BREAKING NEWS
Site Under Development, Content Population and SEO, Soft Launch 1st January 2020
Allergies of the eye may affect the conjunctiva, cornea or the eyelids. Clinical signs are important in diagnosing the type of allergy.
Additional tests, such as brush cytology of the ocular epithelium or tear mediator analysis, may help in doubtful cases.
It is important to note that both Immunoglobulin E (IgE) and T-cell mediated hypersensitivity reactions are in play during an eye allergy. In addition, cytotoxic and inflammatory mediators are released in large quantities by massive eosinophil infiltration and activation.
Non-specific antigen recognition also plays a role in the allergic process. Thus adequate and intensive treatment is required to control the inflammation and prevent long-term damage to the eye.
The mechanisms involved in the pathogenesis of eye allergies include:
When the conjunctiva is exposed to an environmental allergen, specific IgE binds to the conjunctival mast cells producing an acute response, which lasts for up to 30 minutes. This involves the release of mast cell mediators, such as histamine and tryptase, as well as prostaglandins and leukotrienes.
There are about 5000 – 6000 mast cells/mm3. This increases by about 60% during exposure to pollen, whether in the hay fever season or beyond it, depending upon the type of allergy.
In the acute phase of inflammation, T-helper cell type 1 and type 2 (Th 1 and Th 2) cytokines are greatly increased, including interferon-gamma (IFN-y). In fact, the difference between the various identified forms of ocular allergy is determined by the amount rather than the types of the cytokines released.
The late phase of ocular inflammation begins with the activation of vascular endothelial cells, releasing chemo-attractants like the RANTES and MCP molecules, as well as eotaxins and various molecules, which promote intercellular adhesion. These lead to the recruitment of inflammatory cells that characterize and prolong inflammation in the conjunctival mucosa. This is further maintained by the activation and recruitment of fibroblasts and epithelial cells, which further release cytokines, chemokines and adhesion factors.
Intense eosinophilic infiltration occurs and the activation of these cells leads to epithelial toxicity, such as punctate keratitis. This may evolve to form corneal ulcerations.
In addition, Th-2 cytokines, interleukins 3 and 4 (IL-3 and IL-4) also stimulate ocular fibroblasts. These cells migrate into the area of inflammation and become activated to proliferate, as well as synthesize new collagen. Local enzyme imbalances lead to the deposition of extracellular matrix and the formation of giant papillae.
All of these lead to persistent inflammation and tissue remodeling in the eye. The inflamed tissue shows epithelial transformation and an increase in the amount of connective tissue, as well as edema and the inflammatory recruitment of mast cells, lymphocytes and fibroblasts.
Tissue remodeling causes thickening of the conjunctiva with fibrosis of the subepithelial tissue. In addition, neovascular changes are brought about with glandular metaplasia. This process ends in scarring.
Current modes of management depend on:
Identification of the Cause
Triggers of eye allergy may include:
Avoiding Exposure to the Offending Agent
Controlling the Pathways of Inflammation
Avoiding the allergen is very difficult in cases of environmental aerogens, and therefore the mainstay of management remains medical treatment. It focuses on the following four classes of medication:
These include sodium cromoglycate, nedocromil, or lodoxamide, which are administered in the form of eye drops. It is important to make sure that these do not contain benzalkonium chloride or other preservatives, which may themselves cause irritation, dryness and inflammation in the already sensitive eye.
These antagonize the natural effects of histamine release on the eye. Effects antagonized include vasodilation, exudation and irritation of nerve endings that causes itching and discomfort.
Anti-Inflammatory Drugs
Corticosteroids reduce the number of granulocytes in the inflamed tissue, and produce lymphopenia. They also reduce prostaglandin synthesis, thereby reducing the levels of interleukins and other prostaglandin derivatives. In addition, they may stabilize the lysosomal membranes.
Calcineurin Inhibitors
In severe inflammation, the calcineurin inhibitors cyclosporine A, tacrolimus and pimecrolimus are used. These produce local immunosuppression. They reduce the proliferation, cytokine synthesis and release by T-helper cells and other inflammatory cells. They prevent eosinophil migration, as well as mast cell and basophil degranulation.
Seasonal allergic conjunctivitis is treated with antihistamines, anti-inflammatory drugs, or the mast cell stabilizer cromoglycate. Immunotherapy (sublingual or subcutaneous) may be required in severe cases.
Perennial allergic conjunctivitis requires prolonged and intensive treatment until all symptoms and signs of inflammation subside. This includes the use of mast cell stabilizers and antihistamines. In cases of chronic inflammation, local steroids may be needed.
Vernal keratoconjunctivitis is a disease that lasts for years, and may result in sight-reducing corneal ulcers. It demands treatment with mast cell inhibitors and antihistamines, and corticosteroids during exacerbations. If long-term corticosteroid use becomes necessary, it should be switched for cyclosporine A, with steroids added as necessary for acute relapses.
In atopic keratoconjunctivitis, both eczematous blepharitis and ocular inflammation must be treated over the long term. This is usually with calcineurin inhibitors like tacrolimus for the blepharitis, and with mast cell stabilizers and antihistamines for the conjunctival irritation. If relapse of conjunctivitis occurs upon cessation of treatment, corticosteroids are administered. If continuous corticosteroid use becomes necessary, cyclosporine A eye drops are preferred.
Hypo-sensitization of a subject to the allergen is produced by specific immunotherapy (SIT). Both sublingual and subcutaneous routes have been used with good results. Administered over 3 years, it provides a decrease in the need for medication and symptom severity, which lasts for about 10 years.
This is an anti-IgE drug, which binds free IgE, thus preventing it from binding to mast cells with subsequent activation and mediator release. It must be given early and for a prolonged duration to gradually arrest the chronic allergic process. In most cases it must be given lifelong.