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Ophthalmic Preservatives: The Past, Present, and Future

Statement of Need and Program Description
Almost all multiuse topical ophthalmic agents are preserved to prevent microbial contamination. As preservatives evolved from the highly toxic thimerosal to quaternary ammonium compounds such as benzalkonium chloride (BAK), toxicity diminished. BAK and similar preservatives have an acceptably low level of toxicity when ocular exposure to them is limited.

However, chronic use of preserved medication to treat glaucoma and other chronic ocular conditions can have serious sequelae in a significant number of patients.1-3 This point was essentially moot while there were no alternatives to BAK- or similarly-preserved medications.

In recent years, however, several manufacturers have introduced alternative preservative systems that reduce still further the toxic effect of long-term instillation of topical antihypertensive medication.

This CME activity reviews the history of ophthalmic preservatives, describes the toxic effects of common and novel preservative systems, and suggests evidence-based strategies for lowering exposure to toxic ocular preservatives.

A literature search reveals that while the prevalence of ocular surface disease is approximately 15%, in patients on long-term topical antihypertensive medications, the prevalence is as high as 50%.1-3 Now that it is possible to reduce patients’ exposure to more toxic medications, there is a need to educate physicians on effective means for accomplishing this end, especially among patients whose medical therapy requires daily dosing with antihypertensive agents.


  1. Fechtner RD, Budenz DL, Godfrey DG, et al. Prevalence of ocular surface disease symptoms in glaucoma patients on IOP-lowering medications. Washington DC, 18th Annual Meeting of the American Glaucoma Society, March 2008. Abstract 46.
  2. Yu JY, Wu E, Kahook MY, et al. Prevalence and significance of ocular surface disease in glaucoma patients. Las Vegas, American Academy of Ophthalmology Annual Meeting, November 2006. Abstract 123.
  3. Noecker R. Effects of common ophthalmic preservatives on ocular health. Adv Ther. 200q;18(5):205-215.

Learning Objectives:

Upon completion of this activity, physicians should be able to:

  • State why almost all topical multidose medications for ocular application are preserved.
  • Name the most common preservatives and describe their potential for ocular toxicity.
  • Describe two novel preservatives and state how they might be used in a regimen designed to lower the overall toxic burden placed upon a medically managed glaucoma patient’s eye.