts [64, 65]. NIBUT, LLT, and osmolarity and suggested that
Xue et al. [63] (I) observed an inhibition of Co- patients with lower BUT responded better to the
rynebacterium macginleyi growth after IPL treat- treatment. Finally, Yurtasser et al. [75] (III)
ment, although the effect was not observed in found an improvement in symptoms and
all the bacterial species evaluated. Conversely, NIBUT at 1 month and an improvement in
Albietz et al. [66] (III) found no short-term symptoms, NIBUT, MG dropout, and corneal
changes in the eyelid margin colony counts staining in the mild and moderate MG atrophy
cultured after IPL treatment. Another proposed groups, lasting up to 12 months. No improve-
mechanism is that IPL may increase the skin ment was observed in patients with severe MG
temperature and the heat could be absorbed by atrophy. However, another study (II) compared
haemoglobin to eliminate the superficial blood IPL with eyelid hygiene and found that
vessels, especially when they are large [67]. The although both groups improved in symptoms,
MG inflammation would be reduced by the BUT, and MG score; the IPL group also
removal of these blood vessels [68] and also improved in conjunctival staining [76].
because of photomodulation. According to the
Ophthalmol Ther (2020) 9:797–807 803

Several studies evaluated the IPL treatment above, a clinical trial (I) compared the effec-
along with other treatments. Piyacomn et al. tiveness of LipiFlowÒ and iLuxÒ, without find-
[70] (I) observed a higher and faster improve- ing differences [42].
ment in the MG function in patients who
combined conventional eyelid hygiene and IPL
than in those patients who performed hygiene CONCLUSION
alone. Huang et al. [72] (I) compared IPL with
intraductal MG probing. They reported that the New therapies for MGD management are con-
combination of both methods was more effec- tinuously becoming commercially available,
tive than separately in improving symptoms, which help clinicians and patients to better
BUT, meibum grade, and telangiectasias. IPL cope with the anomaly. There are several
alone was more suitable for relieving intraductal warming and humidity devices as well as eyelid
inflammation, while MG probing was better for massaging and cleaning devices that have
patients with severe MG obstruction or MG showed improvement of MGD. However, treat-
scarring. Some studies combined IPL treatment ment sessions must be performed regularly to
with MG expression. While Toyos et al. [77] (II) maintain the therapeutic effect. Other instru-
only found an improvement in symptoms and ments based on thermal pulsation and intense
BUT, Dell et al. [78] (III) also observed pulsed light technology have also demonstrated
improvements in MG score and corneal stain- their ability to improve the MGD status for a
ing. However, Arita et al. [79] conducted a ran- longer time, and even in only one session, in
domized clinical trial (I) comparing a combined case of thermal pulsation. The wide variety of
therapy and MG expression alone. They found commercial devices can allow clinicians to
an improvement in the symptoms, NIBUT, adequately counsel patients based on the MGD
BUT, and MG score in both therapies. However, severity and therapeutic compliance.
the improvement was higher after the com-
bined therapy, and this group also improved the
LLT and corneal staining. ACKNOWLEDGEMENTS
There is a lack of agreement in the IPL
treatment protocol. The number of sessions
varies among three [74, 76], four [73, 77, 78], Funding. No funding or sponsorship was
and eight [79], and the period between sessions received for this study or publication of this
can fluctuate between 15 [73, 74, 77], 21 [78, 79] article.
and 30 [76, 77] days. Finally, the number of
flashes is not standardized, 4–5 being the most Authorship. All named authors meet the
frequent [73–75, 80], although other authors International Committee of Medical Journal
double the flashes or apply even more [78, 79]. Editors (ICMJE) criteria for authorship for this
article, take responsibility for the integrity of
the work as a whole, and have given their
MASSAGING AND LIGHT-BASED approval for this version to be published.
DEVICES
Disclosures. Laura Valencia-Nieto, Andrea
These devices combine the application of pres- Novo-Diez, Marta Blanco-Vázquez, and Alberto
sure to the eyelids along with the light-based López-Miguel do not have any commercial or
therapeutic effect to facilitate the release of proprietary interest in any product or company
meibum to the ocular surface. mentioned throughout the manuscript.
The iLuxÒ (Alcon, USA) is a handheld device
that applies light-based heat and compression Compliance with Ethics Guidelines. This
to the eyelids. An inner pad slips behind the article is based on previously conducted studies
eyelid and an outer pad is pressed against the and does not contain any studies with human
outer surface of the eyelid [58]. As mentioned
804 Ophthalmol Ther (2020) 9:797–807

participants or animals performed by any of the 5. Butovich IA, Millar TJ, Ham BM. Understanding
authors. and analyzing meibomian lipids—a review. Curr
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