Inflammatory Mediators Involved in Conjunctival and Corneal Remodeling of Vernal Keratoconjunctivitis

Vernal keratoconjunctivitis (VKC) is a chronic condition that causes remodeling of the cornea and conjunctiva through recurring episodes of allergic inflammation of the ocular surface. This can lead to corneal scarring, keratoconus, and chronic conjunctival papillae. However, the details of the immunopathological processes behind these remodeling changes are not completely understood. Despite involving IgE-modulated mechanisms, about half of patients with VKC test negative on systemic allergy tests. This calls for the need to understand the common and novel inflammatory mediators involved in the pathogenesis of VKC development and severity levels. Eye rubbing stimulates the release of inflammatory cytokines TNF-alpha, IL-4, IL-5, and IL-13 and remodeling enzymes MMP-1, MMP-3, MMP-9, and MMP-10, which drive a dysregulated cycle of stromal tissue remodeling that leads to progressive ectasia. Eosinophilic activity is driven by CCL11 and ICAM-1 and eye rubbing, which leads to degranulation and the release of EMBP, ECP, and MMP-9. These inflammatory mediators drive the remodeling changes that lead to corneal scarring and ectasia. The purpose of this comprehensive review paper is to shed light on common and novel immunological mediators that help us further understand VKC and eventually lead to the discovery of more effective and targeted treatment options.