Ocular allergy is represented by a group of hypersensitivity disorders where the eyes produce an abnormal immunological response to normally harmless antigens (allergens). Approximately 15-20% of patients with allergies have a form of ocular involvement. However, the global prevalence of allergy is expected to increase, with estimates as high as 50% by 2015. (1,2) Although the majority of cases are relatively mild, ocular allergies may be potentially sight threatening and exhibit a significant impact on quality of life. (1-3) In the UK, many ocular allergy I sufferers self-manage the condition, but their symptoms often persist. (4) An increased awareness of ocular allergies and their detection and treatment is therefore paramount. This article provides a detailed overview of the different ocular allergy subtypes, including a discussion on optometric management strategies.
Allergic conjunctivitis (AC) is the most common form of ocular allergy, with prevalence estimated to range from 15-40%. (5) AC is subdivided into two subtypes: seasonal (SAC) and perennial (PAC). SAC is more common, accounting for 90% of all ocular allergy cases, and is often caused by grass, tree and weed pollens and outdoor moulds. PAC occurs year round and is often caused by house dust mites, animal dander, insects and indoor moulds. (1,6,7) SAC is more common in children and those with a history of atopy including eczema, asthma, and rhinitis. (1,5,8) It is also frequently associated with allergic rhinitis as part of seasonal hay fever (seasonal rhino-conjunctivitis). (5)
SAC is a classic Type I hypersensitivity reaction, initiated by the allergen binding to immunoglobulin E (IgE) antibodies on the surface of previously sensitised mast cells. Cross-linking of the bound IgE causes the mast cell to release preformed inflammatory mediators (such as histamine) as part of an early-phase response by a process called degranulation. This process may then trigger or enhance the production of newly formed inflammatory mediators via the arachidonic acid pathway, and attract Th2-lymphocytes, eosinophils, neutrophils and basophils to the site of inflammation--this forms part of a process called the late-phase response. (7,9) This complex series of events lead to the acute signs and symptoms associated with SAC, which are often bilateral and include diffuse conjunctival hyperaemia, chemosis, eyelid swelling, and occasionally papillae on the palpebral conjunctiva (see Figures 1 and 2, page 54). (1) Symptoms include sudden onset of ocular itching (pathognomonic indicator of allergy), irritation, burning sensation and watering. (1) Chronic mast cell activation and Th2-lymphocyte infiltration lead to the year round signs and symptoms associated with PAC, which tend to be milder than SAC but may involve seasonal flare-ups. (1,7,8)
Anti-allergic medications are often indicated to provide symptomatic relief during acute episodes of SAC. Topical antihistamine/sympathomimetic combination drops, such as antazoline 0.5% and xylometazoline 0.05%, are available over the counter but are only effective in the short-term (seven days) owing to potential rebound hyperaemia with longerterm use. (10) Antihistamines are competitive antagonists of histamine receptors on effector cells in the conjunctiva and eyelids, which, when stimulated by histamine, would otherwise cause capillary dilation and increased vascular permeability resulting in symptoms of itching and localised redness and oedema, typical of the hypersensitivity reaction. (9,11-13) Sympathomimetics stimulate adrenergic receptors causing capillary constriction and decrease blood flow, thereby reducing hyperaemia, chemosis and eyelid swelling. (10) Other drug types include mast cell stabilisers, such as sodium cromoglycate 2% and lodoxomide 0.1%, available as pharmacyonly medicines (in specific pack sizes and formulation); these are effective in the long-term and may be used as prophylactic agents where they can be applied 10-14 days before symptoms are known to occur. (14,15) Mast cell stabilisers work by preventing the calcium ion influx into the mast cell after antigen stimulation and subsequently inhibit degranulation and release of inflammatory mediators. (9,13)
The application of cold compresses and artificial tears may provide relief in mild cases, and can be used in between topical drug applications to aid resolution. (7,16) A recent study has found that both cold compresses and artificial tears produce significant improvement in ocular surface temperature, conjunctival hyperaemia and ocular symptoms, with efficacy enhanced further when these steps are combined. (16) Patients should also be advised to avoid rubbing the eyes as this may cause mechanical disruption of the mast cells and subsequent degranulation, resulting in signs and symptoms persisting. Oral antihistamines should be advised when other organs are involved as in hay fever (nose, throat), and offer improved efficacy when they are combined with topical treatment. (10,15)
In severe cases, or those unresponsive to the above treatment, the patient should be referred to their GP or a therapeutically-qualified optometrist for more potent anti-allergic medications (prescription only medicines); such as olopatadine or epinastine for SAC and azelastine for PAC, which exhibit both mast cell stabilising and antihistamine properties. (15,17) A list of topical treatments for ocular allergy is shown in Table 1. Interestingly, artificial tears and cold compresses used alone or in combination have been found to be equally effective as epinastine in relieving conjunctival hyperaemia and reducing ocular surface temperature, although symptoms reduced more effectively with epinastine. (16) However, the efficacy of epinastine may be enhanced with the addition of cold compresses immediately after application. (16)
In the long term, allergen avoidance strategies are the most effective method of preventing SAC, and PAC in particular, owing to its chronic nature (see Table 2) and should be advised to all patients. (18-20) Thus, a detailed and thorough history must be elicited to determine the time of year that symptoms develop, or the patient can be asked to keep a diary throughout the year to monitor when symptoms occur. This information can be cross-referenced with a pollen calendar to help identify the causative allergen(s). Referral to an allergist/immunologist may be required when signs and symptoms persist, to perform skin prick tests and conjunctival allergen challenge if the allergen(s) cannot be determined. (1,15,21) However, a negative skin prick test does not preclude ocular allergy, as the eyes may be locally sensitised in the absence of systemic response. (22,23)
It has been shown that contact lenses may help prevent binding of allergens to the ocular surface as part of a 'barrier effect'--a recent study compared the signs and symptoms of ocular allergy in patients with and without contact lenses (two daily disposables; one with enhanced lubricating agents) following exposure to grass pollen in a conjunctival airborne allergen challenge model. The authors found that the severity of burning and stinging symptoms were significantly reduced with the enhanced lubricating agent lens, and signs of bulbar conjunctival hyperaemia, ocular surface staining and palpebral conjunctival roughness were significantly reduced with daily disposable lens wear compared to no lens wear. In addition, the duration of symptoms was shorter by 1.7 to 2.0 times with lens wear compared to no lens wear. Further, limbal and palpebral conjunctival redness were also significantly reduced by use of the enhanced lubricating lens. (24)
Previous studies have compared the use of a daily disposable lens to habitual lens wear in patients with allergies during the allergy season--a greater reduction in bulbar and palpebral hyperaemia, corneal staining and lid roughness from baseline was observed with the daily disposable compared to the habitual lenses and 67% of subjects found the daily disposable more comfortable compared to 18% with a new pair of their habitual lenses. These results are very interesting as the traditional view is to cease lens wear until resolution, as the allergens may bind to the contact lens surface and potentiate the allergic response by prolonging exposure. (1,25,26) However, based on this evidence, patients with mild to moderate AC may continue or switch to daily disposable lens wear if symptoms and signs allow. If they persist, twice-daily dosing topical anti-allergic medication can be advised before insertion and after removal of the lenses to maintain contact lens wear. If symptoms continue, temporarily ceasing contact lens wear while initiating anti-allergic therapy until resolution is advised. (26)
In severe SAC and PAC and cases unresponsive to conventional anti-allergic medications described above, anti-inflammatory agents may be necessary such as non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids. (1,8,17) NSAIDs work by preventing the formation of prostaglandins which are responsible for symptoms of itching by blocking the cyclo-oxygenase pathway in the hypersensitivity response. (6) The efficacy of the NSAIDs ketorolac trometamol 0.5% and diclofenac sodium 0.1% in treating AC has been demonstrated in several environmental challenge studies, (27-30) but only the latter has been licensed for use as treatment for SAC in the UK. Corticosteroids reduce inflammation by: suppressing the activation, recruitment and production of late-phase inflammatory mediators; increasing the availability of histaminases (enzymes which break down histamine); preventing histamine production in mast cells; inhibiting T-cell activity and reducing the permeability of conjunctival blood vessels. (6)
Giant papillary conjunctivitis
Giant papillary conjunctivitis (GPC) is most likely to arise due to a combination of inflammatory events and mechanical trauma to the palpebral conjunctiva. (31,32) The inflammation may be caused by Type I hypersensitivity (with contact lens protein deposits and bacterial cell wall components as potential antigens) and delayed T-cell mediated Type IV hypersensitivity. The
mechanical trauma may cause neutrophils to infiltrate the site of inflammation. (7,32) Sources of mechanical trauma include ocular prostheses, extruding scleral buckles, exposed sutures and corneal deposits but is most frequently associated with contact lens wear, and is referred to as contact lens related GPC (CLGPC). (31,32)
The prevalence of CLGPC is reported to be 1-20% and is far more common in soft compared to rigid gas permeable (RGP) lenses (85% versus 15%). (31-34) Predisposing risk factors for CLGPC include history of atopy, meibomian gland dysfunction, the presence of contact lens deposits, and poor lens fitting, hygiene and design. (32)
CLGPC is often bilateral and is characterised by the presence of macropapillae (0.3-1mm in diameter) or giant papillae (>1mm), swelling and hyperaemia on the superior palpebral conjunctiva and may be accompanied by mucous discharge and increased lens movement when in situ. (31,32) Burning, irritation and itching symptoms are common and may increase on lens removal due to direct contact of the papillae on the highly sensitive cornea and manipulation of the eyelids causing mechanical degranulation of mast cells. (31-33) While wearing contact lenses, patients may also experience reduced comfort, vision and lens tolerance. (32,34) Ceasing contact lens wear or removing the source of mechanical trauma often brings about resolution without pharmacological intervention within four weeks in moderate cases, but may take longer in severe cases. (32) Patients should also be advised to use cold compresses to provide symptomatic relief, artificial tears to increase lubrication of the ocular surface, and avoid eyelid rubbing to prevent mechanical stimulation of mast cells. Patients may continue to wear contact lenses following resolution of signs and symptoms and provided the cornea is not compromised. (32,33) Indeed, the rate of recurrence is reduced when refitting after a period of lens wear cessation, compared to during active disease (6% versus 22%). (33) Although the rate of recurrence is reduced by 61-66% when refitting with new lenses of the same material, refitting with a lens of different material or increasing the replacement frequency. (33-35) However, owing to the smaller area in contact with the palpebral conjunctiva and relative ease to keep clean, changing to an RGP lens reduces recurrence by 80%.33 It is important to stress careful rubbing and rinsing of the lenses before insertion and after removal to minimise the build-up of surface deposits; in some cases enzymatic treatment or peroxide based cleaning systems may be required. (32,33)
Topical mast cell stabilisers such as sodium cromoglycate have been shown to be effective in moderate to severe CLGPC or to aid resolution in cases resistant to conservative management. (32,36) Studies have found that 70-73% of patients with moderate to severe CLGPC treated with sodium cromoglycate during a period of cessation may continue contact lens wear following resolution. (36,37) Although unavailable in the UK, the NSAID suprofen 1% used four times daily has been demonstrated to significantly reduce signs and symptoms in CLGPC patients compared to a placebo. (38) Steroid therapy is also indicated where therapeutic (bandage) contact lenses are required for corneal complications in GPC, such as ulcer formation, but these are uncommon in CLGPC. (6) Indeed, the steroid loteprednol etabonate has been shown to be significantly more effective in treating the signs and symptoms of CLGPC compared to a placebo in several randomised controlled trials. (39-41) However, olopatadine may be used as an alternative to steroid therapy in GPC with recent studies showing comparable efficacy compared to the topical steroid fluorometholone. (42)
Vernal keratoconjunctivitis (VKC) is a non-classic Type I IgE-mediated, Th2-lymphocyte driven allergic disorder involving mast cells and eosinophils, although the exact mechanism is not fully understood. (7,43,44) Involvement of neural factors and an increased presence of sex hormone receptors suggest that the pathogenesis of VKC is complex and multi-factorial in origin. (43,44) Although uncommon and unlikely to be encountered in optometric practice, VKC mainly affects young men (malefemale ratio of 2:1 to 4:1) in hot and dry countries, typically during the spring but may persist year round in 23% of cases. (44) Approximately 60% of cases recur during winter and 16% of cases develop into chronic disease. (44) The exact prevalence of VKC is unknown, but usually occurs before 10 years of age and resolves 4-10 years after initial onset. (45) Much like other ocular allergic conditions, predisposing factors include a history of atopy (43, 44)
VKC is frequently bilateral (98% of cases) and signs include giant papillae (>1mm diameter) on the palpebral conjunctiva (cobblestone appearance) or at the limbus, Horner-Tranta's dots at the superior limbus (gelatinous accumulation of degenerate eosinophils and desquamated epithelial cells; white in appearance), diffuse conjunctival hyperaemia and oedema, and thick, white/yellow, stringy mucous discharge. (44,46) Due to the close apposition of the palpebral conjunctiva, the cornea is often affected and signs include superficial punctuate keratopathy, macroerosion, 'shield' ulcer (see Figure 3), plaque formations and neovascularisation--thus, VKC has sight threatening potential. (43) Regions of the cornea next to previously inflamed limbus may display pseudogerontoxon, which resembles arcus senilis. Occasionally, conjunctival fibrosis and symblepharon may develop in severe cases, where the bulbar conjunctival tissue adheres to the palpebral conjunctival tissue due to scar formation. (43) Symptoms include intense itching, burning, watering, blurred vision, photophobia and occasionally eyelashes may be matted together upon waking. (43,44) Complications of VKC include irregular astigmatism, keratoconus, corneal hydrops, and limbal hyperplasia. (47)
Due to sight threatening potential, entry level optometric treatment of VKC is limited to advising the use of cooled artificial tears and cold compresses for symptomatic relief, the use of sunglasses to minimise photophobia and protect the eyes from exposure to wind and dust which may irritate the eyes, and should be referred routinely to an ophthalmologist or IP-trained optometrist. (6,43,44) However, the presence of limbal or corneal disease requires urgent referral--while patients await their appointment, pharmacyonly mast cell stabilisers may be advised such as sodium cromoglycate 2% and lodoxamide 0.1% (43,48) These two mast cell stabilisers are considered first-line ophthalmological therapy for VKC as they have been shown to be effective in several randomised controlled trials, can be used long-term and have excellent safety profiles. (48) Mucolytics, such as acetylcysteine, are useful in breaking down the mucous discharge and, therefore, help prevent eyelash matting. (44) However, cycloplegia to help minimise pain following pupillary spasm, topical anti-infectives to reduce the risk of infection and a bandage contact lens to prevent interaction between the papillae and cornea may also be advised. (6) In severe cases, topical steroid therapy is required but patients must be closely monitored due to the potential risk of cataract and glaucoma development. (44, 47) Alternative medications that have proved effective in reducing the inflammation in VKC include NSAIDs, such as ketorolac tromethamine, and immunomodulators, such as cyclosporine, which also helps re-epithelialisation of the cornea. (48,49) Surgical intervention via C[O.sub.2] laser or cryotherapy is necessary to remove papillae that are unresponsive to topical therapy and/or causing corneal ulcers or plaque formation. However, superficial keratectomy or laser phototherapeutic keratectomy may be necessary to remove plaques and amniotic membrane overlay graft with tarsorrhaphy or lamellar keratoplasty potentially required for persistent corneal lesions. (43,44,46)
Histopathogical findings and tear film analysis in atopic keratoconjunctivitis (AKC) patients suggest that the pathogenesis is a complex non-classic Type I IgE eosinophil-mediated allergic reaction involving mast cells and Th2-lymphocytes, but as with VKC the exact mechanism is not fully understood. (7,50,51) AKC may follow from childhood VKC (5% of cases) and is considered to be part of the same spectrum of disease clinically. (7)
AKC is uncommon, with one study estimating that 4.4% of patients with ocular allergy have AKC, but the exact prevalence is unknown. (52) Approximately 20-40% of patients with atopic dermatitis suffer from AKC, and is, therefore, considered to be the ocular manifestation of this skin condition. (51) As with VKC, AKC is more common in men but often occurs between the ages of 18 to 40 years. (50) Predisposing factors include a history of atopy, atopic dermatitis and VKC in childhood. (50,51)
The condition is often bilateral, with sight loss potential. Signs include giant papillary hypertrophy (which may become flattened and featureless over time) and scarring of the palpebral conjunctiva (typically superiorly), limbal papillae and diffuse oedema and hyperaemia of the conjunctiva. (50,53) The eyelids of patients with AKC are often thickened, macerated, erythmatous and fissured; symblepharon, cicatricial conjunctivitis and caruncle keratinisation may occur in severe cases; and chronic staphylococcal blepharitis may be present. (50,53) Further, tightening of the lower eyelid skin may cause ectropion and subsequent epiphora. Corneal involvement includes superficial punctuate keratopathy, ulcer and plaque formation. As the condition progresses, persistent epithelial defects, corneal scarring and peripheral neovascularisation may develop thus predisposing to secondary viral, bacterial, and fungal infection. (50,53) In addition, the cornea may become thinned (predisposing to keratoconus) and pre senile atopic 'shield' cataract may occur. (53,54) Symptoms are similar to VKC but more severe and include intense itching, burning, watering, mucous discharge and photophobia. (6,50,53) Blepharitis should be treated with regular eyelid hygiene such as dedicated lid scrubs to remove bacteria, collarettes and crusting from eyelids along with warm compresses to express the meibomian glands in the presence of any posterior blepharitis to help restore normal meibum secretion and tear film lipid layer function. (55) Topical antibiotic ointment, such as chloramphenicol 1% or fusidic acid 1%, is required along the eyelid margins if infection is present, but referral for long-term systemic tetracyclines (doxycycline or azithromycin) may be required if resistant to conservative treatment. (55)
As with VKC, AKC requires long-term therapy with topical mast cell stabilisers such as sodium cromoglycate, lodoxamide and nedocromil to treat the allergic inflammation in mild cases. (7,50,56) Cold compresses and artificial tears may help relieve the intense symptoms between doses. (7,16) In addition, systemic antihistamines may also be used, particularly if other allergies are present. (54) However, most cases of AKC require additional topical steroid therapy to relieve the inflammation, thus patients should be referred for treatment and closely monitored, although the immunomodulator cyclosporine may be used as an effective anti-inflammatory alternative in long-term severe cases and in steroid responders. (50,51,57,58)
Unfortunately, corneal, limbal or severe conjunctival and eyelid disease is often present in these cases and requires urgent ophthalmological referral owing to sight threatening potential. As with VKC, bandage contact lenses, ocular lubricants and prophylactic antibiotics and sometimes cycloplegics are required for corneal ulcers or persistent epithelial defects. (26) However, due to the high levels of bacteria on the eyelid margin, surgery for persistent corneal lesions and cataract carry an increased risk of infection.
Based upon a careful and detailed history and examination of the eyes and surrounding tissue, a correct clinical diagnosis of the particular ocular allergy subtype can be determined. Although the pathogenesis is not well understood, improvements in knowledge of the immune response and the role of inflammatory mediators in ocular allergy have enabled the development of a wide range of effective drug treatments with different pharmacological mechanisms. The majority of ocular allergy cases may be managed to resolution without the need for referral in optometric practice for those with entry-level status. However, in cases unresponsive to conservative treatment or where the cornea is compromised, referral to an independent prescribing optometrist or ophthalmologist is necessary.
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Dr Paramdeep Bilkhuis an optometrist and post-doctoral researcher with numerous publications in peer-reviewed journals. He is the postgraduate module leader for the therapeutics and prescribing course at Aston University.
Dr Shehzad Naroois a qualified optometrist and senior lecturer at Aston University. He is an examiner for the College of Optometrists, editor-in-chief for the journal Contact Lens and Anterior Eye and holds fellowships with the International Association of Contact Lens Educators, the American Academy of Optometrists, and the British Contact Lens Association.
Professor James Wolffsohnis deputy executive dean for life and health sciences at Aston University, teaching and researching in the field of anterior eye. He has been awarded fellowships from the International Association of Contact Lens Educators, the American Academy of Optometrists, the British Contact Lens Association, and the College of Optometrists
Table 1 Topical ophthalmic medications available for the treatment of ocular allergy in the UK Medication Name Formulation Optometrist class availability Mast cell Sodium Sodium Entry level stabiliser Cromoglycate Cromoglycate 2% but in (non- maximum proprietary) pack size of 10mL Catacrom Sodium At least (Moorfields Cromoglycate 2% Additional Pharmceu- (single use) Supply level ticals) Rapitil Nedocromil At least (Sanofi- Sodium 2% Additional Aventis) Supply level Alomide Lodoxamide 0.1% Entry level (Alcon) Antihistamine Otrivine- Antazoline Entry level Antistin Sulphate 0.5% (Novartis) and Xylometazoline Hydrochloride 0.05% eye drops Emadine Emedastine At least (Alcon) Hydrochloride Additional 0.05% Supply level Dual action Opatanol Olopatadine At least (Alcon) Hydrochloride Additional 1mg/mL Supply level Optilast Azelastine At least (Meda) Hydrochloride Additional 0.05% Supply level Relestat Epinastine At least (Allergan) Hydrochloride Additional 500[micro]g/mL Supply level Zaditen Ketotifen At least (Novartis) Fumarate Additional 250[micro]g/mL Supply level Non-Steroidal Voltarol Diclofenac At least Ophtha Anti- Multidose Sodium 0.1% Additional Inflammatory (Novartis) Supply level Drugs Voltarol Diclofenac At least Ophtha Sodium 0.1% Additional (Novartis) (single use) Supply level Vasocons- Murine Naphazoline Entry Level trictor irritation Hydrochloride (Pharmacy and redness 0.012%w/v only relief medicine) (Prestige Brands) Optrex Naphazoline Entry Level Bloodshot Hydrochloride (Pharmacy Eye Drops 0.01%w/v and only (Reckitt Witch Hazel medicine) Benckiser) (Hamamelis water) 12.5%v/v Table 2 Allergen avoidance measures for seasonal and perennial allergic conjunctivitis Allergen Avoidance strategies Pollen and outdoor moulds * Minimise outdoor activities when symptoms are known to develop * Plan outdoor activities by monitoring pollen levels using TV, internet and radio * Wear close-fitting sunglasses and avoid rubbing eyes or nose when outdoors * Wash hands after being outdoors * Close doors and windows when indoors * Use air conditioning, circulate air internally and close windows when in a vehicle House dust mites * Wash bedding regularly (temperatures at least 60[degrees]C) * Damp dust and vacuum entire house weekly * Remove or regularly clean curtains, upholster carpets and any areas which may gather dust * Reduce humidity to 30-50% in the home with a de-humidifier Animal dander * Avoid contact with animals * Remove pets from home or do not keep at all * Regularly vacuum and clean entire home * Wash hands and clothes and avoid rubbing eyes or nose after being in contact with animals
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|Title Annotation:||CET: CONTINUING EDUCATION & TRAINING|
|Author:||Bilkhu, Paramdeep; Naroo, Shehzad; Wolffsohn, James|
|Date:||Mar 28, 2014|
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