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, Mark J. Mannis, MD, FACS
University of California, Davis
Department of Ophthalmology & VIsion Science
2. Professor and Chair, Department of Ophthalmology & VIsion Science, UC Davis Eye Center UC Davis Eye Center
4860 Y St, Suite 2400
Funding: None Sacramento, CA 95817
Proprietary/financial interest: None E-mail: mjmannis@ucdavis.edu

Abstract refers to meibomian gland dysfunction. In the most advanced form, meibomian
Blepharitis is one of the most common The type of blepharitis can occasionally be secretions can be difficult to express due to
disorders encountered in ophthalmology. determined based on patient symptoms. For a paste-like consistency. Chronic disease will
Despite this, it can often be overlooked and example, symptoms of early morning irritation lead to telangiectasia of the eyelid margin with
misdiagnosed. Blepharitis can manifest as or eyelid sticking are more typical for anterior cicatricial changes resulting in an irregular lid
anterior and/or posterior disease. The form blepharitis, whereas symptoms that worsen as margin and misdirection of the meibomian
of blepharitis can be determined based on the day progresses suggest posterior disease. gland orifices. It is also important to note that
patient symptoms or clinical presentation. An However, there is often overlap, and it can be recurrent or irregular appearing chalazia can
appropriate treatment plan can be made once difficult to determine the etiology based on be a harbinger for malignancy. While this is
the form of blepharitis is elucidated. Three key symptoms alone. Patients often complain of rare, these lesions should be biopsied to rule
strategies should be addressed in the treatment redness, irritation, burning, tearing, itching, out potential sebaceous cell carcinoma.10
of blepharitis: (1) management of symptoms, eyelash crusting, blurring or fluctuating vision, Once the type of blepharitis has been
(2) control of any inflammation that is present to photophobia and contact lens intolerance. They categorized, it is possible to target the specific
prevent long-term damage, and (3) prevention may describe a history of multiple styes and/ pathophysiology with the appropriate treatment.
of recurrence. This review focuses on the or chalazia. Other factors, such as rosacea or Treatment goals will vary based on the clinical
treatment of this disease as well as suggestions atopy, can contribute to the diagnosis as well. presentation, but three key strategies should be
for treating the most severe cases while keeping The clinical presentation of anterior addressed: (1) management of symptoms, (2)
these goals in mind. blepharitis usually signals the underlying control of any inflammation that is present to
Key words: Blepharitis; clinical cause. Staphylococcal anterior blepharitis prevent long-term damage, and (3) prevention
management; eye disorders is more common in young to middle-aged of recurrence.
women.7 It is often associated with the
Relevant evidence-based presence of “scurf” or collarettes at the eyelid Results
information margin and on lashes as well as madarosis
Although multiple classification schemes and trichiasis. In more severe cases, other Treatment of anterior blepharitis
have been introduced over the last century, findings associated with staphylococcal The basis of the treatment of blepharitis
there has not been a uniformly accepted hypersensitivity, such as perilimbal infiltrates is improving the local environment of
classification scheme. Elsching is credited and corneal neovascularization, can be found. the eyelids. Therefore, one of the first
for first describing the condition in 1908.3 In contrast, seborrheic disease tends to affect interventions that should be undertaken is
Thygeson established the first major an older population without a predilection patient education and effective lid hygiene,
classification scheme in 1946. He defined for gender.8 These patients will exhibit including warm compresses and lid scrubs.
the disorder as a chronic inflammation of the erythematous and flaking skin around the Warm compresses liquefy debris and oils,
lid border and described the disease in two eyelids and eyebrows with oil hypersecretion making it easier to remove them with lid
general categories: squamous and ulcerative.4 on the skin and seborrheic hypertrophy. scrubs. Compresses should be performed at
McCulley provided a much more complex Other causes, such as rosacea and Demodex least twice daily early in the disease course
classification, splitting blepharitis into 6 infestation, must also be considered as and can be performed daily or once every
categories.5 Recently, the American Academy treatment strategies may vary. few days once symptoms are controlled. Lid
of Ophthalmology’s Preferred Practice Posterior blepharitis and meibomian scrubs can be performed with either dilute
Patterns have offered a more simplified gland disease can be acquired or secondary.9 baby shampoo (e.g. Johnsons® Natural®
classification of blepharitis, splitting it into However, the clinical presentation will often baby shampoo) or commercially available
anterior blepharitis, posterior blepharitis, and be similar. Patients may present with internal scrubs, such as OcuSoft® Lid Scrub®.
a combination of the two.6 Anterior blepharitis horedola or chalazia. The meibomian gland Patients should be instructed not to use cotton
includes such entities as seborrheic or orifices can be obstructed with epithelial debris tipped applicators or cotton swabs for the lid
staphylococcal disease. Posterior blepharitis or may express turbid secretions with pressure. scrubs, since these are generally ineffective.

PAN-AMERICA 67
 REVIEW / Vis. Pan-Am. 2014;13(3):67-69

periocular skin and eyebrows with a gentle, generation tetracyclines and possesses anti-
non-detergent antifungal shampoo in addition to angiogenic and anti-inflammatory properties
warm compresses and lid scrubs can be helpful. (via anti-matrix metalloproteinase inhibition)
Given that dry eye states and tear film as well. The treatment dose for doxycycline
insufficiency often accompany anterior usually starts at 100mg once or twice daily for
blepharitis, artificial tears can provide a period of 6-12 weeks.17 It often takes a few
substantial symptomatic relief. Preserved tears weeks for the therapeutic effect of doxycycline
may be adequate between flares. However, to be realized, so the aforementioned methods
when the patient is acutely symptomatic, non- of immediate symptomatic control should be
preserved tears should be used since they can used early in the treatment course. Oracea® is
Figure 1: Pediculosis infestation be used frequently (i.e. more than four times a controlled-release tablet of doxycycline that
of the eyelashes. a day) without fear of worsening preservative- has been used for the treatment of rosacea. It
related surface toxicity. Thicker formulations contains 30 mg of an immediate-release form
such as gels and ointments can be used for and 10 mg as a delayed-release doxycycline
more severe cases. that can be taken once daily. It has been shown
Antibiotic therapy is warranted for moderate to improve symptoms and findings of ocular
to severe cases of anterior blepharitis. rosacea significantly with minimal side effects.
Traditionally, this has been accomplished with Doxycycline is also beneficial in those patients
bacitracin and aminoglycosides (gentamicin with moderate to severe staphylococcal-related
and tobramycin).12 More recently, macrolide anterior blepharitis.
antibiotics (including azithromycin and Severe cases of blepharitis often necessitate
erythromycin) have been advocated due to a short course of topical corticosteroid treatment
Figure 2: Blepharitis with seborrhea possible anti-inflammatory properties in addition to modulate the inflammatory component
to their anti-infective properties.13 Azithromycin of the disease. It is crucial to start with the
is particularly desirable, since it has a long lowest effective dose of steroid to avoid any of
half-life in both oral and topical forms. Using the potential complications of chronic topical
ointments, which are best tolerated when instilled corticosteroid use, such as cataract formation,
at bedtime due to their propensity to blur vision, ocular hypertension, and exacerbation of the
can increase contact time of the drug with the infectious process leading to a superinfection.19
eye. One must be wary of the acute worsening Induction therapy during an acute flare can be
of symptoms after initiating an antibiotic as an accomplished by using a steroid-antibiotic
indication of a possible allergic reaction to the combination, such as tobramycin with
drug. Use of the antibiotic should be stopped dexamethasone. However, some severe cases
immediately, and the reaction should be allowed require long-term treatment with steroids, in
Figure 3: Corneal thinning and perforation to subside prior to initiation of another drug. which case it would be best to use low-dose
in the setting of severe ocular rosacea Antibiotic therapy can be helpful in not formulations with less intraocular penetration
only the acute stage, but in long-term therapy and activity than their counterparts, such as
Lid scrubs help control the impetus for as well. Azithromycin can be dosed at 1 gram fluorometholone 0.1% or loteprednol 0.5%.
inflammation by removing not only debris by mouth weekly for three consecutive weeks. Corticosteroid use can also be avoided all
but also any bacterial toxins, and by reducing This can then be repeated after a 3-4 week together in patients requiring long term therapy
the bacterial load of the eyelids. Cosmetics period, until symptom control is achieved and by using topical cyclosporine 0.05%.20
should be avoided during flares. Make-up may on an “as needed” basis thereafter. Azithromycin Cases of anterior blepharitis that are resistant
incite inflammation and prevent clearance of is relatively well tolerated when taken orally; to the above therapies should raise concern for
debris from the lid margin. however, there have been cases of acute cardiac less common etiologies. Herpes simplex-related
Improving the local surface can prove to be arrest induced by the medication.14 Although blepharitis will require therapy with systemic and/
difficult in contact lens wearers, since the lens more recent studies have disputed this15, it may or local antiviral therapy. Demodex-related disease
may act as a reservoir for debris and can lead to be best to obtain clearance from a cardiologist can be treated with eyelid scrubs combined with
the formation of more depositis.11 It may be best prior to initiating systemic azithromycin therapy tea tree oil or sulfur oil.21 Phthiriasis pubis-
for patients wearing extended-wear soft contact in patients with a cardiac history. Topical related disease is treated by carefully removing
lenses to switch to daily wear lenses or rigid gas azithromycin is used twice daily in the acute the lice and louse eggs and local application of
permeable lenses. Discontinuation of contact phase for rapid control of the bacterial load and a pediculocide. Sexual contacts will also need
lens wear may be necessary. inflammation but can be used once daily on a treatment to prevent re-infestation.
The local environment must be approached long-term basis for prevention.
differently in patients with anterior blepharitis Treatment for rosacea requires long-term Treatment of posterior blepharitis
in combination with seborrhea. It is thought therapy as well. Oral tetracyclines have been There is significant overlap in the
that fungi and yeast may feed on lipids in the established as efficacious in the treatment of modalities used in anterior and posterior
skin and perpetuate the inflammatory response ocular rosacea.16 Doxycycline is the preferred blepharitis, particularly since some etiologies
in patients with seborrhea.8 Cleansing the agent, since it is better tolerated than first- are a combination of anterior and posterior

68 PAN-AMERICA
 Mand P, Mannis MJ. Treatment of severe blepharitis.

disease (e.g. rosacea). With that said, of plugging of the meibomian gland orifices.25 accomplished with appropriate topical and
the treatment of posterior blepharitis is Control of inflammation is an important systemic drug therapy. Inflammation must
primarily focused on the meibomian glands. part of the treatment of meibomian gland also be controlled to improve symptoms
Similar to anterior blepharitis, the first goal disease. This is partly modulated with the and prevent long-term damage. Once the
of therapy should be improvement of the use of tetracyclines and azithromycin, but can acute flare is resolved, the therapy can be
local environment. Patient education, eyelid necessitate the use of topical corticosteroids tailored and tapered to a regimen focused on
hygiene, warm compresses, and eyelid for more rapid and complete control of preventing recurrence.
massage should be the basis of treatment of inflammation in severe cases. Additionally,
anyone with symptomatic meibomian gland the use of corticosteroids will often be REFERENCES
dysfunction. Warm compresses are typically necessary when blepharitis is complicated by
1. Hom MM, Martinson JR, Knapp LL, et al. Prevalence of meibo-
applied with a washcloth soaked in warm phlyctenular keratitis. The previous discussion mian gland dysfunction. Optom Vis Sci 1990;67:710-2.
water, but other methods have been described. on the need for caution during the use of 2. Lemp MA, Nichols KK. Blepharitis in the United States 2009: a
survey based perspective on prevalence and treatment. Ocul Suft
These include warming a soaked washcloth corticosteroids is applicable to posterior 2009;7(Suppl. 2):S1-S14.
or potato in the microwave or by using disease as well. 3. Mathers WD, Shields WJ, Sachdev MS, et al. Meibomian gland
dysfunction in chronic blepharitis. Cornea 1991;10:277-285.
commercially available warm compresses or Multiple other modalities have been 4. Thygeson P. Etiology and treatment of blepharitis. Arch Ophthal-
masks. Care must be taken not to overheat the proposed as therapies for treatment of mol 1946; 36:445-77.
5. McCulley JP, Dougherty JM, Deneau DG. Classification of chronic
compresses, since facial burns can result. meibomian gland disease. The LipiFlow® blepharitis. Ophthalmology 1982;89:1173-90.
These measures can be supplemented with system is a newer thermodynamic method of 6. American Academy of Ophthalmology Cornea/External Disease
Panel. Preferred Practice Pattern® Guidelines. Blepharitis. San
oral supplementation with omega-3 essential expressing meibum from obstructed glands. It Francisco, CA: American Academy of Ophthalmology; 2013.
fatty acids. Optimal dosage for omega-3 consists of an eye cup that is placed on the 7. Jackson WB. Blepharitis: current strategies for diagnosis and
management. Can J Ophthalmol 2008;43:170-9.
supplementation has not been established, but external surface of the eye and a lid warmer 8. McCulley JP, Dougherty JM. Blepharitis associated with
dosages between 2000 to 6000 milligrams per that is placed in the inner surface of the lid. acne rosacea and seborrheic dermatitis. Int Ophthamol Clin
1985;25:159-72.
day are typically used. A one-year study evaluating The lid warmer is insulated, thus shielding 9. Nelson JD, Shimazaki J, Beitez-del-Castillo JL, et al. The Interna-
tional Workshop on Meibomian Gland Dysfunction: report of the
patients taking two 1000 milligram capsules of heat from the eye and vaults over the surface definition and classification subcommittee. Invest Ophthalmol Vis
omega-3 fatty acids three times a day found that of the cornea to prevent contact. The lid Sci 2011;52:1930-7.
10. Shields JA, Demirci H, Marr BP, et al. Sebaceous carcinoma of
patients on the fatty acid supplementation had warmer applies continuously-monitored the eyelids: personal experience with 60 cases. Ophthalmology
improved tear break up time and fewer dry eye directional heat to the inner eyelid while 2004;111:2151-7. Review.
11. Holland EJ, Mannis MJ, Lee WB. Ocular Surface Disease: Cornea,
symptoms than those not taking the capsules.22 inflatable air bladders underneath the eye cup Conjunctiva, and Tear Film. Elsevier Inc. 2013. p55-76
It is not advised to start omega-3 fatty acid apply variable pressure to the outer eyelids. 12. Abelson M, Shapiro A, Tobey C. Breaking down blepharitis. Rev
Ophthalmol 2011;74-8.
supplementation in patients on anti-coagulants This facilitates expression of meibum into 13. Giamarellos-Bourboulis EJ. Macrolides beyond the conventional
because of an increased risk of bleeding. the eye cup. A single LipiFlow treatment has antimicrobials: a class of potent immunomodulators. Int J Antimi-
crob Agents 2008;31:12-20.
Further symptomatic relief can be obtained been shown to be at least as effective in the 14. Ray WA, Murray KT, Hall K, et al. Azithromycin and the risk of
cardiovascular death. N Engl J Med 2012;366:1881-1890.
by supporting the tear film with topical treatment of meibomian gland dysfunction 15. Khosropour CM, Capizzi JD, Schafer SD, et al. Lack of association
lubricants, since dry eye is often a complicating as a 3-month, twice daily lid margin regimen between azithromycin and death from cardiovascular causes. N
Engl J Med 2014;370:1961-2.
factor in posterior blepharitis. This is best of warming and lid massage.27 Intraductal 16. Stone DU, Chodosh J. Oral tetracyclines for ocular rosacea: an
achieved with lipid-promoting artificial tears as meibomian gland probing has also been evidence-based review of the literature. Cornea. 2004;23:106-9.
17. Vieira AC, Hofling-Lima AL, Mannis MJ. Ocular rosacea—a
lipid layer dysfunction is often the source of dry proposed as a method of relieving meibomian review. Arq Bras Oftalmol. 2012;75:363-9.
eye symptoms in these patients.24 gland obstruction. Topical anesthesia is 18. Pfeffer I, Borelli C, Zierhut M. Treatment of ocular rosacea with
40 mg doxycycline in a slow release form. J Dtsch Dermatol Ges.
Tetracyclines and azithromycin are administhered and a 2-mm probe is passed 2011;9:904-7.
also beneficial in the treatment of posterior through the meibomian gland orificies. This 19. David DS, Berkowitz JS. Ocular effects of topical and systemic
corticosteroids. Lancet 1969;294:149-51.
blepharitis. In addition to their aforementioned is then followed by a 4-mm probe for deeper 20. Donnenfeld E, Pflugfelder SC. Topical ophthalmic cyclosporine:
anti-inflammatory properties, tetracyclines probing and expression of the meibum. This pharmacology and clinical uses. Surv Ophthalmol 2009;54:321-
38.
are also thought to alter abnormal meibum. has been reported to provide instant relief of 21. Kheirkhah A, Casas V, Li W, et al. Corneal manifestations of ocular
This is, in part, secondary to alteration in symptoms in 96% of patients (24/25), with all Demodex infestation. Am J Ophthalmol 2007;143:743-9.
22. Macsai MS. The role of omega-3 dietary supplementation in
lipase enzyme activity, thereby preventing patients achieving relief at 4 weeks.28 blepharitis and meibomian gland dysfunction (an AOS thesis).
Trans Am Ophthalmol Soc 2008;106:336-56.
degradation into smaller diglycerides. Both 23. Dougherty JM, McCulley JP, Silvany RE, et al. The role of
doxycycline and azithromycin are thought Conclusion and recommendation tetracycline in chronic blepharitis-Inhibition of lipase production in
staphylococci. Invest Ophthalmol Vis Sci 1991;32:2970-5.
to increase the amount of carotenoids in Blepharitis is a common ocular condition 24. enelli U. Systane lubricant eye drops in the management of ocular
the meibum, thus stabilizing the tear film and is a frequent cause for office visits. The dryness. Clin Ophthalmol 2011;5:783-90.

and improving symptoms of dry eye.25 presentation can be varied, but signs and 25. Foulks GN, Borchman D, Yappert M, et al. Topical azithromycin
and oral doxycycline therapy of meibomian gland dysfunction:
Azithromycin has also been shown to promote symptoms often reflect underlying dry eye, a comparative clinical and spectroscopic pilot study. Cornea
2013;32:44-53.
phospholipidosis of the meibomian gland infection/infestation, and inflammation. Once 26. Liu Y, Kam WR, Dinj J, et al. One man’s poison is another man’s
epithelial cells, further stabilizing the ocular the etiology has been elucidated and the meat: using azithromycin-induced phospholipidosis to promote
ocular surface health. Toxicology 2014;320:1-5.
surface.26 The two therapies are similar in severity of signs and symptoms has been 27. Finis D, Hayajneh J, Konig C, et al. Evaluation of an automated

efficacy; however, four weeks of topical graded, therapy can be individualized. thermodynamic treatment (LipiFlow®) system for meibomian
gland dysfunction: a prospective, randomized, observer-masked
azithromycin treatment has been shown to be All therapy should start with patient trial. Ocul Surf 2014;12:146-54.
28. Maskin SL. Intraductal meibomian gland probing relieves
slightly more effective than oral doxycycline education, lid hygiene and warm compresses. symptoms of obstructive meibomian gland dysfunction. Cornea.
in improving foreign body sensation and signs Management of remaining symptoms can be 2010;29:1145-1152.

PAN-AMERICA 69