Therapy for ocular allergy has shown significant progress in recent years. Topical antihistamine/mast cell stabilizers currently
available provide a rapid relief of the primary symptoms of allergy, and the newest of these displays a duration of action
that permits once-daily dosing for most allergy sufferers.1
These drugs act both directly (by interfering with the action of histamine released by conjunctival mast cells in response
to allergen exposure) and indirectly (by reducing the ability of allergens to stimulate histamine release) to attenuate allergic
signs and symptoms.
Despite these improvements, many patients with chronic ocular allergies, particularly those with both seasonal and perennial
allergy, do not have a full response to antihistamine therapy and so require anti-inflammatory agents such as topical non-steroidals
or corticosteroids. Thus a major focus of current and future anti-allergic drug development is to identify therapies to address
this unmet need.
Chronic allergy differs from the more acute forms in that it is primarily mediated by cellular factors, and is dependent upon
the activity of immune cells such as basophils and eosinophils that have infiltrated the conjunctiva over the course of prolonged
Increased prevalence of chronic atopic diseases such as allergic conjunctivitis in recent years is also believed to result
from the 'modern lifestyle' that includes exposure to exacerbating agents such as air pollutants and volatile chemicals. Pollutants
and allergens act to prime the immune response, while at the same time they promote a breakdown of the epithelial barriers
that function as the first line of ocular surface defence. This combination acts to accelerate the process of immune cell
infiltration and ocular surface damage that is the hallmark of chronic allergy.3
Patients who display poor or incomplete response to antihistamine therapy appear to fall into two groups: those with chronic
allergies and breakthrough seasonal allergies. Patients in the first group are those with the combination of seasonal and
perennial ocular allergies; for these patients, it is always allergy season. The second group exhibits robust responses to
seasonal allergens, so that on days with particularly high pollen levels they present an allergic response that simply overwhelms
the ability of any topical antihistamine to suppress.
Both patient types are subject to exacerbation of their allergies by environmental pollutants such as auto exhaust and industrial
haze, and both show recruitment of immune cells to the conjunctiva. With continued allergen exposure, these examples of chronic
allergic conjunctivitis evolve into a pathologic condition dominated by ocular surface inflammation. The goal of any new therapy
is to 'calm' the conjunctiva, allow the recruited cells time to dissipate and, at the same time, reduce the inflammatory features
of this 'late phase' response.