Tolstoy once wrote: “… he knew his soul, it was dear to him, and he guarded it as the eyelid guards the eye, and never let anyone enter his heart without the key of love.” If eyes are the windows to the soul, then perhaps it’s not too much of a stretch to say that the eyelids, as Tolstoy wrote, are its gatekeepers. As such, they must be tended to, cared for and nourished. In this and next month’s columns, we will drill down on two related and often confused lid conditions: blepharitis and meibomian gland dysfunction. Blepharitis is one of the most common, chronic ocular surface diseases seen in the ophthalmologist’s clinic, affecting more than 20 million individuals worldwide.
In 1946, ophthalmologist Phillips Thygeson described blepharitis as a chronic inflammation of the lid border and, oddly enough, identified the condition as one of the most common causes of disability observed in military air crew personnel. Patients can present with a range of signs and symptoms that include swelling and crusting of the eyelid and palpebral conjunctiva; superficial keratitis; dry eye; itching; burning; photophobia; incomplete blinks; vision loss and asthenopia.
In this article, we’ll examine the classification and prevalence of blepharitis, look at its presentation and diagnosis, describe some associated conditions, and then discuss current and promising new treatment modalities for controlling symptoms and minimizing complications.
The symptoms and causes of blepharitis can overlap with many disorders, complicating the clinician’s diagnosis and treatment plan.
Blepharitis, defined simply as inflammation of the eyelids, can affect all age and ethnic groups.
The etiology of blepharitis can be described in several different ways, but in the clinical setting, patients don’t fall neatly into categories. Evaluations of structural and functional changes to the lid margin, ocular surface, meibomian and accessory glands, as well as measures of tear-film stability and location of inflammation may be the best approaches to properly diagnose the disease. Dr. Thygeson’s early description of the etiology of blepharitis classified it into three main types: seborrheic; staphylococcic; and mixed.
These efforts to classify and categorize highlight the heterogeneity of the disease etiology and help to explain the therapeutic challenges posed by the disease. In 2006, the research group at Ora developed a structure-specific and clinically relevant photographic scale for evaluating signs and symptoms of blepharitis and meibomitis. This seven-item scale provides investigator grading for lid margin redness and bulbar and palpebral conjunctival redness on a scale of zero to 3 (corresponding to gradings of none to severe), as well as subject-reported signs and symptoms (lid swelling, itchy eyelids and gritty eyes). This grading scale is suitable for the Food and Drug Administration development process of therapeutics and has now become an accepted industry standard.
Organisms such as Demodex mites have also been implicated in the development of blepharitis in some cases. Infestation, characterized by cylindrical dandruff or sleeves around the eyelashes, has been found in 30 percent of patients with chronic blepharitis. These mites live in the eyelash follicles; their eggs and decomposing bodies can clog the follicles and meibomian glands and cause an inflammatory response.
Colonization of the eyelid by bacteria such as staphylococcus also plays a role in blepharitis; although this and other bacterial species are resident in both healthy and blepharitic eyelids, overgrowth is common in blepharitic eyelids.
Unfortunately, the symptoms and causes of blepharitis often overlap with a range of disorders that can complicate diagnosis and treatment. A patient history that includes symptoms associated with systemic disease (e.g., lupus erythematosus, scleroderma), recent systemic and topical medications, and contact lens use is important in determining the diagnosis.
Staphylococcal blepharitis is recognized under the slit lamp by erythema, edema and irregular eyelid margins, all of which disrupt normal blink patterns, especially with incomplete blinks, resulting in dry spots, disruption of the tear film and inferior punctate keratitis. Telangiectasia can also be seen on the eyelid.
If the condition is mild, scales at the lash line may form collarettes or cuffs of fibrin (appearing as matted, hard scales), which encircle the lash at the base. Keratinization appears as a greasy coating, and lashes may be missing or broken (madarosis), suggesting folliculitis.
In severe and long-standing cases, the lid margin may be irregular due to fibrosis and thickening of the lid, trichiasis (misdirection of eyelashes toward the eye), poliosis (depigmentation of the eyelashes) and eyelid ulceration and damage to the meibomian glands.
Meibomian gland dysfunction is often present in these patients, and is characterized by inflammatory changes at the eyelid margins, in the structural anatomy of the gland orifices, and in the character of the glands’ lipid secretions. The opening to the meibomian glands may develop an operculum with a pouting appearance, while the orifices may become keratinized, obstructed and scarred. Due to gland dropout, secretions may diminish, giving the appearance of infection with their thickened consistency and opaque color.
Before the clinician can make a diagnosis of blepharitis, it’s important to rule out conditions that mimic the lid disease’s signs and symptoms. Associated conditions like dry-eye syndrome, chalazia, acne rosacea, allergic conjunctivitis, demodicosis and ocular pemphigoid should all be considered.
In addition, clinicians should be on the lookout for lesser-known systemic conditions associated with blepharitis such as hormonal dysregulation, certain cardiovascular conditions, inflammatory diseases, imbalance of gastrointestinal tract flora and psychological stress. A better understanding of the pathophysiologic association between those diseases and blepharitis may help in the treatment and prevention of blepharitis.
The goal of treating inflammation in blepharitis with a topical steroid is a rapid, potent suppressive burst that will quiet the eye in a window of time that’s too brief for the well-known adverse effects of steroids to develop.
Managing blepharitis relies heavily on the patient-doctor relationship. Treatment is based on the practice of careful lid hygiene, possibly combined with the use of topical antibiotics, with or without topical steroids or topical anti-inflammatory agents. Systemic antibiotics may be appropriate in some patients.
Initial treatment is eyelid hygiene, which includes lid scrubs, warm compresses and lid massage. Warm compresses raise the temperature of the eyelid above the melting point for meibomian gland secretions, thus aiding in secretion.
Massage can enhance the flow of secretions from the meibomian glands. To perform it, the patient holds the lid at the outer corner with one hand while the index finger of the other hand applies pressure and sweeps from the inner corner of the lid toward the ear.
Eyelid scrubs, which involve just a gentle scrubbing of the eyelids twice daily with a wet washcloth and detergent such as baby shampoo applied with a cotton-tipped swab applicator, are performed after the warm compresses to clear away crusts (scale and debris) that have accumulated on the eyelid margin.
If substantial inflammation is present, patients may benefit from a short course of treatment with a topical corticosteroid. The goal of treating ocular inflammation is a rapid and potent suppressive burst, an “attack-and-retreat” approach that will successfully quiet the eye in a window of time too brief for developing the well-known adverse effects of steroids.
One such therapy in development is NCX 4251 (Nicox SA; Sophia Antipolis, France) a novel nano-crystalline formulation of fluticasone propionate that utilizes a unique applicator for topical delivery to the eyelid margin. In lymphocyte proliferation assays, fluticasone propionate has been observed to have a tenfold greater immunosuppressive potency than dexamethasone and a hundredfold greater potency than prednisolone acetate, which are currently the two leading ophthalmic steroids. It’s thought that a more potent steroid could effectively quiet an inflamed eye in one- or two-week bursts of therapy, allowing for cessation of the therapy before any side effects ensue.
The proposed route of delivery for this blepharitis product is topical dosing directly to the eyelid with a sterile applicator. This eyelid applicator also features a lid scrubbing movement to aid in the efficacy of the product. The drug’s potency might also allow for once-daily dosing, which would be a significant advantage over other steroid options.
Decreasing bacterial colonization of the lids can be beneficial. A topical antibiotic ointment such as erythromycin or bacitracin may be indicated in some cases; it may be applied after lid hygiene techniques once or twice daily at the base of the eyelashes, depending on the severity of the inflammation.
Patients who do not respond to lid hygiene therapies or those suffering from ocular rosacea may benefit from orally administered tetracyclines. Clinical improvement with tetracycline use may be related to inhibition of bacterial lipases in both S. aureus and S. epidermidis.
In 2011, ophthalmologist Gail Torkildsen and her colleagues evaluated the clinical efficacy and safety of a tobramycin and dexamethasone ophthalmic suspension (TobraDex ST, Alcon) compared to azithromycin ophthalmic solution 1% (Azasite, Inspire Pharmaceuticals) in the treatment of moderate to severe blepharitis/blepharoconjunctivitis.
Since many blepharitis patients also have both evaporative and aqueous tear deficiency, topical lubrication with artificial tears may improve symptoms when used as an adjunct to eyelid cleansing and medications. The LipiFlow system (TearScience, Morrisville, N.C.) is a novel thermal pulsation approach that applies simultaneous heat and pressure to the eyelid tissue to express the meibomian glands. Jack Greiner, DO, PhD, of the Schepens Eye Research Institute, and his colleagues found that a single 12-minute treatment with the LipiFlow system improved both signs (based on tear breakup time, corneal fluorescein staining and meibomian gland secretion scores) and symptoms (based on Ocular Surface Disease Index and standard patient evaluation of eye dryness scores) of meibomian gland dysfunction for up to one year after the treatment.
Blepharitis is a common, complex, chronic disease of the eyelids that can present with a range of signs and symptoms. It’s critical that patients and their caregivers remain on the lookout for the signs of blepharitis even after a flare-up is controlled. Careful and consistent lid hygiene, with the occasional use of topical antibiotics with or without topical steroids, remain the mainstays for disease management. Going forward, improvements in technology and diagnostics will help clinicians to better understand the complex manifestations of this disease, ultimately aiding in the future development of customizable treatment plans.
With eyelids standing as the guardians of our most precious sense, encouraging sensible lid hygiene and prompt response to blepharitis outbreaks seems a small price to pay for ocular health.
Dr. Abelson is a clinical professor of ophthalmology at Harvard Medical School. Mr. Shapiro is vice president at Ora, where Mr. Rimmer is a medical writer. Dr. Abelson may be reached at MarkAbelsonMD@gmail.com.