Over the past 10 years, the group of medications known as prostaglandin analogues has become the front-line treatment for glaucoma.But now a Canadian researcher – on a sponsored speaking tour of Australia – has queried whether the preservatives found in eye drops – and in particular a preservative known as benzalkonium chloride (BAK) – could be causing ocular surface disease (OSD) in some patients.
Known as the ‘Sneak Thief of Sight’, glaucoma is a devastating disease that is the leading cause of irreversible blindness in the world.
Glaucoma Australia estimates more than 300,000 Australians have glaucoma, however, many more – perhaps up to 50 per cent more – have the disease but are not yet diagnosed.1
While glaucoma more commonly appears as people get older, it can occur at any age. There is no cure and lost vision cannot be regained. Early diagnosis and treatment, however, can prevent, or at least minimise, vision loss.
On a speaking tour of Australia, Canadian ophthalmologist and researcher Professor Cindy Hutnik said there was increasing evidence that BAK was potentially damaging to the ocular surface.
The speaking tour featured Professor Hutnik, from Canada’s Ivey Eye Institute, and Professor Tarek Shaarawy, Head of the Glaucoma and Glaucoma Surgery Units at the University of Geneva in Switzerland.
The pair spoke at seminars held in Brisbane, Melbourne and Sydney in September, organised by global pharmaceutical company Merck Sharp & Dohme (MSD) to launch a preservative-free prostaglandin analogue eye drop, tafluprost.
Tafluprost, which has been available for some time in Europe and America, has just been released for use in Australia and is indicated for the reduction of elevated intraocular pressure in open-angle glaucoma or ocular hypertension. Tafluprost is also listed on the Pharmaceutical Benefits Scheme (PBS) Schedule as an anti-glaucoma medicine.
BAK Related Issues
Speaking at the Sydney CPD event, which was also a live webcast, Professor Hutnik highlighted the ongoing debate about the role of preservatives in anti-glaucoma eye drops.
“Intuitively, we think about preservatives in terms of being bad for safety and tolerance…why are we being so cruel to preservatives? They are doing in the bottle what they are designed to do. Preservatives are not there to lower intraocular pressure. They are there to prevent contamination and they do that by killing cells. That is their job.
“The problem is, that they are non discriminatory. They kill the cells they’re supposed to kill but perhaps they may be also damaging cells they are not supposed to affect, and therein lies the problem.”2
But she said, “…because tafluprost is preservative free, there can be no preservative related harm to the conjunctiva or corneal cells.”
She referred to two studies that investigated the ocular signs and symptoms in a total of almost 10,000 patients using preserved eye drops, compared to preservative-
free drops.2, 3
“Across the board, there was a reduction in symptoms that patients complained about,” Professor Hutnik said.2,3 (Table 1).
PESO Study
Professor Hutnik said the results of a retrospective study in Preservative Exposure and Surgical Outcome (the PESO Study)4 compared case rates of surgical failure. The study found that increased preoperative exposure to ophthalmic solutions preserved with BAK is a risk factor for earlier surgical failure.
She said one of the conclusions of the study was that “for each additional BAK-containing drop used daily the risk of surgical failure increases by a factor of 1.21 (Hazard Ratio P<0.05)”. 4
She went on to explain that the study found “the impact of BAK exposure was dependent on the number of drops administered, but not the number of glaucoma medications used.” 4
Professor Hutnik concluded by encouraging the audience to assess all patients using preserved ophthalmic medications for signs and symptoms of ocular surface disease.
Comfort
In his presentation, Professor Shaarawy reminded the audience not to underestimate ocular discomfort.
He cited the case of a 40-year-old patient in his Swiss practice who had moderately advanced glaucoma but who was unhappy because he “feels his eyes” constantly.
“I switched him to a preservative free prostaglandin analogue and he no longer felt his eyes.” He advised the audience not to underestimate the ocular discomfort of a patient suffering from ocular surface disease.
“If a patient is dissatisfied with their medication, their adherence to treatment may suffer; and if they are not taking their medication, it will not work,” Professor Shaarawy said.
Professor Shaarawy, who also spoke about advances in surgical treatment of glaucoma, said even if patients didn’t complain of OSD symptoms, preservatives could cause “a degree of chronic inflammation”.3
“If you put them under the knife, you are potentially taking a knife to an inflamed eye. They (glaucoma surgeries) fail in a higher percentage because the eye is inflamed.”5
He noted that BAK is a detergent,4 saying ophthalmologists “should not be surprised that some patients may have ocular discomfort.”
Professor Shaarawy said glaucoma patients could expect a similar decrease in intraocular pressure when using prostaglandins analogues – with or without preservatives.6
“There is little difference in efficacy, but in patients with signs and symptoms of OSD, there were significantly less symptoms when switched to preservative free tafluprost,” he said.6
Surgical Options
Professor Shaarawy concluded his presentation with a roundup of various surgical options for the treatment of glaucoma.
He said he was particularly excited by the emergence of new types of surgical implants and stents for glaucoma.
Professor Shaarawy said while the implants would not make a big difference to his own practice in Switzerland, they had the potential to “revolutionise” treatment of glaucoma in developing nations, because they could be inserted without a microscope.
Professor Shaarawy said in many developing countries, the morbidity rate from lost vision meant having glaucoma was “akin to having cancer”.
He said cardiologists once had the options of treating patients with the extremes of either “a few pills or opening the chest”, but now were able to deal with many cases of heart failure through the use of stents.
Professor Shaarawy said in much the same way, it would make sense for ophthalmologists to increasingly use stents.
“They will have their place, but they are here to stay,” Professor Shaarawy said.
References
1. Glaucoma Australia, online source, www.glaucoma.org.au/what.htm (accessed 17 October 2013).
2. Pisella, et al. Prevalence of ocular symptoms and signs with preserved and preservative free glaucoma medication. Br J Ophthalmol. 2002; 86: 418–423.
3. Jaenen N et al. Ocular symptoms and signs with preserved and preservative-free glaucoma medications Eur J Ophthalmol. 2007; 17: 341-349,
4. Boimer C & Birt CM. Preservative Exposure and Surgical Outcomes in Glaucoma Patients: The PESO Study. J Glaucoma: 2013 Mar 20. [Epub ahead of print]
5. Broadway D et al. Adverse Effects of Topical Antiglaucoma Medication II. The Outcome of Filtration Surgery. Arch Ophthalmol. 1994; 112: 1446-1454.
6. Uusitalo H, Chen E et al Switching from a preserved to a preservative-free prostaglandin preparation in topical glaucoma medication. Acta Ophthalmol 2010; 88: 329-336.
Disclaimers
Before prescribing please refer to PBS and Product Information in the primary SaflutanTM (tafluprost) advertisement on page two of this publication. Product Information is also available at www.msd-australia.com.au
Merck Sharp & Dohme (Australia) Pty Limited.Level 1, Building A, 26 Talavera Road, Macquarie Park, NSW, 2113. Copyright © (2013) Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA. All rights reserved.OPHT-1099817-0000 First issued December 2013.
