Introduction

Allergy is an over-reaction of the body's immune system to innocuous foreign substances or allergens that the body perceives as a potential threat or undesirable. It has a signi? cant impact on the quality of life of the individual. Allergic diseases are those conditions in which an antibody- and/or T-cell mediated mechanisms are involved. The management of allergic eye disease is aimed at preventing the release of mediators of allergy, controlling the allergic in? ammatory cascade and preventing ocular surface damage secondary to the allergic response. In the management of ocular allergic disease, non-pharmacologic and pharmacologic therapeutic regimens that address the acute presentation of ocular allergy and provide prophylaxis aimed at providing long-term maintenance therapy are advised to be recommended. This approach to the management of allergic eye diseases aims to minimize the impact of the allergic reaction on the individual's quality of life

Allergy is an over-reaction of the body's immune system to harmless foreign substances or allergens, which the body perceives as undesirable. It is a malady that is estimated to affect approximately 20% of the population, of which, at least 20% suffer from ocular allergy. Allergic diseases have a significant impact on the quality of life and wellbeing of the individual. It affects learning performance in school-aged individuals and work productivity in adults.

Irritants or allergens such as pollen, animal dander, drugs, cosmetics, molds, and house dust mite, aromatic hydrocarbons from diesel exhaust fumes can trigger ocular allergy. The mechanism of allergic eye disease includes: (1) sensitization process (allergen-induced IgE production and mast cell sensitization); (2) early phase response (allergen-induced IgE-mediated mast cell degranulation and the release of preformed mediators and chemotactic factors); and (3) late phase response (persistent mast cell activation and TH₂- mediated DTH reaction involving the actions of newly formed mediators and chemotactic factors that incite the recruitment of additional inflammatory cells that leads to the allergen-induced late phase allergic response).

The treatment options for management of allergy range from non- pharmacological to pharmacological management using supportive therapy, prophylaxis and therapeutic pharmaceuticals. The adequate knowledge of the disease process of the different types of ocular allergies along with the different classes of anti-allergic pharmaceutical agents used in the management of these diseases will ensure success in the management of ocular allergy and that the prescribed drug is the most appropriate for the patient's allergic eye disease.

The primary aim of a non-pharmacological approach is to prevent the onset of allergic eye reaction and/or minimize the effect of the allergens. It is considered the first-line treatment of ocular allergy and includes avoidance of known allergens; saline irrigation; avoid eye rubbing; and palliative therapy with cold compresses and preservative-free ocular lubricants.

Patients should be advised to stay indoors and keep the windows closed or wear a filtermask if it is necessary for them to stay outside on days when the pollen count is high. They should also be advised to be more aware of the pollen count through the weather forecast; avoid cutting grass on windy days and when the pollen count is high; and avoid going near freshly cut grass during the height of the allergy season. Furthermore, the patient should be advised to avoid damp areas as these are potential breeding grounds for moulds; keep pets out of the bedroom, since their hair/fur can collect allergens; and keep the kitchen and bathroom clean and dry, so as to minimize the growth and/or breeding of mould. Also patients should be advised to keep preservative free ocular lubricants in the refrigerator given that the cold temperature of the refrigerated preservative-free ocular lubricants in conjunction with cool compresses induces vasoconstriction. Preservative-free ocular lubricants dilute and flush away allergens that may come into contact with the ocular surface. They also form a barrier to inhibit allergen contact with the ocular surface.

Pharmaceutical agents used in the management of allergic eye diseases can be classified in two main categories: anti-inflammatory and anti-allergic therapeutic agents. The anti-allergic therapeutic agents available for the management of acute expressions of ocular allergy and for prophylaxis are as follows:

Antihistamine/vasoconstrictor combinations contain both an antihistamine (e.g. antazoline phosphate) and vasoconstrictor (e.g. naphazoline or phenylephrine). The antihistamines in these drops help to decrease the itch associated with allergic conjunctivitis. The vasoconstrictors in these agents are adrenergic agonists that stimulate α-adrenoreceptor, and as such are capable of reducing the chemosis, redness and eyelid edema in allergic eye diseases that occurs as a result of tissue congestion.

Antihistamine/vasoconstrictor combination agents are indicated for relieving the symptoms and signs of allergic conjunctivitis. These combination agents are relatively fast acting but the duration of action last only 2-4 h, so patients may need to dose more frequently, which may cause ocular adverse effects.

The adverse effects of these agents include burning and stinging on instillation; mydriasis, especially in patients with lighter irides; follicular conjunctivitis; eczematoid blepharoconjunctivitis; and rebound hyperemia or conjunctivitis medicamentosa with long-term use.

The nonspecificity of the pharmacologic action of antihistamine/ vasoconstrictors combination agents in dealing with the ocular allergic response and its adverse ocular effects makes it inappropriate for long- term use.

Antihistamines are very beneficial and effective pharmaceutical agents for treating individuals who present with clinical expressions of IgE-mediated ocular allergic response. They prevent histamine released from mast cells from interacting with histamine receptors by binding competitively to H₁ receptors on the nerves and blood vessels which results in reduced itching sensation and relief from conjunctival redness and swelling.

The first-generation and second-generation oral antihistamines, such as chlorpheniramine and cetirizine, are H₁ antagonists but they may lead to tear film insufficiency with consequential weakening of the protection the tear film offers against environmental allergens and pollutants.

The new generation topical antihistamines such as levocabastine 0.05% and emedastine 0.05% are superior to the first generation topical antihistamines and work by competitively blocking histamine receptors on the ocular mucosal surface.

Emedastine difumarate 0.05% ophthalmic solution, a safe and effective selective histamine H₁-receptor antagonist, is indicated for the temporary relief of the signs and symptoms associated with allergic conjunctivitis.

Levocabastine HCl ophthalmic suspension 0.05%, a cyclohexy-3- methylpiperidine derivative, is a potent topical antihistamine suspension with rapid onset of action of 15 min and prolonged clinical effect lasting up to 4 h.

Antihistamine/mast cell stabilizer is a multimodal action antiallergic agent that acts as both a histamine receptor antagonist and mast cell stabilizer. Olopatadine ophthalmic solution, Epinastine ophthalmic solution, Ketotifen ophthalmic solution, and Azelastine ophthalmic solution are topical anti-allergic pharmaceutical agents that are readily available.

Olopatadine HCl ophthalmic solution is a multimodal antiallergic agent that possesses selective H1-receptor antagonism and mast-cell stabilizing features. It inhibits the release of allergic mediators from mast cells and prevents histamine from providing its effects on the eye. It has a rapid onset of action and prolonged clinical effect. The prolonged clinical effect of Olopatadine could be attributed to its ability to suppress the release of allergic mediators and inhibit inflammatory cell recruitment. It reduces all signs and symptoms of allergic conjunctivitis, including redness, itching, chemosis, tearing and eyelid edema. Olopatadine is approved for the treatment of the signs and symptoms of allergic conjunctivitis.

Azelastine HCl 0.05% ophthalmic solution, a phthalazinone derivative, is a twice-a-day dosed multiple-action anti-allergic agent. It has a rapid onset of action and is capable of inhibiting release of allergic mediators. Azelastine ophthalmic solution is indicated for the treatment or relief of ocular itching associated with allergic conjunctivitis. It has a noticeable bitter taste and causes ocular stinging upon instillation.

Ketotifen fumarate 0.025% ophthalmic solution, a benzocyclo- heptathiophene derivative, is a twice-a-day dosed multi-modal anti- allergic agent. It possesses both mast-cell stabilizing and strong H1 receptor antagonism. It is approved for the temporary prevention of ocular itching due to allergic conjunctivitis.

Epinastine 0.05% ophthalmic solution, an antihistamine with mast- cell stabilizing and anti-inflammatory properties, is a twice daily dosed multimodal action anti-allergic agent. It is indicated for the prevention of itching associated with allergic conjunctivitis. It has affinity for H1 and H2 receptors with prolonged therapeutic effect lasting up to 12 h and onset of action within 3 min

Azelastine, Ketotifen and Epinastine are indicated for itching associated with allergic conjunctivitis, except Olopatadine that is indicated for the relief of all signs and symptoms of allergic conjunctivitis.

Topical mast cell stabilizers prevent the release of allergic mediators from mast cells by suppressing mast cell degranulation. The blockade of mast cell degranulation will inhibit the release of preformed and newly formed mediators of allergy as well as chemokines and cytokines. They also achieve their clinical effect by preventing calcium influx across the cell membrane. Mast cell stabilizers are safe and effective for the long term therapeutic management of allergic eye diseases. They require a loading time of up to two weeks since it has no effect on acute allergic reactions induced by histamine already released on the ocular surface.

Sodium cromoglycate is a mast cell stabilizer that is suitable for long- term prophylaxis and therapeutic management of ocular allergy. It is not as effective at inhibiting the degranulation of mucosal mast cells and this may explain the poor response of chronic ocular allergies to sodium cromoglycate. The major adverse effect is burning and stinging.

Lodoxamide tromethamine 0.1% ophthalmic solution possesses mast-cell stabilizing properties that are considered to be 2500 times more potent than that of sodium cromolyn. It is safe for use in children and adults on a four-times-daily dosing for up to 3 months. The most common side effects are burning or stinging.

Pemirolast potassium ophthalmic solution, a pyridopyrimidine compound, is a mast cell stabilizer that is used for the treatment of seasonal allergic and vernal conjunctivitis. It is dosed four times daily and it is safe for use in children as young as 2 years of age.

Nedocromil sodium 2% ophthalmic solution, a pyranoquinoline dicarboxylic acid, is a potent stabilizer of both connective and mucosal type mast cells. In patients with chronic ocular allergies, nedocromil sodium has been shown to be more effective than sodium cromoglycate in preventing release of allergic mediators from the mucosal type mast cell. It is safe and well tolerated for the long-term management of ocular allergies. It is associated with ocular stinging or burning upon instillation and a distinctive taste.

Non-steroidal anti-inflammatory drugs are safe for long-term use and act by blocking the cyclooxygenase pathway; thus preventing the subsequent formation of prostaglandins, which are responsible for the itch associated with allergic eye diseases.

Ketorolac tromethamine and diclofenac sodium are approved for use in seasonal allergic conjunctivitis for the relief of ocular itching. Diclofenac sodium 0.1% is capable of controlling signs and symptoms of vernal keratoconjunctivitis (VKC).

Ketorolac tromethamine 0.5% ophthalmic suspension, a pyrazolon, is a four times- a-day-dosed NSAID. It is valuable as an adjunctive treatment in ocular allergic inflammation due to its potential to reduce the ocular pruritus, edema and conjunctival hyperemia associated with ocular allergy. It does cause mild transient ocular burning and stinging upon instillation, which could be alleviated by advising the patient to refrigerate the agent prior to administration.

Topical NSAIDs blocks the production of prostaglandins but have no effect on other allergic inflammatory mediators, such as histamine and leukotrienes that contribute to the ocular manifestations of allergic eye disease. For this reason, it is likely to be of limited use in the treatment of ocular allergy.

Corticosteroids are potent anti-allergic agents that are considered most appropriate for the treatment of chronic ocular allergic conditions. They have the ability to suppress the recruitment and activation of pro- inflammatory allergic mediators during the late phase of ocular allergic response. It blocks the action of mast cell phospholipase A2, an enzyme necessary for the hydrolysis of arachidonic acid, thereby reducing the production of late-phase allergic inflammatory mediators such as prostaglandins and leukotrienes.

Steroids are incapable of blocking histamine receptors. However, they can inhibit histamine production in mast cells by blocking the action of histidine decarboxylase. Additionally, corticosteroids can reduce the amount of unbound histamine on the ocular surface by increasing the availability of histaminases. Corticosteroids are not effective in stabilizing mast cells due to their inability to prevent calcium influx into the mast cell. However, they are capable of inhibiting T-lymphocyte response and production of cytokines such as interleukin (IL)-4 and IL-5 production. Furthermore, corticosteroids can also inhibit neovascularisation and reduce capillary permeability.

Loteprednol Etabonate ophthalmic suspension, a site-specific soft steroid, primarily targets the late phase inflammatory aspect of the ocular allergic response. Loteprednol is more lipophilic than ketone corticosteroids such as prednisolone, and it's highly lipophilic nature may contribute to its increased efficacy by enhancing penetration into target inflammatory cells. The long-term use of loteprednol is most likely to have a lower propensity to induce IOP elevation. Loteprednol is a suitable long-term therapeutic option for chronic ocular allergies due to their superior safety profile relative to the ketone corticosteroids. Clinical studies have shown that loteprednol etabonate is a safe treatment option for individuals with allergic ocular inflammation. It has been demonstrated to be effective in treating allergic conjunctivitis and giant papillary conjunctivitis (GPC).

Prednisolone acetate is an excellent choice for treating severe inflammatory disorders due to its good ocular penetrability while prednisolone sodium phosphate may be considered a suitable drug for moderate inflammatory disorders of the ocular surface due to its reduced ocular penetrability when compared to prednisolone acetate.

The fluorometholone-based steroids are used for treating mild to moderate ocular surface inflammatory conditions and chronic inflammatory conditions requiring prolonged steroidal therapy. They have reduced propensity to induce an IOP rise. The acetate form of fluorometholone-based steroids has greater anti-inflammatory activity than the alcohol form (FML) due to their enhanced bioavailability. Clinical studies have shown that FML reduces the clinical expression of VKC, including discharge, conjunctival redness, papillary hypertrophy and tranta's dots.

Immunomodulators, such as cyclosporine and tacrolimus, play vital roles in the treatment of allergic eye diseases due to their ability to inhibit calcineurin, a phosphate that is essential to the FceRI-mediated release of preformed mediators from mast cells. They are capable of blocking mast cell proliferation, inhibiting histamine release, blocking release of cytokines from T-lymphocytes, and reducing eosinophil chemotaxis.

Tacrolimus is a potent macrolide immunosuppressor in ocular allergy. It exerts its action by inhibiting IgE production by activated B-cells as well as inhibiting T-cell activation and associated proinflammatory cytokine production. It also interferes with mast cell degranulation; inhibits the antigen-presenting role of Langerhans cells and late phase responses in ocular allergy. It has been shown to be well tolerated with an excellent safety profile for the long-term management of dermatitis and also it could be therapeutically beneficial for patients with atopic keratoconjunctivitis (AKC), atopic eyelid disease and atopic dermatitis. Transient burning sensation and recurrent herpetic lesions are reported side effects of tacrolimus.

Cyclosporine is a fungal anti-metabolite that inhibits T-lymphocyte activation via IL-₂ by blocking IL-₂ production. It also reduces eosinophil chemotaxis via inhibition of IL-₂ production. Furthermore, it inhibits TH-₂-lymphocyte proliferation and IFN-g with consequential modulating effect on Th1- lymphocyte mediated DTH. Cyclosporine is prescribed, when steroids are contraindicated or unsafe, for treating the severe form or steroid resistant cases of chronic ocular allergy.

In the management of ocular allergic diseases, non pharmacologic and/or pharmacologic therapeutic regimens that address the acute presentation of ocular allergy and provide prophylaxis should be recommended. This approach to the management of allergic eye diseases will minimize the adverse effect the allergic reaction may have on the individual's quality of life.

Allergic conjunctivitis, a bilateral, self-limiting IgE-mast cell mediated conjunctival inflammatory process. Seasonal allergic conjunctivitis (SAC) is an IgE-mast cell mediated hypersensitivity response to seasonal allergens such as pollen whereas Perennial or persistent allergic conjunctivitis (PAC) is an IgE-mast cell mediated hypersensitivity response to perennial allergens such as animal dander and dustmite.

The first line of therapy for patients with allergic conjunctivitis is to avoid the offending allergens. Mild to moderate cases of allergic conjunctivitis will respond to antihistamine, topical multimodal anti-allergic agents, mast cell stabilizers and supportive therapy. Individuals that present with hyperacute expressions of allergic conjunctivitis, severe allergic conjunctivitis or allergic conjunctivitis that is refractory to conventional anti-allergic therapy would benefit from short-term steroidal therapy aimed at suppressing the allergic inflammatory cascade.

Patients who present with allergic rhinoconjunctivitis would benefit from using a nasal spray (e.g. antihistamine nasal spray {Azelastine hydrochloride}) or oral antihistamine to provide therapeutic relief for the rhinitis and a topical multimodal anti-allergic ophthalmic agent to treat the allergic conjunctivitis.

In the strict sense of it, giant papillary conjunctivitis is not a true allergic condition; rather it is a chronic inflammatory condition that results from chronic irritation of the tarsal conjunctiva. The pathophysiology of GPC is a combination of mechanical trauma to the tarsal conjunctiva and mast cell- eosinophil-TH₂ lymphocyte mediated immune hypersensitivity reaction. A poorly fitted contact lens can potentially irritate the superior tarsal conjunctiva resulting in mechanically induced GPC. Immunologic GPC and ocular surface inflammation in contact lens wearers may occur due to an immune response to denatured protein in the biofilm on the contact lens surface. It has been shown that contact lens tends to attract proteinaceous deposits on their surface. These proteinaceous deposits may become antigenic with the potential of developing a hypersensitivity response. In order to prevent or minimize the buildup of potential antigenic biofilm on the contact lens surface, the clinician should recommend precautionary measures, such as regular contact lens cleaning with appropriate solutions and weekly enzymatic treatment.

GPC is characterized by itching, tearing, burning, increased mucus production, giant papillae on the superior tarsal conjunctiva and conjunctival injection (Fig 1). In severe cases, corneal erosion and superficial punctate keratitis may occur. The stages include preclinical, mild, moderate and severe GPC.

The aim of management is to reduce or prevent the clinical expression of GPC by controlling, avoiding or removing the causative agents or antigen. In case of failure of this approach, patients with GPC may benefit from either anti-allergic therapy or pulse topical steroidal therapy depending on the degree of clinical expression of the condition.

Patients who have GPC with significant conjunctival papillary hypertrophy or inflammatory component require both a mast cell stabilizer and topical steroid with the intention of tapering the steroid once an adequate clinical response has been achieved.

Contact lens wearers with allergic conjunctivitis or GPC may benefit from a topical anti-allergic agent, using either once or twice-a-day dosing. The dose for the anti-allergic agent can be administered 5-10 min prior to contact lens insertion and if a second dose is used, it is taken after contact lens removal at the end of the day.

Nedocromil, a twice-a-day dosed mast cell stabilizer, may be beneficial be for long-term prophylaxis (prior to the allergy season in seasonal allergic sufferers or all year round in perennial allergic sufferers) for contact lens wearers who have either GPC or allergic conjunctivitis. Olopatadine 0.2% may be suitable topical multimodal anti-allergic agent for contact lens wearers who have allergic conjunctivitis.

The most suitable course of therapy for patients with mild GPC or allergic conjunctivitis is to discontinue contact lens wear or make several changes in their contact lens regime. The best course of management for contact lens wearers with moderate-to-severe GPC or allergic conjunctivitis is to cease contact lens wear until the symptoms have completely resolved.

Vernal keratoconjunctivitis is a sight-threatening, bilateral, chronic allergic inflammation of the ocular surface that predominantly affects children and young adult males. Patients who have VKC are very symptomatic during spring and summer and experience symptoms such as tearing, extreme itching, photophobia and mucus discharge. In VKC, the corneal findings include superficial punctate epithelial keratitis, epithelial macroerosion, shield ulcer and corneal plaque. The palpebral form of VKC is characterized by giant papillae on the upper tarsal plate while the limbal form is characterized by gelatinous limbal infiltrates (Trantas dots) (Fig. 2 and 3).

The immunopathogenesis of VKC is a chronic IgE-mast cell and eosinophil-Th2 lymphocyte mediated allergic inflammatory reaction with an over expression of eosinophils, Th2- lymphocytes, Th2-derived cytokines, chemokines and other inflammatory cells or mediators. Bonini et al. proposed a clinical grading to help physicians in the diagnosis and management of VKC as mild, moderate or severe.

The clinical manifestations of the mild form of VKC includes occasional pruritus, mild tearing, mild discomfort including burning, stinging, foreign body sensation, mucoid discharge, mild photophobia, mild to moderate papillary reaction, mild corneal epithelial defects with or without corneal neovascularization, subepithelial fibrosis of the conjunctiva and mild redness and edema of the eyelid. The clinical manifestations of the moderate form of VKC includes persistent itching, intermittent tearing, moderate discomfort, moderate mucoid discharge with the presence of crust upon awakening, moderate photophobia, moderate tarsal papillary hypertrophy and hyperemia with hazy view of the deep vessels, Horner-Trantas dots, moderate corneal epithelial defects with corneal neovascularization, moderate subepithelial fibrosis and moderate eyelid inflammation with Meibomian Gland Dysfunction. The clinical manifestations of the severe form of VKC includes constant itching and tearing, severe discomfort, marked mucoid discharge with agglutination of the eyelids upon awakening, extreme photophobia, severe tarsal papillary hypertrophy and hyperemia obscuring the visualization of the deep tarsal vessels, severe corneal epithelial defects in the form of corneal erosion or ulceration with corneal neovascularization, numerous Horner-Trantas dots, the presence of symblepharon and severe inflammation of the eyelid.

In the management of VKC, the clinician should provide therapy that suppresses the allergic inflammatory process before the patient becomes symptomatic. The supportive therapy of VKC includes avoiding the trigger factors such as sun, wind, and salt water with the use of sunglasses, hat with visors and swimming goggles, avoiding eye rubbing and applying cool compress and/or administering preservative-free ocular lubricants. Patients with a history of VKC should be started on prophylactic therapy with mast cell stabilizers prior to the allergy season or should remain on the therapy all year round, depending on the allergic exposure and duration of the allergic expression.

Patients with mild VKC may benefit from supportive therapy as well as topical multimodal anti-allergic agents and/or mast cell stabilizers to provide symptomatic relief. However, a pulse topical steroidal therapy will become necessary to control the inflammation, if the anti-allergic therapy does not provide satisfactory therapeutic relief.

Patients with moderate or severe VKC require concurrent use of topical steroids and mast cell stabilizers or antihistamine/mast cell stabilizer combinations to achieve an adequate therapeutic effect. E.g.: Loteprednol etabonate 0.5% and prednisolone acetate 0.1%. Topical cyclosporine is a suitable substitute for topical steroid and it has been shown to be an effective long-term therapeutic agent for VKC. However, treatment with systemic corticosteroids may become necessary when individuals present with very severe VKC that does not respond to conventional topical therapy.

Atopic keratoconjunctivitis is a sight-threatening, bilateral, chronic allergic inflammation of the ocular surface and the eyelids often associated with atopic dermatitis and other allergic disorders. It affects mostly males usually in their late teens with a peak onset between the ages of 30 and 50. It is characterized by chronic itching, burning, tearing, photophobia, papillary hypertrophy, conjunctival hyperemia, chemosis, and thickened, erythematous, swollen eyelids. In AKC, the effect of toxic allergic mediators on the ocular surface can cause corneal complications such as neovascularisation, pannus and corneal thinning and scarring (Fig. 4).

AKC is a chronic IgE-mast cell and eosinophil-T-lymphocyte mediated allergic inflammation of the ocular surface and eyelids with an over-expression of T-lymphocytes, eosinophils, mast cells, TH₁- and Th₂-derived cytokines and other inflammatory cells and mediators. Calonge et al. proposed a clinical grading to help physicians in the diagnosis and management of AKC as Patients with mild forms of AKC (Grade I) present with mild/occasional itching, burning and photophobia, Patients with mild-to-moderate forms of AKC (Grade II) present with mildly persistent or moderate/occasional itching, burning and photophobia, Patients with moderate forms of AKC (Grade III) present with moderately persistent itching, burning and photophobia and Patients with severe forms of AKC (Grade IV) present with severe itching, burning and photophobia.

In managing individuals with AKC, focus should be on developing a management plan that will provide symptomatic relief and prevent the development of ocular complications associated with AKC, as well as advise the patient on the need to avoid potential trigger factors. Patient with the mild form of AKC may benefit from the use of supportive therapy as an adjunct to topical anti-allergic pharmacologic therapy and oral antihistamine. Moderate and severe cases of AKC associated with corneal compromise require topical steroids and prophylactic antibiotics.

Topical immunomodulators such as cyclosporine could be used as a substitute for patients with steroid-dependent AKC. Cool compresses and preservative- free ocular lubricants provide symptomatic relief when there is intense ocular irritation and burning due to tear film insufficiency. The chronic blepharitis and meibomianitis associated with AKC requires regular eyelid hygiene, warm compresses and long-term therapy with systemic antibiotics such as doxycycline that are capable of inhibiting the action of lipase, an enzyme that converts glandular lipids into free fatty acids. Preservative-free ocular lubricants and prophylactic antibiotics should be considered as an essential adjunctive therapeutic strategy when therapeutic bandage contact lens are used in managing corneal complications associated with AKC.

Contact Ocular Allergy is predominantly a TH₁-lymphocyte mediated hypersensitivity response that involves the ocular surface, eyelids and periocular skin. It is characterized by itching, conjunctival hyperemia, chemosis, follicular/papillary conjunctival reaction, punctate keratitis, as well as dermatitis of the periocular skin and eyelids (Fig. 5). Drug-induced allergic conjunctivitis (DIAC), an ocular adverse reaction, is a hypersensitivity reaction to pharmaceutical agent applied to the eyes or periorbital region.

The management of patients with contact ocular allergy or drug-induced allergic conjunctivitis involves identifying and removing or avoiding the offending allergen or irritant. The mild form of these conditions may respond to palliative therapy and antihistamine, as well as, avoiding the offending allergen or irritant. Moderate to severe cases of contact ocular allergy or DIAC require multimodal anti-allergic agents, oral antihistamine and topical steroid to provide symptomatic relief and control of the inflammatory process. Tacrolimus is a very effective and safe steroid sparing option for treating the periocular skin inflammation in patients with contact ocular allergy.

It is important to understand the different types of anti-allergic and/or anti- inflammatory medications, particularly their mode of action, the range of anti-allergic or anti-inflammatory indications, side-effect profile, contra-indications, and relative efficacies. To ensure effective management of ocular allergies, an inquiry about the patient's personal and family history of allergy should be done.

To promote patient compliance, anti-allergic and/or anti-inflammatory therapeutic agents that provide a rapid clinical response and prolonged therapeutic effect should be prescribed. Also therapeutic agents should be cost-effective, easy and convenient to use, safe for extended use, and comfortable.

The mainstay of the management of ocular allergy consists of the use of anti-allergic therapeutic agents such as antihistamine, multiple action anti- allergic agents and mast cell stabilizers. When anti-allergic therapeutic agents are incapable of providing adequate therapeutic relief or does not control the allergic inflammatory process, then an anti-inflammatory agent such as topical steroid should be prescribed. Topical immunomodulators such as tacrolimus are steroid-free alternatives that could be used when long-term use of topical steroids is not considered a safe therapeutic option.

The management of ocular allergy depends on the severity of the allergic expression and type of ocular allergy. To avoid ocular surface compromise and complications, accurate diagnosis and/or differential diagnosis should be done which will guide in prescribing the most appropriate anti-allergic medication.

The management of allergic eye diseases presents a challenge to the clinician, calling for adequate knowledge of the immunopathophysiology, clinical features and differential diagnosis of the different types of ocular allergy. Furthermore, an adequate knowledge of anti-allergic and anti- inflammatory pharmaceutical agents used in the management of allergic eye diseases is necessary. Knowledge of the patient's life style is helpful in promoting compliance with recommended treatment protocols. When non-pharmacological management fails to provide adequate relief, the next option is to prescribe anti-allergic therapeutic agents. The optimal anti- allergic pharmaceutical agent will have a good safety profile, rapid onset of action and prolonged clinical effect. However, pulse steroidal therapy would become necessary if the allergic expression does not respond to anti-allergic therapy. In acute ocular allergy, the use of anti-allergic medications along with supportive therapy is usually sufficient. In hyperacute cases and chronic ocular allergy, it is preferable to control the inflammatory condition with an anti-inflammatory agent, such as steroids, and a prophylactic anti-allergic agent, such as mast cell stabilizers for long-term maintenance therapy. The management of allergic eye disease is aimed at preventing the release of mediators of allergy, controlling the allergic inflammatory cascade and preventing ocular surface damage secondary to the allergic response. Such management can be regarded as an essential part of primary eye care.