Ocular Allergic Disease Dr Paramdeep Singh Bilkhu BScHons

Ocular Allergic Disease Dr Paramdeep Singh Bilkhu BSc(Hons) PGCert Ph. D MCOptom FBCLA Dip. Tp(IP)

Objectives By the end of this lecture you should be able to: • Understand the mechanism of ocular allergy • Diagnose the different forms of ocular allergy • Appropriately treat ocular allergy

What are allergies? • Defined as an “intolerance to environmental factors” or an “inappropriate response to innocuous foreign substances • Four major types of allergic reaction - Type I or immediate hypersensitivity reaction most common • Atopy is the term given to those who have a hereditary predisposition to Type I hypersensitivity ▫ Common Type I allergies includes asthma, rhinitis, dermatitis, gastrointestinal disorders and allergic conjunctivitis

Ocular Allergies • Represents a group of allergies affecting the ocular tissue, typically the conjunctiva • Acute ocular allergy = Type I; Chronic ocular allergy = Type I and T-cell mediated response • 20% of allergy sufferers have a form of ocular allergy, and up to 40% have experienced ocular allergy symptoms in their lifetime • 8% prevalence of ocular allergies in patients attending optometric practice • 60. 8% of people with allergies in optometric practice have ocular reactions • Ocular symptoms 2 X more likely to affect individual than nasal symptoms

Epidemiology • Most common ocular condition seen in general practice • Affects 15 -20% of the population – 50% of Europeans by 2015 • Responsible for 3. 4 million lost work days • Responsible for 2 million lost school days • Economic impact exceeds $18 billion annually • Responsible for diminished quality of life in 20 -25% of the US population

Ocular Allergies • Significant quality of life and economic impact ▫ ▫ Reduced income (days off work) Reduced productivity Reduced school performance Healthcare costs �£ 64. 61 per year for pensioner �£ 123. 69 per year for employed • Ocular allergies pose a significant problem that needs to be tackled

Type I Ocular Allergic Response Mechanism • Immediate allergic response mechanism • Mediated (predominantly) by Ig. E antibody • Involves multiple cell types and multiple chemical processes – very complex reaction • Is divided into 3 phases ▫ Sensitization phase ▫ Early (or activation) phase ▫ Late phase

Type I Ocular Allergic Response Mechanism

Preformed Mast Cell Mediator Responses • Primary inflammatory mediator is Histamine ▫ Blood vessel �Vasodilation (H 1 and H 2) = Redness �Increased permeability (H 1) = Swelling ▫ Nerve �Nerve stimulation = Itching ▫ Epithelial cells �Epithelial cell activation = Recruitment of additional inflammatory cells and mediators

Newly Formed Mast Cell Mediator Responses • Prostaglandins ▫ PGD 2 contributes to vasodilation = Redness and Swelling • Leukotrines ▫ LTC 4 causes vasoactivity and mucous secretion = Redness and Swelling • Platelet activating factor ▫ Blood vessel vasodilation and increased permeability = Redness and Swelling ▫ Chemotaxis and Eosinophil activation = Late phase responses (allergic inflammation) • Cytokines ▫ Multiple cellular effects = Allergic inflammation

Classification of Ocular Allergy • Typically manifested in the conjunctiva • Classified based upon cause, signs, symptoms, duration and severity of condition ▫ Allergic conjunctivitis �Seasonal (SAC) �Perennial (PAC) ▫ ▫ Vernal Keratoconjunctivitis (VKC) Atopic Keratoconjunctivitis (AKC) Giant Papillary Conjunctivitis (GPC) Contact and Drug induced allergy

Allergic Conjunctivitis • Acute (seasonal) or chronic (perennial) • Seasonal (SAC) accounts for 25 -50% of all ocular allergy cases and is typically caused by pollen; affects up to 40% of population • Perennial (PAC) affects 0. 03% of population, ~ 1% of ocular allergy cases – occurs all year round • Signs ▫ Conjunctival hyperaemia ▫ Lid swelling and chemosis ▫ Stringy mucous discharge • Symptoms ▫ Itchy eyes ▫ Burning/stinging ▫ Watery or dry eyes ▫ Photophobia • Type I hypersensitivity

Allergic Conjunctivitis

Seasonal V Perennial Allergic Conjunctivitis • Seasonal – occurs in spring, fall or both • Perennial – occurs year round, may have periodic exacerbation (seasonal) • Seasonal – caused by grass, tree or ragweed pollen; outdoor moulds • Perennial – caused by animal dander, dust mites and indoor moulds • Signs and symptoms similar but less severe and more constant in perennial allergic conjunctivitis

• Avoidance Strategies Allergen Avoidance Measure Pollen & Outdoor Moulds • • • Minimise outdoor activities when symptoms known to develop Monitor pollen levels using TV, internet and radio to plan outdoor activities Wear close fitting sunglasses and avoid rubbing eyes Wash hands after being outdoors and wash hair regularly before sleeping Close windows and doors Use AC and circulate air internally in car House Dust Mites • • Wash bedding regularly at least at 60°C Damp dust and vacuum weekly Regularly clean all areas that gather dust Reduce humidity to 30 -50% in the home using dehumidifier Animal Dander • • Avoid contact with animals Remove pets from home or not keep at all Regularly vacuum and clean home Wash hands, clothes and avoid rubbing eyes or nose after contact with animals

Treatment of SAC and PAC • Often not possible to completely avoid allergens • Non-pharmacological treatments are useful during active phase of disease ▫ Cold compress, artificial tears (Bilkhu et al. , 2014) • Pharmacological treatments therefore become necessary • Mast Cell Stabilisers ▫ Competitive antagonist of Ig. E bound to mast cell surface ▫ Therefore prevent binding of allergen to mast cell and preventing allergic response ▫ Loading dose often required ▫ Best used as a prophylactic ▫ E. g. Sodium Cromoglygate 2% or 4%, Nedocromil 2%, Lodoxamide 0. 1%

Treatment of SAC and PAC • Antihistamines ▫ Competitive antagonist of histamine receptors on blood vessels, nerves, and epithelial cells ▫ Therefore prevents binding of histamine to receptor sites and allergic symptoms following mast cell degranulation ▫ Fast acting (within 10 minutes) ▫ Best used during an active phase of disease i. e. when symptoms and signs develop ▫ E. g. Azelastine 0. 05%, Antazoline 0. 5%, Emedastine 0. 05% ▫ Most are POMs ▫ Oral antihistamines useful where other tissues involved

Treatment of SAC and PAC • Dual Action Medications ▫ Combine both mast cell stabilising and antihistaminic properties ▫ Often reserved for cases unresponsive to conventional drugs ▫ E. g. Olopatadine 1 mg/m. L, Epinastine 500µg/m. L, Ketotifen 250µg/m. L ▫ Only require twice daily dosing • Vasoconstrictors ▫ Relieve redness and swelling ▫ May be combined with antihistamine ▫ Long term use not recommended (max 7 days)

Non-IP options • P-only medications are available to prescribe ▫ Must state treatment plan on record �Drug name, strength, dosage, duration • Sodium cromoglycate 2% (up to 10 ml) • Lodoxamide (Alomide) 0. 1% (up to 5 ml) • Antazoline + xylometazoline (Otrivine-Antisitin) up to 5 ml • Oral antihistamines ▫ ▫ Loratadine Cetirizine Chlorphenamine (Piriton) Acravastine (Benadryl)

Allergic Conjunctivitis & CL Wear • Allergens may bind to CL surface ▫ May prolong symptoms • Management typically involves ceasing CL wear ▫ But new anti-allergy drugs allow CL wear to be maintained �Brodsky (2000): lens wearing time and comfort following 2 Xdaily 0. 1% olopadatine Tx �Nichols et al. (2009): lens wearing time and comfort following 1 drop 0. 05% epinastine prior to lens insertion compared to re-wetting drops

Allergic Conjunctivitis & CL Wear • Other options include: ▫ Increase lens replacement frequency � 67% improved comfort with daily disposable versus 18% with new pair of habitual monthly lenses ▫ Daily disposables; especially if enhanced lubricating properties (Wolffsohn & Emberlin, 2011) �Sx of ocular allergy and their duration actually reduced with CL in situ compared to no lens wear, and was further reduced when lens contained enhanced lubricating properties �CLs may therefore offer a “barrier effect”

Giant Papillary Conjunctivitis • Caused by combination of mechanical irritation and chemical reaction • Occurs most often in contact lens wearers due to build up of surface deposits • Signs ▫ ▫ Conjunctival hyperaemia Mucous strands Abnormal thickening and opacification of palpebral conjunctiva Characteised by large papillae (>1 mm in diameter) • Symptoms ▫ Mild itching on lens removal ▫ Slight blurring of vision ▫ Contact lens intolerance

Giant Papillary Conjunctivitis

Treatment of GPC • Optimise lens fitting • Change lens wear modality ▫ Monthly to 2 weekly; 2 weekly to daily • Change material ▫ Soft to rigid gas permeable ▫ Or switch to soft with enhanced surface treatments to increase wettability and comfort • Often a combination of these • If severe, unresponsive to lens changes or cornea is involved, must initiate pharmacological therapy and cease lens wear until resolution ▫ Mast cell stabilisers

Vernal Keratoconjunctivitis • Chronic bilateral disease, usually affecting males 3 -25 years old in warm climates • Accounts for 0. 5% of ocular allergy cases • Peaks at puberty, then resolves but may manifest as atopic keratoconjunctivitis in later life • Most common in families with a history of atopy • Signs ▫ Characterised by large papillae in palpebral conjunctiva or limbus ▫ Ropy mucous discharge ▫ Potential corneal involvement therefore sight threatening • Symptoms ▫ Intense itching ▫ Photophobia ▫ Possibly pain • Type I hypersensitivity and Type IV (T-lymphocyte mediated) in later stages

Vernal Keratoconjunctivitis

Atopic Keratoconjunctivitis • • Serious, sight threatening condition Onset in teenagers to early 20 s unless childhood VKC Associated with a family history of atopy Associated with atopic dermatitis – 25 -40% of AD patients have ocular involvement • Signs ▫ ▫ ▫ Thickened, macerated and fissured eyelids Conjunctival hyperaemia Flattened, velvety papillae Possible limbal cystic lesions Corneal scarring from corneal epitheliopathy, corneal ulcer (shield) and inflammatory cellular toxic effects can cause visual loss ▫ Blepharitis may also be present ▫ Symblepharon in advanced disease • Type I hypersensitivity and Type IV (T-lymphocyte mediated) in later stages

Atopic Keratoconjunctivitis

Treatment of VKC and AKC • Pharmacological treatments initiated immediately ▫ Mast cell stabilisers and topical steroids • Steroids are powerful anti-inflammatory drugs ▫ Interfere with cytokine and adhesion molecule production ▫ Block release of enzymes used in metabolising arachidonic acid which would otherwise produce prostaglandins and leukotrines • Steroid use requires close monitoring • Side effects: IOP elevation, cataract formation, delayed corneal healing, secondary infection • E. g. Loteprednol etabonate (Alrex 0. 2%), Rimexolone 1%, Fluoromethalone 0. 1% and 0. 25%

Treatment of VKC and AKC • Non-steroidal anti-inflammatory drugs (NSAIDs) • Alternative to corticosteroids • Inhibits cyclooxygenase pathway thus stopping the productions of prostaglandins and thromboxanes • Prostaglandins are hypothesised to be synergystic with histamine, potentiating itching • Contraindicated in patients with asthma and nasal polyps • Can delay corneal healing by interfering with wound repair • E. g. Ketorolac tromethamine (Acular 0. 5%; Acular LS 0. 4%) POM, Diclofenac 0. 1% POM

Treatment of VKC and AKC • Effective alternative to corticosteroids • Immunosuppressive against T-lymphocytes and Ig. E • Cyclosporin (2% in oil) ▫ Effective in VKC and AKC • Tacrolimus (Protopic 0. 1% and 0. 03%) • No systemic effects, but may cause mild local effects

Treatment of VKC and AKC • Corneal ulcers may become infected ▫ Scraping or swab often taken to identify infectious cause ▫ Typically bacterial �Requires strong antibiotics (quinolones) �Ofloxacin, Ciprofloxacin, moxifloxacin, levofloxacin • If left untreated, can lead to blindness and loss of the eye

Contact Ocular Allergy • Comprises contact dermatitis and drug induced allergic conjunctivitis • Predominantly T-cell mediated (Type IV) • Hypersensitivity due to chemicals ▫ Toxicity maybe due to incorrect usage ▫ Contact lens solution preservatives e. g. Benzalkonium chloride, thiomersal ▫ Drugs e. g. Pilocarpine, gentamycin ▫ Cosmetics, shampoo, irritants • Sunlight exposure can induce photo-contact dermatitis

Differential Diagnosis of Ocular Allergy • • Itching is pathognomic of ocular allergy Dry eye Blepharitis Viral conjunctivitis Bacterial conjunctivitis Superior limbic keratoconjunctivitis Molluscum Contagiosum Medicamentosa

Case Study 1 • Patient arrives complaining of mild itching, mucous discharge from both eyes. Examination reveals history of monthly soft lens wear, and several large papillae on both tarsal conjunctiva. The cornea is unaffected. What would be the most appropriate course of action? A) Immediate referral to A&E B) Cease lens wear completely and initiate antihistamine therapy C) Cease lens wear completely and initiate 4 x day mast cell stabilising therapy D) Change to 2 weekly enhanced comfort lens and 2 x day mast cell stabilising therapy

Case Study 2 • Patient arrives complaining of intermittent itching in both eyes. History reveals sudden onset when outdoors, reduces when indoors, started in July. Examination reveals conjunctival redness and oedema. What is the likely diagnosis? A) Perennial allergic conjunctivitis B) Vernal keratoconjunctivitis C) Contact dermatitis D) Seasonal allergic conjunctivitis

Case Study 3 • 50 year old patient arrives complaining of itching, soreness and pain in both eyes. History reveals asthma and atopic dermatitis. Examination reveals bilateral thickened and inflamed eyelids, large papillae on tarsal conjunctiva and shield ulcer on left eye. What is the likely diagnosis? A) Microbial keratitis B) Atopic keratoconjunctivitis C) Vernal keratoconjunctivitis D) Giant papillary conjunctivitis

Case study 4 • For the patient in case study 3, what would be the appropriate course of action? A) Topical mast cell stabilisers 4 x day and review in 4 weeks B) Topical NSAID and monitor closely C) Topical mast cell stabilizer 4 x day and topical steroid for 4 weeks and discharge D) Topical mast cell stabiliser 4 x day and topical steroid and monitor closely

Case study 5 • For the patient in case study 3, what would be the most appropriate way to alleviate the pain? A) Topical anaesthetic B) Topical mydriatic C) Topical mydriatic and anaesthetic D) Topcial mydriatic and oral analgesic

Case study 6 • 12 year old male patient arrives complaining of chronic intense itching, photophobia and mucous discharge. History reveals onset during spring and previous eczema. Examination reveals large papillae on tarsal conjunctiva and limbus. What is the likely diagnosis? A) Atopic keratoconjunctivitis B) Seasonal allergic conjunctivitis C) Perennial allergic conjunctivitis D) Vernal keratoconjunctivitis

Summary • • • Allergy is the hypersensitivity to normally harmless substances Ocular allergy encompasses a group of allergic conditions affecting the eye Ocular allergy impairs quality of life Ocular allergy, like allergies are increasing in prevalence Need to identify each type of ocular allergy and differentially diagnose to formulate effective management plan Non-pharmacological treatments and allergen avoidance needs to be encouraged Use of topical pharmacological agents however often becomes necessary Wide range of medications available OTC and POM with different pharmacological actions Majority of SAC, PAC and GPC can be treated by optometrists VKC and AKC need to be managed in hospital setting Systemic medications are useful where another tissue is affected alongside the conjunctiva

Further Reading • Bilkhu PS, Wolffsohn JS, Naroo SA. A review of non-pharmacological and pharmacological management of seasonal and perennial allergic conjunctivitis. Cont Lens Anterior Eye. 2012; 35(1): 9 -16. • Bilkhu PS, Wolffsohn JS, Naroo SA. Ocular Allergy and Contact Lens Wear. Optometry Today. 2012; 52(6): 49 -53.

• Thank you to: ▫ Dr Shehzad Naroo ▫ Prof James. Wolffsohn Thank you for listening!