Comparison of novel lipid-based eye drops with aqueous eye drops for dry eye: a multicenter, randomized controlled trial

Abstract

Background: Dry eye may be caused or exacerbated by deficient lipid secretion. Recently, lipid-containing artificial tears have been developed to alleviate this deficiency. Our study compared the efficacy, safety, and acceptability of lipid-containing eye drops with that of aqueous eye drops.

Methods: A non-inferiority, randomized, parallel-group, investigator-masked multicenter trial was conducted. Subjects with signs and symptoms of dry eye were randomized to use one of two lipid-containing artificial tears, or one of two aqueous artificial tears. Subjects instilled assigned drops in each eye at least twice daily for 30 days. The primary efficacy analysis tested non-inferiority of a preservative-free lipid tear formulation (LT UD) to a preservative-free aqueous tear formulation (AqT UD) for change in Ocular Surface Disease Index (OSDI) score from baseline at day 30. Secondary measures included OSDI at day 7, tear break-up time (TBUT), corneal and conjunctival staining, Schirmer's test, acceptability and usage questionnaires, and safety assessments.

Results: A total of 315 subjects were randomized and included in the analyses. Subjects reported instilling a median of three doses of study eye drops per day in all groups. At days 7 and 30, all groups showed statistically significant improvements from baseline in OSDI (P<0.001) and TBUT (P≤0.005). LT UD was non-inferior to AqT UD for mean change from baseline in OSDI score at day 30. No consistent or clinically relevant differences for the other efficacy variables were observed. Acceptability was generally similar across the groups and there was a low incidence of adverse events.

Conclusion: In this heterogeneous population of dry eye subjects, there were no clinically significant differences in safety, effectiveness, and acceptability between lipid-containing artificial tears and aqueous eye drops. The results suggest that lipid-containing artificial tears can be used to counteract lipid deficiency that is common in dry eye, without compromising overall acceptability.

Keywords: Ocular Surface Disease Index; artificial tears; dry eye; emulsion; tear break-up time; tear film lipid layer.

Figures

Figure 1

Mean OSDI scores at baseline and days 7 and 30 of study treatment. Notes: OSDI scores were assessed on a scale of 0–100, where a higher score represents a more severe disease status. P<0.001 for LT UD, AqT UD, LT MD, and AqT MD at day 7 and day 30 compared with baseline; error bars represent SEM. Abbreviations: LT UD, preservative-free unit-dose lipid tear formulation; AqT UD, preservative-free unit-dose aqueous tear formulation; LT MD, preserved multidose lipid tear formulation; AqT MD, preserved multidose aqueous tear formulation; OSDI, Ocular Surface Disease Index; SEM, standard error mean.

Figure 2

Mean change in OSDI scores at day 30 by baseline OSDI score. Notes: OSDI scores ≥18–32 were grouped as mild/moderate; scores >32–65 were grouped as severe. P=0.004 for LT UD compared with LT MD in the mild/moderate group; error bars represent SEM. Abbreviations: LT UD, preservative-free unit-dose lipid tear formulation; AqT UD, preservative-free unit-dose aqueous tear formulation; LT MD, preserved multidose lipid tear formulation; AqT MD, preserved multidose aqueous tear formulation; OSDI, Ocular Surface Disease Index; SEM, standard error mean.

Figure 3

Mean TBUT at baseline and days 7 and 30 of study treatment. Notes: The eye with the shorter average TBUT at baseline for each subject was used in the analysis. P≤0.005 for LT UD, AqT UD, LT MD, and AqT MD at day 7 and day 30 compared with baseline; error bars represent the SEM. Abbreviations: LT UD, preservative-free unit-dose lipid tear formulation; AqT UD, preservative-free unit-dose aqueous tear formulation; LT MD, preserved multidose lipid tear formulation; AqT MD, preserved multidose aqueous tear formulation; TBUT, tear break-up time; SEM, standard error mean.

Figure 4

Mean Schirmer’s score at baseline and days 7 and 30 of study treatment. Notes: Schirmer’s score was measured for 5 minutes (with anesthesia). P≤0.01 for LT UD at day 7 and day 30 compared with baseline; P<0.04 for LT MD at day 7 compared with baseline; P<0.01 for LT MD at day 30 compared with baseline; P≤0.001 for AqT UD at day 7 and day 30 compared with baseline; P=0.004 for AqT MD at day 30 compared with baseline; error bars represent SEM. Abbreviations: LT UD, preservative-free unit-dose lipid tear formulation; AqT UD, preservative-free unit-dose aqueous tear formulation; LT MD, preserved multidose lipid tear formulation; AqT MD, preserved multidose aqueous tear formulation; SEM, standard error mean.

Figure 5

Acceptability of study treatment at day 30 of study treatment. Notes: Acceptability was assessed with a 5-item questionnaire, scored on a visual analog scale of 0–100, with 0 representing minimal acceptability and 100 representing maximum acceptability. Abbreviations: LT UD, preservative-free unit-dose lipid tear formulation; AqT UD, preservative-free unit-dose aqueous tear formulation; LT MD, preserved multidose lipid tear formulation; AqT MD, preserved multidose aqueous tear formulation.