This article is more than 5 years old. Information may no longer be current.

Woman complains of red eye, irritation

An area of epithelial ulceration inferonasally about 1 mm from the limbus was found on examination.

Issue: June 25, 2012

ByHelen K. Wu, MD

ByMichael B. Raizman, MD

ByJordana G. Fein, MD, MS

Add topic to email alerts

Receive an email when new articles are posted on

Please provide your email address to receive an email when new articles are posted on .

Subscribe

Added to email alerts

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

Back to Healio

We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com.

Back to Healio

A 51-year-old woman was referred to the cornea service complaining of a red and irritated right eye for 2 days. The patient reported a slight decrease in vision, associated with ocular pain and foreign body sensation. She had tried artificial tears without relief. The patient denied any new flashes or floaters. She denied any previous similar episodes.

Ocular history was remarkable only for dry eyes, for which she was using artificial tears. Medical history was significant for rheumatoid arthritis, osteoporosis and celiac disease. She was taking methotrexate 15 mg by mouth weekly to treat the arthritis. Of note, the patient had recently discontinued low-dose oral prednisone (5 mg by mouth daily) secondary to low bone density.

Examination

On examination, visual acuity without correction was 20/40 in the right eye and 20/25 in the left eye without improvement with pinhole. Both pupils were reactive without an afferent pupillary defect. IOP was 16 mm Hg in both eyes. Extraocular movements were full. Anterior segment examination of the right eye was notable for 2+ conjunctival injection, as well as an area of epithelial ulceration inferonasally about 1 mm from the limbus, roughly 4 mm 3 2 mm in diameter with 20% thinning. There was also a small infiltrate located at the inferior margin of the epithelial ulceration. There was no associated anterior chamber cell (Figures 1 and 2). The left eye demonstrated a few central corneal guttae without corneal edema, a quiet anterior chamber and a mild nuclear sclerotic cataract. The posterior segment was unremarkable in both eyes.

 

Figure 1. Color photograph of the right eye. Conjunctival injection is present with associated perilimbal epithelial ulceration and thinning. There was a small infiltrate located at the inferior margin of the ulceration, which is difficult to appreciate in this photograph.

 

Figure 2. Slit lamp color photograph of the right eye. Corneal thinning is seen in the area of peripheral ulceration.

Images: Fein JG, Wu HK, and Raizman MB

What is your diagnosis?

Peripheral corneal ulceration

The differential diagnosis of peripheral corneal ulceration can be divided into four major categories: ocular infectious, ocular noninfectious, systemic infectious and systemic noninfectious.

Ocular infectious causes include bacteria, such as staph marginal, viral, amoebic or fungal. Although this patient appeared to have an infiltrate adjacent to the epithelial defect, it was very small and more likely to be secondarily infected than responsible for the large peripheral ulceration. Ocular noninfectious causes include local disease that leads to secondary ulceration, such as acne rosacea, keratoconjunctivitis sicca, Mooren’s ulcer, post-surgical, neurotrophic keratitis, contact lens wear and progressive peripheral corneal degeneration. In this patient there was normal corneal sensation and no history of contact lens wear, corneal degeneration or previous intraocular surgery. The lid margins and upper malar region demonstrated no evidence of concurrent blepharitis or rosacea, making ocular noninfectious causes less likely.

Systemic infectious etiologies include gonorrhea, bacillary dysentery, tuberculosis, syphilis, borreliosis, varicella zoster, helminthiasis and HIV. The patient was healthy without any associated symptoms, so systemic infectious infection was also felt to be less likely. Systemic noninfectious causes of peripheral corneal ulceration include collagen vascular diseases such as rheumatoid arthritis, Wegener’s granulomatosis, polyarteritis nodosa, systemic lupus erythematosus, microscopic polyangiitis, Churg-Strauss syndrome and scleroderma. Other systemic autoimmune diseases such as pemphigoid, inflammatory bowel disease, Sjögren’s syndrome, leukemia, sarcoidosis, Henoch-Schönlein purpura and Stevens-Johnson syndrome may also produce a similar clinical picture.

Discussion

Peripheral ulcerative keratitis (PUK) is characterized by destructive inflammation of the peripheral cornea leading to sloughing of the corneal epithelium and keratolysis (corneal melt). Local or systemic autoimmune diseases cause a majority of these cases. Roughly half of patients with PUK are diagnosed with an associated systemic disease before presentation. Rheumatoid arthritis is the most common; however, 50% of noninfectious causes are secondary to collagen vascular disease. Most importantly, PUK may be the initial presenting feature of potentially lethal systemic vasculitis in up to 25% of patients; therefore, the ophthalmologist should order appropriate serologic testing for every patient. As an example, Wegener’s granulomatosis is a rare but devastating disease associated with PUK, and it can be properly treated if identified early in the disease process.

The clinical presentation of PUK is typically nonspecific, with foreign body sensation, pain, photophobia and decreased vision in the affected eye. If there is associated scleritis, then the pain may be more severe. Typically, epithelial loss, stromal inflammatory infiltration and/or thinning associated with limbal, conjunctival and episcleral injection are present. The presence of scleritis suggests an underlying but active vasculitis.

Although the majority of the cornea is relatively avascular, the peripheral cornea receives blood supply from anterior ciliary arteries that extend 0.5 mm onto the cornea. Because of this, increased concentrations of Langerhans cells, IgM and C1 complement are present at the limbus when compared with the central cornea. While the pathogenesis of PUK is not completely understood, circulating immune complex deposition, autoimmune reactions to corneal antigens, and hypersensitivity to exogenous antigens have been proposed to be involved in this humoral immune response.

PUK is largely a clinical diagnosis. A careful history is important to the evaluation, including information about any previous ocular infections, use of contact lenses, current or previous medications, history of trauma or surgery to the eye, and a complete review of systems. If a patient with PUK reports a nonspecific review of systems and no history of collagen vascular disease, appropriate laboratory tests should include a CBC, rheumatoid factor, anti-CCP antibody, c-ANCA, p-ANCA, ESR, CRP, a chest X-ray and a urinalysis.

Treatment

In terms of treatment strategies, topical steroids can be used to treat mild unilateral PUK that is not associated with systemic collagen vascular disease. In contrast, Wegener’s, microscopic polyangiitis, Churg-Strauss and polyarteritis nodosa will not respond to topical steroids alone, and this treatment strategy may even promote corneal perforation. For more severe disease, the mainstay of therapy is oral prednisone at a dose of 1 mg/kg/day. If progression occurs despite high-dose steroids, pulsed methylprednisolone or systemic immunosuppression with cyclophosphamide, methotrexate, azathioprine and/or cyclosporine may be helpful. Topical cyclosporine may also be used as adjunctive therapy. Systemic therapy is typically continued for at least 6 to 12 months.

Surgical management is rarely needed but may include conjunctival resection to temporarily remove local cellular mediators and collagenases that worsen ulceration. Conjunctival biopsy may be helpful as well if the diagnosis is uncertain. Cyanoacrylate adhesive can be used for impending corneal perforation. Conjunctival flaps, amniotic membrane grafts, tectonic lamellar keratoplasty and penetrating keratoplasty may eventually be required to preserve the integrity of the globe.

The prognosis of PUK depends on its underlying etiology, as well as how promptly the patient can receive treatment. PUK due to underlying collagen vascular disease or associated with scleritis carries a more guarded prognosis.

Our patient was treated with an increased dose of methotrexate (20 mg by mouth weekly instead of 15 mg by mouth weekly), as well as with topical prednisolone acetate 1% four times a day and gatifloxacin every 2 hours. The cornea was cultured at the location of the peripheral infiltrate and found to be sterile. With treatment, the infiltrate resolved, and the epithelial defect healed. The peripheral cornea continued to appear thin; therefore, topical prednisolone acetate was continued at a frequency of twice a day with plans for a slow taper over several months.