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Ocular Allergic
Disease
Dr Paramdeep Singh Bilkhu
BSc(Hons) PGCert PhD MCOptom FBCLA DipTp(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 2X 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
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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 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
Type I Ocular Allergic Response
Mechanism
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
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
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)
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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
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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
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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
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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 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%
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 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)
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
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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 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
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
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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
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
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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
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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
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
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
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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 4x day mast cell
stabilising therapy
D) Change to 2 weekly enhanced comfort lens and 2x
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 4x day and review
in 4 weeks
B) Topical NSAID and monitor closely
C) Topical mast cell stabilizer 4x day and topical
steroid for 4 weeks and discharge
D) Topical mast cell stabiliser 4x 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
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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
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 JamesWolffsohn
Thank you for listening!