The overall anti-allergic eye drop market consists of about 25 products developed and approved in the United States (with some marketed abroad) to address the needs of the seasonal allergic conjunctivitis patient population.
The overall anti-allergic eye drop market consists of about 25 products developed and approved in the United States (with some marketed abroad) to address the needs of the seasonal allergic conjunctivitis (SAC) patient population.
For nearly 15 years, we have been treating patients with dual-acting antihistamine/mast cell stabilizers that largely have satisfied clinicians and patients alike. As we learn more about the disease, though, we need to ensure the proper treatment is identified for each patient.
Clinicians have a battery of treatment options available with which to treat patients with SAC. The over-the-counter (OTC) market, once flooded with first-generation antihistamine/vasoconstrictor combination products, now is burgeoning with ketotifen products (Refresh Eye Itch Relief, Allergan; Alaway, Bausch & Lomb; Visine All Day, McNeil Pharmaceuticals; Zyrtec, McNeil Pharmaceuticals; Zaditor, Novartis; and Claritin Eye, Schering-Plough) whose presence has shifted the market indelibly from antihistamine/vasoconstrictor combinations.
Additionally, the indication for all signs and symptoms of allergic conjunctivitis provided patients with a choice previously unavailable in a twice-daily formulation. The product has been reformulated into olopatadine 0.2% (Pataday, Alcon Laboratories), which requires only a once-daily dosing regimen, encouraging compliance in the treatment of ocular itching.
Antihistamine/mast cell stabilizers are not, however, the only method of treating allergic conjunctivitis. Persistent allergy symptoms, particularly the presence of inflammation, may require steroidal intervention. Loteprednol etabonate 0.2% (Alrex, Bausch & Lomb) is indicated for use as a pulse therapy for up to 2 weeks in these cases of allergic conjunctivitis.
Beyond mast cell stabilization
The tear film is the first natural defense that allergens encounter. Artificial barriers, such as goggles or glasses, are useful but often impractical in thwarting allergen penetration to the eye. The next logical point to intercept allergens is at the conjunctival epithelium. Here, allergens can be blocked from traversing the conjunctiva and reaching the mast cell.
Therefore, a potential new target for anti-allergics is this barrier or, more specifically, modulation of it to prevent allergen passage. Allergens carry enzymes on their surface that they use to penetrate the conjunctiva and reach the mast cells.1,2 If therapies could focus on this stage of the allergic process-the induction phase-less allergen might reach the mast cells and the allergic response might be subdued.
Furthermore, combining this action with traditional antihistamine/mast cell stabilizing properties may represent a means of both protection from and treatment of allergy symptoms.
One way to characterize the integrity of the conjunctival epithelium is to measure the expression of key adhesion proteins (zonula occludins, zonula adherins, and E-cadherins). Downregulation of these adhesion proteins can cause weakening of tight junctions, which normally act as a barrier to microorganisms, toxins, and allergens. Reduced staining for tight junction protein 1 (ZO-1) and occludin has been shown following exposure to house dust mite fecal particles.3 These staining techniques may provide a diagnostic tool for researchers to visualize the effect of drugs on epithelial fortification.
A study assessing the integrity of the conjunctival epithelium in normal, non-atopic individuals and atopic patients outside allergy season showed that, even outside allergy season, atopic patients demonstrate suppression of tight junction protein expression, which contributes to disorganization of the conjunctival epithelium.4 This reminds us that part of the pathophysiology of allergy is the weakening of the conjunctival epithelium to allow allergens to pass through more easily as well as to prime the pathway for eosinophil migration to the ocular surface during the allergic late phase.