Clinical assessments
The TOSS was used during both the CAC and EEC exposures. This score was first described10 as the sum of four conjunctival symptom scores: itching, redness, chemosis, and tearing (range: 0-13). It was evaluated after instillation of the allergen on one side, with the other eye serving as a negative control after instillation of the physiological serum. A slit lamp examination was used to score redness and chemosis only. Itching was assessed by the patient using a 5-point severity scale from 0 (none) to 4 (very severe: incapacitating itch with irresistible urge to rub), with 1=mild (intermittent tickling sensation), 2=moderate (continual awareness but without the desire to rub), and 3=severe (continual awareness with the desire to rub). For ocular redness, ratings were collected for the nasal and temporal area of each eye and averaged by the study physician using a 4-point severity score (0=absent, 1=mild, 2=moderate, 3=severe). Tearing was also rated by the physician using a 4-point severity score (0=absent; 1=mild, eyes feel slightly watery; 2=moderate, blows nose occasionally; and 3=severe, tears rolling down cheeks). Chemosis was rated by the study physician as follows: 0=absent, 1=mild (detectable with slit lamp, conjunctiva separated from sclera), 2=moderate (visually evident, raised conjunctiva, especially at the limbal area), and 3=severe (ballooning of conjunctiva). The patient left the EEC when the mean TOSS of both eyes was ≥ 5.
Safety monitoring of pulmonary function was performed by clinical survey. The Total Nasal Symptom Score (TNSS) and portable spirometry were performed every 20 minutes during exposure. Early asthma response was defined as a drop in the forced expiratory volume in 1 second (FEV1) of 20%. Patients with this asthma response during allergen exposures were discharged. At the end of an exposure, all patients were treated as needed with topical antihistamines, eye drops, and oral second generation H1-antihistamines according to the persistence and severity of the conjunctival or rhinitis symptoms. When an early asthmatic response occurred, patients remained under supervision for 6 hours. Thereafter, they were discharged with a rescue therapy kit containing oral antihistamines, topical mast cell stabilizers, and short-acting beta 2 agonist inhaler.
This study was approved by an independent ethics committee and was conducted according to Good Clinical Practice (GCP) standards using the guidance documents and practices offered by the International Conference on Harmonization (ICH) and European directive 2001/20/CE. The study was registered at ClinicalTrials.gov under number NCT04641130.