Preservatives in Topical Ophthalmic Medications: Historical and Clinical Perspectives

P. David Freeman; Malik Y. Kahook


Expert Rev Ophthalmol. 2009;4(1):59-64. 

In This Article

Abstract and Introduction


Patients may be subject to a variety of different topical medications when undergoing treatment for ocular disease. Preservatives are added to multidose medication bottles to inhibit microbial contamination. An assortment of different preservative formulations has been used in ophthalmic medicines and many of these preservatives have been linked to unwanted ocular surface side effects. Benzalkonium chloride in particular has been linked to a number of different adverse effects, such as disruption of the tear film as well as damage to ocular surface epithelial cells. As a result, the manufacturers of ocular medications have developed innovative new preservative systems in an attempt to limit these toxic side effects. This article reviews the different ophthalmic preservative formulations, their benefits, detriments, mechanisms of action and historical aspects. Future prospects and clinical objectives with regard to ophthalmic preservatives are also discussed.


Topical medications remain the cornerstone of treatment for ocular diseases including infections, uveitic diseases, ocular hypertension and glaucoma, among others. Patients are often exposed to a variety of different classes of medications to treat disease processes and treatment regimens range from short-term courses to chronic therapy lasting years. In order to inhibit the growth of microbial contaminants and suppress biodegradation within these medications, preservatives are added to all multidose bottles as mandated by the US FDA.[1]

A variety of different preservatives have been used in ophthalmic preparations. The repetitious use of ophthalmic medicines, which is often necessary to treat diseases such as glaucoma and dry eye syndrome, has been linked to irritation, dryness and surface epithelial cell loss, among other unwanted side effects. It has been well established that ophthalmic preservatives, similar to the medications they preserve, also have many adverse effects.[2] The severity of these effects are related to the duration for which the medications are used, the types and concentrations of preservatives used in the medications and the total number of all eye drops used by the patient throughout the day.

Owing to the potential adverse effects of ophthalmic preservatives, it is necessary to educate eyecare professionals on the chronic effects of preservatives. Also as a consequence of these deleterious effects, there has been recent interest in the pharmaceutical industry to develop novel preservatives that cause fewer toxic insults on the eye. Here we review the different ophthalmic preservative formulations, their mechanisms of action and some of their historical features.