The Conjunctival Provocation Test Model of Ocular Allergy: Utility for Assessment of an Ocular Corticosteroid, Loteprednol Etabonate

Two studies were conducted using the conjunctival provocation test (CPT) model of ocular allergy. The objective of the first study was to evaluate the sensitivity of the CPT model to a topical corticosteroid. Selected was loteprednol etabonate 0.5%, previously found effective in the treatment of ocular allergy and inflammation. The study was a randomized double-masked, placebo-controlled, paired-comparison of loteprednol etabonate 0.5% (LE), b.i.d. or q.i.d. Sixty subjects who had a minimum pre-determined allergic response received LE in one eye and placebo in the fellow eye for 28 days from Day 7 to Day 35. Antigen challenges were carried out on Days 0, 7 (baseline), 21 and 35. The primary endpoints were interocular differences in itching and mean redness (the average of ciliary, conjunctival and episcleral vessel beds). LE (either b.i.d. or q.i.d.) was significantly more effective than placebo for reducing mean redness and itching. No clinical or statistically significant changes in intraocular pressure were observed. Based upon the results of Study 1, we used the CPT model to aid in the selection of a concentration of loteprednol etabonate for subsequent studies in environmental seasonal allergic conjunctivitis. This was a randomized double-masked, placebo-controlled, paired-comparison of loteprednol etabonate 0.1%, 0.2% and 0.3%, q.i.d. in 88 subjects. The dosing and testing regimen was similar to the first portion of the study. Loteprednol etabonate, 0.1%, 0.2% and 0.3%, was numerically superior to the placebo in reducing mean redness and itching. At the 20-minute post allergen challenge, the 0.1% concentration was significantly superior (p0.05) to the placebo on Visit 4 (2 and 4 hour challenge) in reducing the mean redness; however, LE was only numerically superior in relieving itching. The 0.2% concentration was significantly superior (p0.05) to the placebo in the reduction of mean redness and itching on Visit 3 (Day 21) and in reduction of mean redness on Visit 4 (4 hour challenge). The 0.3% concentration was significantly superior (p0.05) to the placebo in the reduction of mean redness on all visits, and statistically significant in the reduction of itching on Visit 4 (4 hour challenge). While there were some elevations of IOP with LE 0.2%, they were not clinically significant. In conclusion, the CPT model of ocular allergy is useful in the evaluation of corticosteroids. Furthermore, based upon a dose-response study in this model, 0.2% loteprednol etabonate was selected for further evaluation in environmental seasonal allergic conjunctivitis studies.