Allergy

• An abnormally high sensitivity to certain substances, such as pollens, foods, or microorganisms is called as allergy.

• Substances causing allergy : Allergens

May be I am allergic to

flowers

Ocular allergy :Allergic conjunctivitis

Allergic Conjunctivitis : Causes

POLLEN

PET DANDER

POLLUTION

DUST MITES

MOLDS

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 SymptomsItching : Is the hall mark of allergy

Redness

Teary, watery eyes

Stinging and burning sensationFeeling of grittiness and discomfort

Photophobia (extra-sensitivity to light)Lid Swelling

Allergic Conjunctivitis : Manifestation

Allergens Ocular Surface Allergen binds with IgEon 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

ProstaglandinsLeukotrienesPlatelet-activating factorsCytokines (TNF)Chemokines (IL-8)

Redness, swelling Infiltration of eosinophils & neutrophils

Calcium enters the cells

Mast cell degranulation

Release of Mediators

Primary

Mediator

H1 receptor on nerve cells H2 receptor on blood vessels

Mast cell Degranulation

Histamine released

Itching Redness and Swelling

Mediators of Allergy :Roles

• Histamine: Itching, redness, edema • Prostaglandins: Sensitized nerves, enhanced

pain, edema and redness • Leukotrienes: Chemotaxis, edema and

vascular permeability • Chemotactic factors: Recruitment of

eosinophils and neutrophils leading to tissue destruction

Role Of Adhesion Molecules

• Adhesion molecules are found on the surface of the conjunctiva and on the endothelium of blood vessels,

• Help to attract eosinophils, basophils and neutrophils, and their migration into the tissue.

• High expression of ICAM1 will lead to large number of inflammatory cells attacking the corneal epithelium.

• These cells then rupture to release toxic mediators of allergic response.

• E.g of adhesion molecule : ICAM 1• Conjunctival intercellular adhesion molecule 1

Allergic Conjunctivitis :Reduced QOL

• 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

“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 : IndicationsDrug Category Example Indication

Vasoconstrictor Naphazoline For managing redness

Steroids Loteprednol For sever conditions like VKC , manage severe inflammatory conditions

Antihistamines Levocabastine ,

Emedastine

When intensity of itching is higher , antihistamines are preferred.

Mast Cell Stabilizer Sodium cromoglycate , nedocromil

For prophylaxis , prevention of allergy loading doses are administered, also along with antihistaminic agents

Dual Acting agents Olopatadine , azelastine , Epinastine , ketotifen

For controlling signs and symptoms of allergic conjunctivitis

For temporary relief from symptoms

Ideal Ocular Anti-allergic Agent : Features

• Must have both mast cell stabilizing and antihistaminic activity

• Fast Acting • Long lasting relief• Soothes the eyes• Convenient dosing

Ocular Allergies : Require Prompt

Attention and Action

• Mast-cell mediators, such as tumor necrosis factor, stimulate the expression of adhesion molecules on the surface of the conjunctiva.

• Olopatadine decreases adhesion molecule expression demonstrating potent mast-cell stabilizing activity

Conclusion :

Olopatadine is significantly more effective than epinastine in controlling itching, redness and chemosis associated with allergic conjunctivitis in the CAC model.

Adverse Effects

• The following ocular adverse experiences have been reported in less than 5% of patients:

• Blurred vision, • Burning or stinging, • Dry eye, • Foreign body sensation, • Hyperemia, hypersensitivity, • Keratitis, • Lid edema

PDR 2006

Highlights

Potent mast cell stabilizing abilityOlopatadine is the first topical ophthalmic dual acting anti-allergy agent that has clinically shown mast-cell stabilization in human eyes.

Fast Acting Reduces itching symptoms within 3.5 minutes of administration to the eyes

Long lasting relief: Dual mechanism of action gives an immediate

and a long lasting relief.