Can the optimum artificial tear treatment for dry eye disease be predicted from presenting signs and symptoms?

Published:August 12, 2017DOI:


      • In a general dry eye population, the artificial tears tested performed similarly.
      • Artificial tears provide more than transient relief to symptoms, with improvements still evident after 4 months of use.
      • Artificial tears aid in breaking the vicious dry eye disease cycle.
      • Osmolarity balanced drops preferred by those with low baseline tear volume.
      • Lipisomal spray preferred treatment by those with baseline lipid layer deficiency.



      To assess dry eye treatment with four preservative-free dry eye artificial tear treatments to facilitate evidence-based prescribing.


      A randomised, single masked crossover trial of Clinitas Soothe, Hyabak, Tears Again and TheraTears artificial tears was conducted on 50 symptomatic dry eye patients, aged 60.8 ± 14.2 years. At baseline and after trialling each treatment for 4 weeks, signs and symptoms were assessed using the Ocular Surface Disease Index (OSDI), non-invasive tear break-up time, fluorescein tear break-up time, tear meniscus height (TMH), Phenol Red test, lid-parallel conjunctival folds (LIPCOF), ocular surface staining, and lipid layer grading and osmolarity (baseline visit only).


      OSDI (p = 0.002), LIPCOF (p = 0.014) and conjunctival staining (p< 0.001) significantly improved from baseline, however, the impact of each dry eye treatment on ocular symptoms and signs was similar. Clinitas Soothe and Hyabak were preferred by 34%/30% of participants, but only subjective comparison with the other drops influenced this choice. TheraTears was preferred (by 24%) by those with a lower baseline tear volume (p = 0.01) and Tears Again (by 12%) by those with a thinner baseline lipid layer (p = 0.04). The treatment that afforded the greatest improvement in clinical signs did not consistently match each individual’s preferred treatment.


      If prescribed to a general dry eye population, the artificial tears performed similarly, improving symptoms and conjunctival signs. However, osmolarity balanced artificial tears were the preferred treatment in individuals with low baseline tear volume and lipisomal spray for individuals with a baseline lipid layer deficiency.


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        • Heiligenhaus A.
        • Koch J.
        • Kruse F.
        • Schwarz C.
        • Waubke T.
        Diagnosis and differentiation of dry eye disorders.
        Ophthalmologe. 1995; 92: 6-11
        • Johnson M.E.
        • Murphy P.J.
        • Boulton M.
        Effectiveness of sodium hyaluronate eyedrops in the treatment of dry eye.
        Graef. Arch. Clin. Exp. 2006; 244: 109-112
        • Lee J.H.
        • Ahn H.S.
        • Kim E.K.
        Efficacy of sodium hyaluronate and carboxymethylcellulose in treating mild to moderate dry eye disease.
        Cornea. 2011; 30: 175-179
        • Mengher L.
        • Pandher K.
        • Bron A.
        • Davey C.
        Effect of sodium hyaluronate (0.1%) on break-up time (NIBUT) in patients with dry eyes.
        Br. J. Ophthalmol. 1986; 70: 442-447
        • Inoue M.
        • Katakami C.
        The effect of hyaluronic acid on corneal epithelial cell proliferation.
        Invest. Ophthalmol. Visual Sci. 1993; 34: 2313-2315
        • Gomes J.
        • Amankwah R.
        • Powell-Richards A.
        • Dua H.
        Sodium hyaluronate (hyaluronic acid) promotes migration of human corneal epithelial cells in vitro.
        Br. J. Ophthalmol. 2004; 88: 821-825
        • Peppas N.A.
        • Buri P.A.
        Surface: interfacial and molecular aspects of polymer bioadhesion on soft tissues.
        J. Control Release. 1985; 2: 257-275
        • Garrett Q.
        • Simmons P.A.
        • Xu S.
        • Vehige J.
        • Zhao Z.
        • Ehrmann K.
        • Willcox M.
        Carboxymethylcellulose binds to human corneal epithelial cells and is a modulator of corneal epithelial wound healing.
        Invest. Ophthalmol. Vis. Sci. 2007; 48: 1559-1567
        • Craig J.P.
        • Purslow C.
        • Murphy P.J.
        • Wolffsohn J.S.
        Effect of a liposomal spray on the pre-ocular tear film.
        Contact Lens Ant. Eye. 2010; 33: 83-87
        • Dausch D.
        • Lee S.
        • Dausch S.
        • Kim J.
        • Schwert G.
        • Michelson W.
        Comparative study of treatment of the dry eye syndrome due to disturbances of the tear film lipid layer with lipid-containing tear substitutes Efficacy of lipid-containing tear substitutes.
        Klin. Monatsbl. Augenheilkd. 2006; 223: 974-983
        • Pult H.
        • Gill F.
        • Riede-Pult B.H.
        Effect of three different liposomal eye sprays on ocular comfort and tear film.
        Contact Lens Ant. Eye. 2012; 35: 203-207
      1. Methodologies to diagnose and monitor dry eye disease: Report of the Diagnostic Methodology Subcommittee of the International Dry Eye WorkShop. Ocular Surf. 5 (2007) 108-152.

        • Gilbard J.P.
        Dry Eye: pharmacological approaches effects, and progress.
        CLAO J. 1996; 22: 141-145
        • Lee S.
        • Dausch S.
        • Maierhofer G.
        • Dausch D.
        A new therapy concept for the treatment of dry eye?the usefulness of phospholipid liposomes.
        Klin. Monatsbl. Augenheilkd. 2004; 221: 825-836
        • Brignole F.
        • Pisella P.-J.
        • Dupas B.
        • Baeyens V.
        • Baudouin C.
        Efficacy and safety of 0.18% sodium hyaluronate in patients with moderate dry eye syndrome and superficial keratitis.
        Graef. Arch. Clin. Exp. 2005; 243: 531-538
        • Aragona P.
        • Papa V.
        • Micali A.
        • Santocono M.
        • Milazzo G.
        Long term treatment with sodium hyaluronate-containing artificial tears reduces ocular surface damage in patients with dry eye.
        Br. J. Ophthalmol. 2002; 86: 181-184
        • Evangelista M.
        • Koverech A.
        • Messano M.
        • Pescosolido N.
        Comparison of three lubricant eye drop solutions in dry eye patients.
        Optom. Vis. Sci. 2011; 88: 1439-1444
        • Baeyens V.
        • Bron A.
        • Baudouin C.
        Vismed Hylovis Study Group. Efficacy of 0.18% hypotonic sodium hyaluronate ophthalmic solution in the treatment of signs and symptoms of dry eye disease.
        J. Francais D’Ophtalmol. 2012; 35: 412-419
        • Barabino S.
        • Rolando M.
        • Nardi M.
        • Bonini S.
        • Aragona P.
        • Traverso C.E.
        The effect of an artificial tear combining hyaluronic acid and tamarind seeds polysaccharide in patients with moderate dry eye syndrome: a new treatment for dry eye.
        Eu. J. Ophthalmol. 2014; 25: 173-178
        • Simmons P.A.
        • Carlisle-Wilcox C.
        • Chen R.
        • Liu H.X.
        • Vehige J.G.
        Efficacy, safety, and acceptability of a lipid-based artificial tear formulation: a randomised controlled, multicentre trial.
        Clin. Ther. 2015; 37: 858-868
        • Simmons P.A.
        • Liu H.
        • Carlisle-Wilcox C.
        • Vehige J.G.
        Efficacy and safety of two new formulations of artificial tears in subjects with dry eye disease: a 3-month multicentre, active controlled, randomized trial.
        Clin. Ophthalmol. 2015; 9: 665-675
        • Perez-Balbuena A.L.
        • Ochoa-Tabares J.C.
        • Belalcazar-Rey S.
        • Urzua-Salinas C.
        • Saucedo-Rodriguez L.R.
        • Velasco-Ramos R.
        • Suárez-Sánchez R.G.
        • Rodríguez-Carrizalez A.D.
        • Oregón-Miranda A.A.
        Efficacy of a fixed combination of 0.09% xanthan gum/0.1% chondroitin sulfate preservative free vs polyethylene glycol/propylene glycol in subjects with dry eye disease: a multicenter randomized controlled trial.
        BMC Ophthalmol. 2016; 16164
        • Schiffman R.M.
        • Christianson M.D.
        • Jacobsen G.
        • Hirsch J.D.
        • Reis B.L.
        Reliability and validity of the ocular surface disease index.
        Arch. Ophthalmol. 2000; 118: 615-621
        • Höh H.
        • Schirra F.
        • Kienecker C.
        • Ruprecht K.W.
        Lid-parallel conjunctival folds are a sure diagnostic sign of dry eye.
        Ophthalmologe. 1995; 92: 802-808
        • Jones L.
        • Downie L.E.
        • Korb D.
        • Benitez-del-Castillo J.B.
        • Dana R.
        • Deng S.X.
        • Dong P.N.
        • Geerling G.
        • Yudi Hida R.
        • Liu Y.
        • Yul Seo K.
        • Tauber J.
        • Wakamatsu T.H.
        • Xu J.
        • Wolffsohn J.S.
        • Craig J.P.
        TFOS DEWS II management and therapy report.
        Ocular Surf. 2017; 15: 575-628
        • Armstrong R.A.
        • Eperjesi F.
        • Gilmartin B.
        The application of analysis of variance (ANOVA) to different experimental designs in optometry.
        Ophthal. Physiol. Opt. 2002; 22: 248-256
        • Wolffsohn J.S.
        • Arita R.
        • Chalmers R.
        • Djalilian A.
        • Dogru M.
        • Dumbleton K.
        • Gupta P.
        • Karpecki P.
        • Lazreg S.
        • Pult H.
        • Sullivan B.D.
        • Tomlinson A.
        • Tong L.
        • Villani E.
        • Yoon K.-C.
        • Jones L.
        • Craig J.P.
        TFOS DEWS II diagnostic methodology report.
        Ocular Surf. 2017; 15: 539-574
        • Yang C.X.
        • Cao M.L.
        • Liu H.
        • He Y.Q.
        • Xu J.
        • Du Y.
        • Liu Y.W.
        • Wang W.J.
        • Cui L.
        • Hu J.J.
        • Gao F.
        The high and low molecular weight forms of hyaluronan have distinct effects on CD44 clustering.
        J. Biol. Chem. 2012; 51: 43094-43107
        • Condon P.I.
        • McEwen C.G.
        • Wright M.
        • Mackintosh G.
        • Prescott R.J.
        • McDonald C.
        Double blind randomised, placebo controlled, crossover, multicentre study to determine the efficacy of a 0.1%(w/v) sodium hyaluronate solution (Fermavisc) in the treatment of dry eye syndrome.
        Br. J. Ophthalmol. 1999; 83: 1121-1124
        • Zhu S.-N.
        • Nölle B.
        • Duncker G.
        Expression of adhesion molecule CD44 on human corneas.
        Br. J. Ophthalmol. 1997; 81: 80-84
        • Entwistle J.
        • Hall C.L.
        • Turley E.A.
        HA receptors: regulators of signalling to the cytoskeleton.
        J. Cell. Biochem. 1996; 61: 569-577
        • Nishida T.
        • Nakamura M.
        • Mishima H.
        • Otori T.
        Hyaluronan stimulates corneal epithelial migration.
        Exp. Eye Res. 1991; 53: 753-758
        • Wysenbeek Y.
        • Loya N.
        • Sira I.B.
        • Ophir I.
        • Shaul Y.B.
        The effect of sodium hyaluronate on the corneal epithelium. An ultrastructural study.
        Invest. Ophthalmol. Vis. Sci. 1988; 29: 194-199
        • Aragona P.
        • Di Stefano G.
        • Ferreri F.
        • Spinella R.
        • Stilo A.
        Sodium hyaluronate eye drops of different osmolarity for the treatment of dry eye in Sjögren’s syndrome patients.
        Br. J. Ophthalmol. 2002; 86: 879-884
        • Hay E.M.
        • Thomas E.
        • Pal B.
        • Hajeer A.
        • Chambers H.
        • Silman A.
        Weak association between subjective symptoms of and objective testing for dry eyes and dry mouth: results from a population based study.
        Ann. Rheum. Dis. 1998; 57: 20-24
        • Liu Z.
        • Pflugfelder S.C.
        Corneal surface regularity and the effect of artificial tears in aqueous tear deficiency.
        Ophthalmology. 1999; 106: 939-943
        • Lemp M.A.
        The mucin-deficient dry eye.
        Int. Ophthalmol. Clin. 1973; 13: 185-189
        • Lenton L.
        • Albietz J.
        Effect of carmellose-based artificial tears on the ocular surface in eyes after laser in situ keratomileusis.
        J. Refract. Surg. 1998; 15: S227-231
        • Tseng S.C.
        • Hirst L.W.
        • Maumenee A.E.
        • Kenyon K.R.
        • Sun T.-T.
        • Green W.R.
        Possible mechanisms for the loss of goblet cells in mucin-deficient disorders.
        Ophthalmology. 1984; 91: 545-552
        • Murube J.
        • Rivas L.
        Impression cytology on conjunctiva and cornea in dry eye patients establishes a correlation between squamous metaplasia and dry eye clinical severity.
        Eur. J. Ophthalmol. 2003; 13: 115-127
        • Baudouin C.
        • Cochener B.
        • Pisella P.-J.
        • Girard B.
        • Pouliquen P.
        • Cooper H.
        • Creuzot-Garcher C.
        Randomized: phase III study comparing osmoprotective carboxymethylcellulose with sodium hyaluronate in dry eye disease.
        Eur. J. Ophthalmol. 2011; 22: 751-761
        • Gilbard J.P.
        • Rossi S.R.
        An electrolyte-based solution that increases corneal glycogen and conjunctival goblet-cell density in a rabbit model for keratoconjunctivitis sicca.
        Ophthalmology. 1992; 99: 600-604
        • Lozato P.
        • Pisella P.
        • Baudouin C.
        The lipid layer of the lacrimal tear film: physiology and pathology.
        J. Fr. Ophtalmologie. 2001; 24: 643-658
        • Bron A.
        • Tiffany J.
        • Gouveia S.
        • Yokoi N.
        • Voon L.
        Functional aspects of the tear film lipid layer.
        Exp. Eye Res. 2004; 78: 347-360