Having managed patients with wet-age related macular degeneration in Canada and in Australia for the past 13 years, Dr. Matthew Russell has closely monitored the evolution of treatments and welcomed the choices delivered thanks to competing anti-VEGF agents. A vitreo-retinal surgeon, medical retinal diseases specialist and a cataract surgeon with Vision Eye Institute in Queensland, he has published multiple articles on retinal diseases and surgery and been involved in multi-centre clinical research, his credentials are. mivision caught up with this eminent eye surgeon to find out about his experience, preferences and the outcomes he has achieved for patients using anti-VEGF injections.
Wet macular degeneration causes blood to leak out of vessels and build up under the surface of the retina, in the central area of vision.
Vascular Endothelial Growth Factor (VEGF) is predominantly responsible for this, and to slow or stop the process ophthalmologists can inject the anti-VEGF drugs agents Lucentis or Eylea into the eye. Clinical trials have shown the use of anti-VEGF drugs maintains vision in the vast majority of wet MD patients.
How do you choose which anti-VEGF agent to use when treating patients for wet macular degeneration?
The difficulties of keeping regular appointments and the expense are big factors and sometimes these are the reasons why people stop coming back for treatments.
There are no clear-cut guidelines from the available literature as to which agent to use – so the decision is purely at the clinician’s discretion.
The majority of my patients started on Lucentis because until a year ago there was no other anti-VEGF injection that was approved by the Therapeutics Goods Administration and listed on the Pharmaceutical Benefits Scheme in Australia. Patients who have responded well to Lucentis and have required less than 8-weekly treatment have continued to receive Lucentis. In these patients, there would be no significant benefit in transitioning to a new therapy.
For new patients and for patients who have not responded ideally to Lucentis or have required relatively frequent treatment, I use Eylea.
The reason is that when I analyse my own clinical data, collected over 10 months, I can see there are slightly fewer Eylea injections required to stablise the macula in this group of patients. I find fewer of my patients being treated with Eylea require injections every four to six weeks than is the case for those being treated with Lucentis. However, we need to keep in mind, that this is data collected in the first year of treatment with Eylea. When we look at longer-term trials from the US, we see there is only a minor difference between the rate of Eylea and Lucentis injections required in the second year of treatments.
You mentioned you have switched some patients from Lucentis to Eylea. Why and at what point do you make that decision?
There’s no guide as to which patient will respond best to Lucentis or Eylea – no way of predicting which patient will be a poor responder.
If you look at studies of large groups of patients, there is no difference between the visual outcomes achieved by treating with Lucentis or Eylea. But there are groups of people who do not ideally respond to Lucentis and in a limited number of small studies, they have been shown to be more responsive to Eylea. Suboptimal responders can be divided into several groups; those who have a suboptimal response (persistent subretinal and / or intraretinal fluid) from the onset; those who develop recurrent fluid after having stabilised completely early in the treatment period; and those who have no leakage but require very frequent injections in order to maintain stability. I’m sure in time, when Eylea has been around for longer, studies may show there are groups who are more responsive to Lucentis as well. It may be the case that tolerance to any anti-VEGF drug develops over the long run in a portion of patients undergoing treatment with any biologic drug. This may be the biggest benefit of having multiple agents available in our armamentarium to treat wet AMD.
I will always treat patients for three to four months before considering switching between agents, as long as the OCT shows the patient’s intraretinal and subretinal fluid is dissipating. The reason is that most of the vision improvement is seen during this time. However if the patient is not responding to treatment, or their condition is worsening despite treatment, I’d consider immediately converting to another agent. That decision path applies to both Eylea and Lucentis. The second situation in which switching may be helpful is in those patients who have initially responded well to Lucentis but develop recurrent fluid leakage after prolonged use of the drug.
How many patients have you switched?
I’ve switched agents for about 20 – 30 per cent of my patients with wet age related macular degeneration who weren’t responding ideally to treatment. Patients who required Lucentis treatment every eight weeks or more have also transitioned to Eylea treatment. Over all, approximately 60 per cent of our patients are now receiving Eylea treatment.
For a significant portion of those patients, I was able to extend the interval between treatments following the switch – some by as much as two to four weeks.
How important is it to have a choice of agents for the treatment of wet macular degeneration?
I believe it is very important to have a choice – despite the fact that large, head-to-head clinical trials show there appears to be no difference in vision outcomes for patients, there are differences in treatment responses for individual patients. With any drug we see individual variations in responsiveness, maybe due to genetic differences or circumstances that are yet to be elucidated.
We’ve certainly seen cases where patients who required monthly treatments to maintain macula stability have been switched and as a result, they’re now in a situation where their treatment has been extended to every eight weeks. That makes a tremendous difference in quality of life and the patient’s financial circumstances. So having the option to switch agents means there are a greater number of patients whose condition we’re able to control. It is too early at this stage to be sure that these benefits will be maintained over the long run, however, our initial results are encouraging.
How important is it to extend the interval between treatments?
Extending the treatment interval can have a significant impact on a patient’s quality of life. The biggest impact for the patient is reduction in the burden of treatment. Monthly visits to the ophthalmologist for examination or an injection disrupt lives. The difficulties of keeping regular appointments and the expense are big factors and sometimes these are the reasons why people stop coming back for treatments.
Then there is the impact on a patient’s ability to travel. Many older people still enjoy leading active lives so if you can extend their treatment interval they are free to pursue that. For example, I have a patient in her 80s travelling back to the UK for three months and a 94-year-old gentleman travelling to Africa to visit Tobruk then on to Greece where he was in World War Two. If we can extend treatment for these patients by two to four weeks, this really has a positive impact on their lives.
What are the medical advantages of extended intervals?
From a medical point of view there’s a significant reduction of the risk of serious vision threatening infections that come with administering injections. Infection rates sit anywhere between 1:1000 to 1:3500 – so any reduction in these rates we can achieve is a positive.
Extended intervals also help with patient management. There is a substantial group of patients entering into the age bracket where they are at greater risk of developing age related macular degeneration, which means the prevalence of this disease is expected to increase substantially over the next 25 years (according to the Macular Disease Foundation Australia from 2011 to 2030, the number of people with some evidence of Macular Degeneration will increase by 70 per cent to 1.7 million1).
Any reduction in the number of treatments will free us to provide care for other conditions and other patients.
We’re already seeing the benefits of this. For example, the number of injections my practice has administered per patient over the last 12 months has reduced, however the total number of injections hasn’t changed much because of the new patients we’ve acquired.
1. Deloitte Access Economics & Macular Degeneration Foundation, 2011
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