Interventions
This was an open, single-center study designed to determine the concentration of airborne Bet v 1 inducing an allergic conjunctivitis response in patients allergic to birch pollen during allergen exposures to birch pollen extracts in the EEC. During the first screening visit, the patient gave informed written consent and underwent the following procedures and assessments: medical history review, skin prick testing to birch pollen allergen (ALK-Abello® ), and a blood draw for specific IgE to birch (Betula verrucose, Phadia ImmunoCap, Thermofisher®). The second screening visit was for an individual conjunctival allergen challenge (CAC) to birch allergen. All responders in the CAC were included in the present study.
The CAC was performed according to the updated EAACI guidelines.1, 11 This procedure consisted of the instillation of 20 µl of diluted birch allergen extract (100 IR lyophilized extract, Stallergenes Greer®) in the inferior-external quadrant of the bulbar conjunctiva in incremented dilutions at 10-min intervals: 3, 6, 12, 25, 50, and 100 IR/ml.11 The clinical response was assessed by the Total Ocular Symptom Score (TOSS) with the same cumulated positivity criteria for the CAC and EEC exposure. If the TOSS was <5 at 10 minutes after each instillation, the test was considered negative. The next concentrated dose was then instilled until a positive response was reached.
Step 1 of the study consisted of two consecutive EEC exposures to the same birch pollen extract (Expo 1 and Expo 2). The primary endpoint of the study was met when 50% of the patients were positive. The main judgment criteria were the amount of Bet v 1 inducing a positive conjunctival response after EEC exposure. In addition, we compared the intensity of the clinical response induced in patients exposed to birch pollens using the TOSS and the mean time to reach a positive ocular response (i.e., TOSS ≥ 5). In step 2, we studied the reproducibility of the allergen exposure. Patients who responded to Expo 1 and Expo 2 were enrolled in step 2 and exposed two additional times on 2 consecutive days (from Expo 3 to Expo 6). Each double EEC exposure test was separated by 7 days.