A history of connective tissue disease is often (but not invariably) present, although in some patients the ocular finding of peripheral corneal infiltration or frank stromal melting may be the first sign of the underlying systemic illness. Autoimmune PUK generally correlates with exacerbations of systemic disease activity. Follow-up of patients with autoimmune PUK reveals that if they are treated inadequately, severe disease-related morbidity may occur in a high number of these patients. The term keratolysis refers to the significant (and often rapid) stromal melting seen in some cases of immune-mediated PUK associated with systemic autoimmunity.
Although autoimmune PUK can be bilateral and extensive, it is usually unilateral and limited to 1 sector of the peripheral cornea (Fig 11-17). The initial lesions appear in a zone within 2 mm of the limbus and are accompanied by varying degrees of vasoocclusion of the adjacent limbal vascular networks. In most cases, the epithelium is absent in the affected area and the underlying stroma thinned; however, if the disease is detected early, epithelial involvement may be patchy and the stroma still of near-normal thickness. Ulceration may or may not be associated with a significant cellular infiltrate in the corneal stroma, and the adjacent conjunctiva can be minimally or severely inflamed. The sclera can be involved in patients with systemic immune-mediated diseases (eg, necrotizing scleritis in patients with rheumatoid arthritis); careful, complete examination must be performed.
Foster CS. Ocular manifestations of the potentially lethal rheumatologic and vasculitic disorders. J Fr Ophthalmol. 2013;36(6):526–532.
The goal of therapy is to provide local supportive measures to decrease melting. This is achieved through maneuvers intended to promote epithelialization, improve wetting, and suppress immune-mediated inflammation both locally and systemically.
Maintaining enhanced lubrication of the ocular surface is very important, as many patients with rheumatoid arthritis have KCS as a manifestation of their secondary Sjögren syndrome and because lubrication may help diminish the effect of inflammatory cytokines in the tear film. Melting will stop or slow appreciably if the epithelium can be made to heal by means of lubricants, patching, or a bandage contact lens. A number of topical collagenase inhibitors (eg, sodium citrate 10%, acetylcysteine solution 20%, medroxyprogesterone 1%) and systemic collagenase inhibitors such as tetracyclines (eg, doxycycline) are of potential value. Topical cyclosporine has been shown to be effective in patients with central melting that is likely due to a T-cell–mediated process rather than occlusive vasculitis.
Figure 11-17 Peripheral ulcerative keratitis associated with rheumatoid disease.
Topical corticosteroids, which also inhibit collagenase function, can have variable effects. In general, when considering steroids, the clinician must weigh the benefits of treating inflammation against the risks of impaired healing. Excision or recession of adjacent limbal conjunctiva (as has been advocated for Mooren ulcer; see the following section) is often followed by healing of the ulcer, presumably because the procedure eliminates a source of inflammatory cells and collagenolytic enzymes.
Definitive management often cannot be achieved by local measures alone and requires institution or escalation of systemic treatment, including immunosuppression therapy with oral prednisone, cytotoxic agents such as cyclophosphamide, or immuno-modulatory agents such as methotrexate or cyclosporine. Biologic agents such as infliximab have reportedly been used with some success in more severe cases. Patients with severe, rapid melting may require intravenous therapy with high-dose cyclophosphamide, with or without corticosteroid therapy. Threatened perforation should be treated with temporizing measures such as cyanoacrylate glue and bandage contact lens placement until systemic therapy has been initiated, because lamellar and penetrating grafts are also susceptible to melting. Sometimes multiple tectonic grafts are required to preserve the globe while the systemic therapy is being adjusted. Once the underlying disease process has been controlled, keratoplasty for visual restoration can be performed (see Chapter 15). Although conjunctival flaps can be very helpful in controlling the stromal melting in difficult-to-manage microbial keratitis, they are probably best avoided in immune-mediated disease. Bringing the conjunctival vasculature even closer to the area of corneal disease could accelerate melting. It is very important to partner with a rheumatologist in caring for patients with immune-mediated disease, as their risk of morbidity and death is significant.
Bhat P, Birnbaum AD. Diagnosis and management of noninfectious corneal ulceration and melting. Focal Points: Clinical Modules for Ophthalmologists. San Francisco: American Academy of Ophthalmology; 2015, module 3.
Huerva V, Sanchez MC, Traveset A, Jurjo C, Ruiz A. Rituximab for peripheral ulcerative keratitis with Wegener granulomatosis. Cornea. 2010;29(6):708–710.
Kaçmaz RO, Kempen JH, Newcomb C, et al. Cyclosporine for ocular inflammatory diseases. Ophthalmology. 2010;117(3):576–584.
Pham M, Chow CC, Badawi D, Tu EY. Use of infliximab in the treatment of peripheral ulcerative keratitis in Crohn disease. Am J Ophthalmol. 2011;152(2):183–188.e2.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.