Advances in Therapy

, Volume 18, Issue 5, pp 205–215 | Cite as

Effects of common ophthalmic preservatives on ocular health

  • Robert Noecker


Preservatives are an important component of ophthalmic preparations, providing antimicrobial activity in the bottle and preventing decomposition of active drug. Often underrecognized, however, are the significant cytotoxic effects of preservatives associated with long-term therapy and especially use of multiple preserved drugs. The most common preservatives in ophthalmic preparations for glaucoma and surface eye disease—benzalkonium chloride (BAK), chlorobutanol, sodium perborate, and stabilized oxychloro complex (SOC)—were reviewed. Compared with other preservatives, SOC caused the least amount of damage to rabbit corneal epithelial cells. BAK has demonstrated cytotoxic effects in cell culture, as well as in animal and human studies. Physicians should consider treatment with new-generation preparations containing low-risk preservatives such as SOC, especially in patients receiving multiple ophthalmic medications.


ophthalmic preservatives benzalkonium chloride chlorobutanol SOC sodium perborate 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Schein OD, Hibberd PL, Starck T, Baker AS, Kenyon KR. Microbial contamination of in-use ocular medications.Arch Ophthalmol. 1992;110:82–85.PubMedGoogle Scholar
  2. 2.
    Tripathi BJ, Tripathi RC, Kolli SP. Cytotoxicity of ophthalmic preservatives on human corneal epithelium.Lens Eye Toxicol Res. 1992;9:361–375.Google Scholar
  3. 3.
    Pisella PJ, Fillacier K, Elena PP, Debbasch C, Baudouin C. Comparison of the effects of pre served and unpreserved formulations of timolol on the ocular surface of albino rabbits.Ophthalmic Res. 2000;32:3–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Gasset AR, Ishii Y, Kaufman HE, Miller T. Cytotoxicity of ophthalmic preservatives.Am J Ophthalmol. 1974;78:98–105.PubMedGoogle Scholar
  5. 5.
    Berdy GJ, Abelson MB, Smith LM, George MA. Preservative-free artificial tear preparations. Assessment of corneal epithelial toxic effects.Arch Ophthalmol. 1992;110:528–532.PubMedGoogle Scholar
  6. 6.
    Debbasch C, Rat P, Warnet J-M, De Saint Jean M, Baudouin C, Pisella P-J. Evaluation of the toxici ty of benzalkonium chloride on the ocular surface.J Toxicol Cutan Ocul Toxicol. 2000;19:105–115.Google Scholar
  7. 7.
    Baudouin C. Side effects of antiglaucomatous drugs on the ocular surface.Curr Opin Ophthalmol. 1996;7:80–86.PubMedCrossRefGoogle Scholar
  8. 8.
    Baudouin C. Mechanisms of failure in glaucoma filtering surgery: a consequence of antiglauco matous drugs?Int J Clin Pharmacol Res. 1996;16:29–41.PubMedGoogle Scholar
  9. 9.
    Broadway DC, Grierson I, O’Brien C, Hitchings RA. Adverse effects of topical antiglaucoma medication, I: the conjunctival cell profile.Arch Ophthalmol. 1994;112:1437–1445.PubMedGoogle Scholar
  10. 10.
    Sherwood MB, Grierson I, Millar L, Hitchings RA. Long-term morphologic effects of antiglauco ma drugs on the conjunctiva and Tenon’s capsule in glaucomatous patients.Ophthalmology. 1989;96:327–335.PubMedGoogle Scholar
  11. 11.
    Wilson WS, Duncan AJ, Jay JL. Effect of benzalkonium chloride on the stability of the precorneal tear film in rabbit and man.Br J Ophthalmol. 1975;59:667–669.PubMedCrossRefGoogle Scholar
  12. 12.
    Spickett C.Studies of Cellular Responses to Purite and Other Preservatives. Strathclyde, UK: University of Strathclyde; 2001.Google Scholar
  13. 13.
    Block SS.Disinfection, Sterilization, and Preservation. Malvern, Pa: Lea & Febiger; 1991.Google Scholar
  14. 14.
    Kreiner C. Biochemical aspects of ophthalmic preservatives.Contacto. 1979;Nov:10-14.Google Scholar
  15. 15.
    Grant WM, Schuman JS.Toxicology of the Eye. Springfield, Ill: Charles C Thomas; 1990.Google Scholar
  16. 16.
    Grant R, Ajello M, Vlass E. Salt water or high tech? A look at two new rinsing solutions for contact lenses.Optician. 1996;212:38–41.Google Scholar
  17. 17.
    Masschelein WJ, Rice RG.Chlorine Dioxide. Chemistry and Environmental Impact of Oxychlorine Compounds. Ann Arbor, Mich: Ann Arbor Science Publishers; 1979.Google Scholar
  18. 18.
    Rozen S, Abelson M, Giovanoni A, Welch D. Assessment of the comfort and tolerance of 0.5% carboxymethylcellulose preserved with Purite (Refresh Tears) in dry eye sufferers.Invest Ophthalmol Vis Sci. 1998;39(4):S451.Google Scholar
  19. 19.
    Vaughan JS, Porter DA. A new in vitro method for assessing the potential toxicity of soft contact lens care solutions.CLAO J. 1993;19:54–57.PubMedGoogle Scholar
  20. 20.
    Paugh JR, Brennan NA, Efron N. Ocular response to hydrogen peroxide.Am J Optom Physiol Opt. 1988;65:91–98.PubMedGoogle Scholar
  21. 21.
    Seiler JP. The mutagenic activity of sodium perborate.Mutat Res. 1989;224:219–227.PubMedCrossRefGoogle Scholar
  22. 22.
    Campagna P, Macri A, Rolando M, Calabria G. Chronic topical eye preservative-free beta-blocker therapy effect on the ocular surface in glaucomatous patients.Acta Ophthalmol Scand Suppl. 1997;224:53.PubMedGoogle Scholar
  23. 23.
    De Saint Jean M, Debbasch C, Brignole F, Rat P, Warnet JM, Baudouin C. Toxicity of preserved and unpreserved antiglaucoma topical drugs in an in vitro model of conjunctival cells.Curr Eye Res. 2000;20:85–94.PubMedCrossRefGoogle Scholar
  24. 24.
    Yalvac IS, Gedikoglu G, Karagoz Y, et al. Effects of antiglaucoma drugs on ocular surface.Acta Ophthalmol Scand. 1995;73:246–248.PubMedGoogle Scholar
  25. 25.
    Turacli E, Budak K, Kaur A, Mizrak B, Ekinci C. The effects of long-term topical glaucoma medication on conjunctival impression cytology.Int Ophthalmol. 1997;21:27–33.PubMedCrossRefGoogle Scholar
  26. 26.
    Arici MK, Arici DS, Topalkara A, Guler C. Adverse effects of topical antiglaucoma drugs on the ocular surface.Clin Exp Ophthalmol. 2000;28:113–117.CrossRefGoogle Scholar
  27. 27.
    Gobbels M, Spitznas M. Corneal epithelial permeability of dry eyes before and after treatment with artificial tears.Ophthalmology. 1992;99:873–878.PubMedGoogle Scholar
  28. 28.
    Holly FJ. Surface chemical evaluation of artificial tears and their ingredients, II: interaction with a superficial lipid layer.Contact Lens. 1978;4:52–65.Google Scholar
  29. 29.
    Baudouin C, de Lunardo C. Short-term comparative study of topical 2% carteolol with and without benzalkonium chloride in healthy volunteers.Br J Ophthalmol. 1998;82:39–42.PubMedCrossRefGoogle Scholar
  30. 30.
    Tomlinson A, Trees GR. Effect of preservatives in artificial tear solutions on tear film evaporation.Ophthalmic Physiol Opt. 1991;11:48–52.PubMedGoogle Scholar
  31. 31.
    Gupta M, Majumdar DK. Effect of concentration, pH, and preservative on in vitro transcorneal permeation of ibuprofen and flurbiprofen from non-buffered aqueous drops.Indian J Exp Biol. 1997;35:844–849.PubMedGoogle Scholar
  32. 32.
    Fassihi AR, Naidoo NT. Irritation associated with tear-replacement ophthalmic drops. A pharmaceutical and subjective investigation.S Afr Med J. 1989;75:233–235.PubMedGoogle Scholar
  33. 33.
    Tripathi BJ, Tripathi RC. Cytotoxic effects of benzalkonium chloride and chlorobutanol on human corneal epithelial cells in vitro.Lens Eye Toxicol Res. 1989;6:395–403.Google Scholar
  34. 34.
    Collin HB. Ultrastructural changes to corneal stromal cells due to ophthalmic preservatives.Acta Ophthalmol (Copenh). 1986;64:72–78.CrossRefGoogle Scholar
  35. 35.
    Burstein NL, Klyce SD. Electrophysiologic and morphologic effects of ophthalmic preparations on rabbit cornea epithelium.Invest Ophthalmol Vis Sci. 1977;16:899–911.PubMedGoogle Scholar
  36. 36.
    Burstein N. Corneal cytotoxicity of topically applied drugs, vehicles, and preservatives.Surv Ophthalmol. 1980;25:15.PubMedCrossRefGoogle Scholar
  37. 37.
    Doughty MJ. Twice-daily use of a chlorobutanol-preserved artificial tear on rabbit corneal epithelium assessed by scanning electron microscopy.Ophthalmic Physiol Opt. 1992;12:457–466.PubMedGoogle Scholar
  38. 38.
    Lazarus HM, Imperia PS, Botti RE, Mack RJ, Lass JH. An in vitro method which assesses corneal epithelial toxicity due to antineoplastic, preservative and antimicrobial agents.Lens Eye Toxicol Res. 1989;6:59–85.Google Scholar
  39. 39.
    Way WA, Matsumoto S, Apel LJ, Wiese A, Tarlo K, Vehige J. Purite™ as a non-disruptive preservative for lubricating eye drop solutions in comparison to alternative preservatives.Invest Ophthalmol Vis Sci. 2001;42:S39.Google Scholar
  40. 40.
    Walters TR, Batoosingh AL. 12-Month evaluation of brimonidine-Purite compared with brimonidine in patients with glaucoma or ocular hypertension.Invest Ophthalmol Vis Sci. 2001; 42:S558.Google Scholar

Copyright information

© Health Communications Inc 2001

Authors and Affiliations

  • Robert Noecker
    • 1
  1. 1.Tucson

Personalised recommendations