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.