Avoidance of the offending antigen is the primary behavioral modification for all types of allergic conjunctivitis; however, the eyes present a large surface area and thus it is often impossible to avoid ocular exposure to airborne allergens. Artificial tear substitutes provide a barrier function and help to improve the first-line defense at the level of conjunctival mucosa. These agents help to dilute various allergens and inflammatory mediators that may be present on the ocular surface, and they help flush the ocular surface of these agents. When avoidance of non-pharmacologic strategies do not provide adequate symptom relief, pharmacologic treatments may be applied topically or given systemically to diminish the allergic response.
The mainstay of the management of ocular allergy involves the use of anti-allergic therapeutic agents such as antihistamine, multiple action anti-allergic agents and mast cell stabilizers. For example, the H1 topical antihistamine levocabastine hydrochloride is effective in rapidly relieving ocular inflammation when administered topically to the eye [34, 35]. Topical antihistamines competitively and reversibly block histamine receptors and relieve itching and redness but only for a short time. These medications do not affect other proinflammatory mediators, such as prostaglandins and leukotrienes, which remain uninhibited. A limited duration of action necessitates frequent dosing of up to 4 times per day, and topical antihistamines may be irritating to the eye, especially with prolonged use . Combination treatments using decongestants with antihistamines have been shown to be more effective, and are administered to the eye as drops up to 4 times daily . Decongestants act primarily as vasoconstrictors and are effective in reducing erythema, however, adverse effects include burning and stinging on instillation, mydriasis, and rebound hyperemia or conjunctivitis medicamentosa with chronic use . Therefore, these treatments are suitable only for short-term symptom relief, and are not recommended for use in narrow-angle glaucoma patients.
Mast cell stabilizers have a mechanism of action that is unclear. They may increase calcium influx into the cell preventing membrane changes and/or they may reduce membrane fluidity prior to mast cell degranulation. End result is a decrease in degranulation of mast cells, which prevents release of histamine and other chemotactic factors that are present in the preformed and newly formed state.
Mast cell stabilizers do not relieve existing symptoms and they can be used on a prophylactic basis to prevent mast cell degranulation with subsequent exposure to the allergen. Mast-cell stabilizing medications can also be applied topically to the eye, and may be suitable for more severe forms of conjunctivitis. They require a loading period during which they must be applied before the antigen exposure. Therefore, poor compliance should be taken into account as a possible drawback.
In recents years have been introduced several multimodal anti-allergic agents, such as olopatadine, ketotifen, azelastine and epinastine and bepostatine, that exert multiple pharmacological effects such as histamine receptor antagonist action, stabilization of mast-cell degranulation and suppression of activation and infiltration of eosinophils .
Ketotifen inhibits eosinophil activation, generation of leukotrienes and cytokine release [39, 40].
Azelastine is a selective second generation H1 receptor antagonists, and also acts by inhibiting platelet activating factor (PAF) and blocking expression of intercellular adhesion molecule 1 (ICAM-1) . Epinastine has effect on both H1 and H2 receptors (the latter effect may be beneficial in reducing the eyelid swelling), and also has mast-cell stabilizing and anti-inflammatory effects .
These drugs are becoming the drug of choice for providing immediate symptomatic relief for patients with allergic conjunctivitis.
When the abobe mentioned anti-allergic drugs do not allow an adequate control of the allergic inflammatory process, anti-inflammatory agents are used. Non-steroidal anti-inflammatory drug (NSAIDs) can be used as additive drugs, in order to,reduce the conjunctival hyperemia and the pruritus, related in particular to prostaglandin D2 and prostaglandin E2 .
Corticosteroids remain among the most potent pharmacologic agents used in the more severe variants of ocular allergy and are also effective in the treatment of acute and chronic forms of AC [44–48]. Corticosteroids possess immunosuppressive and anti-proliferative properties since they can hinder the transcription factor that regulates the transcription of Th2-derived cytokine genes and differentiation of activated T-lymphocytes into Th2-lymphocytes. They have some limitations, including ocular adverse effects, such as delayed wound healing, secondary infection, elevated intraocular pressure, and formation of cataract. These agents are therefore appropriate for short courses (up to 2 weeks); however, if needed for longer durations, an eye examination should be carried out, including baseline assessment of cataracts and intraocular pressure measurement [3, 49].
The efficacy of immunotherapy against ocular symptoms precipitated by conjunctival antigen challenges was originally demonstrated in 1911 and this well-established method may be considered for the long-term control of AC . Although some more recent studies have focused on nasal rather than ocular symptoms, others have confirmed the efficacy of immunotherapy against ocular symptoms [50–56].
Allergen-specific immunotherapy is an effective treatment for patients with allergic rhinoconjunctivitis that have specific IgE antibodies to allergens. The main objective of this treatment is to induce a clinical tolerance to the specific allergen: it reduces the seasonal increases of IgE specific for that allergen, and it increases the production of specific IgG4 and IgA; such effects are mediated by an increase of the production of IL-10 and TGF-β1 .
However, immune responses to allergen administration are not predictive of the effectiveness of the therapy and the therapy itself can produce systemic reactions, the incidence and severity of which vary dependent on the type of allergen administered [58, 59]. Traditionally, immunotherapy is delivered via subcutaneous injection. However, sublingual (oral) immunotherapy (SLIT) is gaining momentum among allergists. SLIT requires further evaluation for ocular allergy relief; it has been shown to control ocular signs and symptoms, although ocular symptoms may respond less well than nasal symptoms [60–65]. Oral antihistamines are commonly used for the therapy of nasal and ocular allergy symptoms. These newer second-generation antihistamines are recommended in preference to first-generation antihistamines because they have a reduced propensity for adverse effects such as somnolence . Second-generation antihistamines can, however, induce ocular drying, which may impair the protective barrier provided by the ocular tear film and thus actually worsen allergic symptoms [66, 67]. It has therefore been suggested that the concomitant use of an eye drop may treat ocular allergic symptoms more effectively . Intranasal corticosteroids are highly effective for treating nasal symptoms of allergic rhinitis, but the evidence that they may also be effective for the treatment of ocular symptoms is inconsistent [68–70].