Allergic conjunctivitis pathophysiology

Allergic conjunctivitis is a group of diseases affecting the ocular surface and is usually associated with type 1 hypersensitivity reactions. Two acute disorders, seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC) exist, as do three chronic diseases, vernal keratoconjunctivitis (VKC), atopic keratoconjunctivitis (AKC), and giant papillary conjunctivitis (GPC).

Allergic conjunctivitis is the manifestation of a predominantly IgE-mediated hypersensitivity reaction^[1].

Stimulated mast cells release increased amounts of tryptase, histamine, prostaglandins and leukotrienes in tears. This is the immediate response, which lasts for the initial 20-30 min.

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Degranulation of mast cells activates vascular endothelial cells to express adhesion molecules such as intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM) and release chemokines like regulated upon activation normal T cells expressed and secreted (RANTES), monocyte chemoattractant protein (MCP), Interleukin (IL)-8, eotaxin, macrophage inflammatory protein (MIP)-1 alpha.

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Triggers the recruitment of inflammatory cells in the conjunctival mucosa, which mediate the ocular late-phase reaction^[2].

• The allergic reaction in VKC is chronic in nature, mediated by Th2-lymphocyte alongside the over-expression of mast cells, eosinophils, neutrophils, Th2-derived cytokines, chemokines, adhesion molecules, growth factors, fibroblasts and lymphocytes. IL-4 and IL-13 are involved in the formation of the giant papillae by inducing extra-cellular matrix production and conjunctival fibroblast proliferation^[3].
• Th1 lymphocytes are one of the primary mediators in AKC^[4].
• Contact allergy, or allergic contact dermatitis, in contrast is a type-IV delayed hypersensitivity response^[5]

Antigen-MHC class II complex interacts with T-lymphocytes → Differentiation of CD4+ T-lymphocyte into memory T-lymphocyte→ Proliferates to release cytokines^[6]. Th1 derived cytokines, such as IL-2, IL-3, IFN-γ, recruit macrophages. Th2 derived cytokines, such as IL-4 and IL-5, mediate the activation and chemotaxis of eosinophils^[7].

• IL-17-producing T cells (Th-17 cells) and regulatory T cells (Treg cells) have also been found to be contributing to the pathogenesis. However, their role has not yet been clearly elucidated^[8].
• In GPC, the conjunctival tissues do not contain mast cells, basophils, or eosinophils, to the extent of an allergic reaction. No increase in IgE or histaimine has been found in the tears of GPC patients. It appears that protein deposits on the surface of the contact lens become antigenic and stimulate the production of IgE; mechanical trauma and chronic irritation can also drive the release of some mediators (CXCL8 and TNF-α) from the injured conjunctival epithelium^[9].

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