Fighting against glaucoma-therapy related ocular surface disease

Ocular surface disease (OSD) and dry eye disease (DED) are very common problems in the elderly, and they both considerably decrease vision-related quality of life.

Ocular surface disease (OSD) and dry eye disease (DED) are very common problems in the elderly, and they both considerably decrease vision-related quality of life.1,2  For those OSD patients who are chronically treated with preserved topical glaucoma medication, and in particular, drops preserved with benzalkonium chloride (BAK), ocular surface problems are particularly severe.

The condition can be characterised with the term glaucoma-therapy related ocular surface disease. It has been well established that BAK (and possibly, to a less extent, other preservatives or components used in intraocular pressure-lowering drops) damage the ocular surface.

For BAK, the mechanisms comprise a dose-dependent toxic effect, induction of apoptosis and, due to its detergent activity, destruction of the tear film lipid layer, which increases tear film evaporation. Thus, long-term use of preservatives applied in topical glaucoma medication frequently induces OSD in those who have normal ocular surface when the treatment is initiated, and significantly worsens OSD in eyes with OSD or DED, even after a short treatment period.1,2,3

Preservative-free (PF) topical medication has been widely available in the developed world for many years. For example, PF timolol, topical carbonic anhydrase inhibitors, protaglandin analogues, timolol/carboanhydrase inhibitors and prostaglandin/timolol fixed combinations are widely used.

However, numerous patients are still treated with preserved eye drops or eye drop versions, even if they exhibit typical symptoms (tearing, itching, frequent blinking, eye irritation and pain) and signs (red eye, blepharitis) of OSD. Many ophthalmologists think that detecting OSD is time-consuming and difficult, but this is a misconception.


Detecting ocular surface disease

In a busy glaucoma clinic, it is not necessary to measure tear film break-up time, tear secretion and tear osmolarity. In contrast, asking the patients about sudden tearing, red eyes and feelings of eye discomfort takes only a few seconds; and paying attention to the conjunctiva (folds, grainy tear film, redness, filaments), lid margin (Meibomian gland status) and ocular surface staining after fluorescein instillation but before measuring intraocular pressure, is similarly fast.

When OSD is detected, it is recommended to introduce PF artificial tear substitution, and to start topical cyclosporine medication, which has been increasingly available in the past years. Topical cyclosporine therapy targets inflammation, an important and obligatory part of OSD.

However, these efforts, which may be enough for patients who only have OSD, are not sufficient for patients with OSD and topically treated glaucoma. In the latter, common situation, the topical glaucoma medication also needs to be changed for PF medication, in order to eliminate the detrimental effects of BAK on the ocular surface.

Since PF glaucoma medication choices are widely available for almost all drug classes, no technical obstacles against this treatment change exist in most countries. However, ophthalmologists need to understand that OSD does cause suffering to the patients, and need to pay attention to the patients’ complaints and OSD signs.

This is not difficult and nor is it time consuming. It only requires the ophthalmologist to have the intention to pay attention to detecting OSD.


Professor Holló works at the Head, Glaucoma and Perimetry Unit of the Department of Ophthalmology, Semmelweis University, Budapest, Hungary.






1. Holló G, Katsanos K, Boboridis KG, Irkec M, Konstas AGP: Preservative-free prostaglandin analogs and prostaglandin/timolol fixed combinations in the treatment of glaucoma: efficacy, safety and potential advantages. Drugs 2018;78:39–64.


2. Baudouin C, Renard J-P, Nordmann J-P, Denis P, Lachkar Y, Sellem E, et al. Prevalence and risk factors for ocular surface disease among patients treated over the long term for glaucoma or ocular hypertension. Eur J Ophthalmol. 2013;23:47–54.


3. Labbe´ A, Pauly A, Liang H, Brignole-Baudouin F, Martin C, Warnet J-M, et al. Comparison of toxicological profiles of benzalkonium chloride and polyquaternium-1: an experimental study. J Ocul Pharmacol Ther. 2006;22:267–78.