Eric E. Schmidt, O.D. Omni Eye Specialists Wilmington, NC schmidtyvision@msn.com Immunology 101 Basic function of immune system is to detect and eliminate any substance recognized as foreign Antigens (allergens) are the foreign substances that trigger the immune response Basic Immune Response Host recognizes a foreign body (antigen) Host mobilizes a reaction Self vs non-self 1
Immune System Comprised of 3 types of leukocytes Macrophage T- lymphocyte B- lymphocyte Macrophage Roving phagocytizer Engulfs invader Identifies the antigen of the FB Presents antigen to specific T-helper cell T-helper cell switches on immune system T-lymphocytes Cellular mediated immunity T-helper cells multiply and specialize into: Killer T-cells destroy infected cells (more) T-helper cells which Pump up macrophages Strengthen the immune response Activate B-cells Supressor T-cells 2
B-Lymphocytes Humoral immunity B-lymphocytes are activated by T- helpers and divide into plasma cells Plasma cells produce antibodies Antibodies match specific antigens Flag them for destruction After the initial infection: B-cells and T-cells become memory cells Memory allows antibodies to be produced faster on subsequent infections THIS IS IMMUNITY!!!! Allergies Exaggerated Immune Response Body produces immunoglobulins (antibodies) specific to allergen (antigen) Release of chemical mediators, e.g. histamine, cause allergy symptoms 3
Immunoglobulins Ig G, Ig M, Ig A, Ig D, IgE IgE- allergy antibody Minute concentrations, very potent Bound to mast cells Interaction with allergen causes mast cell degranulation Histamine complex is released Immediate hypersensitivity Allergies & The Eye 1. Allergen introduced into tear film 2. Allergen absorbed into conjunctiva 3. Allergen binds to IgE coated mast cells 4. Mast cell degranulates- allergic mediators released 5. Eyes swell and itch! 4
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Allergy Cascade Mast cell coated with IgE Activated by allergen Causes mast cell ot degranulate Histamine is released Itching results Neutrophils leak from blood vessels causing edema Histamine receptors Very prevalent in ocular tissues 3 types have been identified (H1, H2, H3) Selective stimulation of ocular H1 receptors itching and vasodilation Selective stimulation of ocular H2 receptors vasodilation and redness with no itching 9
Ocular Histamine Receptors Histamine Nerves H 1 Vasculature H 1 H 2 Itch Vasodilation Vascular Permeability Hyperemia Chemosis Allergic Inflammation Allergen-stimulated mast cells release Chemokines: attract inflammatory cells Cytokines: activate inflammatory cells Neutrophils, eosinophils and T-lymphocytes cause: Tissue inflammation More eosinophil production 10
Allergy & The Eye Immediate hypersensitivity occurs acute phase Delayed hypersensitivity follows late phase This is what makes allergies chronic 11
Type I hypersensitivity 3 phases Sensitization Activation (early response) Late allergic response Acute or SAC for example Type I Hypersensitivity Itching Chemosis Edema Redness Tearing Anaphylaxis 12
Type IV Hypersensitivity Cell mediated response Hours to days after the exposure Typical inflammation What allergy shots prevent Ocular Allergic Disease Fun Facts! 50 million people suffer some type of allergic disorder Incidence is way up over past 40 yrs 90% Of those have ocular involvement 32% involve only ocular tissue 40% Of population affected Initial onset is trending younger Warm, moist climate SAC responsible for 85% of allergic eye disorders Where in the US are allergies most prevalent? 13
Leading ocular allergens Pollen- 43% Tobacco smoke 33% Animal exposure 32% 14
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Ocular Symptoms Are Frequent Eye Symptoms Patients Aged 12 to 17 Years Juniper et al, J Allergy Clin Immunol 1994;93:413 Ocular vs. Nasal Complaints Ocular symptoms as severe or more severe than rhinitis symptoms in 70% of seasonal allergy patients Wuthrich et al, Schweiz Med Wochenschr 1998;128:139 Allergic Conjunctivitis A Mast Cell mediated hypersensitivity reaction 16
Allergic Conjunctivitis Symptoms Itching Hyperemia Mucus d/c Filmy vision Bilateral Burning Swelling Tearing FB sensation Rhinitis Allergic conjunctivitis objective findings Papillae Follicles Increased lacrimal lake Mucus strands Conjunctival injection Tear film debris Lid edema Conjunctival edema *Symptoms often outweigh the signs* Classification of Ocular Allergy Seasonal allergic conjunctivitis Perennial allergic conjunctivitis Vernal keratoconjunctivitis Atopic keratoconjunctivitis Giant papillary conjnuctivitis 17
Allergy Treatment Treatment depends upon severity Often treating symptoms not signs Must understand mechanism of drug actions Must know what you want to achieve from treatment 18
Jan-06 Mar-06 May-06 Jul-06 Sep-06 Nov-06 Jan-07 Mar-07 May-07 Jul-07 Sep-07 Nov-07 Jan-08 Mar-08 May-08 Jul-08 Sep-08 Nov-08 Jan-09 Mar-09 May-09 Jul-09 Sep-09 Nov-09 Jan-10 Mar-10 May-10 Jul-10 Sep-10 Nov-10 Jan-11 Mar-11 May-11 Jul-11 % of Allergy TRx 09/08/2015 Allergy Treatment Pearls Prescription products safer and more effective than OTC? Confirm symptoms, confirm diagnosis Treatment depends upon severity Treatment may be long term Frequent follow-up necessary Punctal occlusion? CL question What do we look for in a therapy? Control symptoms Work on intended targets No toxicity Comfort No side effects Rapid onset Long duration Easy to use dosing Allergy Specialty Mix 60.0% 50.0% 40.0% 30.0% 20.0% 10.0% 0.0% FP+IM PEDIATRICS OPH+OPT+ALG 64 19
Anti-Histamine Multi-Action Antihistamine Binds histamine receptors 1 Mast cell stabilizing Inhibits release of histamine 2-4 and cytokines 5 Anti-inflammatory Stabilization of eosinophils, 6,7 1 Fugner et al, Arzneimittelforschung basophils, 8 1988;38:1446 2 Amon et al, Inflamm Res 2000;49:112 neutrophils 9 3 Kamei et al, Immunopharm Immunotox 1992;14:191 4 Matsushita et al, Jpn J Pharmacol 1998;78:11 5 Calder et al, ACAAI 2005 6 Koyhama et al, Biochem Biophys Res Comm 1997;230 7 Ohmori et al, Arzneimittelforschung 1998;48 8 Mita et al, Arzneimittelforschung 1995;45 9 Fukuishi et al, Jpn J Pharmacol 1995;68:449 Tear Volume in Ocular Allergy Patients P =.0357 ELESTAT Claritin Tear Volume, L 13.72 14.72 13.34 8.84 34% Reduction 0 N = 18 ELESTAT (Epinastine HCI ophthalmic solution) 0.05% 4 0 4 Days of Treatment Inspire, Inc., Data on file Tear Flow in Ocular Allergy Patients ELESTAT Claritin P =.0378 3.16 Tear Flow, L/min. 2.87 2.65 1.72 35% Reduction 0 N = 18 ELESTAT (Epinastine HCI ophthalmic solution) 0.05% 4 0 4 Days of Treatment Inspire, Inc., Data on file 20
Conjunctival and Corneal Staining Global Fluorescein Staining, 0 12 Scale ELESTAT Claritin 22% Increase P =.0478 3.58 3.53 3.36 4.09 0 4 0 4 Days of Treatment N = 18 ELESTAT (Epinastine HCI ophthalmic solution) 0.05% Inspire, Inc., Data on file Anti-histamine pharmacology Reversible binding to H1 receptor sites Prevent the binding of histamine Thus the histamine effects cannot be released Blocks further release of histaminic symptoms but has no effect on the histamine that is already bound! Side effects of topical antihistamines Surface drying CL dehydration Stinging 21
Mean TBUT, sec 09/08/2015 Do Anti-histamines cause (or treat) dry eye? Altered Tear Film in Patients With Seasonal Allergic Conjunctivitis Tear Film Breakup Time 12.4 *P <.05 vs. control * 3.9 Allergy Eyes Control Eyes n = 78 n = 20 Suzuki et al, Cornea 2006;25:277 22
Ocular Antihistamines 2014 Pataday/Patanol Bepreve Lastacaft Elestat? Alaway 23
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So why one drop over another? Quicker onset Less toxicity Dosage Longer duration Action on eosinophils More comfortable (ph issue) Less drying So Does 1 Topical Antihistamine Work Better Than The Others? Yes!!! Allergy Treatment Are there any indications for NSAID? Steroid? 27
What to do about GPC??? 28