Peripheral Ulcerative Keratitis: Pathogenesis, Diagnosis, and Multimodal Management

Peripheral ulcerative keratitis (PUK) is a sight-threatening corneal disorder characterized by progressive peripheral stromal thinning and ulceration. It often reflects an underlying systemic autoimmune or vasculitic disease and may herald severe morbidity or even mortality. This review offers a comprehensive synthesis of current knowledge on the pathophysiology, clinical presentation, diagnostic approach, and management strategies for PUK, with a special focus on idiopathic forms such as Mooren’s ulcer. We explore the immunological mechanisms driving peripheral corneal destruction, including the roles of complement activation, matrix metalloproteinases, and systemic immune dysregulation. A detailed classification of etiologies, including systemic autoimmune diseases, infectious causes, and iatrogenic forms, is presented, along with recommendations for diagnosis, laboratory workup, and differential diagnosis. Management strategies are reviewed in a stepladder approach, from local anti-collagenase and immunomodulatory therapy to systemic immunosuppressants and biologics, and, when necessary, surgical intervention.