Allergic conjunctivitis future or investigational therapies

Emerging therapies for allergic conjunctivitis include immunomodulators as well as evaluation of novel enzymatic targets.

• They are capable of inducing local immunosuppression by blocking Th2 lymphocyte proliferation and IL-2 production and reducing eosinophils via inhibition of IL-5.
• Topical ^[1] and systemic cyclosporine a (CsA) ^[2] have been suggested in the treatment of severe atopic keratoconjunctivitis.
• Use of CsA appears to be safe and can eliminate the need/dependence of steroids.
• Others calcineurin inhibitors that appears to be well tolerated by patients with severe atopic blepharoconjunctivitis^[3] and severe atopic keratoconjunctivitis are tacrolimus and pimecrolimus^[4].

• Mapracorat is a novel selective agonist of the glucocorticoid receptor, resulting in a lower potential for side effect.
• In vitro, it inhibited migration and IL-8 release from eosinophils and the secretion of IL-6, IL-8, CCL5/RANTES, and TNF-α from a human mast cell line with equal potency as dexamethasone, but it was less potent in inducing annexin I and CXCR4 expression on the human eosinophils.
• Animal model of allergic conjunctivitis demonstrated mapracorat was similar to dexamethasone eye drops in analogous reduction of clinical symptoms and conjunctival eosinophil. Hence,studies suggest this compound as a candidate for clinical trials of ocular allergy.

• It is a biological engineered molecule, targeting the Cε3 domain of the IgE molecule. It binds with free IgE and prevents its attachment to high-affinity receptor (FcεRI) on mast cells, basophils and dendritic cells. An IgE-anti-IgE complex is formed, lowering free IgE^[6].
• Omalizumab has been established for use in asthma^[7] ,urticaria and and rhinitis^[8].
• Clinical trials are needed to asses its real impact in ocular allergies.

• A novel target spleen tyrosine kinase (Syk) regulates the phosphorylation of phospholipase-C, phosphatidylinositol-3 kinase and protein kinase which mediate histamine release. Hence, studies will focus Syk inhibitors.
• Janus protein kinase-3 is involved in the activation and proliferation of T-cells. Thus, novel inhibitors of JAK-3 may be an effective therapy.

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