Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
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. PAN-AMERICA 67 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 68 PAN-AMERICA 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. REFERENCES 1. Hom MM, Martinson JR, Knapp LL, et al. Prevalence of meibomian gland dysfunction. Optom Vis Sci 1990;67:710-2. 2. Lemp MA, Nichols KK. Blepharitis in the United States 2009: a survey based perspective on prevalence and treatment. Ocul Suft 2009;7(Suppl. 2):S1-S14. 3. Mathers WD, Shields WJ, Sachdev MS, et al. Meibomian gland dysfunction in chronic blepharitis. Cornea 1991;10:277-285. 4. Thygeson P. Etiology and treatment of blepharitis. Arch Ophthalmol 1946; 36:445-77. 5. McCulley JP, Dougherty JM, Deneau DG. Classification of chronic blepharitis. Ophthalmology 1982;89:1173-90. 6. American Academy of Ophthalmology Cornea/External Disease Panel. Preferred Practice Pattern® Guidelines. Blepharitis. San Francisco, CA: American Academy of Ophthalmology; 2013. 7. Jackson WB. Blepharitis: current strategies for diagnosis and management. Can J Ophthalmol 2008;43:170-9. 8. McCulley JP, Dougherty JM. Blepharitis associated with acne rosacea and seborrheic dermatitis. Int Ophthamol Clin 1985;25:159-72. 9. Nelson JD, Shimazaki J, Beitez-del-Castillo JL, et al. The International Workshop on Meibomian Gland Dysfunction: report of the definition and classification subcommittee. Invest Ophthalmol Vis Sci 2011;52:1930-7. 10. Shields JA, Demirci H, Marr BP, et al. Sebaceous carcinoma of the eyelids: personal experience with 60 cases. Ophthalmology 2004;111:2151-7. Review. 11. Holland EJ, Mannis MJ, Lee WB. Ocular Surface Disease: Cornea, Conjunctiva, and Tear Film. Elsevier Inc. 2013. p55-76 12. Abelson M, Shapiro A, Tobey C. Breaking down blepharitis. Rev Ophthalmol 2011;74-8. 13. Giamarellos-Bourboulis EJ. Macrolides beyond the conventional antimicrobials: a class of potent immunomodulators. Int J Antimicrob Agents 2008;31:12-20. 14. Ray WA, Murray KT, Hall K, et al. Azithromycin and the risk of cardiovascular death. N Engl J Med 2012;366:1881-1890. 15. Khosropour CM, Capizzi JD, Schafer SD, et al. Lack of association between azithromycin and death from cardiovascular causes. N Engl J Med 2014;370:1961-2. 16. Stone DU, Chodosh J. Oral tetracyclines for ocular rosacea: an evidence-based review of the literature. Cornea. 2004;23:106-9. 17. Vieira AC, Hofling-Lima AL, Mannis MJ. Ocular rosacea—a review. Arq Bras Oftalmol. 2012;75:363-9. 18. Pfeffer I, Borelli C, Zierhut M. Treatment of ocular rosacea with 40 mg doxycycline in a slow release form. J Dtsch Dermatol Ges. 2011;9:904-7. 19. David DS, Berkowitz JS. Ocular effects of topical and systemic corticosteroids. Lancet 1969;294:149-51. 20. Donnenfeld E, Pflugfelder SC. Topical ophthalmic cyclosporine: pharmacology and clinical uses. Surv Ophthalmol 2009;54:32138. 21. Kheirkhah A, Casas V, Li W, et al. Corneal manifestations of ocular Demodex infestation. Am J Ophthalmol 2007;143:743-9. 22. Macsai MS. The role of omega-3 dietary supplementation in blepharitis and meibomian gland dysfunction (an AOS thesis). Trans Am Ophthalmol Soc 2008;106:336-56. 23. Dougherty JM, McCulley JP, Silvany RE, et al. The role of tetracycline in chronic blepharitis-Inhibition of lipase production in staphylococci. Invest Ophthalmol Vis Sci 1991;32:2970-5. 24. enelli U. Systane lubricant eye drops in the management of ocular dryness. Clin Ophthalmol 2011;5:783-90. 25. Foulks GN, Borchman D, Yappert M, et al. Topical azithromycin and oral doxycycline therapy of meibomian gland dysfunction: a comparative clinical and spectroscopic pilot study. Cornea 2013;32:44-53. 26. Liu Y, Kam WR, Dinj J, et al. One man’s poison is another man’s meat: using azithromycin-induced phospholipidosis to promote ocular surface health. Toxicology 2014;320:1-5. 27. Finis D, Hayajneh J, Konig C, et al. Evaluation of an automated thermodynamic treatment (LipiFlow®) system for meibomian gland dysfunction: a prospective, randomized, observer-masked trial. Ocul Surf 2014;12:146-54. 28. Maskin SL. Intraductal meibomian gland probing relieves symptoms of obstructive meibomian gland dysfunction. Cornea. 2010;29:1145-1152. PAN-AMERICA 69