What is allergy ? How do we go about defining and understanding allergy ?
When eyes are allergic , the condition is commonly referred to as allergic conjunctivitis.
Fungus , pet saliva , small microscopic organisms in dust , smoke pollution etc are main causes of allergy . They are different in different people
The most important mediator of allergy is histamine . When mast cells degranulate , histamine is released. This histamine has 2 receptors – H1 receptor located on nerve cells H2 receptors on blood vessels . When histamine binds to H1 receptor it causes itching . When histamine binds to H2 receptor it results in redness and swelling.
Allergy <ul><li>An abnormally high sensitivity to certain substances, such as pollens, foods, or microorganisms is called as allergy. </li></ul><ul><li>Substances causing allergy : Allergens </li></ul>May be I am allergic to flowers
Seasonal Allergic Conjunctivitis (SAC) Exposure to seasonal allergens like pollen Perennial Allergic Conjunctivitis (PAC) Continuous exposure to persistent allergens such as house dust mites Mild form of allergy Vernal keratoconjunctivitis (VKC) Due to severe hot conditions , more common in men . Itchy eyes , with mucous strands seen in the morning after sleep. Increase in goblet cells ( special type of cells in conjunctiva) Giant Papillary Conjunctivitis (GPC) Results from trauma caused by contact lens edges, or post- operative sutures . Allergic Conjunctivitis : Types
Allergic Conjunctivitis : Signs and Symptoms Itching : Is the hall mark of allergy Redness Teary, watery eyes Stinging and burning sensation Feeling of grittiness and discomfort Photophobia (extra-sensitivity to light) Lid Swelling
Allergens Ocular Surface Allergen binds with IgE on mast cell Leads to mast cell activation Preformed Mediators Histamine Chymase Tryptase Proteases Itching , Redness , Swelling Degradation of neighboring cells Inflammatory cells accumulation Newly Formed Mediators Prostaglandins Leukotrienes Platelet-activating factors Cytokines (TNF) Chemokines (IL-8) Redness, swelling Infiltration of eosinophils & neutrophils Calcium enters the cells Mast cell degranulation Release of Mediators
<ul><li>Primary </li></ul><ul><li>Mediator </li></ul>H1 receptor on nerve cells H2 receptor on blood vessels Mast cell Degranulation Histamine released Itching Redness and Swelling
Mediators of Allergy :Roles <ul><li>Histamine : Itching, redness, edema </li></ul><ul><li>Prostaglandins : Sensitized nerves, enhanced pain, edema and redness </li></ul><ul><li>Leukotrienes : Chemotaxis, edema and vascular permeability </li></ul><ul><li>Chemotactic factors : Recruitment of eosinophils and neutrophils leading to tissue destruction </li></ul>
Role Of Adhesion Molecules <ul><li>Adhesion molecules are found on the surface of the conjunctiva and on the endothelium of blood vessels, </li></ul><ul><li>Help to attract eosinophils, basophils and neutrophils, and their migration into the tissue. </li></ul><ul><li>High expression of ICAM1 will lead to large number of inflammatory cells attacking the corneal epithelium. </li></ul><ul><li>These cells then rupture to release toxic mediators of allergic response. </li></ul><ul><li>E.g of adhesion molecule : ICAM 1 </li></ul><ul><li>Conjunctival intercellular adhesion molecule 1 </li></ul>
Allergic Conjunctivitis :Reduced QOL <ul><li>Allergy sufferers experience QoL reductions in general health , well being , in their day-day routine activities and specific aspects of vision as a result of their Allergic Conjunctivitis </li></ul>
“ The goal of treatment for allergic conjunctivitis is to effectively resolve clinical signs and symptoms, and improve quality of life.” – Jose Güell, MD
Allergic Conjunctivitis Conventional Medical Management Overview
Drug Categories : Indications For prophylaxis , prevention of allergy loading doses are administered, also along with antihistaminic agents Sodium cromoglycate , nedocromil Mast Cell Stabilizer For controlling signs and symptoms of allergic conjunctivitis For temporary relief from symptoms Olopatadine , azelastine , Epinastine , ketotifen Dual Acting agents When intensity of itching is higher , antihistamines are preferred. Levocabastine , Emedastine Antihistamines For sever conditions like VKC , manage severe inflammatory conditions Loteprednol Steroids For managing redness Naphazoline Vasoconstrictor Indication Example Drug Category
Ideal Ocular Anti-allergic Agent : Features <ul><li>Must have both mast cell stabilizing and antihistaminic activity </li></ul><ul><li>Fast Acting </li></ul><ul><li>Long lasting relief </li></ul><ul><li>Soothes the eyes </li></ul><ul><li>Convenient dosing </li></ul>
Ocular Allergies : Require Prompt Attention and Action
<ul><li>Mast-cell mediators, such as tumor necrosis factor, stimulate the expression of adhesion molecules on the surface of the conjunctiva. </li></ul><ul><li>Olopatadine decreases adhesion molecule expression demonstrating potent mast-cell stabilizing activity </li></ul>
Conclusion : <ul><ul><li>Olopatadine is significantly more effective than epinastine in controlling itching, redness and chemosis associated with allergic conjunctivitis in the CAC model. </li></ul></ul>
Adverse Effects <ul><li>The following ocular adverse experiences have been reported in less than 5% of patients: </li></ul><ul><li>Blurred vision, </li></ul><ul><li>Burning or stinging, </li></ul><ul><li>Dry eye, </li></ul><ul><li>Foreign body sensation, </li></ul><ul><li>Hyperemia, hypersensitivity, </li></ul><ul><li>Keratitis, </li></ul><ul><li>Lid edema </li></ul><ul><li>PDR 2006 </li></ul>
Highlights <ul><li>Potent mast cell stabilizing ability </li></ul><ul><li>Olopatadine is the first topical ophthalmic dual acting anti-allergy agent that has clinically shown mast-cell stabilization in human eyes. </li></ul><ul><li> </li></ul><ul><li>Fast Acting </li></ul><ul><li>Reduces itching symptoms within 3.5 minutes of administration to the eyes </li></ul><ul><li>Long lasting relief: </li></ul><ul><li>Dual mechanism of action gives an immediate and a long lasting relief. </li></ul>