Ocular allergy

1. Ocular allergy Abdulrahman Al Muammar

2. Ocular allergy • Allergic eye diseases accounts for up to 3% of all the medical consultations seen in general practice. • The milder forms of allergic eye diseases have fluctuating symptoms of itch, tearing, and swelling. • Chronic form of the disease give rise, in addition, to more severe symptoms including pain, visual loss from corneal scarring, cataract or glaucoma, and disfiguring skin and lid changes.

3. Ocular allergy • Clinical classifications: • 1) Allergic conjunctivitis (AC): • Acute allergic conjunctivitis: • Seasonal or hay fever. • Toxic- induced (induced by acute contact with irritant, drugs, preservatives, etc). • Chronic allergic conjunctivitis: • Perennial. • Toxic-induced (long standing).

4. Ocular allergy • 2) Contact dermatoblepharitis. • 3) Vernal keratoconjunctivitis (VKC • 4) Giant papillary conjunctivitis (GPC • 5) Atopic keratoconjunctivitis (AKC • 6) Atopic blepharoconjunctivitis (ABC).

5. Sensitization • Acute and chronic diseases have in common: • 1) sensitization to environmental allergens. • 2)Ig E mast cells activation with subsequent mediator cascade. • 3) conjunctival inflammation with prevalence of eosinphils. • 4) the presence of lymphocytes with a Th2 profile of cytokines production .

6. Sensitization • The conjunctiva is normally exposed to pictogram quantities of environmental allergens such as pollens, dust mite fecal particles, animal dander and other proteins . • When deposited on the mucosa, these antigens are thought to be processed by lagerhans cells and other antigen presenting cells (APC) in the mucosal epithelium .

7. Sensitization • antigen is presented to native Th0 cells expressing antigen – specific T cell receptors recognize the antigenic peptide. Multiple simultaneous contacts and cytokine exchange between APC and T cells are necessary to trigger antigen specific Th0 cells to differentiate into Th2 lymphocyte .

9. Sensitization • . The cytokines released by Th2 cells ( IL3,IL4,IL5,IL6,IL13,GM-CSF) stimulate B cell IgE production and inhibit development of Th1 mediated delayed type hypersensitivity reactions . • B cells which recognize the same allergen that induce Th2 differentiation, in present of appropriate signals such as IL4,IL6 and IL13 undergo heavy chain switching to produce IgE.

11. Mast cells • Mast cells particularly abundant in the conjunctival stroma especially at the limbus. • The number of the mast cells in the conjunctiva has been calculated to be 5000/mm3 . • conjunctival biopsies from symptomatic allergic patients have shown an increase in subepithelial mast cells with evidence of mast cells degranulation • Two different types of mast cells have sown in conjunctiva, differentiated by their content of tryptase alone ( mucosal mast cell or MCT) or both tryptase and chymase ( connective tissue type mast cell or MCTC)

12. Mast cells • Proliferation of these cells in allergic disorders is probably under influence of Th2 cytokins. • Mast cells and basophils, bearing high affinity surface receptors for Ig E are the most important cells in IgE mediated reactions.

13. Mast cells • Mast cells mediators: • Histamine. • Vasodilatation….smooth muscle constriction. • Itching..redness. • Heparin. • Prevent blood coagulation. • Anti-inflammatory. • Tryptase. • Potentiates histamine..activates eosinophils and mast cells

14. Mast cells • Prostaglandins and leukotrienes • Capillary leakage..smooth muscle contraction..increase granulocyte action..platelet aggregation. • Airway hyperresponsiveness…asthma.

15. Mast cells • Eosinophil chemotactic factor-alpha (ECF-alpha). • Attract eosinophils. • Platelet activating factor (PAF). • Platelet aggregation….neutrophil chemotaxis. • Bronchoconstriction…hypotension…hyperemia.. Chemosis.

16. Eosinphils • Influx of eosinphils is essential in allergic inflammation and profound changes in conjuncatival mucosa. • Eosinophils are activated by interaction with other inflammatory cells such as platelet activating factors. • Activated eosinophils release very basic highly charged polypeptide including: • Major basic protein (MBP). • Eosinophil cationic protein (ECP). • Eosinophil derived neurotoxin (EPX). • eosinophil peroxidase (EPO).

18. Eosinphils • These proteins may bind to basement membrane protoglycans and hyaluran to cause cellular disaggregation and epithelial desquamation. • ECP and MBP are epithelial toxic and are involved in corneal damage that may occur in sever chronic allergy. • Eosinphils are also important source of leukotriens, prostaglandins and cytokines such as IL3, IL5, and GM CSF, eotaxin and RANTES. • ECP and EPX tear level are correlated with clinical signs and symptoms of allergic disease and maybe considered local markers of eosinphil activation.

19. Neutrophils • Following allergen challenge, neutrophils are the first cells to appear in tear fluid and the predominant infiltrating cells in the conjunctive during late phase. • Although the role of neutrophils in allergic disorders is not clear, they can release inflammatory mediators including leukotriens ,PAF and cytokines. • Tear level of myeloperoxidase (MPO). a neautrophil activating marker are increased in allergic conjunctivitis.

20. Lymphocytes • One of the most important process responsible for orchestrating and regulating allergic inflammation is the production of cytokines by T cells lymphocytes. • CD4-T cells are the predominant population in conjunctival inflamed tissues. • T cells have been subdivided into two functionally distinct subset on the basis of their cytokine profile: • Th1 and Th2 . • Th1 is known to produce IL2 and interferon gamma(INF-g). • Th2 is known to produce IL3,IL4,IL5.

21. Lymphocytes • T cells in allergic inflamed tissues are mostly CD4 with cytokine production profile of the Th2 type. • An increase in expression of Th2 type cytokine (IL4, IL5, IL3) have been demonstrated in SAC, VKC and AKC. • Compared to SAC, VKC maybe considered a disease with an over expression of these cytokines in addition to other mechanism involved. • Conversely in AKC and GPC in addition to typical Th2 derived cytokines, increases of IL2 and INF-g has been shown suggesting that in the most severe atopic conditions a cell medicated hypersensitivity may also occur.

23. Seasonal allergic conjunctivitis • Is the commonest and one of the mildest forms of allergic conjunctivitis. It accounts for 25%-50% of all cases of ocular allergy. • SAC is often associated by rhinitis and even sinusitis. • 70% of patients provide either a personal of familial allergic history. • SAC can develop suddenly when patient comes in contact with an appropriate antigen, such as pollens, grasses, or trees.

24. SAC • Symptoms: • Itching. • Watery discharge. • Rhinitis. • Sinusitis.

25. SAC • Signs: • Not always present. • Lid swelling. • Ptosis. • Conj hyperemia. • Chemosis (=/- dellen). • Papillary reaction. • Follicular reaction.

28. SAC • Diagnosis: • Clinically. • Family history. • Conj scrapings for eosinophils. • Tear level of IgE, serum tear. • Radioallergosorbent test measures specific IgE levels for a specific antigens. • Mast cells activity by measuring tryptase and histamine levels in tear film.

29. SAC • Pathophysiology: • Type I hypersenstivity. • Late phase reaction (LPR): • Clinical, histological, or chemical response to an antigen that occurs 3 to 12 hours after the initial acute (early phase) mast cell-mediated allergic reaction.

30. SAC • Treatment: • Avoidance of allergen: • Limit outdoor activities. • Use air conditioning or air filter system. • Drive car with windows closed. • Use protective eyegear when outdoor. • Washing allergen. • Antihistamines. • Mast cell stabilizers. • NSAIDs. • Steroids. • Immunotherapy.

31. Acute allergic toxic induced conjunctivitis • Usually triggered by external non- airborne antigens such as drugs, contact lens solution, irritants, and preservatives. • Type I medicated. • Symptoms are similar to SAC but no seasonal component. • Itching, tearing, eyelid erythema and swelling, and conjunctival redness and chemosis. Typically occur within minutes after application of an allergen. • Bactriacin..cephalosporins..sulfacetamide..tetracycline • Atropine…homatropine. • Epinephrine..pilocarpine..apraclonidine. • Antiviral agents. • Thimerosal..chlorhexidine…bezalkonium chloride.

35. Acute allergic toxic induced conjunctivitis • Diagnosis: • Clinical presentation. • Offending agents. • Conj scrapings. • Treatment: • Discontinue the offending agents. • Tears.. • Cold compresses. • Antihistamines.. • NSAIDs.. • Steroid

36. Perennial allergic conjunctivitisPAC • Symptoms persist throughout the year, with seasonal variation in up to 87% of patients. • The clinical signs and symptoms are similar to SAC, but more persistent. • Allergens could be house dust mites, animals, etc.. • Type I mediated.

37. PAC • Treatment: • Avoidance of allergen: • Cover for mattress and pillows. • Washing bedding regularly. • Reduce humidity. • Vaccum and damp dust. • Eliminate animals from house. • Washing allergen. • Antihistamines. • Mast cell stabilizers. • NSAIDs. • Steroids. • Immunotherapy

38. Contact dermatoblepharitis • Reaction that may begin 24-72 hours following instillation of topical medication. • Patients are often sensitized by previous exposure to the offending drugs or preservatives. • Acute eczema with erythema, leatherlike thickening, and scaling of the eyelid. • Lower eyelid ectropion, and hyperpigmentation. • Papillary conjunctivitis and mucoid discharge may develop.

40. Contact dermatoblepharitis • Medications commonly associated with these symptoms: • Atropine..homatropine. • Neomycine..gentamycine..tobramycine. • Idoxuridine..trifluridine. • Thimerosal. • Type IV reaction.

41. Contact dermatoblepharitis • Treatment: • Allergen withdrawal. • In severe cases…brief course of topical steroids applied to the eyelids and periocular skin may speed resolution.

42. VKC • Epidemiology: • Rarely appear in patients younger than 3 or older than 25 years of age. • M:F is 2:1. • The disease usually lasts 4 to 10 years and resolved after puberty, but also can still be present and even worsened in some adult patients. • Occurs more frequently in the Mediterranean area, central Africa, India, and South America. • It also occur in cooler climates, such as Great Britain and other northern European countries, which is possibly as a consequences of migratory movements of the susceptible population. • Association with atopy is 15 to 60%.

43. VKC • VKC is usually bilateral, although monocular forms and asymmetric symptoms do occur. • Three clinical forms can be observed : tarsal, limbal (more common in African and Asian patients), and mixed tarsal/limbal. • In majority of the cases, the disease is seasonal, lasting from the beginning of spring until fall. Nevertheless, perennial cases have been observed, especially in warm subtropical or desert climates.

44. VKC • Symptoms: • Itching. • Tearing. • Mucus secretion. • Photophobia. • Pain. • Blepharospasm. • Decreased visual acuity.