Jay C. Bradley

Introduction

Blepharitis is one of the most common ocular disorders seen by eye care specialists and is found in almost 47% of ophthalmic patients. Approximately 30 million Americans may be affected.¹ Blepharitis is common in middle-aged patients, and its incidence increases with age. Blepharitis may be under-reported as the primary reason for an office visit, since the patient may present for a dry eye assessment, surgical evaluation or routine examination.² Although common, blepharitis is often overlooked, misdiagnosed or inadequately treated. The lack of diagnosis may be due to poor understanding of the condition and the absence of a widely accepted definition and classification scheme, as well as the lack of a clinically straightforward algorithm to aid in the diagnosis and treatment of blepharitis. Recently, diagnostic and treatment algorithms for practitioners have been developed. A simplified clinically relevant terminology based on anatomic location is key to improve diagnosis and management.³

Anterior blepharitis refers to acute or chronic inflammation and its associated signs and symptoms involving the anterior portion of the eyelid (eyelashes and follicles) (Fig. 9.1).¹ In one study, anterior blepharitis was found to account for 12% of all eyecare patients seeking treatment for generalized ocular discomfort or irritation.⁴ Unlike posterior blepharitis, which primarily involves the meibomian glands, anterior blepharitis appears to be more common in younger (mean age of 42) and female (80%) patients. A variety of conditions (including age, allergy, immune system problems, hormonal changes, bacteria, rosacea and dermatitis) may contribute to its development.^1,5

Anterior blepharitis typically involves an excessive colonization of normal lid bacteria (Staphylococcus aureus, Staphylococcus epidermidis, Corynebacterium, or others) and inflammation.1,3,6–7 Infection occurs at the origins of the eyelashes and involves the follicles and surrounding tissues.⁵ Bacteria elaborate virulence factors including toxins, enzymes, and waste products that enter the tear film and contribute to ocular surface inflammation and irritation.^5,8 Lipolytic exoenzymes produced by the lid bacteria hydrolyze wax and sterol esters release irritating free fatty acids.³ These breakdown products can contribute to the disruption of tear film integrity.^5,8

Clinical Presentation and Diagnosis

Diagnosis of anterior blepharitis is typically based on signs, symptoms, history, and external/lid examination. Typically bilateral, anterior blepharitis is both chronic and intermittent and can significantly impact quality of life.¹ In its acute phase, patients often present with bright red, puffy, irritated eyes that itch or burn.³ Additional signs include lid and lash debris, watery eyes, and intermittent effects on vision.

Staphylococcal-related anterior blepharitis affects predominantly young to middle-aged women, and keratoconjunctivitis sicca (dry eye) can present in up to 50% of these patients6,8 Eyelash loss or breakage and misdirection, collarettes or scurf on the eyelids and lashes, and fine eyelid ulcerations along the lash margin can also be seen (Fig. 9.2).⁸ In severe cases, staphylococcal hypersensitivity syndrome may cause ocular surface inflammation, corneal neovascularization and scarring, and decreased vision (Fig. 9.3).

Seborrhea-related disease generally affects older patients and is indiscriminate of gender.6,9 Aqueous tear deficiency can be seen in 25% to 40% of these patients.⁸ Seborrheic dermatitis is a skin condition associated with flaking and scaling, involving the eyebrows and eyelids (Fig. 9.4). The cause of this skin condition is not well understood. Seborrhea sometimes appears in patients with weakened immune systems. Fungi or certain types of yeast that feed on lipids in the skin may also contribute to seborrheic dermatitis with accompanying blepharitis.

A thorough history and comprehensive eye examination is critical to confirming a diagnosis. Patient history can help, as the presence of underlying skin conditions such as seborrheic dermatitis or atopic eczema may point to the diagnosis of seborrheic disease.⁸ Clinicians should look for signs of both infection and inflammation.

The differential diagnosis can be confounded by similar conditions with other etiologies, and includes infectious, inflammatory, and seborrheic etiologies.¹⁰ Infectious etiologies include staphylococcal and other bacteria, herpes simplex virus (Fig. 9.5), Demodex (Figs 9.6 and 9.7) and Phthrisis pubis (Fig. 9.8). Rosacea-related anterior blepharitis is primarily inflammatory but is often associated with bacterial overgrowth as well. Rosacea-related disease, if untreated or inadequately treated, may lead to severe corneal neovascularization and scarring with resultant poor vision (Fig. 9.9). Anterior blepharitis is also found in patients with seborrhea.

With Demodex blepharitis, microscopic mites (Demodex folliculorum) and their waste materials cause clogging of eyelash follicles and associated inflammation (Figs 9.6 and 9.7). Demodex brevis can also affect the oil glands of the skin and eyelids causing secondary blepharitis. While presence of these tiny mites is common, the development of Demodex blepharitis may be due to unusual allergic or immune system responses.

In addition, patients may experience signs or symptoms involving both the anterior and posterior eyelids, since anterior blepharitis is often found concomitantly with meibomian gland disease.³ Chalazion formation and bacterial conjunctivitis may be seen in these patients, due to posterior lid involvement and bacterial overgrowth. In addition, the proximity of the eyelids to ocular structures can lead to other disorders (such as dry eye) due to inflammatory mediator release and/or tear film instability.¹¹

Presentation should be categorized by the presence or absence of key signs and symptoms. Symptoms include stickiness, crusting, burning of the eyelids upon awakening and eyelid irritation, both acute and chronic. Principle signs include erythema, edema and eyelid and lash debris (collarettes and scurf) (Figs 9.10 and 9.11).

Eyelid and lash examinations are generally sufficient to aid in the differential diagnosis of anterior blepharitis. Slit lamp biomicroscopy is necessary for evaluating the tear film, anterior eyelid margin, tarsal conjunctiva, bulbar conjunctiva and the cornea. The external examination should include attention to the anterior portion of the eyelid margins and eyelid skin. Culture and biopsy may facilitate the differential diagnosis of anterior blepharitis but should be reserved for special circumstances (such as resistance to therapy, atypical asymmetric presentation or unifocal recurrent chalazia).

Classification of patients based upon disease severity is a critical element which guides treatment decisions. Anterior blepharitis can be divided into asymptomatic and symptomatic disease. Patients presenting with symptomatic blepharitis may be further subdivided into mild, moderate or severe categories based upon signs and symptoms present and degree of severity (Table 9.1).

Treatment

An algorithm for patient management based upon disease severity has been proposed. While treatment goals can vary based on the clinical picture, they should focus upon and include providing symptomatic relief, managing inflammation, treating the underlying etiology, and minimizing recurrence. In patients presenting acutely, treatment should aim to provide symptomatic relief and improve quality of life by decreasing bacterial burden and inflammation of the eyelid. In patients with chronic disease, minimizing acute flare-ups and damage to ocular structures secondary to chronic inflammation are the primary objectives.

Chronic untreated or inadequately treated disease can result in ectropion, thickened lid margins, dilated and visible capillaries, trichiasis, and entropion. The cornea may exhibit significant erosion and secondary infectious keratitis. In severe cases, corneal scarring and neovascularization, corneal thinning or perforation, and decreased or loss of vision can occur. Due to these potential untoward effects, early and appropriate treatment of anterior blepharitis is crucial.

In patients with anterior blepharitis undergoing ocular surgery (such as cataract or laser in situ keratomileusis), a ‘quiet eye’ without evidence of infection or inflammation is desired, in order to optimize results and prevent the development of postoperative infection.² Therapy should induce remission by impacting these etiologies in the event of an acute exacerbation, followed by some type of maintenance strategy to prevent recurrence. The use of topical antibiotic therapy preoperatively and betadine skin prep on the day of surgery is crucial to decrease the risk of postoperative infection.

The multifactorial nature of anterior blepharitis and the high frequency of mixed anterior/posterior disease, often require combination therapies for optimal patient management. In cases with significant associated posterior disease or tear dysfunction, therapies targeting these pathologies are needed for successful management. Omega-3 nutritional supplements (such as flaxseed oil, fish oil, and other commercially available products) are beneficial and should be utilized in these patients.

Patient education, warm compresses, and lid hygiene should be initiated early and are critical to successful treatment. Patients should be taught to cleanse the eyelid margin and the base of the eyelashes. Warm compresses help liquefy debris for easier removal with scrubs. Initially, warm compresses and scrubs may be needed frequently and for several minutes each time. Once controlled, frequency and duration can be significantly reduced, often to once daily for a few minutes. Finally, medicated scrubs may be used to reduce bacterial colonization, remove lid and lash debris and bacterial toxins and restore ocular health. All three elements (education, warm compresses and lid hygiene) are key to any plan for the treatment of anterior blepharitis.

Contact lens wear in patients with anterior blepharitis can be problematic due to increased propensity for the formation of lens deposits and intolerance, due to borderline tear film. Daily contact lens wear, rigid gas-permeable wear or contact lens discontinuation may be beneficial if problems arise. During flares, use of make-up should be minimized or discontinued since it may interfere with eyelid hygiene and prevent flare treatment or prolong the course of disease.

Pharmacologic therapy for anterior disease should focus on symptomatic relief, inflammation control, and treatment of the underlying etiology. Ideally, treatment should provide rapid symptom resolution, patient-friendly administration, inflammation reduction and bacterial overgrowth eradication.

Since anterior blepharitis is commonly associated with dry eye and ocular surface irritation, frequent artificial tear use can aid in symptomatic relief, during and between flares. Some commercially available artificial tears contain a lipid component and may be helpful in selected patient with concomitant meibomian gland disease.

Topical antibiotic therapy is necessary in the management of moderate to severe disease, especially when bacterial overgrowth is observed. Historically, bacitracin and aminoglycosides (gentamicin and tobramycin) comprised the most commonly used topical antibiotics for the treatment of blepharitis. Administration was generally limited to acute anterior blepharitis flares, to minimize the opportunity for development of resistance and minimize associated ocular surface toxicity. Antibiotic ointments can also be utilized to increase the contact time with the eyelid surface and aid in symptomatic relief from ocular surface irritation.¹¹

Recently, macrolide antibiotics (such as erythromycin and azithromycin) have been advocated since they possess both anti-inflammatory and anti-infective properties. Topical azithromycin has exceptional affinity for tissue and a long half-life, making it an attractive treatment option for eyelid disease.¹² Erythromycin is also available as an ophthalmic ointment but does not penetrate tissue well.

Longer courses of topical antibiotic drops or ointments have been advocated in severe or recurrent disease. Topical azithromycin can be used twice daily, initially to rapidly decrease bacterial load and quiet symptoms, and then once daily to prevent recurrence and improve lid inflammation. To increase its effectiveness, topical azithromycin should be applied immediately after performing warm compresses and scrubs. The optimal duration of this therapy has not been determined. Long-term antibiotic ointment, such as erythromycin or bacitracin at bedtime may also be an effective treatment option to quieten flares and prevent recurrences.

In staphylococcal or rosacea-related anterior blepharitis, long-term oral tetracycline therapy may be beneficial. Minocycline and doxycycline are most commonly used, due to their efficacy and favorable side effect profile. Therapy is generally started at an antimicrobial dosage to decrease bacterial load and then tapered to an anti-inflammatory (via anti-matrix metalloproteinase inhibition) dosage once stable. Sustained-release formulations are available and can be useful in patients experiencing medication-related side effects.

Topical corticosteroids target the inflammatory component of blepharitis. They are generally reserved for moderate to severe inflammation and complicated presentations.⁸ The selection of steroid used should take into account the potency needed for adequate therapeutic response while balancing the risk of side effects.

Simultaneous steroid and antibiotic use as induction therapy can be beneficial in patients with moderate to severe disease. This treatment should be used judiciously since long-term corticosteroid use can increase the risk of elevated intraocular pressure, exacerbate the infectious process leading to superinfection, and stimulate cataract development.¹³ For safety reasons, the lowest effective steroid dose should be used and patients should be monitored closely for safety and efficacy. In patients with moderate or severe disease, the use of fixed-dose combination products may facilitate patient administration and increase convenience. For patients in need of chronic anti-inflammatory therapy to prevent recurrences, low-dose topical steroid (such as fluorometholone or loteprednol) or topical cyclosporine 0.05% may be considered to prevent disease recurrence, while minimizing the risk of long-term side effects.

Treatment of seborrheic anterior blepharitis includes regular cleansing with eyelid scrubs and gentle nondetergent antidandruff shampoos. These therapies can provide significant relief and improve the appearance of the eyelids. In patients with severe seborrheic dermatitis, a dermatologic consultation may be considered.

Treatment of other less common causes of anterior blepharitis targets the underlying etiology. For herpes simplex virus-related blepharitis, topical and/or oral antiviral therapy along with ocular surface lubrication and cool compresses control symptoms and shorten the duration of the active disease. For fungi and yeast overgrowth associated with seborrhea, treatment of the underlying disease and lid hygiene are generally curative. For Demodex-associated anterior blepharitis, eyelid scrubs combined with tea tree oil have been advocated. Sulfur oil and antiparasitic gels (metronidazole) have also been recommended. Topical steroid use may be beneficial in controlling inflammation seen in association with Demodex-related disease.¹⁴ In cases of Phthiriasis pubis-related anterior blepharitis, therapy includes careful removal of the lice and nits (louse eggs) and local application of pediculocide. Patient and sexual contacts need treatment of the infection source to prevent disease recurrence.

Conclusion

Blepharitis is a common ocular condition. Anterior blepharitis involves presenting signs and symptoms reflecting infection and inflammation. Clinical classification is based on severity of signs and symptoms. This condition can negatively affect vision and quality of life for millions of patients and increase the risk of postoperative complications in ocular surgery patients.

Treatment of anterior blepharitis should be individualized, based upon severity and whether the presentation represents chronic disease or an acute flare-up. Patient education, warm compresses, and lid hygiene are vital to treatment at all severity levels. Drug therapy should target infection, inflammation, and symptom resolution. Clinicians should be vigilant when using topical antibiotics and steroids to manage symptoms and pathology and to ensure safety.

References