Classification and Staging of Ocular Surface Disease

Eyelids and Eyelashes

Flaws in the lid–lash complex that can lead to instability of the ocular surface are myriad but fall into two basic groups. Disorders such as trichiasis, distichiasis, and entropion cause ocular surface problems through the mechanical rubbing of lashes against the conjunctival and corneal surfaces. The trauma of the rubbing itself damages the cells of the ocular surface, and the chronic, low-grade trauma causes inflammation, which hurts the surface further. Other disorders, such as lagophthalmos and ectropion, can cause damage to the ocular surface through exposure or incomplete closure of the lids during a blink. Eyes with exposure will experience increased tear film evaporation exclusively in the small area that is exposed. In contrast, the damage to the corneas of patients whose eyelids do not close fully during a blink tends to involve most or all of the corneal surface. This effect is seen because tears in the inferior meniscus require eyelid touch during a blink to pull them superiorly to cover the ocular surface. In cases where the blink is incomplete, the tears stay in the inferior meniscus, rather than coating the ocular surface.

Tear Film

Abnormalities of the tear film are characterized by the component that is abnormal or deficient. As people age, they tend to produce fewer aqueous tears, and this disorder is referred to as primary acquired lacrimal disease . If the decrease in tear production is secondary to nonspecific inflammation, as seen in patients with sarcoidosis and graft-versus-host disease, patients are said to have secondary lacrimal gland disease. Sjögren syndrome is a true autoimmune disease characterized by reduced secretion of the aqueous component of both tears and saliva. Patients with Sjögren syndrome may also have accompanying connective tissue disorders. Reflex tearing may also be hampered by inflammation and scarring of the lacrimal gland or ducts, as seen in mucous membrane pemphigoid (MMP) or Stevens-Johnson syndrome (SJS), or following an alkali or thermal injury to the ocular surface.

The role of mucin is to facilitate even spreading of hydrophilic tears over the hydrophobic corneal epithelium. Deficiency of mucin is typically seen in diseases of the conjunctiva that lead to loss of the mucin-secreting goblet cells. Loss of goblet cells may be secondary to either nonspecific inflammation and scarring, as seen following an alkali injury, or active immune-mediated inflammation, such as that seen in MMP or SJS.

A healthy lipid layer secreted by meibomian glands is necessary to slow the evaporation of tears. Therefore disorders of meibomian gland secretions are labeled as “evaporative” tear film disorders and stand in contrast to the aqueous and mucin disorders described previously. The primary etiology of abnormalities of the lipid layer is blepharitis. In cases of anterior blepharitis, bacteria secrete substances that change lipids into fatty acids which will destabilize the tear film. Meibomian gland dysfunction is a primarily inflammatory process of the meibomian glands themselves that results in abnormal oils being secreted onto the ocular surface. These abnormal oils are not only toxic to the corneal epithelium but also interfere with the ability of tears to properly cover the ocular surface.

Conjunctiva

The hallmark of disorders of the conjunctiva is inflammation, which may be acute or chronic, immune-mediated, or nonspecific. Examples of immune-mediated inflammation range from mild, self-limiting disorders, such as seasonal conjunctivitis and viral conjunctivitis, to severe, potentially blinding conditions, such as MMP and SJS. Nonspecific inflammation may be secondary to chemical, thermal, or traumatic injury to the ocular surface, contact lens overwear, or other similar etiologies. It is important to recognize that chronic inflammation of an immune-mediated condition will also cause inflammation in a nonspecific fashion—in other words, “inflammation begets inflammation.”

The most obvious sign of conjunctival inflammation is injection, caused by dilation of the conjunctival vessels. This conjunctival injection is typically accompanied by cellular infiltration and chemosis. Nonspecific inflammation may be accompanied by a papillary reaction of the tarsal conjunctiva. Immune-mediated inflammation may show follicles of the tarsal or limbal conjunctiva. In severe cases of conjunctivitis, such as seen in vernal conjunctivitis, SJS, or conjunctivitis secondary to adenovirus, Chlamydia , Corynebacterium diphtheriae , or β-hemolytic streptococcus, fibrin membranes that are adherent to the conjunctival surface may develop.

If the conjunctivitis involves only the epithelium and is short-lived, normal conjunctival anatomy and function will return once the inflammation has resolved. If the inflammation is severe and chronic, irreversible changes will start to occur. Goblet cells are located in the conjunctival epithelium and are therefore susceptible to damage from persistent conjunctival inflammation. A decrease in goblet cells may be seen secondary to a number of disorders, such as Sjögren syndrome; viral, bacterial, or chlamydial infections; chemical, thermal, or physical trauma; or immune disorders such as SJS, MMP, or atopic disease. Because goblet cells secrete mucin, which helps the aqueous tears coat the hydrophobic ocular surface, their loss will result in tear film abnormalities.

Patients with conjunctival inflammation will often develop an aqueous deficiency in addition to a mucin deficiency. The accessory glands of Krause and Wolfring are responsible for basal tear secretion. They lie in the conjunctiva, being most numerous near the superior fornix. Conjunctival inflammation can damage these glands directly, causing decreased basal tear secretion.

The main lacrimal gland is responsible for reflex tearing. Although the gland itself is not contained within the conjunctiva, the ducts pass through the conjunctival substantia propria and epithelium on their way to delivering aqueous tears to the conjunctival surface at the level of the superior fornix. Significant acute or chronic conjunctival inflammation may damage these ducts and inhibit the body’s ability to provide reflex tears to the ocular surface. It is interesting to note that inflammation can lead to both mucin and aqueous tear film abnormalities, and vice versa. In patients with significant conjunctival inflammation, inflammation leads to decreased mucin and aqueous tear production, which leads to increased inflammation, which then leads to further decreased mucin and aqueous tear production, and so on, in a potentially endless cycle.

Chronic conjunctival inflammation may lead to changes in the substantia propria of the conjunctiva. Subepithelial fibrosis can occur, and this finding can easily be seen on slit lamp examination as a whitening of the conjunctival subepithelial tissue. If inflammation is allowed to persist, scar tissue can change the forniceal architecture and cause foreshortening of the fornix. Further progression of subepithelial fibrosis may result in symblepharon and potentially even ankyloblepharon. Although a distinction exists between actively inflamed conjunctiva and that which is scarred but not inflamed, it must be understood that both situations represent abnormal conjunctiva. As stated previously, actively inflamed conjunctiva is characterized by injection, chemosis, and the presence of a significant amount of immune mediators. Scarred, noninflamed conjunctiva is characterized by a decrease in mucin and aqueous tears, subepithelial fibrosis, and potentially foreshortening of the fornix and symblepharon. Both situations not only are signs of but also contribute to an unhealthy ocular surface.