Unmet needs spurs research

May 1, 2012

Therapy for chronic ocular allergy a major focus for drug development

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

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.

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.