Nedocromil sodium and levocabastine reduce the symptoms of conjunctival allergen challenge by different mechanisms

Background: Nedocromil sodium and levocabastine are widely used for the tre atment of ocular allergy, but their mechanisms of action are unclear. Objec tive: We sought to compare the efficacy and mechanisms of action of nedocro mil sodium and levocabastine in reducing conjunctival symptoms after ocular allergen challenge. Methods: We performed a double-blind, placebo-controlled study in which 48 subjects were randomized to 3 groups to receive nedocromil sodium (2%), lev ocabastine (0.05%), or placebo eye drops twice daily for 2 weeks before ocu lar challenge with 10 muL of ryegrass extract. Symptom and tear histamine a nd PGD(2) concentrations were determined before challenge and at 10, 20, 30 , 60, 180, and 360 minutes after challenge. Bulbar biopsy specimens were ta ken at 6 and 24 hours after challenge to assess conjunctival inflammatory c ell numbers, adhesion molecule expression, and mast cell-associated IL-4, I L-5, IL-6, IL- 13, and TNF-alpha levels. Results: Both drugs significantly reduced total symptom scores (P < .05) at all times after challenge compared with placebo. Itching, hyperemia, and l acrimation were most affected. Nedocromil sodium treatment reduced tear con centrations of histamine (by 77%) and PGD(2) (by 70%) at 30 minutes after c hallenge (both P < .05). In biopsy specimens nedocromil sodium reduced the number of 3H4-positive mast cells (purportedly the secreted form of IL-4) b y 49% at 6 hours and 59% at 24 hours (both P < .05). Levocabastine reduced intercellular adhesion molecule 1 expression by 52% at 6 hours and 45% at 2 4 hours (both P < .05). Conclusion: Nedocromil sodium and levocabastine both reduced the conjunctiv al symptoms after ocular allergen challenge but appeared to work by differe nt mechanisms. Nedocromil sodium reduced mast cell function, whereas levoca bastine appeared to have primarily antihistaminic actions, although it also reduced the expression of intercellular adhesion molecule 1.