Taking a Fresh Look at Lid Margin Disease

Taking a Fresh Look at Lid Margin Disease

Taking a Fresh Look at Lid Margin Disease

Anterior and posterior blepharitis are beginning to garner more of the attention these common conditions deserve thanks to the development of newer effective treatment options.

Terrence P. O’Brien, MD

“Lid margin disease” is a nonspecific term that says nothing about the condition other than providing a location of the general area affected. “Blepharitis,” literally inflammation of the eyelids, is slightly more specific, but because blepharitis can occur at different sites on the lid, the term does not point clearly to an etiology nor suggest a targeted treatment.

The literature describes several classifications of blepharitis in an effort to elucidate the different forms that are encountered clinically. It is important to distinguish inflammation of the skin of the eyelid, dermatoblepharitis, from inflammation of the lid margin. Dermatoblepharitis may be due to infection, allergy, connective tissue, or other dermatologic diseases. Dermatoblepharitis, involving the skin on and around the eyelids, is typically treated by dermatologists rather than eyecare providers, and will be excluded from this discussion.
   
The most common form of blepharitis involves the lid margin. For the purposes of treatment, I prefer to classify blepharitis into two main types based on the anatomic location of the lid margin most involved with the inflammatory process: anterior blepharitis and posterior blepharitis.

Anterior and Posterior Blepharitis
   
Until recently, the conditions of anterior and posterior blepharitis were largely seen as nuisances rather than serious medical problems. This was due in large part to our limited understanding of these conditions, as well as to the absence of truly effective treatment measures. In fact, a study that Venturino and coworkers presented at ARVO in 2003 found that 54% of patients received initial therapy that was inconsistent with their type of blepharitis.
   
This is a disturbing finding because, improperly treated or untreated, anterior and posterior blepharitis can lead to permanent scarring of the lid margins, as well as a number of other significant problems (Table 1). Appropriate treatment of anterior and posterior blepharitis requires that we increase our systematic understanding of the conditions and their various treatments. Clinical grading of severity can guide the multifaceted treatment approaches for an individual patient. No single treatment is uniformly effective for all forms and levels of severity of blepharitis. Multiple and episodic pulses of adjunctive therapies may be necessary to gain and maintain control of blepharitis. Fortunately, our treatment armamentarium has just gained an important new agent, topical azithromycin 1% (AzaSite®; Inspire Pharmaceuticals).

Anterior Blepharitis
   
Although they share a number of clinical characteristics, and may well coexist, the two types of blepharitis vary by signs, symptoms, and sequelae as well as by location. Treatment approaches may include similar overlapping elements yet may significantly differ. Effective management of the conditions requires that we be able to recognize clinical features of both anterior and posterior blepharitis, as well as their mixed presentation.
    
Anterior blepharitis is characterized by inflammation of the anterior lid margin, which includes the skin adjacent to the lid margin, the cilia, eyelashes, and the glands that support the eyelashes. Anterior blepharitis can be caused by excessive colonization with bacteria, viruses, or parasites such as demodex and the sexually transmitted crab louse. Of these, excessive  colonization with bacteria is the most common cause, and among the bacteria, staphylococci predominate to the degree that the condition is sometimes referred to “staphyloccal blepharitis.”

Posterior Blepharitis
   
Posterior blepharitis is primarily a disorder of the meibomian glands, which produce the meibum that forms the lipid layer of the preocular tear film. Also referred to as meibomian gland dysfunction (MGD), posterior blepharitis contributes to lipid layer insufficiency which may result in an unstable tear film. However, bacteria may still play a role in posterior blepharitis—bacterial toxins may affect meibomian gland function and bacterial lipases released into the tear film degrade the meibum into free fatty acids and soaps. Not only are these directly irritating, but they also do not function properly as tear lipids. The result is reduced tear lipid quality and, frequently, reduced tear film breakup time.
   
Posterior blepharitis, while more common than anterior blepharitis, has typically been somewhat enigmatic and more difficult for providers to treat because there is not one simple inciting factor (like bacterial colonization in anterior blepharitis). Additionally, ocular allergy, dry eye disease, and blepharitis often occur concurrently. In fact, MGD is a very common component of dry eye disease—the dysfunctional lipid layer that occurs in MGD leads to a rapid tear film breakup and evaporative loss of tears resulting in secondary aqueous tear layer insufficiency.
   
Finally, anterior and posterior blepharitis can coexist; mixed disease is characterized by inflammation of both the anterior and posterior lid margins with the signs and symptoms of both conditions.

Clinical Presentation
   
There is no single definitive objective test for blepharitis, so diagnosis and categorization of blepharitis is based on symptoms and clinical examination findings. Both forms of blepharitis can result in irritated, red eyes. The defining symptom of anterior blepharitis is the presence of crusting on the eyelid margins and the presence of lid debris. Upon inspection, collarettes (scales that encircle the lashes) and matter on the lids can be seen clearly in anterior blepharitis (Figure 1). 
   
In posterior blepharitis, physical signs are less overt than those accompanying the anterior form. There may be pouting of the meibomian glands and some associated inflammation with telangiectasias (dilated vessels) along the posterior aspect of the lid margin. Meibomian gland secretions may have an altered composition (instead of clear fluid, an opaque or even a thickened, toothpaste-like lipid may be expressed from the glands), and patients may present with foamy soapsuds visible in their tears (Figure 2).
   
Patients with posterior blepharitis may also complain of significant ocular burning, irritation, and dryness, which some reports say tends to be worst first thing in the morning. These symptoms closely mimic those of dry eye, and, indeed, patients with posterior blepharitis are at high risk for evaporative dry eye if the condition is left untreated. In fact, an inflammatory process similar to that taking place in the meibomian glands may be at work in the lacrimal glands, giving the patient both aqueous-deficient and evaporative dry eye.

Assessing Severity
   
Prior to developing a treatment plan, it is essential to identify the type of blepharitis; it is helpful to then grade the severity of the condition and use disease severity in deciding how aggressively to treat. Grading scales can be used to assess anterior lid disease, lid swelling, MGD secretions, and lid margin redness. For example, the condition of the lashes and lid margins can be graded in anterior blepharitis using the number of collarettes and clumps/strands to grade the eye from normal (no collarettes) to very severe (more than 40 collarettes and the presence of clumps and/or strands) (Table 2).

Treating blepharitis is important because, as with many chronic progressive conditions, long-term damage can become permanent, and no amount of treatment will reverse it and restore healthy function. In addition, even mild early blepharitis can be unsightly and uncomfortable; effective treatment provides significant improvement to the patient’s quality of life. It’s also important to treat because more serious problems can develop if the condition is left untreated.
   
Surgical candidates with clinically significant blepharitis must be treated prior to ocular surgery. In anterior blepharitis, the presence of large colonies of bacteria can greatly increase the chance of postoperative infection, and posterior blepharitis negatively affects the stability of the tear film, degrading the visual outcomes in procedures like cataract surgery and LASIK.

Treatment Options
   
In most cases of blepharitis, it is necessary to treat both excessive bacterial colonization and inflammation to fully resolve the condition. Bacterial colonization is often the cause of the inflammation, so these are linked components. In addition to reducing bacterial colony counts, it is important to reduce inflammation and, through palliative measures, make patients more comfortable.
   
Blepharitis treatment used to include scrubbing the lids with baby shampoo. While this may have temporarily lightened the bacterial load and removed some debris, baby shampoo can break down tear lipids into irritating free fatty acids resulting in tear film instability. Commercial formulations of gentle scrubs and solutions designed specifically for cleaning eyelids are preferred choices.
   
Consider using the following treatment protocols for anterior lid margin disease and MGD. These protocols combine easy, home care measures with effective medications. Milder cases of blepharitis may be controlled with only one or two steps, but more severe cases may require additional treatments sometimes repeated at specified intervals.
   
In addition to the adjunctive use of topical azithromycin, which I will describe below, a staged approach to treating anterior blepharitis could include:

• Warm compresses on the lids once or twice a day
• The use of commercial lid scrubs several times per week
• Antibiotic ointment applied to the lid margins at bedtime for 1 to 2 weeks at a time (although patients dislike this step as it can blur vision, and chronic use may induce resistance)
• Brief pulses of topical corticosteroid (for more severe cases), or alternatively a short pulse of antibiotic-steroid fixed combination (less preferred)

MGD treatment may include:

• Localized hyperthermia with application of warm compresses
• Antibiotic or corticosteroid ointment (or a combination product)
• Oral tetracycline antibiotics (such as doxycycline or minocycline) for their anti-inflammatory effect
• Topical cyclosporine A for long-term treatment, especially when there is concomitant dry eye disease
• Omega-3 nutritional supplementation
• Artificial tears to support the tear film

Topical Azithromycin
   
Topical azithromycin plays an important role in the treatment of both types of blepharitis. This relatively new drop has several very important attributes that make it highly effective in the treatment of blepharitis. First, as a macrolide antibiotic, azithromycin has both antimicrobial and antiinflammatory properties. The medication blocks inflammation by reducing gene expression of proinflammatory cytokines and adhesion molecules at the transcriptional factor level, inhibiting cytokine production and reducing production of proinflammatory mediators.
   
In addition, the azithromycin molecule itself is highly lipophilic and penetrates and then resides in tissue far longer than other ocular antibiotics. Thus, it is possible to achieve sustained high drug levels with very convenient dosing. This tissue reservoir effect is further enhanced by the polymeric vehicle used to solubilize the drug—the vehicle holds the drug on the eye longer than less viscous antibiotic formulaions. These traits make azithromycin the first effective and convenient drug without significant side effects.
   
Finally, once treatment of the acute phase is complete, it is important to consider a maintenance program, as blepharitis is a chronic condition that may recur without preventive measures. For many of my patients, I treat with a course of topical azithromycin for 2 to 4 weeks, several times a year, to keep the disease in check and prevent patients from having to deal with the irritation and unsightly cosmetic effects of blepharitis. In addition, a successful maintenance program may prevent potentially harmful long-term complications.

THE BOTTOM LINE

Lid margin disease takes two primary forms: anterior blepharitis and posterior blepharitis (also known as meibomian gland dysfunction). These conditions, while both characterized by inflammation of the lid margin, differ in etiology, symptoms, and, to some degree, treatment. It is therefore useful to identify the type of blepharitis present and grade its severity before developing a treatment plan. Treatment traditionally consisted of warm compresses and lid scrubbing, with the possible addition of an antibiotic ointment, and, for recalcitrant posterior blepharitis, an oral tetracycline. However, in the last year or so we have come to realize that topical  azithromycin, which has both antiand antiinflammatory properties, can be a highly effective way to bring the condition under control. Topical cyclosporine for immunomodulation and nutritional omega-3 essential fatty acid rich supplements for antiinflammatory effects may be part of longer term maintenance therapy in more severe cases.

Terrence P. O’Brien, MD, is professor of ophthalmology and Charlotte Breyer Rodgers Distinguished Chair at the University of Miami Miller School of Medicine at Bascom Palmer Eye Institute in Palm Beach Gardens, FL.