Blepharitis is a condition that involves the eyelids and associated structures, so why do we treat a blepharitis-affected lid by putting a topical steroid or antibiotic drops in the eye along with some lid scrubbing? We see the eye as our patient, and we don’t want to waste our therapeutic efforts by sending drugs to far-off places such as the liver or the kidneys; instead, it makes much more sense to deliver an effective treatment straight to the source of discomfort, which in this case is the lid.
This month we’ll go over the basics of blepharitis, explore the ins and outs of drug delivery, and consider how current delivery methods may be falling short when it comes to this common ocular disorder. What should become clear is that the eyelids and conjunctiva, while geographically close, may require very different treatment applications, and the course of therapy for blepharitis should be administered accordingly.
Blepharitis is a multifactorial ocular surface disorder that can consist of an inflammation of the eyelid margin, including the lid and its dermis; the eyelashes, the tarsal conjunctiva, the mucocutaneous junction; and the meibomian glands. The condition is typically chronic and characterized by intermittent, acute flare-ups. Blepharitis can also be associated with a variety of systemic diseases like dermatitis, as well as ocular surface diseases such as dry eye, conjunctivitis or keratitis.
We, too, have gotten involved in the classification of blepharitis, and in 2006 we created a classification system known as the Ora Calibra Blepharitis Scales, which consist of standardized, photo-validated scales for blepharitis and meibomitis based on anatomical descriptors. These validated scales have been used in previous clinical trials in order to accurately assess factors such as:
To construct the scales, a panel of clinicians ranked digital images from least severe to most severe, and they selected representative images to generate a scale of 0 to 3 (normal to severe). A lid margin evaluation was also performed, analyzing regional lid edge redness (temporal, medial and nasal) as well as lash folliculitis, lid hyperkeratinization, lash madarosis, cross-sectional posterior lid edge shape and lash debris. Additionally, Ora’s direct meibomian gland tracking technology system is able to track and observe meibomian gland secretion’s viscosity, color and thickness over time.
These scales have been used in multiple studies conducted for the treatment of blepharitis, and have become a standard for blepharitis disease classification.
The inflammation involved in blepharitis, if not addressed by treatment, can result in a significant amount of lid notching and scarring. The scales were also used in a multicenter, randomized, investigator-masked, and active-controlled, 15-day study evaluating the clinical efficacy and safety of tobramycin 0.3%/dexamethasone 0.05% (TobraDex ST) ophthalmic suspension compared to azithromycin 1% (AzaSite) ophthalmic solution in the treatment of moderate to severe blepharitis or blepharo-conjunctivitis. This study demonstrated a statistically significant improvement (decrease, p=0.0002) in mean global score in subjects treated with tobramycin/dexamethasone compared to subjects treated with azithromycin.
The standard treatment regimen for blepharitis has historically consisted of localized lid hygiene, including the use of warm compresses and eyelid scrubs. These treatment modalities may have limited efficacy for many patients, however, especially those with more severe cases of the disease. Topical antibiotics are recommended to decrease the bacterial load, and topical corticosteroids may help in cases of severe inflammation. However, a bacterial etiology for blepharitis and the efficacy of treating it with an antibiotic have yet to be fully proven, and the only recent placebo-controlled study failed to show efficacy.
The inflammation involved in blepharitis, if not addressed by treatment, can result in a significant amount of lid notching and scarring.
For the treatment of blepharitis, the American Academy of Ophthalmology also recommends the use of lid scrubs,
Blepharitis also has an inflammatory component and, if left untreated, it can result in significant lid notching and scarring. This is very uncomfortable for the patient and can also lead to reduced effectiveness of the lid in performing its natural function of spreading the tears across the ocular surface to keep the surface hydrated.
When a drop hits the eye, three parts of the anterior segment—the cornea, conjunctiva, and sclera—act as routes for the drug’s absorption, though the cornea is the primary route for ocular penetration. There is a reason that topical drops have become the delivery method of choice for eye-care practitioners. For one, drops have significant advantages over other methods, including the minimization of adverse systemic effects as well as the avoidance of first-pass metabolism, which restricts the concentration of drug that ultimately reaches its target tissue.
However, drops do have a few shortcomings, as well. First, they can be particularly difficult to physically manage for some patients, especially the elderly. Additionally, there is an array of physical and physiological barriers that protect the eye and significantly diminish the amount of drug being delivered. The cornea acts as a powerful protective wall, due to its relatively small surface area and low permeability.
The eye’s rapid turnover of tears creates quite a problem for an ocular drop. The tear film is typically only about 7 µL in volume, whereas one eye drop is about 30 to 50 µL, depending on the surface tension characteristics of the drug.
In addition to the physical and physiological roadblocks the eye innately creates for a drop, tear flow is also very different from person to person, making an appropriate treatment course all the more difficult. For example, one study showed that dry-eye patients, who already have a compromised tear film, may undergo enhanced drug absorption because the barrier functions mentioned above aren’t working adequately.10
Certain factors in a drug’s formulation can modify its ability to penetrate these delicate yet robustly protective ocular tissues. These factors include the drug’s general physiological mechanism of action, as well as the tissue concentrations of the active ingredient over time. However, there are methods that increase a drug’s dwell time on the affected eye. For example, various compounds like high-viscosity solutions can be added to topically administered ophthalmic drugs in order to enhance corneal absorption, either by increasing corneal residence time or corneal penetration. These types of solutions yield an increased dwell time on the ocular surface, which allows for longer absorption time.
Ideally, treating the lid directly may circumvent problems of topical drug delivery. An optimal vehicle would provide a means for prolonging residence time at the site of application and improving tissue penetration.
By now, it should be clear that we feel improvements in blepharitis therapies are needed, and that these ought to include enhancements in the localized delivery of drugs such as topical steroids. By zeroing in on the local nature of this condition, it’s reasonable to presume that treatment success can also be brought into sharper focus. REVIEW
Dr. Abelson is a clinical professor of ophthalmology at Harvard Medical School and senior clinical scientist at the Schepens Eye Research Institute. Mr. Shapiro is vice president of anti-infectives and anti-inflammatories and Ms. Tobey is a medical writer at Ora Inc., in Andover.