Ocular Allergy Slides PDF - Audio Notes

My name is Gurpreet Bhogal-Bhamra and today I’m going to talk to you about how the allergies can affect the eyes 1 By the end of this lecture, you will hopefully be able to better understand the epidemiology of ocular all...

My name is Gurpreet Bhogal-Bhamra and today I’m going to talk to you about how the allergies can affect the eyes 1 By the end of this lecture, you will hopefully be able to better understand the epidemiology of ocular allergies and mechanism of ocular allergic reactions, be able to differentiate ocular allergic disease from other common external eye disorders and finally better understand the courses of action that can be taken to manage ocular allergies. 2 Allergies are often referred to as an intolerance to environmental factors or an inappropriate reaction to otherwise innocuous foreign substances. We’ve heard from Jean about the variety of allergic conditions that exist, including asthma, rhinitis, and skin disorders such as eczema. 3 In the eye, allergic responses are most commonly encountered in the form of conjunctivitis, which can either be acute or potentially more sight threatening such as in vernal conjunctivitis. Giant Papillary Conjunctivitis, is usually associated with contact lens wear, but I’ll talk about these conditions in a little more detail later on 4 Most people tend to develop allergies during childhood but many of us can still develop an allergy as late as the mid-thirties. Recent research has shown that there is an increasing prevalence of allergies, particularly in recent years, as highlighted by these two studies here. It is possible that genetics play a part in this since allergies can be inherited but they don’t display classic Mendelian inheritance patterns. 5 It is more likely that environmental factors contribute as well as genetic determinants with research revealing high correlations with factors such as cigarette smoke, drugs such as beta blockers and steroids, and nutrition. The biggest factor perhaps is persistent exposure to indoor and outdoor allergens such as pollen and house dust mite, which may give rise to increased sensitivity. 6 Ocular allergies are perhaps the most common ocular condition seen in general practice, affecting 15 to 20% of the population affected with an expected increase to 50% in Europe by 2015. Research by Aston University has actually revealed that nearly 61% of people with allergies presenting in optometric practice suffer from ocular problems as a result of their allergies – this may even be an underestimate as our data was collected during the winter months What is important is that ocular symptoms are twice as likely to affect a person than nasal symptoms with just over 80% report some impairment in daily life as a result of rhinitis type allergies. 7 This can lead to reduced income due to days off work, and increased healthcare expenses for the individual. One particular study has suggested that costs can range from £65 to nearly £125 per year. So it’s apparent that ocular allergies pose a significant problem which needs to be tackled 8 Now before we talk about how allergic reactions occur in the eye I’ll first give you a brief refresher of the immune system. Please read the slide 9 The immune system can be divided into an INNATE system and an ADAPTIVE SYSTEM. The details of both are noted on the slide above. 10 The immune system comprises many different cells, each with different roles to play in immune responses. Details of these individual cells are explained here in the following slides… 11 Additional components of the immune system include mast cells, basophils and macrophages. 90% of mast cells within the eye are actually found in the limbal and palpebral conjunctival stroma, their role is to store, synthesise and release allergic mediators like histamine. The basophils have a similar function but are found within the bloodstream. Macrophages are predominantly seen where there is chronic infection, they collect waste material found in the liver spleen and lungs. 12 Mediators of the immune response include histamine and cytokines. Histamine is the foremost allergic mediator and are stored in mast cells and basophils. Cytokines are potent mediators that are produced by lymphocytes and mast cells. 13 Hypersensitivity reactions represent abnormal immune responses to a particular antigen and allergies are typically associated with a Type 1 hypersensitivity reaction in which there is an immediate reaction. Acute allergy reactions are mediated by IgE whilst chronic reactions also involve a T-lymphocyte immune response. It is thought that in general, people with allergies have a consistently elevated level of IgE in the blood compared to people without allergies, which may be a reason for the increased sensitivity. Other types of hypersensitivity reactions include: Type I, type II, type III and type IV. These are explained fully in this slide and the next 14 Please take a moment to read through the slide 15 It is clear from extensive research that the biochemical mechanism responsible for allergic conditions is the same from person to person regardless of the cause of the allergy. The mechanism of a Type 1 hypersensitivity reaction is divided into three phases, the SENSITISATION PHASE, the EARLY PHASE and the LATE phase 16 The SENSITISATION PHASE occurs at the first exposure to an allergen and initiates a series of events that primes Mast cells for future exposure to the allergen. Most allergens are relatively small, highly soluble protein molecules that are inhaled or encountered on exposed surfaces. 17 When the allergen enters the body tissue usually via a mucosal surface such as the conjunctiva, it is quickly recognized as a foreign substance by macrophages or antigen presenting cells – in the conjunctiva these are called Langerhan cells. These antigen presenting cells engulf and digest the allergen before combining portions of the allergen with major histocompatability complex (MHC) molecules The allergen particles are then transferred and presented at the surface of the cell The antigen-presenting cell then interacts via chemical messengers (cytokines) such as interleukin 4 (IL-4) with helper T lymphocytes and B- lymphocytes through a process that isn’t actually fully understood Ultimately this process leads to the activation and maturation of B- lymphocytes into plasma cells and the production of an allergen specific IgE antibody over a period of several days to several weeks The IgE antibody then binds to a high affinity receptor on the mast cell, priming the cell for its next exposure to allergen, and can remain there for weeks or months. 18 Subsequent exposure to the allergen then initiates the Early or Activation phase of the reaction, in which there is a more visible response and more noticeable symptoms 19 Within seconds of contact between the allergen and human tissue (such as the conjunctival mucosa), the allergen binds to specific IgE antibodies on mast cells Through a series of signaling mechanisms the Mast cells become activated and this causes “degranulation” of the cells in which stored potent chemical mediators which generate allergic symptoms are released. The degranulated cells then regenerate and replenish their supplies of chemical mediators once re-synthesized so that they are ready to resume their function. There are two major groups of symptom-causing mediators that are released from activated mast cells: The first of these are known as PREFORMED mediators and include HISTAMINE and EOSINOPHIL CHEMOTACTIC FACTOR OF ANAPHYLAXIS (ECF-A). These mediators are stored in granules and are released immediately. The second group of mediators is known as NEWLY SYNTHESIZED mediators and these consist of lipids such as Prostaglandins and Leukotrienes, platelet-activating factor, and cytokines. These are synthesized after contact between the allergen and IgE antibodies. 20 Histamine binds to a variety of cells primarily via two major types of receptor, H1 and H2. These receptors are differentially distributed in tissues and they mediate different effects. For example, when Histamine binds to H1 receptors on endothelial cells of blood vessels this causes vascular permeability to increase which contributes to edema ECF-A is a peptide substance that produces a chemotactic gradient for the attraction of eosinophils to the site of the reaction. Release of heparin has no direct effect on the Early Phase of the allergic reaction, but are instead involved in inflammatory reactions in the Late Phase. 21 Newly Synthesized mast cell mediators contribute to the response of histamine and initiate the recruitment of additional inflammatory cells responsible for the Late Phase reaction. 22 The Late Phase usually occurs 6 to 24 hours after exposure to the allergen and can result in tissue damage and is the cause of chronic allergic conditions 23 The action of chemical mediators on blood vessels causes an influx of moncytes, T cells, basophils and eosinophils into the tissue at the site of the allergic inflammatory reaction. These cells secrete substances that can prolong and exacerbate the early symptoms of an allergic reaction and can injure local tissue. Symptoms associated with the late-phase are usually persistent and last for days or results in people being more prone to easily evoked symptoms 24 Now, as I mentioned at the start of the lecture, ocular allergy is typically encountered as variants of conjunctivitis. The classification of ocular allergy is therefore based on the various causes, signs, symptoms, severity and duration of the conjunctivitis 25 Allergic conjunctivitis can be divided into an ACUTE or SEASONAL type and a CHRONIC or PERENNIAL type Seasonal conjunctivitis is the milder of the two and accounts for 25% to 50% of all cases of ocular allergy. It is caused by a variety of pollens such as grass, trees and weeds Perennial conjunctivitis is far less common and people tend to suffer all year round, although they may experience greater seasonal symptoms Typical symptoms include itchy eyes, stinging, watering or dryness and conjunctival oedema Hyperaemia tends to be caused by more physical stimuli such as the wind, the sun and smoke and the presence of conjunctival oedema gives the hyperaemia a more “milky” appearance as opposed to the brilliant red of a bacterial conjunctivitis There can also be a stringy mucous discharge as opposed to the purulent discharge associated with bacterial conjunctivitis and a watery discharge associated with viral conjunctivitis 26 GPC is commonly associated with contact lens wear and represents an allergic response to a build-up of deposits such as proteins. Signs and symptoms include itching on lens removal, hyperaemia and small strands of mucous whilst the presence of papillae larger than 1mm 27 Vernal keratoconjunctivitis is a chronic condition that typically affects both eyes and accounts for 0.5% of ocular allergic disease. It is most common in children and in particular where there is a family history of other atopic disease such as asthma. There can be seasonal variations with symptoms being worst between April and August. The disease is characterised by giant papillae although the presence of a thick mucous discharge can help to differentiate from GPC. There may also be intense itching and possibly pain 28 Vernal Keratoconjunctivitis is a potentially sight-threatening disease if left untreated since corneal epithelial loss can develop into macroerosions. The condition can resolve in adulthood but patients are often left with Atopic Keratoconjunctivitis. 29 Atopic Keratoconjunctivitis is a more serious sight threatening ocular allergic condition that is associated with prolonged symptoms It usually occurs in teenagers or those in their early 20s again with a family history of atopic disease, unless there is previous occurrence of VKC Typical signs include thickening of the lids with associated blepharitis, copious discharge and hyperaemia whilst in advanced cases there may be SYMBLEPHARON, in which the palpebral and bulbar conjunctiva can fuse together 30 The condition is also sigh-threatening as corneal involvement, if left untreated, can lead to the formation of Shield Ulcers as a result of a keratitis that arises from toxic inflammatory effects 31 Ocular allergic responses that are associated with contact dermatitis and drug-induced conjunctivitis are typically T-cell mediated and represent a hypersensitivity to various chemicals and irritants. This is particularly relevant for contact lens wearers who may develop allergies to preservatives in multipurpose solution, such as BAK and polyhexanide. In these situations, patients should then be refitted to daily disposable contact lenses or changed to a preservative-free care system such as HYDROGEN PEROXIDE 32 Allergic Ocular diseases need to be differentiated from a variety of other external eye conditions. The primary differential of an allergic disorder from any other condition is the presence of ITCHING, although 1 in 5 cases can present without itching as a symptom DRY EYE is more prevalent with increasing age, whilst allergies tend to be more common in younger people. People with dry eye also tend to experience a foreign body sensation rather than itching, which is worse at the end of the day BLEPHARITIS tends to be non-specific, with no genetic or seasonal variations. There also tends to be more lid involvement with the presence of lipid deposits Viral conjunctivitis tends to produce a watery discharge with follicles on the palpebral surface and swelling of the preauricular lymph nodes Bacterial conjunctivitis produces more of a purulent discharge 33 SLK can OFTEN BE MISDIAGNOSED BECAUSE symptoms are far greater than clinical signs. The condition may also be associated with thyroid dysfunction Chlamydial conjunctivitis also produces a follicular reaction similar to viral conjunctivitis but in most cases of Chlamydia infection, there is usually a concurrent genital infection Molluscum contagiosum is often a unilateral condition that usually produces a pearly-white nodule on the palpebral conjunctiva 34 The management of ocular allergic disease can take two routes. The non- prescription route involves the use of tear substitutes so that they can provide a barrier to the allergen whilst they can also dilute and flush away the allergen from the surface Cold compresses are more for comfort whilst contact lens wearers should be educated on lens care or potentially re-fitted to frequent replacement lenses The biggest help will come from avoidance of exposure to the allergen altogether but that can be difficult in many cases 35 The second route that can be taken is the Pharmaceutical route in which any of a variety of topical eye drops and systemic medications can be prescribed. Seasonal and perennial conjunctivitis tend to be treated by topical antihistamines and mast cell stabilisers, which are available over the counter 36 Please read from this slide to slide 43 for descriptions of the anti-allergy medications used in ocular treatment… 37 Read above 38 Read above 39 Read above 40 READ FROM SLIDE 41 READ FROM SLIDE 42 Please read above 43 Newer preparations that are becoming increasingly popular are mast cell stabiliser antihistamine combinations. However they are known to cause headaches in some whilst their safety for children under the age of 3 hasn’t yet been established 44 Ketotifen is often used as a combination drop and is explained in the slide above 45 Alternatively, Olopatadine could be used. 46 Vasoconstrictors are essentially sympathomimetic preparations that are used primarily to reduce conjunctival hyperaemia. They aren’t very common on their own and are usually combined with anti-histamines, so that there is an additive effect of reduced itching through blocking H1 histamine receptors 47 NSAIDs act by inhibiting the cycolxygenase enzyme pathway so that there is a reduction in the production of prostagalandins, which are an important part of the body’s inflammatory mechanism. They’re not recommended for people with breathing problems or in those cases where there is corneal involvement, since the healing process will then be interfered with 48 Corticosteroids on the other hand inhibit both cycloxygenase and lipoxygenase pathways so that there is a reduction in both prostaglandins and chemical mediators such as leukotrienes Fundamentally, corticosteroids therefore interfere with the chemical mediators that are involved in the various allergic mechanisms The use of corticosteroids is associated with several side-effects including elevated IOP and cataract formation 49 In more severe cases of ocular allergic disease, it may be necessary to prescribe immunosuppressive medications that act against IgE and T- lymphocytes They are particularly useful in Atopic and Vernal keratoconjunctivitis although there may be some associated side effects such as macular hyperpigmentation, but these aren’t considered to be significant 50 Finally, in some cases, it might be necessary to provide systemic medications in tablet form, or nasal sprays. These can cause eyelid myokymia, which is a spontaneous fascicular contraction of the lid muscles which don’t cause muscular atrophy or weakness – this is often associated with visual tiredness These are more likely to be for those who suffer symptoms all year round, or who experience quite severe seasonal symptoms 51 Well that is ocular allergy in a nutshell - Thanks for listening! 52