Peripheral Ulcerative Keratitis

Peripheral ulcerative keratitis (PUK) is a crescent shaped, destructive inflammation of the peripheral corneal stroma, with epithelial defect, stromal thinning and an adjacent limbal inflammatory focus.

• Mechanism: immune complex deposition in the limbal vascular arcade, complement activation, and release of collagenases and matrix metalloproteinases from neutrophils and macrophages.
• Systemic associations (about 50 percent): rheumatoid arthritis (commonest), granulomatosis with polyangiitis, microscopic polyangiitis, polyarteritis nodosa, systemic lupus erythematosus, relapsing polychondritis, inflammatory bowel disease, Sjogren syndrome, reactive arthritis, and Churg-Strauss disease.
• Infectious causes: herpes zoster, tuberculosis, syphilis, hepatitis B and C, staphylococcal marginal disease, fungal and bacterial keratitis.
• Mooren ulcer is an idiopathic form, with a painful progressive undermined edge and no systemic disease.
• PUK is a marker of severe systemic vasculitis, and untreated disease carries a high mortality.

• Severe pain, redness, photophobia, tearing and reduced vision.
• Crescentic peripheral stromal infiltrate and ulcer with an overhanging, undermined edge; stromal melt may be rapid.
• Scleritis or episcleritis is often present in the adjacent area.
• Progression circumferentially and centrally; perforation in advanced cases.
• Features of systemic disease: joint swelling, rash, nasal crusting and epistaxis, haematuria, haemoptysis, mononeuritis multiplex.

• Slit lamp with fluorescein; corneal thickness mapping with anterior segment OCT; scrape and culture to exclude infection before immunosuppression.
• Blood tests: full blood count, ESR, CRP, rheumatoid factor, anti-CCP, ANA, anti-dsDNA, ENA, ANCA (PR3 and MPO), complement C3 and C4, urea, creatinine and urinalysis (haematuria and proteinuria), hepatitis B and C serology, syphilis serology, interferon gamma release assay, HIV.
• Chest X-ray or CT chest for granulomatosis with polyangiitis and tuberculosis.
• Corneal or conjunctival biopsy in refractory cases.
• Always treat PUK as a medical emergency requiring a systemic evaluation; rheumatology input.

• Systemic immunosuppression is the mainstay; topical steroids alone are not enough and may increase melt (they inhibit repair).
• Induction: prednisolone 1 mg/kg orally daily (maximum 80 mg), or intravenous methylprednisolone 500 to 1000 mg daily for 3 days in severe or vasculitic disease, followed by oral prednisolone with taper.
• Steroid sparing agent early: methotrexate 15 to 25 mg weekly with folic acid 5 mg weekly, azathioprine 2 to 2.5 mg/kg daily, mycophenolate mofetil 1 g twice daily, or cyclophosphamide 2 mg/kg daily orally (or 15 mg/kg intravenously every 2 to 3 weeks) for vasculitis.
• Rituximab 375 mg/m2 weekly for 4 doses or 1 g on days 1 and 15 for ANCA vasculitis and refractory rheumatoid disease; adalimumab 40 mg every 2 weeks or infliximab 3 to 5 mg/kg at 0, 2 and 6 weeks then every 8 weeks for refractory rheumatoid associated PUK.
• Local measures: preservative free lubricants hourly, oral doxycycline 100 mg twice daily (anticollagenase), topical ciclosporin 0.05 to 2 percent, topical antibiotic prophylaxis (moxifloxacin 0.5 percent four times daily) while the epithelium is open, and bandage contact lens.
• Surgery: conjunctival resection (excision of the adjacent limbal conjunctiva 3 to 4 mm wide, removing the source of inflammatory cells and enzymes), cyanoacrylate glue (for perforations up to 2 to 3 mm) with a bandage lens, amniotic membrane graft, patch graft or lamellar or penetrating keratoplasty for large perforations (performed after immunosuppression to avoid recurrence).
• Treat infectious causes with the specific therapy: valaciclovir 1 g three times daily for herpes zoster for 7 to 10 days, standard antituberculous therapy, benzathine penicillin for syphilis.
• Follow weekly at first with corneal thickness imaging; monitor for steroid toxicity (bone protection with calcium, vitamin D, bisphosphonate; gastric protection) and cytopenias.