Download What is the best treatment approach for severe blepharitis?

Mand P, Mannis MJ. Treatment of severe blepharitis.
What is the best treatment
approach for severe blepharitis?
Paramdeep Mand, MD1, Mark J. Mannis, MD, FACS2
Corresponding author:
1. Clinical Fellow, Cornea, External Disease, and Refractive Surgery, UC Davis Eye Center,
University of California, Davis
Mark J. Mannis, MD, FACS
Department of Ophthalmology & VIsion Science
UC Davis Eye Center
4860 Y St, Suite 2400
Sacramento, CA 95817
E-mail: [email protected]
2. Professor and Chair, Department of Ophthalmology & VIsion Science, UC Davis Eye Center
Funding: None
Proprietary/financial interest: None
Abstract
Blepharitis is one of the most common
disorders encountered in ophthalmology.
Despite this, it can often be overlooked and
misdiagnosed. Blepharitis can manifest as
anterior and/or posterior disease. The form
of blepharitis can be determined based on
patient symptoms or clinical presentation. An
appropriate treatment plan can be made once
the form of blepharitis is elucidated. Three key
strategies should be addressed in the treatment
of blepharitis: (1) management of symptoms,
(2) control of any inflammation that is present to
prevent long-term damage, and (3) prevention
of recurrence. This review focuses on the
treatment of this disease as well as suggestions
for treating the most severe cases while keeping
these goals in mind.
Key words: Blepharitis; clinical
management; eye disorders
Relevant evidence-based
information
Although multiple classification schemes
have been introduced over the last century,
there has not been a uniformly accepted
classification scheme. Elsching is credited
for first describing the condition in 1908.3
Thygeson established the first major
classification scheme in 1946. He defined
the disorder as a chronic inflammation of the
lid border and described the disease in two
general categories: squamous and ulcerative.4
McCulley provided a much more complex
classification, splitting blepharitis into 6
categories.5 Recently, the American Academy
of Ophthalmology’s Preferred Practice
Patterns have offered a more simplified
classification of blepharitis, splitting it into
anterior blepharitis, posterior blepharitis, and
a combination of the two.6 Anterior blepharitis
includes such entities as seborrheic or
staphylococcal disease. Posterior blepharitis
refers to meibomian gland dysfunction.
The type of blepharitis can occasionally be
determined based on patient symptoms. For
example, symptoms of early morning irritation
or eyelid sticking are more typical for anterior
blepharitis, whereas symptoms that worsen as
the day progresses suggest posterior disease.
However, there is often overlap, and it can be
difficult to determine the etiology based on
symptoms alone. Patients often complain of
redness, irritation, burning, tearing, itching,
eyelash crusting, blurring or fluctuating vision,
photophobia and contact lens intolerance. They
may describe a history of multiple styes and/
or chalazia. Other factors, such as rosacea or
atopy, can contribute to the diagnosis as well.
The clinical presentation of anterior
blepharitis usually signals the underlying
cause. Staphylococcal anterior blepharitis
is more common in young to middle-aged
women.7 It is often associated with the
presence of “scurf” or collarettes at the eyelid
margin and on lashes as well as madarosis
and trichiasis. In more severe cases, other
findings associated with staphylococcal
hypersensitivity, such as perilimbal infiltrates
and corneal neovascularization, can be found.
In contrast, seborrheic disease tends to affect
an older population without a predilection
for gender.8 These patients will exhibit
erythematous and flaking skin around the
eyelids and eyebrows with oil hypersecretion
on the skin and seborrheic hypertrophy.
Other causes, such as rosacea and Demodex
infestation, must also be considered as
treatment strategies may vary.
Posterior blepharitis and meibomian
gland disease can be acquired or secondary.9
However, the clinical presentation will often
be similar. Patients may present with internal
horedola or chalazia. The meibomian gland
orifices can be obstructed with epithelial debris
or may express turbid secretions with pressure.
In the most advanced form, meibomian
secretions can be difficult to express due to
a paste-like consistency. Chronic disease will
lead to telangiectasia of the eyelid margin with
cicatricial changes resulting in an irregular lid
margin and misdirection of the meibomian
gland orifices. It is also important to note that
recurrent or irregular appearing chalazia can
be a harbinger for malignancy. While this is
rare, these lesions should be biopsied to rule
out potential sebaceous cell carcinoma.10
Once the type of blepharitis has been
categorized, it is possible to target the specific
pathophysiology with the appropriate treatment.
Treatment goals will vary based on the clinical
presentation, but three key strategies should be
addressed: (1) management of symptoms, (2)
control of any inflammation that is present to
prevent long-term damage, and (3) prevention
of recurrence.
Results
Treatment of anterior blepharitis
The basis of the treatment of blepharitis
is improving the local environment of
the eyelids. Therefore, one of the first
interventions that should be undertaken is
patient education and effective lid hygiene,
including warm compresses and lid scrubs.
Warm compresses liquefy debris and oils,
making it easier to remove them with lid
scrubs. Compresses should be performed at
least twice daily early in the disease course
and can be performed daily or once every
few days once symptoms are controlled. Lid
scrubs can be performed with either dilute
baby shampoo (e.g. Johnsons® Natural®
baby shampoo) or commercially available
scrubs, such as OcuSoft® Lid Scrub®.
Patients should be instructed not to use cotton
tipped applicators or cotton swabs for the lid
scrubs, since these are generally ineffective.
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REVIEW / Vis. Pan-Am. 2014;13(3):67-69
Figure 1: Pediculosis infestation
of the eyelashes.
Figure 2: Blepharitis with seborrhea
Figure 3: Corneal thinning and perforation
in the setting of severe ocular rosacea
Lid scrubs help control the impetus for
inflammation by removing not only debris
but also any bacterial toxins, and by reducing
the bacterial load of the eyelids. Cosmetics
should be avoided during flares. Make-up may
incite inflammation and prevent clearance of
debris from the lid margin.
Improving the local surface can prove to be
difficult in contact lens wearers, since the lens
may act as a reservoir for debris and can lead to
the formation of more depositis.11 It may be best
for patients wearing extended-wear soft contact
lenses to switch to daily wear lenses or rigid gas
permeable lenses. Discontinuation of contact
lens wear may be necessary.
The local environment must be approached
differently in patients with anterior blepharitis
in combination with seborrhea. It is thought
that fungi and yeast may feed on lipids in the
skin and perpetuate the inflammatory response
in patients with seborrhea.8 Cleansing the
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periocular skin and eyebrows with a gentle,
non-detergent antifungal shampoo in addition to
warm compresses and lid scrubs can be helpful.
Given that dry eye states and tear film
insufficiency often accompany anterior
blepharitis, artificial tears can provide
substantial symptomatic relief. Preserved tears
may be adequate between flares. However,
when the patient is acutely symptomatic, nonpreserved tears should be used since they can
be used frequently (i.e. more than four times
a day) without fear of worsening preservativerelated surface toxicity. Thicker formulations
such as gels and ointments can be used for
more severe cases.
Antibiotic therapy is warranted for moderate
to severe cases of anterior blepharitis.
Traditionally, this has been accomplished with
bacitracin and aminoglycosides (gentamicin
and tobramycin).12 More recently, macrolide
antibiotics (including azithromycin and
erythromycin) have been advocated due to
possible anti-inflammatory properties in addition
to their anti-infective properties.13 Azithromycin
is particularly desirable, since it has a long
half-life in both oral and topical forms. Using
ointments, which are best tolerated when instilled
at bedtime due to their propensity to blur vision,
can increase contact time of the drug with the
eye. One must be wary of the acute worsening
of symptoms after initiating an antibiotic as an
indication of a possible allergic reaction to the
drug. Use of the antibiotic should be stopped
immediately, and the reaction should be allowed
to subside prior to initiation of another drug.
Antibiotic therapy can be helpful in not
only the acute stage, but in long-term therapy
as well. Azithromycin can be dosed at 1 gram
by mouth weekly for three consecutive weeks.
This can then be repeated after a 3-4 week
period, until symptom control is achieved and
on an “as needed” basis thereafter. Azithromycin
is relatively well tolerated when taken orally;
however, there have been cases of acute cardiac
arrest induced by the medication.14 Although
more recent studies have disputed this15, it may
be best to obtain clearance from a cardiologist
prior to initiating systemic azithromycin therapy
in patients with a cardiac history. Topical
azithromycin is used twice daily in the acute
phase for rapid control of the bacterial load and
inflammation but can be used once daily on a
long-term basis for prevention.
Treatment for rosacea requires long-term
therapy as well. Oral tetracyclines have been
established as efficacious in the treatment of
ocular rosacea.16 Doxycycline is the preferred
agent, since it is better tolerated than first-
generation tetracyclines and possesses antiangiogenic and anti-inflammatory properties
(via anti-matrix metalloproteinase inhibition)
as well. The treatment dose for doxycycline
usually starts at 100mg once or twice daily for
a period of 6-12 weeks.17 It often takes a few
weeks for the therapeutic effect of doxycycline
to be realized, so the aforementioned methods
of immediate symptomatic control should be
used early in the treatment course. Oracea® is
a controlled-release tablet of doxycycline that
has been used for the treatment of rosacea. It
contains 30 mg of an immediate-release form
and 10 mg as a delayed-release doxycycline
that can be taken once daily. It has been shown
to improve symptoms and findings of ocular
rosacea significantly with minimal side effects.
Doxycycline is also beneficial in those patients
with moderate to severe staphylococcal-related
anterior blepharitis.
Severe cases of blepharitis often necessitate
a short course of topical corticosteroid treatment
to modulate the inflammatory component
of the disease. It is crucial to start with the
lowest effective dose of steroid to avoid any of
the potential complications of chronic topical
corticosteroid use, such as cataract formation,
ocular hypertension, and exacerbation of the
infectious process leading to a superinfection.19
Induction therapy during an acute flare can be
accomplished by using a steroid-antibiotic
combination, such as tobramycin with
dexamethasone. However, some severe cases
require long-term treatment with steroids, in
which case it would be best to use low-dose
formulations with less intraocular penetration
and activity than their counterparts, such as
fluorometholone 0.1% or loteprednol 0.5%.
Corticosteroid use can also be avoided all
together in patients requiring long term therapy
by using topical cyclosporine 0.05%.20
Cases of anterior blepharitis that are resistant
to the above therapies should raise concern for
less common etiologies. Herpes simplex-related
blepharitis will require therapy with systemic and/
or local antiviral therapy. Demodex-related disease
can be treated with eyelid scrubs combined with
tea tree oil or sulfur oil.21 Phthiriasis pubisrelated disease is treated by carefully removing
the lice and louse eggs and local application of
a pediculocide. Sexual contacts will also need
treatment to prevent re-infestation.
Treatment of posterior blepharitis
There is significant overlap in the
modalities used in anterior and posterior
blepharitis, particularly since some etiologies
are a combination of anterior and posterior
Mand P, Mannis MJ. Treatment of severe blepharitis.
disease (e.g. rosacea). With that said,
the treatment of posterior blepharitis is
primarily focused on the meibomian glands.
Similar to anterior blepharitis, the first goal
of therapy should be improvement of the
local environment. Patient education, eyelid
hygiene, warm compresses, and eyelid
massage should be the basis of treatment of
anyone with symptomatic meibomian gland
dysfunction. Warm compresses are typically
applied with a washcloth soaked in warm
water, but other methods have been described.
These include warming a soaked washcloth
or potato in the microwave or by using
commercially available warm compresses or
masks. Care must be taken not to overheat the
compresses, since facial burns can result.
These measures can be supplemented with
oral supplementation with omega-3 essential
fatty acids. Optimal dosage for omega-3
supplementation has not been established, but
dosages between 2000 to 6000 milligrams per
day are typically used. A one-year study evaluating
patients taking two 1000 milligram capsules of
omega-3 fatty acids three times a day found that
patients on the fatty acid supplementation had
improved tear break up time and fewer dry eye
symptoms than those not taking the capsules.22
It is not advised to start omega-3 fatty acid
supplementation in patients on anti-coagulants
because of an increased risk of bleeding.
Further symptomatic relief can be obtained
by supporting the tear film with topical
lubricants, since dry eye is often a complicating
factor in posterior blepharitis. This is best
achieved with lipid-promoting artificial tears as
lipid layer dysfunction is often the source of dry
eye symptoms in these patients.24
Tetracyclines and azithromycin are
also beneficial in the treatment of posterior
blepharitis. In addition to their aforementioned
anti-inflammatory properties, tetracyclines
are also thought to alter abnormal meibum.
This is, in part, secondary to alteration in
lipase enzyme activity, thereby preventing
degradation into smaller diglycerides. Both
doxycycline and azithromycin are thought
to increase the amount of carotenoids in
the meibum, thus stabilizing the tear film
and improving symptoms of dry eye.25
Azithromycin has also been shown to promote
phospholipidosis of the meibomian gland
epithelial cells, further stabilizing the ocular
surface.26 The two therapies are similar in
efficacy; however, four weeks of topical
azithromycin treatment has been shown to be
slightly more effective than oral doxycycline
in improving foreign body sensation and signs
of plugging of the meibomian gland orifices.25
Control of inflammation is an important
part of the treatment of meibomian gland
disease. This is partly modulated with the
use of tetracyclines and azithromycin, but can
necessitate the use of topical corticosteroids
for more rapid and complete control of
inflammation in severe cases. Additionally,
the use of corticosteroids will often be
necessary when blepharitis is complicated by
phlyctenular keratitis. The previous discussion
on the need for caution during the use of
corticosteroids is applicable to posterior
disease as well.
Multiple other modalities have been
proposed as therapies for treatment of
meibomian gland disease. The LipiFlow®
system is a newer thermodynamic method of
expressing meibum from obstructed glands. It
consists of an eye cup that is placed on the
external surface of the eye and a lid warmer
that is placed in the inner surface of the lid.
The lid warmer is insulated, thus shielding
heat from the eye and vaults over the surface
of the cornea to prevent contact. The lid
warmer applies continuously-monitored
directional heat to the inner eyelid while
inflatable air bladders underneath the eye cup
apply variable pressure to the outer eyelids.
This facilitates expression of meibum into
the eye cup. A single LipiFlow treatment has
been shown to be at least as effective in the
treatment of meibomian gland dysfunction
as a 3-month, twice daily lid margin regimen
of warming and lid massage.27 Intraductal
meibomian gland probing has also been
proposed as a method of relieving meibomian
gland obstruction. Topical anesthesia is
administhered and a 2-mm probe is passed
through the meibomian gland orificies. This
is then followed by a 4-mm probe for deeper
probing and expression of the meibum. This
has been reported to provide instant relief of
symptoms in 96% of patients (24/25), with all
patients achieving relief at 4 weeks.28
Conclusion and recommendation
Blepharitis is a common ocular condition
and is a frequent cause for office visits. The
presentation can be varied, but signs and
symptoms often reflect underlying dry eye,
infection/infestation, and inflammation. Once
the etiology has been elucidated and the
severity of signs and symptoms has been
graded, therapy can be individualized.
All therapy should start with patient
education, lid hygiene and warm compresses.
Management of remaining symptoms can be
accomplished with appropriate topical and
systemic drug therapy. Inflammation must
also be controlled to improve symptoms
and prevent long-term damage. Once the
acute flare is resolved, the therapy can be
tailored and tapered to a regimen focused on
preventing recurrence.
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