Preserved medications: uncovering the hidden dangers

May 1, 2007

Stating the case for the use of preservative-free medications in glaucoma patients with ocular surface disease.

Ocular surface disease (OSD) in glaucoma patients is surprisingly common, yet it remains an under-recognized condition. Among patients with severe OSD, approximately two-thirds are concurrently afflicted with glaucoma (range, 42.9% to 88.4%).1,2

This discussion will examine the most current information regarding OSD in the glaucoma patient, emphasizing the importance of accurately identifying these patients and offering management strategies that can easily be incorporated into any practice. Particular attention will be paid to minimizing the use of preparations containing preservatives, that can result in damage to the cell biology of the corneal surface, the conjunctival surface, the corneal endothelium and the trabecular meshwork. Simply by removing these preservatives from treatment regimens it becomes possible to increase patient comfort, compliance, vision and maximize clinical outcomes.

Accurate diagnosis of OSD is essential

There are a number of useful diagnostic tests available. In my opinion, the single most useful tool is lissamine green staining. Available in both strips and liquid form, it does not sting the eye when applied and can provide a diagnosis of OSD in seconds. Additional tests are also available, such as fluorescein or rose bengal staining. The former can be used for evaluating tear film break-up time, as well as for assessing the corneal epithelium. While rose bengal is also capable of staining damaged epithelial cells, it tends to be somewhat more irritating than lissamine green.

The Schirmer tear test is a rapid, simple evaluation of tear production and, although it has fallen out of favour because of the difficulty of interpreting results, it remains a useful source of information that should be included in every patient's work-up.

Direct visualization of the ocular surface, lid margins, conjunctiva etc. can be easily achieved using slit lamp examination. In fact, conjunctival inflammation can be readily observed by direct observation of the bulbar conjunctiva.

Why are glaucoma patients prone to OSD?

The corneal epithelial cells are dynamic and constantly in a state of turnover. The rate of degradation, modulated in part by matrix metalloproteinases, is governed by a host of factors including the status and constituents of the tear film as well as environmental assaults (e.g., pollution, airborne toxins, preservatives in ophthalmic solutions, and corticosteroids that inhibit and delay corneal healing). While the corneal epithelial cells are capable of rapid growth in the neonate, cell growth slows considerably as one ages.

A variety of factors contribute to the development and/or exacerbation of ocular surface disorders in the glaucoma patient. Insufficient tear production or the production of abnormal tears arising from various conditions, such as aqueous, lipid, or mucin deficiencies in patients with one or more risk factors (e.g., age, sex, concurrent disease status and recent ocular surgery), can result in decreased tear clearance, increased osmolarity on the ocular surface, and an irritated ocular surface.3

Dry eye, one of the most common forms of OSD, remains an under-recognized clinical manifestation in patients with glaucoma. Artificial tears are often prescribed in glaucoma patients complaining of dry, red, itchy eyes without a full examination. It is important that such drops do not contain toxic preservatives, such as benzalkonium chloride (BAK), because simply prescribing additional preserved medications, such as artificial tears, in response to complaints of dry eye is likely to exacerbate the clinical condition. Thus, the relationship between preserved medications, glaucoma, and dry eye is an important one necessitating the prescription of appropriate preservative-free medications.

Preserved medications could worsen OSD

While a variety of factors may contribute to either the development or exacerbation of OSD, the chronic application of preserved medications, particularly those containing BAK directly to the ocular surface in the population of patients with concurrent OSD and glaucoma, is a major concern. This practice can exacerbate the development and severity of the underlying OSD.