1. an educational program of: Allergic Conjunctivitis Revised guidelines June 2003

2. Slide 2 GLORIA resource documents  Allergic Conjunctivitis: Assessment and Therapy World Allergy Organization-IAACI 2003  Contemporary Approaches to Ocular Allergy Management American College of Allergy, Asthma and Immunology 1998  World Allergy Forum Program Series World Allergy Organization 2000-2003

3. Slide 3 Revised Nomenclature of Allergic Disease  Intermittent – occasional symptoms lasting < 4 days per week on ≤ 4 weeks  Persistent – symptoms lasting > 4 days per week or > 4 weeks

4. Slide 4 Allergic Conjunctivitis  A broad group of allergic conditions involving inflammation of the conjunctiva Acute Allergic Conjunctivitis (AAC) Intermittent/Seasonal Allergic Conjunctivitis (IAC/SAC) Persistent/Perennial Allergic Conjunctivitis (PAC) Giant Papillary Conjunctivitis (GPC) Vernal Keratoconjunctivitis (VKC) Atopic Keratoconjunctivitis (AKC)

5. Slide 5 The Conjunctiva  The surface of the eye is the most obviously exposed mucous membrane of the body  The conjunctival surface is accessible to allergens and is the site of allergic reactions

6. Slide 6 Allergic conjunctivitis: Epidemiology  Acute Allergic Conjunctivitis (AAC) Occurs at any age, especially childhood  Intermittent/Seasonal Allergic Conjunctivitis (IAC/SAC) Affects 5% to 22% of the general population

7. Slide 7 Allergic conjunctivitis: Epidemiology  Persistent/Perennial Allergic Conjunctivitis (PAC) Found in 4% of patients attending an inner city health center during summer months, USA Dart et al, 1986  Giant Papillary Conjunctivitis (GPC) 1 - 5% of rigid gas permeable contact lens wearers; 10-15% of hydrogel (soft) contact lens wearers, USA Abelson, 2000

8. Slide 8 Allergic conjunctivitis: Epidemiology  Vernal Keratoconjunctivitis (VKC) Pre-pubescent boys in warm, dry climate 10% of all eye patients in East Jerusalem, O’Shea, 2000 0.5-1.0% of all patients in eye clinics worldwide, Beigelman, 1950

9. Slide 9 Allergic conjunctivitis: Epidemiology  Atopic Keratoconjunctivitis (AKC) Atopic Eczema/Dermatitis Syndrome affects 3% of US population; 15-40% of AEDS patients develop AKC. Occurs 2nd through 5th decade, males more often affected than females

10. Slide 10 The normal eyelid and conjunctiva

11. Slide 11 Allergic conjunctivitis: Major symptoms  Pronounced itching  Watery, stringy or ropy discharge  Redness

12. Slide 12 Diagnosis of allergic conjunctivitis  Detailed personal and family allergic history and physical examination  History of typical eye symptoms  Appearance of everted (flipped) eyelid

13. Slide 13 Examination of surface of the eye  The surface markings of the conjunctiva extend beyond the visible limits of the eye

14. Slide 14 The everted eyelid

15. Slide 15 Diagnosis of allergic conjunctivitis: Clinical investigations  Allergy skin tests performed by an allergist and/or  Measurement of allergen specific IgE antibody (Radioallergosorbent tests)  Conjunctival scrapings for eosinophils – particularly elevated in VKC, AKC and GPC  Conjunctival challenge

16. Slide 16 Differential diagnosis of allergic conjunctivitis  Acute Allergic Conjunctivitis (AAC) occurs at any age, especially childhood  Large quantity of allergen (eg, plant pollen) inoculated into eye causes: Intense itching Immediate swelling of conjunctiva and lids (eye may close)  Self-limiting

17. Slide 17 Acute allergic conjunctivitis

18. Slide 18 Differential diagnosis of allergic conjunctivitis  Intermittent/Seasonal Allergic Conjunctivitis (IAC/SAC)  Persistent/Perennial Allergic Conjunctivitis (PAC) Related to seasonal or perennial allergens, association with genetic predisposition to allergic rhinitis

19. Slide 19 Everted eyelid in intermittent/seasonal allergic conjunctivitis

20. Slide 20 Persistent/perennial allergic conjunctivitis

21. Slide 21 ‘Allergic Shiners’ Fireman P, Atlas of Allergies, 1996

22. Slide 22  Giant Papillary Conjunctivitis (GPC) Trauma due to contact lens, ocular prosthesis, aggravated by concomitant allergy Differential diagnosis of allergic conjunctivitis

23. Slide 23 The upper tarsal conjunctiva in giant papillary conjunctivitis

24. Slide 24 Differential diagnosis of allergic conjunctivitis  Vernal Keratoconjunctivitis A disease of childhood sometimes associated with atopic constitution. Severe T-cell mediated disease involving the cornea: may be sight-threatening

25. Slide 25 Conjunctival appearance in vernal keratoconjunctivitis

26. Slide 26  Atopic Keratoconjunctivitis A persistent disease of the eyelids usually beginning in young adulthood. Associated with the atopic eczema/dermatitis syndrome (AEDS) infection, corneal thinning, cataracts and environmental allergens. Differential diagnosis of allergic conjunctivitis Severe T-cell mediated disease involving the cornea: may be sight-threatening

27. Slide 27 The eye and periorbital region in atopic keratoconjunctivitis

28. Slide 28 Corneal changes in atopic keratoconjunctivitis

29. Slide 29 Simple differential diagnosis of allergic conjunctivitis and other conditions If it itches, it is allergy; if it burns, it is probably dry eye; if the eyelids are stuck together in the morning, it is a bacterial infection.

30. Slide 30 Globally important allergens  House dust mites  Grass, tree and weed pollen  Pets  Cockroaches  Molds

31. Slide 31 Clinical investigations: Allergy skin prick testing  Skin prick test / positive result

32. Slide 32 Laboratory investigations: Radioallergosorbent tests

33. Slide 33 Different cell types infiltrate the conjunctiva  AAC, IAC, SAC, PAC Mast cells Eosinophils Neutrophils  GPC, VKC, AKC T cells Eosinophils Mast Cells Neutrophils

34. Slide 34 Mediators of the IgE-mediated reaction in allergic conjunctivitis Chemotactic factors from eosinophils and neutrophils cell destruction, disruption of ocular surface. Leukotrienes chemotaxis, edema and vascular permeability Prostaglandins sensitized nerves, enhanced pain, edema and redness Histamine itching, redness and edema

35. Slide 35 Modes and sites of action of allergic conjunctivitis therapies Mast cell B cell T cell (mast cell) Eosinophil IL-4 IL-3, -5 GM-CSF VCAM-1 IgE Immediate symptoms Itch, redness, edema,chemotaxis, edema, vascular permeability Sensitized nerves, enhanced pain, edema, redness Chronic symptoms cell destruction disruption of ocular surface Histamine Leukotrienes Prostaglandins Allergen Allergen avoidance Immuno- therapy Antihistamines Olopatadine Sodium cromoglycate Olopatadine Steroids Eosinophil and Neutrophil chemotactic factors: Anti-IgE

36. Slide 36 Treatment of allergic conjunctivitis: Allergen avoidance Allergen avoidance and environmental control are the first steps in the management of allergic disease

37. Slide 37 Treatment of allergic conjunctivitis: Allergen avoidance  House dust mites: Provide adequate ventilation to decrease humidity Wash bedding regularly at 60°C Encase pillow, mattress and quilt in allergen impermeable covers Dispose of feather bedding Use vacuum cleaner with HEPA filter (when available) Replace carpets with linoleum or wooden floors Remove curtains, pets and stuffed toys from bedroom Provide adequate ventilation to decrease humidity

38. Slide 38 Treatment of allergic conjunctivitis: Allergen avoidance  Pollen Very difficult to avoid! Remain indoors with windows closed at peak pollen times Wear sunglasses and hat outdoors Use air-conditioning, where possible Install car pollen filter

39. Slide 39 Treatment of allergic conjunctivitis: Allergen avoidance  Pet Allergens Exclude pets from bedrooms and, where possible, from home Vacuum carpets, mattresses and upholstery regularly Wash pets regularly

40. Slide 40 Treatment of allergic conjunctivitis: Allergen avoidance  Cockroach Allergens Eradicate cockroaches with appropriate insecticide Eliminate dampness, cracks in floors, ceilings, cover food; wash surfaces, floors, fabrics to remove allergen © 1998-2003 Troy Bartlett

41. Slide 41  Molds Ensure dry housing Use ammonia to remove mold from bathrooms and other wet spaces Treatment of allergic conjunctivitis: Allergen avoidance

42. Slide 42 Treatment of allergic conjunctivitis: Non-pharmacological therapy  Allergen avoidance including physical barriers, eg, hat, sunglasses, allergen-impermeable pillow and mattress covers  Cold compresses  Preservative-free tears

43. Slide 43  Topical NSAIDs Ketorolac – of limited effectiveness  Vasoconstrictors Not recommended for regular use Pharmacotherapy of allergic conjunctivitis: Topical NSAIDs, Vasoconstrictors

44. Slide 44 Pharmacotherapy of allergic conjunctivitis: Topical antihistamines  Topical antihistamines azelastine, emedastine, levocabastine  Topical antihistamine plus vasoconstrictor antazoline-naphazoline, cetirizine- pseudoephedrine, pheniramine-naphazoline

45. Slide 45 Pharmacotherapy of allergic conjunctivitis  Once daily administration  Rapid onset and 24 hour duration of action  No sedation  No interaction with alcohol, foods, drugs  Additive anti-allergic activities Properties required of ideal new generation oral antihistamines

46. Slide 46 Pharmacotherapy of allergic conjunctivitis: Oral antihistamines  Less effective than topical therapies  Beware unwanted effects of ‘dry eye’  If indicated for multiple allergic symptomatology, select non-sedating oral antihistamines: loratadine, fexofenadine, cetirizine

47. Slide 47 Pharmacotherapy of allergic conjunctivitis: Topical mast cell stabilizers Preventative: Do not work immediately  DSCG: Debatable effectiveness  Nedocromil: Twice daily  Lodoxamide: Highly potent, rapid relief, additional anti-eosinophilic effect  Pemirolast: Twice or four times daily dosing, effective for itch

48. Slide 48 Pharmacotherapy of allergic conjunctivitis: Dual-action antihistamine/mast cell stabilizer  Olopatadine: Highly effective, comfortable  Ketotifen: Approved for itch  Azelastine: Approved for itch

49. Slide 49 Pharmacotherapy of allergic conjunctivitis: Topical corticosteroids  Topical corticosteroid therapy must be prescribed and monitored, preferably by an ophthalmologist because: It is only appropriate for treatment of severe allergic ocular disease – not for intermittent/seasonal allergic conjunctivitis Prolonged use can lead to secondary bacterial infection, glaucoma and cataracts

50. Slide 50 Pharmacotherapy of allergic conjunctivitis: Specific allergen immunotherapy (allergen vaccination)  Must be administered by allergy specialist centre with resuscitation facilities  Helpful in managing persistent allergic rhinitis and atopic keratoconjunctivitis  Of value in patients with multi-organ symptoms of IgE-mediated allergic sensitization  Risk-to-benefit ratio must be considered in all cases  Highly effective in selected patients

51. Slide 51 Pharmacotherapy guidelines for persistent/perennial allergic conjunctivitis Topical mast cell stabilizer, or Dual action antihistamine/ mast cell stabilizer Consider immunotherapy/ vaccination at specialist center Step 1 Step 2

52. Slide 52 Pharmacotherapy guidelines for intermittent/seasonal allergic conjunctivitis Topical antihistamine and/or topical NSAID Step 1 Step 2 Step 3 Topical antihistamine with vasoconstrictors Dual action antihistamine/mast cell stabilizer Therapy may be increased in a step-wise fashion until adequate control is achieved, or commenced at Step 3

53. Slide 53 Pharmacotherapy of allergic disease: Future directions – Anti IgE  >75% of allergic asthmatics have rhinitis; >40% of allergic rhinitis patients have allergic conjunctivitis  Humanized monoclonal antibodies against IgE, e.g., omalizumab are effective for treatment of moderate to severe asthma. Such therapy: (cont’d on next slide)

54. Slide 54 Decreases free IgE levels and down-regulates IgE receptors on basophils Inhibits the late phase allergic reaction following allergen bronchial challenge Preliminary study indicates omalizumab is effective for nasal and ophthalmic symptoms of intermittent and perennial allergic rhinitis Ongoing studies to determine the effect of omalizumab in atopic dermatitis may have implications for treatment of AKC Pharmacotherapy of allergic disease: Future directions- Anti IgE, cont’d.

55. Slide 55 Persistent or worsening ocular allergy Persistent or worsening eye symptoms not responsive to therapy are an indication for urgent referral to a physician who specializes in allergic eye disease.