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Learning Objectives

 Understand the pathophysiology of ocular allergies

Ocular Allergies  Identify the aetiologies and clinical features of allergic conjunctivitis

 Recognise the various forms of allergic eye disease Dr Dipika Patel  Discuss the various drugs used in the treatment of Clinical Senior lecturer ocular allergies

Department of Ophthalmology  Formulate an appropriate management plan

SAC - Seasonal Allergic Conjunctivitis Types of Ocular Allergic Disease Most common ocular allergy Half of ocular allergies 10 to 30% world population  Seasonal Allergic Conjunctivitis (SAC) Incidence doubled last 10 years (atmospheric  Perennial Allergic Conjunctivitis (PAC) pollution) Rarely appears before 5 years of age  Contact Lens Papillary Conjunctivitis (CLPC) Allergic response mediated by mast cells  Vernal Kerato-Conjunctivitis (VKC) Ocular component of hayfever (tree, grass, weed pollen)  Atopic Conjunctivitis Occurs when pollen counts high Experience symptoms when count reaches “moderate” (30-49 pollen grains/cubic metre air)

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SAC - Seasonal Allergic Conjunctivitis SAC - Seasonal Allergic Conjunctivitis Signs Symptoms Bulbar conjunctival hyperaemia Red, itchy, burning & watery & oedema eyes Eyelid chemosis and oedema Dryness/irritation Mild watery discharge Papillary hypertrophy of upper Discomfort palpebral conjunctiva (redness & Mucoid discharge roughness) Cornea rarely involved

PAC - Perennial Allergic PAC - Perennial Allergic Conjunctivitis Conjunctivitis 1% of allergy sufferers 90% of housing are contaminated by specific moulds Year round disease due to dust, animal Allergies to moulds are known since 1873 skin and hair, mould, fungus etc Prevalence of allergies to moulds is 20 to 30% for atopic people Allergic response mediated by mast cells 3 to 10% of adults and children (worldwide) Signs and symptoms very similar to SAC would suffer of allergies to moulds Chronic and less severe Even if it is a perennial problem there are some seasonal peaks due to heat and humidity Continue throughout year with seasonal exacerbation

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PAC - Perennial Allergic CLPC – Contact Lens Conjunctivitis Associated Papillary Conjunctivitis Symptoms

Very similar to SAC Incidence 2% – 15% depending on lens type burning Immune and/or mechanical response primarily itching affecting superior tarsal conjunctiva watering eyes Response mediated by T-cells sometimes mucoid secretions

CLPC – Contact Lens CLPC – Contact Lens Associated Associated Papillary Papillary Conjunctivitis Conjunctivitis

CAUSES Aetiology Mechanical Lens edge, material stiffness or poor surface  Mechanical quality of CL in contact with conjunctiva

 Solution related Mineral deposits from tears Allergy  Immune reactions Denatured proteins, accumulated on CL surface

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CLPC – Contact Lens CLPC – Contact Lens Associated Papillary Associated Papillary Conjunctivitis Conjunctivitis Signs CAUSES Palpebral hyperaemia  Cytotoxic components of CL solutions

 Preservatives Tarsal roughness and enlarged papillae  Antiseptic Conjunctival oedema  Wetability agents Mucous strands  Enzymes Mild ptosis if severe

CLPC Symptoms VKC - Vernal Keratoconjunctivitis Mucous discharge Rare but severe: affects children and more often boys Itchiness, irritation (gender ratio 2/1) Blurred vision Resolves at adult age Lens deposition No specific allergen is clearly at the origin of VKC Children who have VKC have a higher incidence of Lens dislocation keratoconus than the general population Discharge Reduced CL comfort and wearing time Asymptomatic in early stages

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VKC - Vernal Kerato- Atopic Keratoconjunctivitis Conjunctivitis Symptoms Intense photophobia Mucus discharge Resembles VKC but not Clinical aspects seasonal Hyperaemia Conjunctival oedema Adults Giant papillary (>1mm) on superior Associated with atopic tarsal conjunctiva Corneal staining dermatitis In advance cases: shield ulcer Superinfection with staphylococcus

Diagnosis of Allergic Conjunctivitis Diagnosis of Allergic Conjunctivitis

•Clinical history Clinical examination and investigations •Typical symptoms Appearance of the everted (flipped) eyelid. •80% of patients are under 30 years of age Skin prick/puncture tests or specific IgE tests to •Strong personal or family history of IgE-mediated diseases identify causative allergens • •Recurrent, intermittent or persistent symptoms

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Diagnosis of Allergic Differential diagnosis Allergic Conjunctivitis Conjunctivitis •Blepharitis Mediators of IgE-related reactions in allergic conjunctivitis •Bacterial conjunctivitis Histamine: Itching, redness, oedema •Chlamydial conjunctivitis •Corneal abrasion or ulceration Prostaglandins: Sensitized nerves, enhanced pain, oedema and redness •Dry eye •Episcleritis Leukotrienes: Chemotaxis, oedema and vascular permeability •Staphylococcal marginal keratitis Chemotactic factors: Recruitment of eosinophils and neutrophils •Superficial punctate keratitis leading to tissue destruction •Tight lens syndrome •Viral conjunctivitis or keratitis

Treatment of ocular allergy Over-the-counter medications

Allergen avoidance Topical decongestants Palliative Cold compresses Reduce chemosis and conjunctival hyperemia by Lubricants an alpha-adrenergic mechanism resulting in vasoconstriction -work within minutes (duration of Over-the-counter medications Topical decongestants/antihistamine about 2 hours). Oral antihistamine Prescription drugs o Phenylephrine Antihistamine o Naphazoline Mast cell stabilizing antihistamine NSAID’s Corticosteroids

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Over-the-counter medications But!! Decongestant/antihistamine combinations Antihistamines mildly suppress the immunological response.  Side effects: rebound redness, dilation of the They help with itch more than straight decongestants. pupil, avoid in narrow angle glaucoma. oOpcon-A (0.315% pheniramine maleate, 0.02675% naphazoline hydrochloride)  Decongestants mask the signs and symptoms of oVasocon-A (0.5% antazoline phosphate, 0.05% allergic conjunctivitis naphzaoline hydrochloride) oNaphcon-A (0.3% pheniramine maleate, 0.025% naphazoline hydrochloride)  Chronic use of vasoconstrictors can lead to toxic, follicular reactions or possibly a contact dermatitis.

Oral Antihistamines Over-the-counter medications •Oral antihistamines  H1 antagonists Oral antihistamines should be used when patient has significant nasal problems (primary care physician)  Do not prevent release of histamine Cetirizine (Zyrtec) Loratadine (Claritin)  Inhibits contraction of bronchial smooth muscle These yield therapeutically effective concentrations of the drug at the anterior surface of the eye.  Inhibits increased vascular permeability Several studies over the past few years have found topical allergy  CNS effects include drowsiness drops to be more effective in relieving symptoms of allergic conjunctivitis than oral antihistamines*.

*Concomitant use of a nasal spray plus a topical allergy drop (e.g., Flonase + Patanol) was more effective than a nasal spray (Flonase) + an oral antihistamine (Allergra) for overall treatment of signs and symptoms of allergic conjunctivitis.

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Over-the-counter medications Prescription drugs

Topical antihistamines These drops work by competing with histamine for the H1 receptor Oral antihistamines sites. Have unexplained vasoconstrictive properties. All antihistamines (even nonsedating types) have a drying effect on the ocular surface. Antihistamines have atropine-like oLivostin (levocabastine 0.05%)--suspension; qid dosing for properties that decrease the tear production via the lacrimal 1-2 weeks, then 1-3 times/day as needed for itching. gland. They could also be decreasing mucin production by the goblet cells. oEmadine (emedastine dirfurmarate 0.05%)--virtually Be sure to check to see whether your patient is taking OTC identical to Livostin; same qid dosing; works immediately to antihistamines. reduce itch, redness, chemosis, and tearing.

Side effects: Stinging, burning, headache, fatigue, nausea. Disadvantages: Do not prevent inflammation or release of histamine; short duration of action.

Prescription drugs Mast cell stabilisers • Mast cell stabilizers Act by preventing release of Histamine A • Mast cell stabilizers work by inhibiting degranulation of mast cells (believed to prevent the influx of calcium to the mast cell).  Sodium cromoglycate (Opticrom)

• Mast cell stabilizers can be used for months  Nedocromil sodium (Rapitil) without any significant side effects.  Lodoxamide (Alomide) • They are good “prophylaxis” . (2,500 x more potent than sodium chromoglycate) • They can prevent the ocular allergic outbreak all together.

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Mast-cell stabilisers: Na cromoglycate Sodium cromoglycate (Opticrom)

 Course of treatment - QID  Sodium cromoglycate  Prophylactic  Prophylaxis of ocular allergy and vernal  Not an antihistamine conjunctivitis  Ineffective once histamine released  Stabilises membrane of mast cell  Available over the counter as Opticrom  Prevents release of Histamine

Nedocromil sodium (Rapitil) Lodoxamide (Alomide)

 Superior/equal to sodium cromoglycate in:  Mast cell stabiliser

 Vernal conjunctivitis  Eosinophil inhibitor  Seasonal allergic conjunctivitis   Perennial conjunctivitis** 2,500 x more potent than sodium cromoglycate  Effective against other inflammatory cells: macrophages, eosinophils & inhibits release  TDS – QDS

of inflammatory & chemotactic mediators  All forms of allergic conjunctivitis

 Twice a day (**4 times per day)

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Prescription drugs Prescription drugs

Mast cell stabilizing antihistamine NSAIDs (Non-Steriodal Anti-Inflammatory Drugs) ie Dual action •Patanol (olopatadine hydrocholride 0.1%) Specifically inhibit the enzyme cyclooxygenase which blocks the production of prostaglandins from arachidonic acid metabolism. •Zaditor (ketotifen fumarate 0.025%) NSAIDs alter the patient's sensitivity to itch by raising the sensory threshold of peripheral nerve endings. Acular (ketorolac tromethamine 0.5%) is the only NSAID approved Dosing: bid for the treatment of itch (as well as p/o cataract inflammation). Acular basically works as an analgesic to decrease pain. Onset of relief occurs within an hour. It is considered safe with few Side effects: eye burning/stinging, headaches, contraindications, although it does sting quite a bit. bitter or metallic taste.

Prescription drugs Common topical steroids Topical Steriods Dexamethasone alcohol 0.1% Maxidex Topical steroids are particularly helpful in severe cases of VKC, AKC, GPC, and allergic contact Prednisolone Na Phosphate 0.5% Predsol dermatitis. They reduce the inflammatory response by: Betamethasone Na Phosphate 0.1% Betnesol •Decreasing the production of prostaglandins and leukotrienes Prednisolone Acetate 1.0% Predforte •Reducing capillary permeability •Suppressing lymphocyte circulation Fluoromethalone 0.1% Flucon •Inhibiting mast cell degranulation, therefore, preventing the release of histamine

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Why Steroids are “devil’s work”? Corticosteroids & ocular infections Ocular HSV can be reactivated by a single dose ! Side effects of topical Steriods Established HSV keratitis is exacerbated by steroid Ocular infection

Glaucoma

Cataract

Corticosteroids & microbial keratitis Elevation of IOP with corticosteroids May mask presentation & delay appropriate management of severe keratitis, particularly acanthamoeba 4-6% high responders > 15mmHg Tay-Kearney ML, McGhee CN et al. Acanthamoeba keratitis a masquerade of presentation. Aust NZ J Ophthalmol 1993;21(4):237-45 1/3rd moderate responders 6 – 15mmHg Topical steroids shown to be a significant risk factor in severe keratitis requiring hospitalisation in Australia 2/3rd non-responders < 6mmHg

Gebauer A, McGhee CN et al. Severe microbial keratitis in temperate and tropical Western Australia. EYE 1996;10:575-80 Higher risk in glaucoma, myopia, diabetes, RA.

Onset days to weeks usually 4-6 weeks

Children – peak Dexamethasone response in 8 days !

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Corticosteroids: Miscellaneous Corticosteroid induced cataract complications

1. Ocular surface toxicity Association first identified by Black et al in 1960 2. Delayed epithelial healing 3. Reduced wound strength Relative risk: 4. Keratocyte apoptosis 5. Corneal phosphate deposits 86 keratoconic subjects post-graft 6. Exacerbation of microbial infections At 18 months 28 (32.6%) exhibited PSC 7. Reactivation of HSV 8. Crystalline keratopathy Donshik PC, Cavanaugh HD et al. Posterior subcapsular cataracts induced by topical cortico-steroids 9. Steroid glaucoma following keratoplasty for keratoconus. Annals of Ophthalmology 1981:13(1);29-32 10. Steroid cataract 11. Lid ptosis PSC reported after 4 months of QDS 12. Dilated pupil fluorometholone 13. Extra-ocular imbalance 14. Orbital fat atrophy Bilgihan K, Gurelik G et al. Fluorometholone-induced cataract after photorefractive keratectomy. 15. Intraocular penetration/injection Ophthalmologica 1997;211(6):394-6 16. Systemic absorption McGhee CN, Dean S, Danesh-Meyer H. Locally administered ocular corticosteroids: benefits and risks. Drug Safety 2001

Contact Lens Performance Allergies and Contact Lens Wear with Allergy Sufferers Easy to manage in practice History of atopy leads to increase of symptoms Question patients about allergies Reduction in wearing time may be necessary Identify signs and symptoms allergic eye during peak allergy season – depends on severity disease (reduced comfort and wearing time, of condition dryness and itching) Differences in performance between lens types Management and advice With careful monitoring, successful CL wear in If managed, SAC and PAC should not most patients with ocular allergies contraindicate CL wear even in peak seasons

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Managing CL Wearing Allergy Sufferer Managing CL Wearing Allergy Sufferer

Reduce allergen exposure Alleviate symptoms Daily disposables Cold compresses Increase lens replacement frequency during peak Re-wetting drops during wear (non-preserved, single dose) season Anti-allergy eye drops pre and post daily wear, prior to and Preservative free care products (oxygen peroxide) during allergy season for SAC Surfactant cleaner Topical mast cell stabilizer Change lens material Topical antihistamine Reduce wearing time

CLPC Management How can you describe the Increase lens replacement frequency observation? disposables – 2 weekly or daily disposables Alter lens type material, thickness Alter care system improve cleaning, avoid MPS Improve hygiene washing, lid hygiene Cease lens wear and pharmaceutical agents if severe Patient education

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Bulbar Redness How can you describe the observation?

Corneal Staining How can you describe the observation?

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Palpebral Redness How can you describe the observation?

Lid Roughness Case 1

32-year-old white female complaining of itchy eyes (especially in corners; no burning). History of seasonal and ocular allergies since childhood. Takes oral antihistamine

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Case 1 Case 1

VA 20/20 OD, OS; no conjunctival injection; How would you manage this case? grade 1 papillae on lower and upper palpebral conjunctiva

Case 1 Case 1- to remember

Seasonal Allergic Conjunctivitis (SAC) Patanol bd Significant dry eye plus allergic conjunctivitis: Lubricants Topical antihistamines or antihistamine/mast cell Stabilizer.

Treatment with artificial tears + mast cell stabilizer. Oral antihistamines may be drying out eye; consider having patient switched to nasal inhaler.

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Case 2 Case 2

VA 20/20 OD, OS with contact lenses. Grade 3+ papillae on upper palpebral conjunctiva.

28-year-old white male having difficulty wearing contact lenses can only wear 4-6 hours comfortably. Reports that they itch and burn (especially when removing)

Case 2 Case 2 Discontinue lenses for 1 month Diagnosis (DD)? Short term steroids/mast cells stabiliser How would you manage this case? Switch to daily disposables or RGP

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Case 2 – take home Case 2 – take home message message GPC -Traditional therapeutic strategies: Controversial as to best treatment with drops.

GPC -Traditional therapeutic strategies: Recommend one of the following: a mast cell stabilizing antihistamine OR Decrease wearing time a topical steroid alone (if patient discontinues lens wear) OR Switch to disposable contact lenses or RGP a mast cell stabilizer plus a topical steroid drop Consider daily disposable lenses discontinue steroid drop after 1-2 weeks; Consider extra strength daily cleaner or increasing enzyme use continue with mast cell stabilizer

Note: Allergy drops can be used with contact lenses (preferably disposable).

Case 3 Case 3

Diagnosis ? 45-year-old white female complaining of chronic ocular irritation and redness for several years. History of eczema. Has used punctal plugs, How would you manage this case? topical steroids, artificial tears, allergy medications with no improvement in symptoms.

Objectively: VA 20/80 OU. Signs: 4+ SPK OU, 3+ conjunctival injection OU, ectropia OU red scaly lids, grade 1 papillae OU.

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Case 3 Case 3 – take home message Hygiene, avoid eye rubbing Atopic Keratoconjunctivitis (AKC) Short term steroids/mast cells stabilizer Requires: Mast cell stabilizer – prophylaxis Long term treatment Palliative treatment Lid hygiene Treat the skin – steroid cream Consider steroids Mast cell stabilizers – the key

Case 4 Case 4

15-year-old white male complaining of "right eye watering, Diagnosis? stinging, eyes matted all the time." History of seasonal and "skin" allergies (no history of eczema or asthma). History of acute allergic and bacterial conjunctivitis since How would you manage this case? age 6. Current diagnosis of chronic allergic conjunctivitis.

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Case 4 Case 4

Management Vernal conjunctivitis: Acute treatment: Mast cell stabilizing antihistamine OR History Age Topical steroid plus mast cell stabilizer. Gender Associated pathology Long-term treatment: Mast cell stabilizer & observation

Management strategies Management strategies

Most qid allergy meds can maintain a good therapeutic There is a good chance that when the patient presents to you, effect at bid following a qid loading dose. they have likely tried and failed to treat their symptoms on their own: Don't forget palliative therapies-cold compresses and Take a thorough ocular history on anyone who has a history of artificial tears. systemic allergies. In dry eye patients, nasal inhalers are often as effective in Try to identify the offending allergen. reducing allergy symptoms as oral antihistamines without Remind patients not to rub their eyes. drying the eye and without the systemic side effects.

Rubbing causes mast cell degranulation which perpetuates the A bid topical allergy drug is always preferable in those allergic cycle. patients wearing contact lenses.

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