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Purpose: To study the efficacy and toxic effects of bepotastine besilate 1.5% preservative-free (BB-PF) and olopatadine 0.2% BAK-preserved (OL-BAK) drops on the ocular surface of patients with allergic conjunctivitis.Patients and Methods: Ninety-seven patients with allergic conjunctivitis diagnosis participated in a prospective, multicenter, randomized, double-blind, controlled, parallel-group clinical trial. Patients received either BB-PF (n=48) or OL-BAK (n=49), both administered once daily in the morning. The patients were followed for 60 days. Ocular itching was the primary outcome measure. Secondary outcomes included ocular symptoms, signs, and non-ocular symptoms associated with rhinoconjunctivitis. Conjunctival impression cytology (CIC) was performed to evaluate histopathological changes related to the toxic effects of preservatives.Results: BB-PF treatment was associated with a 1.30 more probability of diminished ocular itching than OL-BAK (odds ratio (OR)=1.30; 95% CI=(0.96– 1.7); p=0.086). No statistically significant differences were found between treatments in the resolution of other ocular symptoms or signs, except for tearing, which was superior in the BB-PF (OR=1.37; 95% (1.26– 1.47); p< 0.0001). BB-PF was superior in terms of the resolution of rhinorrhea (p=0.040) and nasal itching (p=0.037). After 60 days of treatment, the BB-PF group exhibited 2.0 times higher probability of having a lower Nelson scale score compared to the OL-BAK group (OR=2.00; 95% CI=(1.19– 3.34); p=0.010).Conclusion: Both medications presented a similar efficacy in terms of the resolution of ocular signs and symptoms associated with ocular conjunctivitis. BB-PF is superior in the resolution of non-ocular symptoms and safer for the ocular surface than OL-BAK. [ABSTRACT FROM AUTHOR]