Pain, photophobia, red eye; may be asymptomatic.

Peripheral corneal thinning (best seen with a narrow slit beam); may be associated with sterile infiltrate or ulcer.

Infectious infiltrate or ulcer. Lesions are often treated as infectious until cultures come back negative. See 4.12, Bacterial Keratitis.

• Peripheral ulcerative keratitis (PUK), idiopathic or related to systemic connective tissue disease: Rheumatoid arthritis, GPA, relapsing polychondritis, polyarteritis nodosa, systemic lupus erythematosus, others. Peripheral (unilateral or bilateral) corneal thinning/ulcers may be associated with sterile inflammatory infiltrates. The sclera may be involved. May progress circumferentially to involve the entire peripheral cornea. Perforation may occur. This may be the first manifestation of systemic disease (see Figure 4.23.1).

  Figure 4.23.1: Peripheral ulcerative keratitis with both scleral and corneal involvement.

  

• Terrien marginal degeneration: Usually bilateral, often asymptomatic. Slowly progressive thinning of the peripheral cornea; typically superior; more often in men. The anterior chamber is quiet, and the eye is typically not injected although may be associated with inflammatory signs and symptoms secondary to epithelial breakdown and inflammatory or infectious infiltrates. A yellow line (lipid) may appear, with a fine pannus along the central edge of the thinning. The thinning may slowly spread circumferentially. Refractive changes, including irregular and against-the-rule astigmatism are often present. The epithelium usually remains intact, but perforation may occur with minor trauma.

• Mooren ulcer: Unilateral or bilateral. Painful corneal thinning and ulceration with inflammation. Initially starts as a focal area in the peripheral cornea, nasally or temporally with involvement of the limbus; later extends circumferentially or centrally. Unlike PUK, Mooren ulcer usually does not involve the sclera. An epithelial defect, stromal infiltrate/thinning, and an undermined leading edge are typically present. Limbal blood vessels may grow into the ulcer, and perforation can occur. Often idiopathic (autoimmunity may play a key role); diagnosis of exclusion after ruling out the aforementioned systemic causes of PUK. Mooren-like ulcer has been associated  with systemic hepatitis C virus infection. Bilateral cases are more resistant to treatment than unilateral cases.

• Pellucid marginal degeneration: Painless, noninflammatory bilateral asymmetric corneal thinning of the inferior peripheral cornea (usually from the 4- to 8-o’clock positions). There is no anterior chamber reaction, conjunctival injection, lipid deposition, or vascularization. The epithelium is intact. Corneal protrusion may be seen above the area of thinning. The thinning may slowly progress.

• Furrow degeneration: Painless corneal thinning just peripheral to an arcus senilis, typically in the elderly. Noninflammatory without vascularization. Perforation is rare. Usually nonprogressive and does not require treatment.

• Delle: Painless oval corneal thinning resulting from corneal drying and stromal dehydration adjacent to an abnormal conjunctival or corneal elevation. The overlying epithelium may be compromised but is often intact. See 4.24, Delle.

• Staphylococcal hypersensitivity/marginal keratitis: Peripheral, white corneal infiltrate(s) with limbal clearing that may have an epithelial defect and mild thinning. See 4.19, Staphylococcal Hypersensitivity.

• Dry eye syndrome: Peripheral (or central) sterile corneal melts may result from severe cases of dry eye. See 4.3, Dry Eye Syndrome.

• Exposure/neurotrophic keratopathy: In severe cases, a sterile oval ulcer may develop in the inferior interpalpebral portion of the cornea without signs of significant inflammation. May be associated with an eyelid abnormality, a fifth or seventh cranial nerve defect, or proptosis. The ulcer may become superinfected. See 4.5, Exposure Keratopathy and 4.6, Neurotrophic Keratopathy.

• Sclerokeratitis: Corneal ulceration may be associated with scleritis. Scleral edema with or without nodules develops, scleral vessels become engorged, and the sclera may develop a blue hue. An underlying connective tissue disease, especially GPA, must be ruled out. See 5.7, Scleritis.

• Ocular rosacea: Typically affects the inferior cornea in middle-aged patients. Erythema and telangiectasia of the eyelid margins, corneal neovascularization. See 5.9, Ocular Rosacea.

• Others: Cataract surgery, inflammatory bowel disease, previous HSV or VZV infections, and leukemia can rarely cause peripheral corneal thinning/ulceration.

1. History: Contact lens wearer or previous HSV or VZV keratitis? Connective tissue disease or inflammatory bowel disease? Other systemic symptoms? Seasonal conjunctivitis with itching (vernal)? Prior ocular surgery or trauma?

2. External examination: Old facial scars of VZV? Lagophthalmos or other eyelid closure problem causing exposure? Blue tinge to the sclera? Rosacea facies?

3. Slit-lamp examination: Look for infiltrate, corneal ulcer, hypopyon, uveitis, scleritis, old herpetic corneal scarring, poor tear lake, SPK, blepharitis. Check corneal sensation prior to instilling anesthetic. Look for giant papillae on the superior tarsal conjunctiva or limbal papillae. Measure IOP.

4. Schirmer test (see 4.3, Dry Eye Syndrome).

5. Dilated fundus examination: Look for cotton wool spots consistent with connective tissue disease or evidence of posterior scleritis (e.g., vitritis, subretinal fluid, chorioretinal folds, exudative retinal detachment).

6. Corneal scrapings and cultures when infection is suspected. See Appendix 8, Corneal Culture Procedure.

7. Consider systemic workup including serum erythrocyte sedimentation rate, complete blood count with differential, rheumatoid factor, antinuclear antibody, antineutrophilic cytoplasmic antibody levels, ACE, and chest x-ray or CT to rule out connective tissue disease and leukemia.

8. Scleritis workup, when present (see 5.7, Scleritis).

9. Refer to an internist (and/or rheumatologist) when connective tissue disease is suspected.

See sections on delle, staphylococcal hypersensitivity, dry eye syndrome, exposure and neurotrophic keratopathies, scleritis, vernal conjunctivitis, and ocular rosacea.

1. PUK-associated systemic immune-mediated disease: Management is usually coordinated with an internist or rheumatologist.

   • Ophthalmic antibiotic ointment (e.g., erythromycin ointment) or preservative-free artificial tear ointment q2h. 

   • Cycloplegic drop (e.g., cyclopentolate 1% or atropine 1% b.i.d. to t.i.d.) when an anterior chamber reaction or pain is present.

   • Consider doxycycline 100 mg p.o. b.i.d. for its metalloproteinase inhibition properties and ascorbic acid (vitamin C 1 to 2 g daily) as a collagen synthesis promoter.

   • Systemic steroids (e.g., prednisone 60 to 100 mg p.o. daily; dosage is adjusted according to the response) and antiulcer prophylaxis (e.g., ranitidine 150 mg p.o. b.i.d. or pantoprazole 40 mg daily) are used for significant and progressive corneal thinning, but not for perforation.

   • An immunosuppressive agent (e.g., methotrexate, mycophenolate mofetil, infliximab, azathioprine, cyclophosphamide) is often required, especially for GPA. This should be done in coordination with the patient’s internist or rheumatologist.

   • Excision or recession of adjacent inflamed conjunctiva is occasionally helpful when the condition progresses despite treatment.

   • Punctal occlusion if dry eye syndrome is present. Topical cyclosporine 0.05% to 2% b.i.d. to q.i.d. or lifitegrast 5% b.i.d. or varenicline nasal spray 0.03 mg b.i.d. may also be helpful. See 4.3, Dry Eye Syndrome.

   • Consider cyanoacrylate tissue adhesive or corneal transplantation surgery for an impending or actual corneal perforation. See Video: Cyanoacrylate Corneal Glue. A conjunctival flap or amniotic membrane graft can also be used for an impending corneal perforation.

   • Patients with significant corneal thinning should wear their glasses (or protective glasses [e.g., polycarbonate lens]) during the day and an eye shield at night.

2. Terrien marginal degeneration: Correct astigmatism with glasses or contact lenses if possible. Protective eyewear should be worn if significant thinning is present. Lamellar grafts can be performed if thinning is extreme.

3. Mooren ulcer: Underlying systemic diseases must be ruled out before this diagnosis can be made. Topical steroids, topical cyclosporine 0.05% to 2%, limbal conjunctival excision, corneal gluing, and lamellar or penetrating keratoplasty may be beneficial. Systemic immunosuppression (e.g., oral steroids, methotrexate, cyclophosphamide, and cyclosporine) has been described.

4. Pellucid marginal degeneration: See 4.25, Keratoconus.

5. Furrow degeneration: No treatment is required.

NOTE Topical steroids should be used with caution in the presence of significant corneal thinning because of the risk of perforation. Gradually taper topical steroids if the patient is already taking them. Notably, corneal thinning due to relapsing polychondritis may improve with topical steroids (e.g., prednisolone acetate 1% q1–2h).

Patients with severe disease are examined daily; those with milder conditions are checked less frequently. Watch carefully for signs of superinfection (e.g., increased pain, stromal infiltration, anterior chamber cells and flare, conjunctival injection), increased IOP, and progressive corneal thinning. Treatment is maintained until the epithelial defect over the ulcer heals and is then gradually tapered. As long as an epithelial defect is present, there is risk of progressive thinning and perforation.