12/3/2011. Disclosure. Allergic Eye Disease: Diagnostic Pearls and Treatment Options. Symptoms. Allergy Eye Disease

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1 Disclosure Allergic Eye Disease: Diagnostic Pearls and Treatment Options I have no financial relationships to disclose. Ophthalmology Update 2011 Matilda Chan MD, PhD Department of Ophthalmology, UCSF F.I. Proctor Foundation Allergy Eye Disease Symptoms Affects up to 40% of the general population. Subtypes: 1. Seasonal 2. Vernal 3. Atopic 4. Giant Papillary Conjunctivitis (GPC) Redness Itching Tearing Burning Stinging Photophobia Watery or ropy discharge Nasal symptoms 1

2 Associated/Predisposing Factors Seasonal Environmental allergens Vernal Hot, dry environments Environmental allergens and irritants for acute exacerbations Atopic Genetic predisposition to atopy Environmental allergens and irritants for acute exacerbations Seasonal Allergic Conjunctivitis clinical signs Bilateral Conjunctival injection Chemosis Watery discharge Giant papillary conjunctivitis (GPC) Contact lens wear (soft lenses, infrequent lens replacement, prolonged wearing time, poor lens hygiene) Exposed sutured and prostheses Mild mucous discharge Vernal Allergic Conjunctivitis clinical signs Bilateral Giant papillary hypertrophy of superior tarsal conjunctiva Chemosis Limbal Trantas dots Watery and mucoid discharge Shield ulcer Atopic Allergic Conjunctivitis clinical signs Bilateral Eczematoid blepharitis Eyelid thickening, scarring, lash loss Papillary rxn of superior and inferior tarsal conjunctiva Watery or mucoid discharge Conjunctival scarring Subcapsular cataract Keratoconus Guglielmetti, S, Curr Opin Allergy Clin Immunol

3 Giant Papillary Conjunctivitis clinical signs Papillary hypertrophy of superior tarsal conjunctiva Mucoid discharge Papillae with white fibrotic centers can be seen in patients with long-standing disease Natural History Seasonal Recurrent Vernal Onset in childhood Chronic course with acute exacerbations (during spring and summer) Gradual decrease in activity within 2 to 30 years Atopic Onset in childhood Chronic course with acute exacerbations (perennial) Kuryan, J, Eyenet 2010 Giant papillary conjunctivitis (GPC) Chronic gradual increase in symptoms and signs with contact lens wear, exposed sutures, ocular prosthesis Potential Sequelae Seasonal Minimal, local Vernal Eyelid thickening; ptosis Conjunctival scarring Corneal neovascularization, thinning, ulceration, infection, keratoconus Visual loss Atopic Eyelid thickening; loss of lashes Conjunctival scarring Corneal scarring, thinning, ulceration, neovascularization, infection, keratoconus Cataract Visual loss Giant papillary conjunctivitis (GPC) Ptosis, rarely Diagnostic Test Conjunctival Scraping 1. Anesthetize the conjunctiva with topical 0.5% proparacaine hydrochloride for about 5 minutes 2. Using a Kimura spatula, the inner surface of the lower lid is gently scraped several times. 3. The material is spread on a microscope slide. 4. The slide is stained with Giemsa stain and examined for eosinophils. 3

4 Stages of Allergic Conjunctivitis (Type I Hypersensitivity Reaction) Sensitization 1. Sensitization. 2. Early-phase. 3. Late-phase. antibodies specific to an allergen are created. Mast cell Sensitization Early-Phase Mast cell produces histamine, prostaglandins, and leukotrienes and is now primed. Returning allergens Mast cell Mast cell 4

5 Early-Phase Early-Phase Degranulation s bind to antibodies Histamine Prostaglandins Leukotrienes Late-Phase Treatment Antihistamines The chemotactic factors released from mast cell degranulation attract, recruit, and activate: Eosinophils Dendritic cells/monocytes Neutrophils Inhibit the action of histamine on H1 receptors. Oral H1 antagonists may cause systemic adverse effects and have a slower onset of action. 1 st generation side effects include sedation and cardiac arrhythmia. Histamine 2 nd generation non-sedating Brief duration of action about 4 hours Prostaglandins Leukotrienes Chronic Inflammation 5

6 1 st Generation 2nd Generation Treatment Antihistamines Chlorpheniramine Cyclizine Levocabastine Emedastine Triaminic Allergy Marezine Livostin Emadine Treatment Mast-cell Stabilizers Inhibit mast cell degranulation and blocks the release of preformed mediators that reside in mast cells (histamine, proteases, cytokines). For a mast-cell stabilizer to be effective, the mast cell has to be deactivated before the allergic reaction is triggered Require a loading period during which they are applied for several weeks before antigen exposure (compliance can be difficult). Minimal ocular side effects Treatment Mast-cell Stabilizers Cromolyn sodium Nedocromil Lodoxamide tromethamine Pemirolast potassium Crolom Alocril Alomide Alamast Treatment Dual Acting Agents Inhibit the action of histamine on H1 receptors and inhibit mast cell degranulation. Provide rapid symptom relief through antihistamine action and long-term control by inhibiting mast cell degranulation. No loading dose required so better compliance. 6

7 Treatment Dual Acting Agents Olopatadine Ketotifen Azelastine Epinastine Bepostatine Alcaftadine Patanol, Pataday Alaway, Zaditor Astelin, Optivar Elestat Bepreve Lastacaft Treatment NSAIDS Inhibit the production of inflammatory mediators by acting on cyclooxygenase enzymes (COX-1 and COX-2). Discomfort on instillation Ketorolac Acular, Acular LS, Acular PF Treatment Corticosteroids Treatment Corticosteroids Reserved for cases of refractory or severe chronic forms of allergic conjunctivitis (VKC, AKC, GPC). Because there is no direct inhibition of mast cell degranulation or inhibition of mediators, they are not ideal for treatment of seasonal allergic conjunctivitis. Side effects cataracts, glaucoma, superinfection, corneal melting. Prednisolone acetate Prednisolone phosphate Fluorometholone Dexamethasone Loteprednol etabonate Rimexolone Pred Forte Inflamase FML, FML Forte AK-Dex, Ocu-Dex Alrex, Lotemax Vexol 7

8 Treatment Seasonal Allergic Conjunctivitis Treatment Vernal/Atopic Conjunctivitis Mild cases antihistamine Frequently recurrent or persistent mast cell stabilizer Acute or chronic disease dual acting agents Not adequately controlled brief course (1-2 weeks) of topical steroid or NSAID Other measures artificial tears, cool compresses, oral antihistamines, allergen avoidance, frequent clothes washing, bathing before bedtime, avoid contact lens use. General treatment measures - modify environment to minimize exposure to allergens or irritants; cool compresses; ocular lubricants Topical and oral antihistamines and topical mastcell stabilizers have important roles in chronic treatment. Acute exacerbations topical corticosteroids and/or topical cyclosporin 2%. Severe cases Supratarsal corticosteroid injection and/or systemic immunosuppression may be warranted. Supratarsal injection of corticosteroid in the treatment of refractory vernal keratoconjunctivitis. Treatment Giant Papillary Conjunctivitis Modify the causative entity: Remove or rotate suture knots or use a therapeutic contact lens Clean, polish, or replace ocular prostheses Mild contact lens-related replace lenses more frequently, decrease wear time, use preservativefree lens care systems, refit contact lenses, switch to disposable lenses. Holsclaw DS, Am J Ophthalmol Moderate to severe contact lens-related discontinue contact lens wear for several weeks to months and a brief course of topical corticosteroid treatment. 8

9 Future Directions Novel Targets Spleen tyrosine kinase (Syk) inhibitors Syk regulates the release of histamine. H4 inhibitors H4 receptors regulate T-cell mediated responses. Janus protein kinase-3 (JAK-3) inhibitors JAK-3 is involved in the activation and proliferation of T-cells. Monoclonal antibody against eotaxin 1- regulates conjunctival mast cells Conclusions The main subtypes of allergic conjunctivitis include seasonal, vernal, atopic, and giant papillary conjunctivitis (GPC). Ocular allergies can be chronic or acute. Chronic allergies can be vision threatening. Treatment includes modifying the environment or causative entity. Current drugs include topical or systemic antihistamines, mast cell stabilizers, dual acting agents, NSAIDs, corticosteroids. 9