1. Ocular Allergic Disease
Dr Paramdeep Singh Bilkhu
BSc(Hons) PGCert PhD MCOptom FBCLA DipTp(IP)

2. 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

3. 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 pre- disposition to Type I hypersensitivity
Common Type I allergies includes asthma, rhinitis, dermatitis, gastro- intestinal disorders and allergic conjunctivitis

4. 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 2X more likely to affect individual than nasal symptoms

5. 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 % of the US population

6. 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
£ per year for employed
Ocular allergies pose a significant problem that needs to be tackled

7. Type I Ocular Allergic Response Mechanism
Immediate allergic response mechanism
Mediated (predominantly) by IgE 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

8. Type I Ocular Allergic Response Mechanism

9. Preformed Mast Cell Mediator Responses
Primary inflammatory mediator is Histamine
Blood vessel
Vasodilation (H1 and H2) = Redness
Increased permeability (H1) = Swelling
Nerve
Nerve stimulation = Itching
Epithelial cells
Epithelial cell activation = Recruitment of additional inflammatory cells and mediators

10. Newly Formed Mast Cell Mediator Responses
Prostaglandins
PGD2 contributes to vasodilation = Redness and Swelling
Leukotrines
LTC4 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

11. 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

12. 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

13. Allergic Conjunctivitis

14. 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

15. 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

16. 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 IgE 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%

17. 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

18. 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 1mg/mL, Epinastine 500µg/mL, Ketotifen 250µg/mL
Only require twice daily dosing
Vasoconstrictors
Relieve redness and swelling
May be combined with antihistamine
Long term use not recommended (max 7 days)

19. 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 10ml)
Lodoxamide (Alomide) 0.1% (up to 5ml)
Antazoline + xylometazoline (Otrivine-Antisitin) up to 5ml
Oral antihistamines
Loratadine
Cetirizine
Chlorphenamine (Piriton)
Acravastine (Benadryl)

20. 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 2Xdaily 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

21. 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”

22. 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 (>1mm in diameter)
Symptoms
Mild itching on lens removal
Slight blurring of vision
Contact lens intolerance

23. Giant Papillary Conjunctivitis

24. 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

25. 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

26. Vernal Keratoconjunctivitis

27. Atopic Keratoconjunctivitis
Serious, sight threatening condition
Onset in teenagers to early 20s 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

28. Atopic Keratoconjunctivitis

29. 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%

30. 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

31. Treatment of VKC and AKC
Effective alternative to corticosteroids
Immunosuppressive against T-lymphocytes and IgE
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

32. 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

33. 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

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

35. 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 4x day mast cell stabilising therapy
D) Change to 2 weekly enhanced comfort lens and 2x day mast cell stabilising therapy

36. 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?
Perennial allergic conjunctivitis
Vernal keratoconjunctivitis
Contact dermatitis
Seasonal allergic conjunctivitis

37. 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?
Microbial keratitis
Atopic keratoconjunctivitis
Vernal keratoconjunctivitis
Giant papillary conjunctivitis

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

39. Case study 5
For the patient in case study 3, what would be the most appropriate way to alleviate the pain?
Topical anaesthetic
Topical mydriatic
Topical mydriatic and anaesthetic
Topcial mydriatic and oral analgesic

40. 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?
Atopic keratoconjunctivitis
Seasonal allergic conjunctivitis
Perennial allergic conjunctivitis
Vernal keratoconjunctivitis

41. 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 all 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

42. 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):

43. Thank you for listening!
Thank you to:
Dr Shehzad Naroo
Prof JamesWolffsohn
Thank you for listening!