Wednesday, December 6, 2023
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The conjunctiva is the most immunologically active component of the external eye. As summarized in a number of recent reviews, allergic ocular diseases have the capacity to elicit IgE-mediated type I, type IV, or a combination of type I and IV hypersensitivity reactions.[12,13] Upon exposure to environmental allergens, conjunctival antigen-presenting cells including macrophages, Langerhans cells, and dendritic cells encounter the allergen and present peptide fragments to naïve CD4+ T cells. The encounter with the antigen-presenting cells and cognate peptide results in a cascade of events and subsequent binding of allergen-specific IgE to FcεRI receptors present on mast cells within the conjunctiva. Upon provocation, cross-linking of the FcεRI receptors can occur, resulting in mast cell degranulation and the release of preformed (histamine, proteases, proteoglycans) and newly formed (prostaglandins, leukotrienes, platelet activating factor) mediators.[2-4,14] Mast cell-derived mediators contribute to the development of type I hypersensitive reactions that occur in allergic conjunctivitis, characterized by itching, vasodilation, chemosis, and increased vascular permeability.[2,4,7**,14]
Mast cells are increased in most forms of ocular allergy, with the addition of increased CD4+ T cells in the more severe/chronic forms (VKC, AKC, and GPC). Mast cells also synthesize and release cytokines of the T helper type 2 profile (IL-4, IL-5, IL-6, IL-8, IL-13, and tumor necrosis factor-α).[15] These cytokines promote T-cell growth and differentiation, class switching of B cells to produce IgE, adhesion molecule expression, inflammatory cell infiltration, and mediator release from activated cells.[15] Release of histamine by mast cells also causes the pathognomonic itching associated with allergic eye disease and can result in chronic eye rubbing and further mechanical degranulation of mast cells.[16,17] This chronic mechanical disruption of mast cells due to repetitive eye rubbing may initiate ocular inflammation as well as potentiate other existing forms of ocular allergy (A. Keane-Myers, personal communication).
Seasonal and perennial allergic conjunctivitis results from type I hypersensitive reactions. Symptoms include ocular itching, tearing, conjunctival hyperemia, chemosis, clear white mucoid discharge, and a glassy appearance of the eye. These symptoms occur chronically in PAC patients, as the allergens that cause PAC are continuously present in the environment. In both forms of the disease, elevated IgE levels are detected. These levels, however, are found in a higher percentage of patients diagnosed with PAC.[8**]
Some cases of ocular allergy cannot be explained by mast cell degranulation alone, especially in late-phase responses. This finding suggests that degranulation and mediator release of other cells such as basophils, eosinophils, and neutrophils may trigger and perpetuate inflammatory responses observed in allergic conjunctivitis.[6**,15] Type IV hypersensitivity reactions (delayed allergic reactions) occur hours after allergen challenge and mast cell activation. VKC and AKC are mediated by a combination of type I and type IV hypersensitive reactions.[18] VKC is characterized by intense ocular itching, conjunctival hyperemia, photophobia, foreign body sensation, and mucous secretion, and at times corneal damage.[1,14,19**] This ocular disease has two forms: tarsal and limbal. Tarsal VKC presents giant papillae on the upper tarsal conjunctiva. These giant papillae are often described as having a cobblestone appearance. A fibrinous mucus discharge containing eosinophils is also known to be present. The limbal form is associated with multiple thick gelatinous infiltrates of epithelial cells and eosinophils, known as Horner-Trantas dots around the limbus.[2,8**] Corneal involvement in VKC is more common in the tarsal form than the limbal form. Punctate keratitis, plaque, sterile corneal ulcers, subepithelial scarring, and pseudogerontoxon, keratoconus are all forms of corneal damage associated with VKC.[2,8**] AKC differs from VKC in that it consistently involves inflammation of the eyelid (blepharitis) and is closely related to atopy in the form of asthma and eczema.
