Advances offer better understanding of allergic diseases, remedies, relief for children
The prevalent allergic conditions in paediatric patients are seasonal and perennial allergic conjunctivitis (SAC/PAC); conditions that are less prevalent in these patients are vernal and atopic keratoconjunctivitis (VKC/AKC).
Dr Pflugfelder explained that in SAC the most recent findings in the early disease of the stage indicate that allergen binds to IgE or conjunctival mast cells and causes degranulation and release of histamine, kinins, prostaglandins and leukotrienes. In the disease's late phase, mast-cell derived cytokines and chemokines promote leukocyte recruitment and retention, and chronic inflammation.
In VKC, like SAC, there is an allergen-mediated component in which pollens bind to mast cells; there is also an adaptive immune component in which allergens bind to dendritic cells in the conjunctiva that activate type 2 helper lymphocytes. These in turn produce cytokines, such as interleukin (IL)-3, IL-5, and IL-13, that mediate other events. In AKC, thymic stromal lymphopoetin is produced by epithelial and dendritic cells that become inflamed and activate type 2 helper T cells, resulting in production of IL-4, IL-5, and IL-13. The mechanisms of these diseases dictate that inhibition of the T cells is key for therapy.
"A number of therapeutic advances have been achieved," claimed Dr Pflugfelder, who is professor, James and Margaret Elkins Chair, Department of Ophthalmology, Baylor College of Medicine, Houston Texas, USA. "We now have an array of antihistamine and mast cell stabilizer drugs, including alcaftadine (Lastacaft, Allergan, Irvine, California, USA), azelastine (Optivar, Meda Pharmaceuticals, Somerset, New Jersey, USA), bepostatine (Bepreve, Bausch + Lomb, Rochester, New York, USA), epinastine (Elestat, Allergan), ketotifen (Zaditor, Novartis Pharmaceuticals, Basel, Switzerland) and olopatadine (Pataday, Alcon Laboratories, Fort Worth, Texas, USA). These drugs block histamine receptors and stabilize the mast cells and they have been approved to relieve itching associated with SAC."
In addition, some patients with severe disease require topical steroids that inhibit a variety of mediators that promote chronic allergic disease. The esterified corticosteroid loteprednol etabonate (Lotemax, Bausch + Lomb) has been approved to treat SAC and has an excellent safety profile with prolonged use. Subtarsal triamcinolone 20 mg injections are safe and effective for treating AKC and VKC that are unresponsive to topical therapy.
Montelukast (Singulair, Merck & Co., Whitehouse Station, New Jersey, USA) is an oral leukotriene receptor antagonist that improves the signs and symptoms of VKC in patients with asthma at a dose of 5 mg/day. Burning, tearing, photophobia and ocular redness improved in 15 days from the start of treatment.
Regarding the key factor of inhibition of T cells, calcineurin inhibitors inhibit activation and cytokine production by CD4+ T cells and significantly improve the conjunctival and corneal disease associated with AKC and VKC. Dr Pflugfelder noted that cyclosporine C administered topically or systemically is effective for AKC and VKC.
Another treatment approach, prosthetic replacement of the ocular surface ecosystem (PROSE, Boston Foundation for Sight), is a specially designed, fluid-filled contact lens that can protect the cornea from damage resulting from irregular lids and the superior tarsal conjunctiva in patients with visionthreatening VKC and AKC.
"This device shields the cornea from the irregularity of the eyelids and can help patients who have severe corneal epithelial disease," he said.
Tacrolimus, oral cyclosporine, administered as a 0.1% suspension on the ocular surface or in a 0.03% ointment applied to the lid margins or in the conjunctival sac can also effectively treat AKC and VKC.
"We now have an improved understanding of immunopathologic mechanisms in these allergic conditions," Dr Pflugfelder concluded. "Seasonal and perennial allergic conjunctivitis involve an innate mast cell response to allergens; the disorders respond to histamine blockers and corticosteroids. AKC and VKC have adaptive T cell components that require calcineurin inhibitors to treat sight-threatening ocular surface disease."