Mechanism of Lipid Release and Clinical Performance of an Advanced Lipid-Containing Artificial Tear Formulation

Abstract

Purpose: : Lipid is an important component of the tear film, and is thought to be deficient in many dry eye patients. An advanced artificial tear formulation (AATF) that contains lipids was developed to deliver both lubricating polymers and lipids to the tear film. This study examined the formulation’s mechanism of lipid release, and its clinical performance.

Methods: : To study lipid release, viscosity was measured before and after dilution of AATF 1:1 with H₂O or saline ranging from 30 to 600 mOsm NaCl. An optical detector (Lumisizer) was used to measured uniformity of the AATF. For clinical performance, AATF was compared with an existing product (Refresh Dry Eye Therapy, DET), which contains 5 times more lipid than AATF, on patients with dry eye signs and symptoms in a controlled, randomized, multi-center clinical trial. Measurements were made on day 1 (baseline) and days 7, 30, 60, and 90. The study endpoints included ocular surface disease index (OSDI^© ) score, symptom of dryness (SESoD) score, TBUT, ocular surface staining, and comfort.

Results: : When diluted, viscosity of AATF decreased proportionally to saline strength. The AATF diluted 1:1 with H₂O lost 51% of its viscosity. AATF diluted 1:1 with 30 to 600 mOsm saline lost 62.7% to 78.0% of its viscosity. In the optical detector, AATF was uniform undiluted or diluted with water, but dilution with saline decreased uniformity, consistent with lipid release. 95 dry eye patients in each of the AATF and DET groups completed the clinical study, and the primary hypothesis of non-inferiority was met: dry eye signs and symptoms improved similarly among groups. AATF was superior to DET in ocular comfort (p=0.019), with less burning/stinging (p=0.007) and discomfort (p=0.011) on instillation. Both AATF and DET significantly increased TBUT for approximately 2 seconds from baseline after 90 days usage (p<0.001).

Conclusions: : This advanced formula was uniform when undiluted or diluted with water. Lipid was released when mixed with saline, consistent with separation of the aqueous and lipid components. This mechanism of action should allow appropriate delivery of lipid to the lipid layer on eye. Clinically, the advanced tear formulation demonstrated improvements in signs and symptoms of dry eye.

Clinical Trial: : http://www.clinicaltrials.gov NCT01010282

Keywords: cornea: tears/tear film/dry eye • clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials