Ocular Manifestation and Treatment of Allergic Disorders April 18, 2015 Disclosures Ocular Manifestation and Treatment of Allergic Disorders Greg Caldwell OD, FAAO Nebraska Optometric Association 2015 Spring Conference Lincoln, NE April 18, 2015 $ Greg A. Caldwell, OD, FAAO will mention many products, instruments and companies during our discussion, I don’t have any financial interest in any of these products, instruments or companies. $ In the past 12 months I have lectured or participated in a focus group which I received a honorarium for: ¬ Allergan, Alcon, and Optovue $ All of these cases have entered/referred to my practice Disclosure Statement (next slide) Learning Objectives $ Develop a better understanding about ocular allergic diseases and their treatments $ Identify new therapeutic options and discuss their benefits $ Review immune reaction and hypersensitivity reaction $ Prepare you to educate peers and patients about allergic conjunctivitis and its treatment Ocular Allergy Statistics $ Ocular allergies affect 20% of the population ¬ 90% of all allergy patients have ocular symptoms ¬ 50 million people suffer from ocular allergies It’s not just an opportunity it is an Optom-portunity What is an Allergy? $ Allergy-is a result of a beneficial immune Normal Immune Response Antigen is eliminated response that has gone awry B lymphocyte $ Hypersensitivity-is a result of a beneficial immune response that has gone awry Antibodies IL-4 Major Histocompatibility Complex Allergy = Hypersensitivity T lymphocyte Plasma cell IgG, IgA, IgM, IgE Antigen-presenting cell Greg Caldwell, OD, FAAO [email protected] 814-931-2030 cell 1 Ocular Manifestation and Treatment of Allergic Disorders April 18, 2015 Coombs and Gell Classification Hypersensitivity When a specific immune response is not appropriately controlled, a phenomenon termed hypersensitivity ensues. $ Type I $ Type II $ Type III $ Type IV Allergy Cytotoxic, antibody-dependent Immune Complex disease Delay Type Hypersensitivity $ Type 5- often used in Britain used to help differentiate Type II Allergy = Hypersensitivity Why This Language Gets So Confusing? $ The same language is used to describe ¬ Hypersensitivity-Type I, II, III and IV ¬ Autoimmune disease-Type I, II, III and IV $ Immune disorders=Hypersensitivity + Autoimmune diseases ¬ Instead of binding to cell surface, the AB binds to the cell surface receptor ¬ Graves and Myasthenia Gravis ¬ Rare to use Why This Language Gets So Confusing? $ Type I-allergy, atopy, IgE ¬ Only hypersensitivity-atopic dermatitis, allergic conjunctivitis ¬ There are no autoimmune disease $ Type II-antibody dependent cell mediated cytotoxicity IgM, IgG ¬ Hypersensitivity-Pernicious anemia ¬ Autoimmune-Rheumatic fever, Graves, Myasthenia gravis $ Type III-Immune Complex ¬ Hypersensitivity-Reactive arthritis ¬ Autoimmune-Systemic lupus erythematosus, rheumatoid arthritis $ Type IV-cell mediated, T-cells ¬ Hypersensitivity-contact dermatitis ¬ Autoimmune-DM type 1, Hashimoto’s and GCA Conclusion $ True ocular allergy ¬ Hypersensitivity Type I and IV $ We may see ocular side effects from Type I thru IV hypersensitive and autoimmune diseases but they are secondary and not true ocular allergy Greg Caldwell, OD, FAAO [email protected] 814-931-2030 cell Hypersensitivity $ Type I ¬ Allergy (immediate) ¬ Atopy syndrome, anaphylaxis, asthma 2 Atopy-affecting parts of the body not in direct contact with the allergen. Elevated levels of IgE in the blood…result positive skin prick test to common allergens. ¬ IgE 2 Ocular Manifestation and Treatment of Allergic Disorders April 18, 2015 Hypersensitivity Hypersensitivity $ Type I- IgE response to a particular antigen termed an allergen ¬ Typically mediated by mast cells and particularly histamine ¬ Ex. Allergic conjunctivitis $ Type II- IgM or IgG response. Antibody binds to cell surface antigens on cells or tissues ¬ IE. Autoimmune hemolytic anemia, thrombocytopenia, pemphigus IgE antibodies IgM or IgG antibodies One’s own cells Sensitized mast cell Hypersensitivity Hypersensitivity $ Type III- Immune complex disease. Normally antibody antigen combine, an immune complex is formed. These complexes usually are cleared from systemic circulation by phagocytes. Poorly cleared immune complexes that persist in circulation can lead to systemic disease. ¬ IE. Systemic Lupus Erythematosus and Polyarteritis nodosa Antigen is eliminated $ Type IV- Delayed type hypersensitivity ¬ Regulated by T-cells ¬ Sub-categories: 2 Contact Ø Medicated by Langerhan’s cells and keratinocytes B lymphocyte Antibodies Major IL-4 Histocompatibility Complex T lymphocyte 2 Tuberculin 2 Granulomatous ¬ IE. Contact Dermatitis Plasma cell IgG, IgA, IgM, IgE Antigen-presenting cell Classification of Ocular Allergy $ Allergic conjunctivitis ¬ Seasonal ¬ Perennial $ Atopic keratoconjunctivitis $ Vernal keratoconjunctivitis 32 year old man $ My eyes itch so bad I want to claw them out $ I went golfing today (May) $ Rubbing them feels good but I think it makes it worse $ Vision and externals are normal $ Giant papillary conjunctivitis $ Contact dermatitis Greg Caldwell, OD, FAAO [email protected] 814-931-2030 cell 3 Ocular Manifestation and Treatment of Allergic Disorders Seasonal Allergic Conjunctivitis $ Happened the last 2 April 18, 2015 Allergic Conjunctivitis Seasonal years but not this bad $ Occurs in spring, fall or both $ Grass, tree pollen or ragweed Perennial $ Year round with periods that are more pronounced $ Animal dander, dust mites, mold, grass $ History of other atopic diseases Signs and Symptoms of Allergic Conjunctivitis Seasonal $ Itching $ Redness $ Burning $ Excessive tearing $ Stringy white mucus $ Rhinitis Perennial $ Similar to seasonal allergic conjunctivitis $ Milder than seasonal allergic conjunctivitis $ More constant than seasonal allergic conjunctivitis $ Seasonal exacerbations Non-pharmacologic Interventions $ Allergen avoidance ¬ Pet control ¬ Use air conditioning, HEPA filters ¬ Avoid outdoor activities during high pollen periods $ Cold compresses $ Lubricating eye drops $ Wash your hair before going to bed Pharmacologic Interventions $ Lastacaft™ $ Pataday™ $ Pazeo™ $ Alrex™ $ Lotemax™ $ Topical eye drops 2 Vasoconstrictors 2 Antihistamines 2 Antihistamine/vasoconstrictor combination 2 Antihistamine/mast cell stabilizer combination 2 Mast cell stabilizers 2 Non-steroidal antiinflammatory drugs (NSAIDs) 2 Corticosteroids What is happening and how do these pharmaceuticals work? $ Oral antihistamines $ Allergen immunotherapy Greg Caldwell, OD, FAAO [email protected] 814-931-2030 cell 4 Ocular Manifestation and Treatment of Allergic Disorders April 18, 2015 Allergic Sensitization Ocular Allergy is Mainly Type I Hypersensitivity Antigen in tears $ Consists of three phases ¬ Sensitization phase- patient unaware ¬ Activation phase (early allergic response) ¬ Late allergic response Conjunctival epithelium B lymphocyte IL-4 Major Histocompatibility Complex “Treatment failure may occur if you fall short to IgE antibodies T lymphocyte identify which phase the hypersensitivity is in” Plasma cell Sensitized mast cell Antigen-presenting cell Early Allergic Response Late Allergic Response (Second Exposure) Leukotrienes Antigen in tears Conjunctival epithelium Histamine m Im e iat ed Activated mast cell ECF-A $ Leukotrienes Arachidonic Acid Newly-Formed Peroxidase Eosinophil Prostaglandins Leukotrienes Cationic Proteins Thromboxines Lysosomal Enyzmes Platelet Activating Factor Cell-Mediated Cytotoxicity Tissue damage Edema 28 year old man Three subtypes of the histamine receptor have been pharmacologically defined (H1, H2, H3) $ Was helping set up tents and tables for a Selective stimulation of ocular H1 receptors results in ocular itching and vasodilation $ Eye became itchy, he rubbed it and within Selective stimulation of ocular H2 receptors produces vasodilation and redness without itching H2 H1 church event H1 H1 $ Histamine Prostaglandins Histamine Receptors $ Tryptase Chymase Pre-Formed Synthesis Phospholipids Basophil Histamine ECF-A Heparin Prostaglandins H1 one hour it became very swollen $ The eye is still very itchy and watery H2 Greg Caldwell, OD, FAAO [email protected] 814-931-2030 cell 5 Ocular Manifestation and Treatment of Allergic Disorders April 18, 2015 Is this a Type 1 or Type 4 Hypersensitivity Reaction? Slit Lamp Exam $ Type 1 hypersensitivity $ Diagnosis? (immediate) $ Treatment? 2 days later ¬ Occur within minutes of challenge by antigen ¬ Etiology: pollens, insect stings, insect bites, foods, systemic drugs ¬ IGE mediated ¬ Lid manifestations 2 Red, swollen, itchy lids 6 year old boy $ Eyes are red and itchy again since the beginning of April, now May 10th $ “He rubs them all the time” $ He is already using Pataday 1 gtt qd OU, Rxed by pediatrician, uses it everyday $ Used to get mucous and discharge from the eye but has not since on Pataday™ $ Let’s take a look Vernal Conjunctivitis $ Ages 3-25, peak incidence 11-13y/o, lasts 4-11 yrs $ males>females $ Thick ropy discharge, severe itching and corneal involvement Worse spring and summer ¬ Important clinical signs: 2 Large papillae, Horner-Trantas dots 2 SPK 2 Well demarcated sterile ulcer (shield ulcer) $ Type I hypersensitivity ¬ With early and late phases $ Children generally will outgrow this allergy ¬ Their super-immune system slows down Greg Caldwell, OD, FAAO [email protected] 814-931-2030 cell 6 year old boy $ Take a shower and wash hair before going to bed $ NP AT $ Cont Pataday™ $ Add Alrex™ qid 6 Ocular Manifestation and Treatment of Allergic Disorders April 18, 2015 25 year old man $ My eyes are red and itchy all year round ¬ At times of the year they are worse, like today $ I do cold compresses, artificial tears and Pataday ¬ This seems to help but my eyes are really never white, clear and have some itch ¬ “I thought allergies occurred in the spring and summer” $ I work with the public and my clients always ask about my eyes $ Patient has eczema and avoids many detergents and fragrances/colognes $ Patient also suffers from asthma and uses inhalers $ Let’s take a look Atopic Keratoconjunctivitis $ Atopic keratoconjunctivitis (AKC) is the result of a condition called "Atopy" $ Atopy is a genetic condition whereby the immune system produces higher than normal antibodies in response to a given allergen $ There is usually a family history of multiple allergies $ Although AKC is a perennial disease, symptoms tend to worsen in the winter (dryness) $ Atopic dermatitis which is generally seen early in childhood 64 year old woman $ Diagnosed with bacterial conjunctivitis 8 days ago OD $ Used tobramycin qid OD, appeared to be worsening, was told to use q2 hours $ In today for second opinion ¬ Atopic keratoconjunctivitis appears during late adolescence ¬ Men are more commonly affected than women. Discussion Diagnosis: contact dermatitis Type 4 Hypersensitivity Treatment $ Delayed/cell mediated ¬ Occur in hours, days to months after antigen challenge ¬ T cell mediated ¬ Etiology: contact dermatitis, topical medications, jewelry, nail polish ¬ Manifestations: 2 Itching 2 Red lids 2 Superficial skin changes 6 days later Greg Caldwell, OD, FAAO [email protected] 814-931-2030 cell 7 Ocular Manifestation and Treatment of Allergic Disorders Contact Dermatitis $ Causes: ¬ Topical Medications 73 year old man $ In today because his “pink eye” that he 2 Alpha agonists, B-blocker, Pilocarpine, Atropine ¬ Contact lens solutions ¬ Cosmetics ¬ Fingernail polish ¬ Pet dander ¬ Molds ¬ Detergents ¬ Latex ¬ Hair dye ¬ Metals: nickel Discussion $ Glaucoma patient using April 18, 2015 Conjunctivitis? ¬ ½ Betimol™ qd OU AM ¬ Alphagan-P™ 0.15% bid OU ¬ Travatan Z™ qd OU PM contracted from his granddaughter will not clear up $ Started 3 weeks ago, worsened for 2 weeks, now stable Is this a Type 1 or Type 4 Hypersensitivity Reaction? $ Type 4 hypersensitivity (delayed/ cell mediated) ¬ Occur in hours, days to months after antigen challenge ¬ Etiology: contact dermatitis, topical medications, jewelry, nail polish ¬ Manifestations: 2 Itching 2 Red lids 2 Superficial skin changes Which is most likely the offending agent? $ Patient has been using Alphagan-P™ 0.15% for 9 months $ Contact Dermatitis Another 0.2% Brimonidine Hypersensitivity Type 1 and Type 4 Ocular Allergy Giant Papillary Conjunctivitis 1 week later Greg Caldwell, OD, FAAO [email protected] 814-931-2030 cell 8 Ocular Manifestation and Treatment of Allergic Disorders 37 year old woman $ Previously treated for contact lens overwear with Maxitrol™ (antibiotic and steroid) qid, told she had sterile ulcers $ With Maxitrol eyes feel better in 2 days $ Her eyes are red and irritated, 3rd time this year, wants 2nd opinion and treatment $ Wore contact lens for 3 weeks, average wearing time 8-10 hrs, before this episode started Giant Papillary Conjunctivitis $ Condition characterized by formation of large papillae (>0.3mm) on the superior palpebral conjunctiva $ No seasonal variation $ Etiology ¬ Contact lens wear ¬ Exposed sutures (conjunctiva or cornea) ¬ Prosthesis April 18, 2015 Slit lamp exam $ Any thoughts? ¬ Why so recurrent? $ Treatment? ¬ D/C CL wear 2 Until resolved ¬ Pataday™ ¬ Tobradex™ 2 Until cornea clear ¬ Lotemax™ ¬ Artificial tears $ Once resolved ¬ Maintenance dose of mast cell stabilizer ¬ SCL - vs – GP – vs - vision correction Giant Papillary Conjunctivitis $ Treatment ¬ Decreased CL wearing time ¬ Change to disposable soft CL’s, Dailies SCL, RGP ¬ Mast cell stabilizers (Pataday™) ¬ Topical steroids (short term) 2 Lotemax™ $ Pathophysiology ¬ Mechanical trauma induces inflammatory cascade and mast cell degranulation ¬ No increase in histamine levels ¬ Plasma cells, mast cells, eosinophils and basophils are found in cytologic scrapings. (Type I & IV) 2 Over-reaction of body’s immune system ¬ Arachidonic acid cycle main component 14 year old boy Diagnosis and Treatment? $ My eye is red, watery and very painful $ Started about 10 days ago $ Tried artificial tears without help $ Child is healthy $ Does not wear contact lens $ Let’s look at the photo Greg Caldwell, OD, FAAO [email protected] 814-931-2030 cell 9 Ocular Manifestation and Treatment of Allergic Disorders Phlyctenulosis $ Focal nodule of inflammatory tissue $ Two forms ¬ Conjunctival ¬ Corneal $ Focal nodule can migrate from conjunctiva to cornea $ Etiology ¬ Staphylococcus (most common) ¬ Rosacea ¬ Tuberculosis $ Treatment ¬ Rule out tuberculosis if suspicious 2 Chest X-ray and PPD ¬ Combination antibiotic/steroid ¬ Treat underlying lid disease 2 Blepharitis 2 Rosacea Greg Caldwell, OD, FAAO [email protected] 814-931-2030 cell April 18, 2015 Thank-You and Hope You Enjoyed Greg Caldwell OD, FAAO [email protected] 10
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