Resisting a Drop in Standards

As a partner in the Clayton Eye Center – one of the largest glaucoma eye care practices in the US – I am no stranger to ocular surface disease (OSD) within my patient base. Many of the pharmacology-related studies that opened new treatment avenues from the mid-1980s through the early 21st century bore the Clayton Eye Center’s name – or the name of Harvey B. Dubiner, my current glaucoma specialist partner.

After thousands of clinical study-related visits employing several different pharmaceutical agents, it became obvious to some eye care professionals that the cornea was under attack from the available treatment options. Many – if not all – of the study drugs we used have preservatives to prevent contamination from various bacterial elements. Historically, the use of these preservatives was mandated by the US government and were considered the standard of best patient care.

BAK (benzalkonium chloride) has been the workhorse preservative commonly used in ophthalmic eye drops – not only for the treatment of glaucoma but additionally for many ocular maladies. Though it became clear early on that these preservatives were causing forms of OSD, there were no completed clinical studies looking at the mechanism or issues with corneal toxicity. Damage to conjunctival and corneal epithelial cells results in many signs and symptoms of OSD, including ocular surface staining and increased tear break-up time, and other related patient reported OSD symptoms were occurring in many instances (1).  In addition, long-term use of preservatives may result in chronic drug-induced pemphigoid, which is characterized by a marked and self-sustaining inflammatory process leading to cicatrizing and shortening of the conjunctival fornices.

Fortunately, there are now glaucoma medications available in preservative-free formulations, which makes it unnecessary to expose our patients’ corneas to the potential development of OSD. Many patients who undergo mono therapy can successfully use drops with preservatives in them, but it is when we start adding second and third tier medications and/or switching medications that they begin to present with problems or symptoms. Our clinic currently has a strict policy on using preservative-free drops with all our contact lens patients. As glaucoma is a life-long condition, we should be cautious in treating these patients with preserved drops, as opposed to patients with short-term conditions such as seasonal allergies or ocular infections. Studies duplicated in animals have also demonstrated an increase in inflammatory markers, diminished goblet cells and impression cytology changes suggestive of apoptosis, as well as corneal permeability changes (2).  Several switch studies still point to BAK toxicity in preserved medications. The bulk of patient treatment dropouts in our clinic always seem to be related to the unpleasant side effects on the cornea from preserved medications.

After years of dealing with noxious effects from preservative-laden eye drops, I recommend using only preservative-free modalities when possible. This can avoid long-term problems for both doctor and patient. My wife, for example, who has particularly sensitive eyes, always carries with her individual preservative-free vials of lubricating eye drops. There are now several preservative-free glaucoma medications available for patients – they should become the first line of defense to support the treatment of glaucoma.