Excerpt from Peripheral Ulcerative Keratitis

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Background

Peripheral corneal ulceration is a potentially devastating disorder consisting of a crescent-shaped destructive inflammation at the margin of corneal stroma that is associated with an epithelial defect, presence of stromal inflammatory cells, and progressive stromal degradation and thinning. Commonly referred to as peripheral ulcerative keratitis (PUK), it can quickly produce progressive necrosis of the corneal stroma, leading to perforation and blindness (Mondino, 1988).

Pathophysiology

The peripheral cornea has distinct morphologic and immunologic characteristics that predispose it to inflammatory reactions. Unlike the avascular central cornea, the peripheral cornea is closer to limbal conjunctiva and derives part of its nutrient supply from the limbal capillary arcade, a source of immunocompetent cells, eg, macrophages, Langerhans cells, lymphocytes, and plasma cells (Shiuey, 1998; Messmer, 1999). Any inflammatory stimulus in the peripheral cornea that is caused by invasion of microbial organisms (bacteria, virus, fungi, and parasites), immune complex deposition (in systemic immune diseases), trauma, malignancy, or dermatologic conditions may produce local and systemic immune responses, resulting in neutrophil recruitment and complement activation (both classic and alternative pathways) in both tissue and vessels (Shiuey, 1998).

Activated complement components can increase vascular permeability and further generate chemotactic factors for neutrophils (eg, C3a, C5a). Neutrophils, in turn, infiltrate the peripheral cornea and release proteolytic and collagenolytic enzymes, reactive oxygen metabolites, and proinflammatory substances (eg, platelet-activating factor, leukotrienes, prostaglandins), causing dissolution and degradation of the corneal stroma (Foster, 1993; Gregory, 1996). In addition, the inflamed limbal conjunctiva itself is capable of producing collagenase, which contributes to stromal degradation (Eiferman, 1979).

Systemic diseases that may cause immune complex deposition at the peripheral cornea and PUK include such collagen vascular diseases as rheumatoid arthritis (RA), Wegener granulomatosis (WG), polyarteritis nodosa (PAN), relapsing polychondritis (RP), and systemic lupus erythematosus (SLE). Infectious conditions, whether systemic (eg, hepatitis, syphilis) or local (eg, herpes simplex keratitis, fungal keratitis), and noninfectious local disorders (eg, Mooren ulcer, marginal keratitis) also may cause PUK.

In summary, the major pathophysiologic mechanism of PUK is a result of degradation and tissue necrosis of corneal stroma produced by degradative enzymes, which are released primarily by neutrophils attracted into the area by diverse stimuli.

Frequency

United States

PUK is uncommon. RA has been reported as the most common collagen vascular disorder that causes PUK, accounting for 34% of noninfectious PUK (Eiferman, 1979; Brown, 1968; Tauber, 1990). PUK may be the initial manifestation of WG and PAN. PUK is rare in patients with RP; only 2 of 112 patients with RP were reported to develop PUK in a clinical review study (Hoang-Xaun, 1990). PUK also has been reported to be associated with SLE, although this is uncommon (Messmer, 1999; Watson, 1976). Mooren ulcer is a rare local autoimmune disease associated with PUK, with only 287 cases reported in the world literature, although some of these cases may have been the presenting manifestation of an occult systemic disease rather than true Mooren ulcer (Sangwan, 1997).

Mortality/Morbidity

PUK produces great morbidity from the pain and resultant visual disability. It can be a harbinger of death if the underlying disease is not diagnosed and successfully treated.

Race

No good data are available on racial predilection for PUK.

Sex

Since PUK is more common in people with collagen vascular disorders (especially RA), it is more common in females than in males. However, PUK caused by Mooren ulcer is more common in males than in females (Sangwan, 1997; Tabbara, 1986).

Age

Age varies and is dependent on the associated systemic or local disorder.

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