Efficacy, safety, and acceptability of a lipid-based artificial tear formulation: a randomized, controlled, multicenter clinical trial

Abstract

Purpose: Dry eye disease is highly prevalent worldwide, causing discomfort and visual disturbances that can limit basic activities such as reading and driving. Although artificial tears represent first-line therapy, there is a paucity of published controlled clinical trials. The present study compared the efficacy, clinical safety, and acceptability of 2 multicomponent, lipid-based tear formulations (ADV1 and ADV2) to those of an existing lipid-based tear formulation (DET) in patients with signs and symptoms of dry eye disease.

Methods: This 3-month, multicenter, double-masked study was conducted in patients with dry eye symptoms, reduced tear break-up time (TBUT), and ocular surface damage. Patients were randomized to receive 1 of 2 lipid-based tear formulations containing carboxymethylcellulose, glycerin, polysorbate 80, and emulsified lipid (ADV1 or ADV2) or DET, and instilled 1 to 2 drops per eye at least twice daily. The primary end point was the mean change from baseline in Subjective Evaluation of Symptom of Dryness score at day 90 to determine noninferiority of the 2 ADV formulations versus DET. Secondary end points included Ocular Surface Disease Index (OSDI) score, TBUT, ocular surface staining, and tolerability.

Findings: Of 288 randomized patients, 256 completed the study. All 3 groups showed improvement in symptoms, and the 2 lipid-based formulations were noninferior to DET in reducing the severity of symptoms of dryness at 90 days. Of the 3 treatment groups, the ADV2 group had the greatest improvements in TBUT and OSDI. Significant improvements in mean tolerability scores for comfort, soothing, burning/stinging, and discomfort were observed in the ADV2 group versus the DET group at 90 days. Treatment-related adverse events were reported in 13 patients (13.4%) receiving ADV1, 8 (8.4%) receiving ADV2, and 21 (21.9%) receiving DET. Four patients (4.1%) in the ADV1 group and 2 (2.1%) in the ADV2 group discontinued owing to an adverse event compared with 14 (14.6%) receiving DET.

Implications: In these patients with dry eye symptoms, ADV2 was an effective and relatively well-tolerated artificial tear for first-line therapy and should be considered as a treatment option for dry eye, especially in those patients who would benefit from a lipid-based formulation in addition to lubrication. https://ichgcp.net/clinical-trials-registry/NCT01010282.

Keywords: artificial tears; carboxymethylcellulose; dry eye syndrome; lipid layer; osmoprotection; tear film.

Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.