Taking the combined appraoch
With surgery taking the role of second-line treatment, therapeutics continue to be the first choice option for many glaucoma specialists and Dr Shaarawy is enthusiastic about the direction that this field is moving in. "We have witnessed the introduction of multiple new options for medical therapies, notably combination drugs."
"As the number of choices increase,
we are at risk of falling into
a certain degree of confusion on which drug
to use, how to use it and
when to switch to something different"
Combination drugs have indeed opened up a whole new range of options for the glaucoma specialist but "they also raise challenges," commented Dr Shaarawy. "As the number of choices increase, we are at risk of falling into a certain degree of confusion on which drug to use, how to use it and when to switch to something different," he cautioned.
Counting the cost
Dr Shaarawy admits that, although surgery is still used as a second-line treatment in the majority of glaucoma cases, it is beginning to present a more attractive option because of the heavy cost burden imposed by glaucoma therapies. "Placing a patient on medication costs $1 per day, weighing heavily on a country's resources directed to ophthalmic care," he said.
In fact, a recent study conducted across four European countries (Denmark, France, the UK & Germany) found the average annual health maintenance costs for a patient with late-stage glaucoma is €830, excluding costs of surgery.3 The costs for devices and home care averaged out at €2,045 and €2,703 per patient per year, respectively.
To preserve or not to preserve?
The overall safety and efficacy of most glaucoma therapies is no longer in doubt but a new issue has come to the fore that is arousing the interest of ophthalmologists: "Should we remove the preservatives from glaucoma therapies?"
"I would like to see prostaglandins
Ocular surface disease (OSD) is common among glaucoma patients and this is often attributed to the preservatives used in medications that can result in damage to the cell biology of the eye.
This year the results of a long-term study examining this issue were published in the European Journal of Ophthalmology.4 The multicentre, cross-sectional epidemiologic survey was conducted in Belgium, France, Italy and Portugal and enrolled 9,658 non-consecutive subjects using preservative or preservative-free beta-blocking eye drops between June 1997 and December 2003. It found that patients using preserved medications were far more likely to experience pain during instillation (48% vs 19%), foreign body sensation (42% vs 15%), stinging/burning (48% vs 20%) and symptoms of dry eye (35% vs 16%), when compared with non-preserved therapies, respectively. So why do preserved medications cause these problems?
Most of the medications on the market currently contain a toxic preservative, such as benzalkonium chloride (BAK). BAK is a quaternary ammonium compound that has detergent-like and cationic surface surfactant properties that alter cell membrane permeability of microorganisms, resulting in lysis of cytoplasmic contents. However, the cytotoxic effects are not limited to microorganisms invading the ocular environment. Instead BAK is a 'natural-born killer' that targets corneal epithelium and endothelium, conjunctival epithelium and trabecular meshwork.
Dr Mermoud is among those who are calling for preservative-free therapies, "I would like to see prostaglandins without preservatives." In response to demand, BAK-free alternatives are now beginning to hit the market, for example, Alcon's Travatan Z 0.004% which contains Sofzia, an ionic buffered preservative system that is more gentle on the ocular surface, was approved in the US this year.
The compliance factor
Hopefully, more and more preservative-free solutions will be made available in time. Sadly, however, non-compliance has continued to be an issue with patients. "Compliance has been and always will be a problem since glaucoma patients are often aged and have difficulties in following their treatment," Dr Mermoud reminded. So what has been done to address this and what still needs to be done?
"We have seen the introduction of devices that make eye drop instillation easier. However, I really do believe that the best way to make a patient comply is to offer them adequate time to communicate with specialists, and for specialists to discuss with them the importance of medical therapy, compliance and the consequence of non-compliance," explains Dr Shaarawy. "Communication, communication, communication is the best medicine for compliance issues!"
This sentiment is backed up by a report out this year, which concluded that patient education is the best way to improve compliance.5 Results of a structured questionnaire, completed by 100 patients with chronic open-angle glaucoma attending a glaucoma clinic, found that 13% were unaware that they even had glaucoma and 23% had no idea what medication they were taking. In terms of compliance, 18% depended on family members for the drops, 14% admitted to forgetting their drops once in every 15 days, 15% would forget once a month and 20% would forget once in every six weeks. The researchers also discovered that 87% had no idea about their own IOP and about the pressure range of a normal eye, and 80% did not understand the technique or relevance of field tests.
"Communication, communication, communication
is the best medicine for
"We have tried to spend more time with our patients, to distribute materials to them and we have tried to involve patient groups in discussions and encouraged them to share their experiences," explained Dr Shaarawy. "We have installed films in waiting areas to explain the importance of compliance. The patient only attends the clinic for a short period of time so we need to do all we can to maximize the benefit of this time," he stressed.
Dr Mermoud agrees with this, "For many patients information is very important. If they understand the nature of the disease we are more likely to keep their interest in follow-up visits and continuous treatment."
Neuroprotection continues to hold the attention of glaucoma specialists but it looks like there is a long way to go before it becomes an integral part of glaucoma therapy.
Neuroprotection has long been studied for therapeutic applications in various conditions, including Alzheimer's disease and stroke. The possible link with Alzheimer's was supported by the results of a study by researchers from University College London, UK who discovered that the protein beta-amyloid, which causes damaging plaques in the brains of Alzheimer's patients, is also responsible for harm to the optic nerve.6
However, studying the potential benefit of neuroprotection in glaucoma therapy is difficult because disease progression is a very slow process and trials would require many years and a large number of patients. It has been suggested that currently-used IOP-lowering drugs could be evaluated for neuroprotective ability, which may lessen the time before a neuroprotective strategy could be proven safe and effective.
In the meantime, memantine hydrochloride, a moderate affinity NMDA-receptor antagonist, has been used in Parkinson's disease and Alzheimer's disease for some time now. In a study of memantine for glaucoma therapy in a monkey model, the drug was shown to protect neurons from shrinkage.7 It is now being studied in a worldwide clinical trial with visual field as the endpoint.
Elsewhere, a study published in the July/August issue of the European Journal of Ophthalmology8 has found that supplementing treatment for glaucoma with the antioxidant alpha-tocopherol helps protect the retina from glaucomatous damage. A total of 30 glaucomatous patients (60 eyes) were included in the study and divided into three groups: patients in Group A did not receive tocopherol as a supplement to their therapy; Groups B and C received 300 and 600 mg per day of oral alpha-tocopherol acetate, respectively. At six and 12 months follow-up, both study groups had significantly lower mean differences between pulsatility and resistivity indices in both the ophthalmic and posterior ciliary arteries compared with controls. Furthermore, the study groups also demonstrated significantly lower differences in mean visual field deviations. The researchers concluded that alpha-tocopherol deserves attention beyond its antioxidant properties.
Dr Shaarawy is pragmatic about the future of neuroprotection in glaucoma, "I really hope that we can find a breakthrough in neuroprotection. However, it still seems a very elusive dream."