History
Patients with corneal ulcer usually experience pain, redness, foreign object sensation, tearing, photophobia, and decreased vision.
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
A thorough physical examination should be performed, in addition to a complete ophthalmologic examination.
Keratitis sicca is quite common in patients with corneal ulcer associated with autoinflammatory diseases. 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.
Granulomatosis with polyangiitis 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.
Rheumatoid arthritis
Rheumatoid arthritis (RA) is the most common systemic disorder to involve the ocular surface. Patients with RA who have high titers of rheumatoid factor are most likely to have extra-articular manifestations, including ocular diseases such as keratoconjunctivitis sicca, episcleritis, scleritis, peripheral ulcerative keratitis (PUK), and, rarely, retinal vasculitis. [19] 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. [20]
Granulomatosis with polyangiitis (Wegener granulomatosis)
Granulomatosis with polyangiitis (Wegener granulomatosis) is a necrotizing granulomatous vasculitis that involves the upper respiratory tract, lungs, and kidneys. A limited form of granulomatosis with polyangiitis exists in which renal lesions are not present. Ahmed et al reported cases of very limited Wegener granulomatosis with only ocular involvement and no respiratory or renal manifestations. [21] Granulomatosis with polyangiitis is a leading autoimmune condition associated with PUK. PUK often manifests at the onset of GPA, leading to the diagnosis of the systemic condition. [22]
Sjögren syndrome
Sjögren syndrome is a multisystem disease that commonly occurs in middle-aged women but can affect both sexes and all ages and may be associated with other autoimmune disorders. It is the major cause of keratoconjunctivitis sicca (dry eye syndrome) in patients with auto-immune disorders and can lead to corneal ulceration.
Systemic lupus erythematosus
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder that causes ocular complications in the anterior and posterior segments, including keratitis sicca, episcleritis, corneal ulceration, uveitis, and retinal vasculitis. [23, 24] Peripheral ulcerative keratitis rarely occurs in SLE, but some cases have been reported.
Polyarteritis nodosa
Polyarteritis nodosa is a vasculitis of small- and medium-sized arteries that leads to multiple organ diseases.
Scleroderma
Scleroderma is a connective-tissue disorder characterized by extreme skin tautness that results in vascular insufficiency, vasospasm, and Raynaud phenomenon.
Other causes
There are a few reports of peripheral ulcerative keratitis associated with sarcoidosis [22, 25] and Behçet disease. [26]
Relapsing polychondritis is a rare autoimmune disease characterized by episodic inflammation of cartilaginous structures in the body. PUK occurs in fewer than 10% of patients with relapsing polychondritis. A 2017 case report describes a resistant case of relapsing polychondritis with rapid corneal thinning and corneal perforation. [27]
Paracentral corneal melting has been reported in a patient with Vogt-Koyanagi-Harada syndrome, psoriasis, and Hashimoto thyroiditis. [28]
A unique case of peripheral ulcerative keratitis secondary to hepatitis B virus–associated cryoglobulinemia and vasculitis has been reported. [29]
Several cases of corneal melting associated with topically applied nonsteroidal anti-inflammatory drugs have been reported in the literature. [30, 31, 32, 33, 34] Furthermore, corneoscleral melting has been reported following amniotic membrane in a patient who had undergone multiple previous ophthalmologic surgical procedures [35] and in 14% of patients who underwent Boston keratoprosthesis. [36]
Complications
Corneal ulceration, if not managed properly and in a timely fashion, can lead to stromal necrosis, corneal perforation, and blindness. The presentation of corneal ulcer with a known or unknown systemic disease requires immediate workup and referral to a rheumatologist.
Serious systemic and local complications occur in patients with corneal ulceration due to autoimmune diseases. In many cases, these underlying conditions are associated with a high mortality rate.
The most serious ocular complications of corneal ulcer include corneal perforation with secondary infections, corneal scarring, and secondary cataract and glaucoma.
