Table 2.
Representative Clinical Studies Performed with Lipid-Based Products
| Lipid-based product family | Brand name | Main components (lipid/oil components in bold face) | Study design | Study main results | Ref. |
|---|---|---|---|---|---|
| Liposome | Tears Again® | Liposomal soy lecithin, ethanol, phenoxyethanol, vitamin A palmitate, vitamin E | Multicenter, double-masked, randomized trial; 80 healthy and DED patients total; single application to 1 eye versus a competitor eye spray to the contralateral eye | Improved ocular comfort and tear film stability compared with competitor spray | 48 |
| Efficacy assessments: ocular comfort and TBUT | |||||
| Liposome | Tears Again | Same as above | Prospective, randomized, double-masked trial; 22 healthy and borderline dry eye patients total; single application to 1 eye versus a saline spray to the contralateral eye | Improved ocular comfort, lipid layer thickness, and tear film stability in normal eyes for ≥1 h postadministration compared with saline | 42 |
| Efficacy assessments: ocular comfort, lipid layer thickness and TBUT | |||||
| Liposome | Tears Again | Same as above | Randomized trial of 24 normal and 24 dry eye patients; single application of spray, AT or both interventions | Largest improvements in ocular comfort scores at 1 h with combination therapy; no change in Strehl ratios postinstillation with any intervention | 49 |
| Efficacy assessments: ocular comfort scores and Strehl ratios for higher-order aberrations | |||||
| Liposome | Tears Again | Same as above | Prospective, controlled, open-label observational study; 72 patients total with seasonal allergic rhinoconjunctivitis Efficacy assessments: conjunctival symptom scores and QoL questionnaire |
Noninferior symptom reduction and favorable tolerability vs conventional cromoglycate treatment when given in combination with liposomal nasal spray | 41 |
| Liposome | Lacrisek® ofta mono | Vitamin A palmitate, vitamin E, hydrogenated phospholipids | Prospective, open-label, comparative study; 15 patients with moderate evaporative dry eye; single instillation in one eye | Improvements in interblink interval, TBUT, and tear film evaporation rate were greater with Lacrisek ofta mono vs Artelac® Rebalance (polyethylene glycol and hyaluronic acid) from 10 min after instillation until the end of the assessment period (min 60) | 50 |
| Efficacy assessments: interblink interval, TBUT, tear film evaporation | |||||
| Anionic emulsion | Refresh Endura® | 1% glycerin, 1% polysorbate 80, castor oil | Comparative, nonrandomized open-label study; 5 normal and 10 ATD patients; single instillation | Rapid restructuring of the lipid film, improved mean spread time, and the majority of patients did not experience discomfort at instillation of the emulsion | 60 |
| Efficacy assessments: tear interference imaging | |||||
| Anionic emulsion | Under development | Same as above | Open-label, randomized pilot study; 5 normal and 10 DED patients; single instillation in both eyes | Residence time of ≥1–4 h postinstillation, clinically significant improvements in tear film stability, and a significant decrease in ocular symptoms | 61 |
| Efficacy assessments: tear residence time, TBUT, ocular symptomology | |||||
| Anionic emulsion | Under development (Allergan) | Same as above | Randomized, parallel-group, longitudinal, investigator-masked trial; 53 patients with mild-to-moderate DED; instillation 3 times a day for 30 days | Greater reduction in tear evaporation and greater improvements in tear film quality with the emulsion than HPMC at 30 days | 62 |
| Efficacy assessments: lipid film stability and tear evaporation | |||||
| Anionic emulsion | Optive Plus® | Carboxymethylcellulose, polysorbate 80, glycerol, l-carnitine, erythritol, boric acid, castor oil, PURITE® (stabilized oxychloro complex) | Prospective, multicenter, noninterventional study; 1209 DED patients; instillation according to package instructions for 4 weeks | Improvements in dry eye severity, TBUT and Schirmer's scores observed at 4 weeks | 63 |
| Efficacy assessments: DED symptoms, TBUT and Schirmer's scores | |||||
| Anionic emulsion | Emustil | Soybean oil 7%, egg yolk phospholipids 3% | Longitudinal, randomized, 3-arm, parallel, investigator-masked trial; 75 patients with mild-to-moderate DED total; administration 4 times daily for 90 days | Improved tear stability and decreased osmolarity and corneal staining compared with HA or HPMC. No significant modification in tear turnover rate for all tested products | 34 |
| Efficacy assessments: symptoms, tear film evaporation, tear turnover rate, TBUT, tear osmolarity, and corneal staining | |||||
| Anionic emulsion | Emustil | Same as above | Three-month, controlled, randomized, single-masked study in 71 moderate DED patients Efficacy assessments: Total CFS score and TBUT at 1- and 3-month time points |
VAS score statistically improved at Month 3. Significantly inferior reduction in tear film osmolarity compared with Cationorm | 64 |
| Anionic emulsion | Systane Balance | Propylene glycol, hydroxypropyl-guar, borate, sorbitol, dimyristoyl phosphatidylglycerol, mineral oil, polyquaternium-1 | Open-label 4-week trial; 49 mild-to-moderate MGD patients | After switching to study medication, clinically significant improvements in visual acuity remained statistically similar to previous therapy; study drug significantly improved corneal staining and TBUT and reduced habitual therapy use; patients preferred the study medication to their habitual therapy | 66 |
| Efficacy assessments: QoL, visual acuity, meibomian gland expression and dropout, TBUT and corneal staining | |||||
| Anionic emulsion | Systane Balance | Same as above | Randomized, parallel-group, controlled, investigator-masked comparison trial; 49 patients with lipid-deficient DED; administered 4 times daily for 4 weeks | Improved tear film stability, ocular surface staining, and meibomian gland functionality at 4 weeks when compared with saline | 67 |
| Efficacy assessments: noninvasive TBUT, ocular surface staining, goblet cell density, meibomian gland expression, ocular signs and visual acuity | |||||
| Anionic emulsion | Systane Balance | Same as above | Randomized, open-label, parallel-group, single-center, investigator-masked, 1-month study; 115 adult habitual contact lens wearers experiencing CLD symptoms; administered 1 drop 5 min after lens insertion and every 2 h for up to 4 drops daily | Significant improvements in contact lens comfort, wearing time, LWE, and corneal staining in patients switching to Systane Balance from their typical rewetting drops | 65 |
| Efficacy assessments: subjective comfort, contact lens wearing time, LWE grading, and severity of corneal staining | |||||
| Anionic emulsion | Refresh Dry Eye Therapy | Glycerin, 1% polysorbate 80, boric acid, carbomer, castor oil, purified water, PURITE, and sodium hydroxide | Randomized investigator-masked study of 41 dry eye patients; single instillation | Improved lipid layer thickness at 1–15 min postinstillation with emulsion compared with Soothe® (active ingredients: light mineral oil, 1.0%; mineral oil, 4.5%) | 68 |
| Efficacy assessments: symptom questionnaire and lipid layer thickness | |||||
| Anionic emulsion | Under development | 2% castor oil, polyoxyethylene castor oil | Randomized, prospective double-masked, placebo-controlled crossover clinical trial; 20 patients with noninflamed MGD; instillation 6 times daily for 2 periods of 2 weeks each | Significant improvements in symptom scores, tear interference grade, tear evaporation, rose bengal scores, TBUT, and orifice obstruction in oil eye drop periods compared with the placebo periods, with no improvement in fluorescein staining | 69 |
| Efficacy assessments: symptoms, tear interference grade, tear evaporation, fluorescein and rose bengal staining, TBUT, and meibomian gland orifice obstruction | |||||
| Anionic emulsion | Liposic® Ophthalmic Liquid Gel | Medium chain triglycerides, carbomer, cetrimide, sorbitol | Prospective, open-label, randomized, parallel-group, noninferiority 4-week trial; 30 DED patients | Noninferior improvement in symptoms and TBUT, but superior improvements in Schirmer's test at 2 and 4 weeks compared with Systane eye drops; well tolerated | 70 |
| Efficacy assessment: Schirmer's test, TBUT, and symptom assessment | |||||
| Anionic emulsion | Systane Balance | Same as above | Single-center, prospective, open-label, investigator-masked, randomized trial; 26 patients with lipid-deficient and evaporative DED; administered 4 times daily for 3 months | Greater improvements in meibomian gland functionality (MGYLS) and symptoms with combination treatment; no significant safety concerns | 71 |
| Efficacy assessments: meibomian gland function and ocular symptoms | |||||
| Cationic emulsion | Cationorm | 1% mineral oil (heavy and light chains), glycerin, tyloxapol, poloxamer, cetalkonium chloride | Three-month, controlled, randomized, single-masked study in 71 patients with moderate DED | Significant improvement of VAS score from 1 month, significant improvement of TBUT and reduced CFS staining at Month 3. Significant improvement in tear film osmolarity compared with Emustil | 64 |
| Efficacy assessments: total CFS score and TBUT at 1- and 3-month time points | |||||
| Cationic emulsion | Cationorm | Same as above | Randomized, multicenter, open-label, comparative trial; 79 patients with mild-to-moderate DED; administered 4 times daily for 28 days | At Day 7, improvement of the palpebral erythema score and symptoms | 84 |
| Efficacy assessments: TBUT, Schirmer's test, lissamine green staining, CFS, and oculopalpebral examination | At Day 28, greater improvements in TBUT and lissamine green staining were observed with Cationorm vs Refresh (PVA-P). Overall efficacy assessed by the investigators was favorable for Cationorm | ||||
| Cationic emulsion | Cationorm | Same as above | Prospective, multicenter, randomized, single-masked, parallel-group, reference-controlled, 3-month trial; 85 patients with moderate-to-severe DED associated with keratitis or keratoconjunctivitis | Cationorm was noninferior to Vismed® (HA) in improving objective signs but was superior in improving global symptoms score of ocular discomfort with a similar safety profile as Vismed | 85 |
| Efficacy assessment: CFS, TBUT, Schirmer's test and symptoms | |||||
| Others (ointment) | Lacri-Lube® ointment (Allergan) | 55% white petrolatum, 42.5% mineral oil, 2% nonionic lanolin derivatives, 0.5% (w/w) chlorobutanol | Two-way randomized crossover trial; 7 healthy patients; single administration | Improved precorneal residence and total residence time compared with HPMC solution, but associated with blurred vision. Adequate for night-time administration | 89 |
| Efficacy assessments: ointment residence time | |||||
| Others (semifluorinated alkanes) | NovaTears® | Perfluorohexyloctane | Prospective, multicenter, observational 6-week trial; 30 DED patients; instilled 4 times daily in both eyes | Significant beneficial effects in all the relevant parameters tested, with no significant changes in visual acuity or IOP | 98 |
| Efficacy assessments: visual acuity, IOP, Schirmer's test, tear fluid osmolarity, TBUT, corneal staining, meibum secretion, and OSDI |
ATD, aqueous tear deficiency; CFS, corneal fluorescein staining; CLD, contact lens discomfort; DED, dry eye disease; LWE, lid wiper epitheliopathy; MGD, meibomian gland deficiency; MGYLS, meibomian glands yielding liquid secretion; OSDI, ocular surface disease index; PVA-P, polyvinyl alcohol–povidone formulation; QoL, quality of life; SDI, surface disease index; TBUT, tear break-up time; VAS, visual analogue scale; w/w, weight/weight.