What is the pathophysiology of Allergic Conjunctivitis?

From the Guidelines

Allergic conjunctivitis is triggered by an immunoglobulin E (IgE)-mediated hypersensitivity reaction in the conjunctiva, leading to the release of inflammatory mediators like histamine, which causes symptoms of redness, itching, tearing, and swelling. The process begins when allergens like pollen, animal dander, or dust mites contact the ocular surface in sensitized individuals, binding to IgE antibodies on mast cells in the conjunctiva, causing degranulation and release of inflammatory mediators 1. These allergens trigger an early phase reaction within minutes of exposure, characterized by the release of histamine and other mediators like leukotrienes, prostaglandins, and cytokines, producing the characteristic symptoms of allergic conjunctivitis. A late phase reaction may develop 4-24 hours later due to recruitment of inflammatory cells like eosinophils and neutrophils, contributing to ongoing inflammation and chronic symptoms.

Some key factors that contribute to the development of allergic conjunctivitis include:

• Allergen exposure: Avoiding airborne allergens is crucial in managing allergic conjunctivitis, and wearing sunglasses can act as a barrier to these allergens 1.
• Mast cell degranulation: Mast cells play a significant role in the pathophysiology of allergic conjunctivitis, and mast-cell stabilizers can be used to prevent degranulation and alleviate symptoms 1.
• Inflammatory mediators: Histamine and other inflammatory mediators like leukotrienes, prostaglandins, and cytokines produce the characteristic symptoms of allergic conjunctivitis, and antihistamines like olopatadine or ketotifen can effectively relieve symptoms.

Treatment of allergic conjunctivitis typically targets these inflammatory pathways using:

• Antihistamines: Topical antihistamine/vasoconstrictor agents or second-generation topical histamine H1-receptor antagonists can be used to treat mild allergic conjunctivitis 1.
• Mast cell stabilizers: Mast-cell stabilizers can be used to prevent degranulation and alleviate symptoms, especially in cases of frequently recurrent or persistent allergic conjunctivitis 1.
• Anti-inflammatory agents: Corticosteroids may be used for severe cases of allergic conjunctivitis, but their use should be carefully considered due to potential side effects.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Corticosteroids inhibit the inflammatory response to a variety of inciting agents and probably delay or slow healing. They inhibit the edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation associated with inflammation There is no generally accepted explanation for the mechanism of action of ocular corticosteroids. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid.

The pathophysiology of Allergic Conjunctivitis is not directly explained in the provided drug label. However, it mentions that corticosteroids inhibit the inflammatory response to various inciting agents, which is relevant to allergic conjunctivitis. The label also discusses the possible mechanism of action of ocular corticosteroids, including the induction of lipocortins and the inhibition of prostaglandins and leukotrienes. However, this information does not directly address the pathophysiology of allergic conjunctivitis. 2

From the Research

Pathophysiology of Allergic Conjunctivitis

• Allergic conjunctivitis is an allergen-induced immune response secondary to the binding of immunoglobulin-E (IgE) to sensitized mast cells 3.
• The activation and degranulation of mast cells lead to increased tear levels of histamine, tryptase, leukotrienes, cytokines, and prostaglandins, which initiates the recruitment of inflammatory cells in the conjunctival mucosa 3.
• The release of these factors causes the late-phase reaction, resulting in signs and symptoms of ocular allergies, including itching, tearing, chemosis, and hyperemia 3, 4.

Types of Allergic Conjunctivitis

• Seasonal allergic conjunctivitis and perennial allergic conjunctivitis are two acute disorders, while vernal keratoconjunctivitis, atopic keratoconjunctivitis, and giant papillary conjunctivitis are three chronic diseases 4.
• Each type of allergic conjunctivitis has distinct clinical symptoms and pathogenesis, requiring different treatment approaches 4, 5.

Treatment Options

• Topical antihistamines and mast cell stabilizers are commonly used to treat allergic conjunctivitis, with dual-action agents being the most effective for mild forms of the disease 6, 5.
• Antihistamines, such as alcaftadine, levocabastine, and azelastine, have been shown to be effective in reducing symptoms of allergic conjunctivitis 6, 5.
• Mast cell stabilizers, such as sodium cromoglycate, have also been used to treat allergic conjunctivitis, although their efficacy may vary depending on the specific agent and concentration used 6, 5.

New Therapeutic Approaches

• Nutraceuticals, such as Vitamin D3, Perilla extract, and quercetin, have been proposed as potential therapeutic options for allergic rhinoconjunctivitis, although more research is needed to confirm their efficacy 7.
• The development of new biotargets for the treatment of allergic conjunctivitis is an active area of research, with the goal of creating more effective and safe treatment regimens 4.