Incidence, Prevalence, and Pathophysiology of Ocular Surface Disease and Blepharitis

Blepharitis refers to inflammation of the glands and lash follicles along the margin of the eyelids, hence the use of “lid margin disease” to describe the condition. The ocular surface is, however, the site of numerous pathologies, the management of which is complicated by the fact that the pathologies have overlapping signs and symptoms. One pathology, dry eye syndrome (DES), was recently redefined as “a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface.”¹ DES and blepharitis/lid margin disease are frequently encountered by ophthalmologists in their daily practice, and they are often seen in association with seasonal allergic conjunctivitis or exposure conjunctivitis. In addition, more than one-third of patients with DES have concurrent blepharitis, and two-thirds of patients with Sjögren’s syndrome, a condition included in the subset of dry eye patients who are aqueous deficient, have blepharitis.

The complexity of overlapping conditions can present a therapeutic challenge. —Richard L. Lindstrom, MD

This complexity of overlapping conditions can present a therapeutic challenge to even the most diligent practitioner. For example, in a study of 1148 patients with ocular discomfort or irritation, 54% had initial therapy inconsistent with their diagnosis, 24% had posterior blepharitis, 21% had dry eye, and 12% had anterior blepharitis.² Accordingly, accurate diagnosis and appropriate treatment are critical because outcomes depend on the therapy applied.

Mild DES has been estimated to affect up to 20% of the United States population, and moderate DES affects 15% of those aged >65 years. Moderate-to-severe DES is more common in women than men aged >50 years, with an estimated prevalence of 7.8% and 3.5%, respectively. The prevalence of lid margin disease also varies among populations and age groups and can approach 50% with increasing age and contact lens use, although in one study it was also reported in 39% of normal healthy controls.³

Anterior blepharitis can be either infectious or seborrheic, whereas posterior blepharitis affects the meibomian glands, which play a critical role in tear film integrity (Figure 1). Anterior and posterior disease share common symptomatology, including burning, itching, tearing, foreign body sensation, light sensitivity, and tired, dry, and red eyes. Clinical signs including conjunctival and lid margin hyperemia contribute to cosmetic and social discomfort, adversely impacting general daily activities. Although anterior and posterior blepharitis are separate clinical entities, they can present simultaneously, and one condition can initiate and propagate the other. Posterior blepharitis produces dry eye symptoms due to altered meibomian gland secretions that result in abnormalities of the lipid layer of the tear film.

With anterior blepharitis, either scurf or collarettes are present, with inflammation and redness on the outside portion of the eyelids and conjunctival hyperemia (Figure 2). Collarettes, usually developing on the lash margins, are more common with staphylococcal infections, whereas scurf is seen more often with seborrheic blepharitis. Infection normally occurs at the origins of the eyelashes and involves the lash follicles and the meibomian glands. Morning crusting of lashes is common.

Patients with posterior blepharitis usually have dry eye symptoms including burning, foreign body sensation, and contact lens intolerance. Similar to patients with anterior blepharitis, patients with posterior blepharitis have red, thickened lid margins and conjunctival hyperemia. Meibomian gland orifices may be dilated and plugged with toothpaste-like material (Figure 3). Turbid secretions will have clumps. The tear film will often have a foamy layer from the abnormal fatty acids, which can produce filmy vision. Severe cases will have scowling and posterior dragging of the meibomian gland orifices, and severe scarring can result.

Three layers comprise the tear film: a thin surface lipid layer (0.1–0.2 µm) produced by the meibomian glands, a thick middle aqueous layer (7–8 µm) produced by the lacrimal glands, and an inner mucus layer (1 µm) associated with the corneal epithelial cells and produced by goblet cells in the cornea and conjunctiva (Figure 4).⁴ Even minimal disruption of the tear film on the ocular surface can severely degrade visual acuity and, without a healthy ocular surface, recent advances that have been made in cataract and corneal refractive surgery are lost.

The aqueous component and most of the proteins found in tears are secreted by the lacrimal glands. The architecture is similar for the main and accessory lacrimal glands, with lacrimation promoted by both parasympathetic and sympathetic nerves.⁵ Androgens provide hormonal support for glandular homeostasis and aqueous tear secretion.⁶ Consistent with this, chronic dry eye is prevalent among postmenopausal women. Secretions from individual acinar cells are collected in a system of ducts and are finally directed onto the ocular surface.⁷

The soluble mucin in tears is secreted by goblet cells, specialized cells of the conjunctival epithelium that are believed to arise by a branch of the epithelial differentiation pathway. The superficial layer of the conjunctiva shows a regular pattern of terminally differentiated epithelial cells that produce soluble mucin. Approximately 5% to 20% of epithelial cells in normal conjunctiva are goblet cells, which are more dense in the nasal aspects of the forniceal and tarsal conjunctiva. Soluble mucin is essential for the viscosity of the normal tear film, to resist thinning and tear break-up.⁸ Goblet cells can be damaged during ocular surgery, particularly LASIK and cataract surgery.

Meibomian glands, which are found in the lids and have orifices at the lid margins, secrete the lipid species in the outer lipid layer. The lipid layer reduces evaporation of the aqueous component of tears to 5% to 10% of the tear flow and is a viscosity-increasing agent that provides lubrication during the blink cycle when the secretions are released. Obstruction of meibomian gland ducts reduces the amount of lipid secreted, which can result in increased evaporation of the aqueous component.

Blepharitis can cause significant irreversible scarring. —Richard L. Lindstrom, MD

In patients with meibomian gland disease, the composition of the secretions changes, which can lead to inflammation, irritation, and an unstable, altered tear film. The normal lipids that are secreted by the meibomian glands are triglycerides. With age, and in patients with meibomian gland disease, these triglycerides often degrade into proinflammatory monoglycerides and diglycerides. They are thicker; accordingly, their secretion is impaired, which results in a breakdown in the homeostatic interblink tear film stability.^9,10 This disruption of the tear film causes a significant increase in tear evaporation, contributing to dry eye, with the development of interblink dry spots and epithelial desiccation. It can also cause degradation of the visual image, increased higher-order aberrations, and loss of contrast sensitivity. Finally, lipases may produce free fatty acids that can be irritating and toxic to the ocular surface.

Diagnostic tests for DES can range from evaluating tear break-up time with fluorescein to quantifying the time required for the smallest readable line in a vision chart to blur. A normal time is 8 to 10 seconds; less than that is considered abnormal. The latter test also can indicate tear film break-down.

Key questions asked in the history can assist with a differential diagnosis of ocular surface diseases. —Richard L. Lindstrom, MD

Because ocular surface diseases tend to overlap, key questions asked in the history can assist with a differential diagnosis. Itching or the presence of caruncles is often associated with seasonal allergic conjunctivitis or exposure to an allergen. Burning is a classic symptom of blepharitis and a gritty, irritated, dry feeling is more associated with dry eye. Exploring the presence of heavy, puffy lids, epiphora, and tearing or watering, especially in the morning, is useful. Eyes may feel irritated after computer sessions, because the blink rate decreases when concentrating on work. The clinician should inquire about the presence of crusts or flakes on the eyelashes and whether eyes are stuck together or red in the morning. Additional questions include: Has the patient ever had bumps on the lids, styes, or hordeola? Have the eyelashes become thinner during recent months or years? Is there trouble wearing contact lenses? Has the patient been told by a physician that he or she has blepharitis or dry eye?

Many patients with mild blepharitis, however, are asymptomatic. Regardless, a diagnosis should be pursued and, when present, these patients should also be treated before mild blepharitis progresses to a chronic condition. As more effective regimens with high safety profiles become available, it is even more important to be aggressive in diagnosing this disease and treating it, to interrupt the cycle that can lead to significant evaporative dry eye. If left untreated, blepharitis can cause significant irreversible scarring and telangiectasia. In addition, chronic red eyes, recurrent styes and silacea, and eyelash loss should not be ignored. Finally, it is essential to rehabilitate the ocular surface preoperatively to increase both safety and surgical outcome.

In summary, there is ample justification to look more carefully at blepharitis. It is an important and potentially visually disabling disease and, as the next sections substantiate, safer and more effective therapies are becoming available.

References

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