Introduction
Background
This type of corneal ulcer is usually associated with a connective tissue disease, such as rheumatoid arthritis (RA), Sjögren syndrome, Mooren ulcer, or a systemic vasculitic disorder (eg, systemic lupus erythematosus [SLE], Wegener granulomatosis, polyarteritis nodosa).
RA is the most common systemic vasculitic disorder to involve the ocular surface. Patients with severe RA often present with indolent progressive ulceration of the peripheral or pericentral cornea with minimal inflammation that eventually may result in corneal perforation.
Sjögren syndrome is a particular multisystem disease that commonly occurs in middle-aged women, but it can be seen in both sexes and all ages in association with other autoimmune disorders.
Mooren ulcer is an idiopathic noninfectious ulceration of the peripheral cornea that has been classified into 2 clinical types. One is a milder, unilateral, less progressive form of the disease generally seen in elderly patients that responds well to therapy. The second type is a much more aggressive, frequently bilateral, relentless disease usually seen in younger patients that is poorly responsive to any therapy and often leads to corneal destruction.
SLE is a multisystem autoimmune disorder with ocular complications in the anterior and posterior segments, including keratitis sicca, episcleritis, corneal ulceration, uveitis, and retinal vasculitis.
Polyarteritis nodosa, Wegener granulomatosis, and scleroderma are other vasculitides that also may result in a corneal ulcer.
Polyarteritis nodosa is a vasculitis of small- and medium-sized arteries, which leads to multiple organ disease.
Wegener granulomatosis is a necrotizing, granulomatous vasculitis involving the upper respiratory tract, lungs, and kidneys. A limited form of Wegener granulomatosis exists in which renal lesions are not present.
Scleroderma is a connective tissue disorder characterized by extreme skin tautness, resulting in vascular insufficiency, vasospasm, and Raynaud phenomenon.
Paracentral corneal melting has been reported in a patient with Vogt-Koyanagi-Harada syndrome, psoriasis, and Hashimoto thyroiditis.
Recently, several cases of corneal melts associated with topically applied nonsteroidal anti-inflammatory drugs have been reported in the literature. Furthermore, corneoscleral melting has been reported following amniotic membrane in a patient who had undergone multiple previous ophthalmologic surgical procedures.
Pathophysiology
The pathogenesis for these corneal ulcers is not clear. Possibilities include immunologic responses to unknown antigens and genetic susceptibility, such as genetic predisposition to the development of defective suppressor T-lymphocyte function, production of autoantibodies (eg, antinuclear antibodies), and activation of the complement pathway.
Genetic and environmental factors are associated with SLE. In a genetically susceptible individual, certain environmental stimuli, such as a viral infection or contact with certain drugs, induce alterations in DNA, immunoregulatory networks, or both, with resultant formation of autoantibodies, including antinuclear antibody (ANA).
The pathogenesis of polyarteritis nodosa is not clear, but, in some patients, it may be related to hepatitis B antigen-associated immune complex disease or other immune complexes.
Recently, an association has been reported between Mooren ulcer and hepatitis C infection.
Frequency
United States
The incidence of corneal ulcers is uncommon.
Mortality/Morbidity
- Development of a corneal ulcer associated with a connective tissue disease or a vasculitis carries a poor prognosis.
- Patients who have RA with scleritis and a corneal melt die within 5 years without aggressive treatment. This type of corneal ulcer may lead to corneal thinning and perforation in the perilimbal region or paracentrally.
Race
No racial predilection exists with Wegener granulomatosis.
Sex
RA primarily affects middle-aged females.
- Scleroderma is 3-4 times more common in women than in men.
- Polyarteritis nodosa is 2.5 times more likely to affect males than females.
- No sexual predilection exists with Wegener granulomatosis.
Age
This type of corneal ulcer does not affect children. Except for the malignant form of Mooren ulcer, patients with this pathology are usually older than 30 years.
- Wegener granulomatosis can affect all age groups.
- Scleroderma usually starts in individuals aged 30-50 years.
- Polyarteritis nodosa is more frequent in middle-aged males.
Clinical
History
A complete systemic medical history and a review of systems are imperative in these patients, including questions regarding the presence of weight loss, malaise, muscle pain, or weakness, and symptoms involving the neurologic, respiratory, and renal systems.
Physical
- Keratitis sicca is quite common with these patients. Superficial punctate keratitis, chemosis, recurrent episcleritis, and scleritis also are common findings.
- In the case of SLE, retinal vasculitis is evident on fluorescein angiography, with intraretinal hemorrhages and cotton-wool spots. Of patients, 95% develop arthralgia and articular findings, and 70-80% of patients develop skin lesions at some point. The butterfly rash across the nose and cheek occurs in about 30% of patients with SLE.
- Mooren ulcer begins as a gray-white infiltrate in the peripheral cornea followed by epithelial breakdown and stromal melting. Eventually, it develops into a chronic, painful peripheral corneal ulcer that progresses circumferentially and centrally, creating an overhanging edge at its central border. The adjacent conjunctiva and sclera usually are inflamed and hyperemic.
- Wegener granulomatosis is characterized by nasal or oral inflammation, necrotizing and granulomatous inflammation of the vessels of the upper and lower respiratory tract, glomerulonephritis, and other organ involvement with small vessel inflammation.
Causes
All the underlying systemic conditions leading to these types of corneal ulcers are likely to have an autoimmune etiology that is linked to genetic susceptibility.
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References
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Lambiase A, Bonini S, Aloe L, et al. Anti-inflammatory and healing properties of nerve growth factor in immune corneal ulcers with stromal melting. Arch Ophthalmol. Oct 2000;118(10):1446-9. [Medline].
Paroli MP, Pinca M, Speranza S. Paracentral corneal melting in a patient with Vogt-Koyanagi-Harada's syndrome, psoriasis, and Hashimoto's thyroiditis. Ocul Immunol Inflamm. Dec 2003;11(4):309-13. [Medline].
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Schechter BA, Rand WJ, Nagler RS. Corneal melt after amniotic membrane transplant. Cornea. Jan 2005;24(1):106-7. [Medline].
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Further Reading
Keywords
corneal melt, chronic serpiginous ulcer of the cornea, ulcus rodens, corneoscleral melting
