Treatment options for wet AMD
Today we are fortunate in the plethora of treatments that we can access for managing wet AMD. Just a few years ago simple argon laser treatment was the only option – and even that was only ever applicable for less than 10% of all wet AMD cases.
The arrival of ‘anti-VEGF’ injection treatments from 2006 onwards in the UK was the most significant step forward in treating wet AMD. At present we currently have three major options for treating wet AMD as follows :
- Anti-VEGF therapy injection treatments
- Photodynamic therapy
- Argon Laser Photocoagulation
Of these options anti vegf injections have the greatest applicability for the vast majority of eyes with wet AMD.
Below we outline our view of these options , with Anti VEGF therapy treatments first.
Anti-VEGF injection Injection Therapy
Research studies had indicated the importance of a particular molecule termed ‘vascular endothelial growth factor’ shortened to VEGF, in the development of wet AMD in many cases. This protein molecule is one of the most important drivers for wet AMD. The VEGF molecule is able to encourage the growth of the abnormal blood vessels that are the hallmark of wet AMD. Blocking the VEGF molecule was thought to be a potential method of treating wet AMD. Thankfully research clinical trials conducted in the early 2000′s showed clear and enequivocal benefits of anti-VEGF treatments in wet AMD.
A very important point that patients must understand is, that given the strong likelihood of significant vision decline occuring in wet AMD without treatment, the major aim of treatment is vision stabilisation. Some patients can & do achieve amazing eyesight improvement with anti-VEGF injections however this is not a common finding and in most cases it really is a case of trying to prevent further decline in eyesight.
At present all currently available types of anti-VEGF treatments are administered as an eye injection. The usual programme is for 3 injections administered over the first 3 months after which a long period of monitoring and repeat injections would be offered as and when required.
The eye is numbed with eyedrops before the injection is administered. In our experience most people undergoing such eye injection treatments experience only a mild discomfort rather than significant pain.
Anti-VEGF injections are generally very safe however as with all treatments some risks are present and these are similar across the range of treatments currently available. The major isks of anti-VEGF therapy injections are similar across the three different injections – as follows :
- Risk of serious internal eye infection – which unfortunately can have severe consequences for eyesight – circa 1/1000 to 1/2000 risk.
- Risk of Retinal detachment – we consider this risk to be circa 1/1000 injections or less.
Below we outline some important points of distinction between the 3 major anti-VEGF agents.
- Lucentis™ (RANIBIZUMAB)
Lucentis injections first became available in late 2006 in the UK. This was the very first licenses anti – VEGF injection treatment specifically designed to work for wet AMD. Lucentis was a major step forwards in the treatment of acute wet AMD. Lucentis is a chemically engineered antibody that blocks the VEGF molecule to discourage the growth of the abnormal new blood vessels that lead to wet AMD. Current UK guidance for the NHS is for Lucentis to be made available for all patients with the following criteria
The condition must be ‘active’
The vision must be better than a level of 6/96
There must be no structural damage to the central part of the macula.
There are occasions where people present with wet AMD that does not meet the above criteria in which case they may not be able to access Lucentis on NHS funding.
Lucentis is applicable for all types of wet AMD and also for many other conditions such:
Other types wet Macular degeneration
Retinal Vein Occlusions
Diabetic Macular Oedema.
The initial results from clinical trials where the eye injections were given on a monthly basis – irrepsective of need – were startling. Both major clinical trials – called the MARINA and ANCHOR trials showed a similarly positive benefit with close to a 40% difference in keeping ‘stable’ vision in the treatment group. Also the average level of vision change was also markedly positive with upto 4 lines of vision difference on a standard chart test between the treatment and non treatment groups. For these reasons and despite its expense NICE gave Lucentis a postive appraisal for use in the NHS in 2007 onwards.
Although the best outcome results are generally seen with monthly treatment – most experts agree that on demand treatment with careful monitoring can work very well indeed – helping to maintain vision with a reduced burden of treatments for patients along with a lower overall level of risk from the injections.
Current UK practice is thus a initial ‘loading regime’ of 3 injections over 3 months and then careful observations with ‘as required’ re-injections on a four to six weekly basis.
At Bettersight we have developed enormous experience of Lucentis anti -VEGF therapy injection and our views tally closely with expert international opinion in that:
We can achieve excellent vision stability with a significant reduction in treatment burden for our patients by the above ‘as required’ re-treatment approach.
We now know that many patients will require on going treatment on a long term (possibly lifelong in some cases) in order to maintain the impact of Lucentis.
A small portion (circa 10%) of patients do not show an optimal response to therapy in which case other treatments could be considered.
A similar small portion (circa 5%) only ever need 3 initial injections !
Some patients will show an good initial response but over time this may wane – in which case other treatments could be considered
Unfortunately around 10-20% of patients may eventually show a gradual decline in eyesight despite optimal treatment. In such cases it may be best to withdraw treatment.
At Bettersight we have also seen cases where people have not been able to meet the NHS criteria for wet AMD treatment due to very poor eyesight upon first diagnosis and have opted for initial private or insurance funded treatment with Lucentis. In some patients they may be able to show enough of a rise in vision with initial treatments to then allow re-access to NHS treatment on an ongoing basis.
- Eyelea ™ (AFLIBERCEPT)
Eyelea is the most recently introduced anti -VEGF agent in the UK. This new treatment works by blocking the VEGF molecule in a slightly different way to Lucentis. Eyelea works by binding to the VEGF molecule as well as another molecule called Placental growth factor (PGF). Both molecules are involved in wet AMD. Eyelea is thought to have a slightly longer lasting effect for each administered eye injection than Lucentis.
Eyelea is also given as an eye injection with 3 injections over 3 months. One of the potential advantages of Eyelea over Lucentis is that after the first 3 months it can be given either as required on a two monthly basis or on a regular – prescribed – two monthly programme until the condition is stable.
The overall results of Eyelea are very similar to Lucentis and most experts consider Lucentis and Eyelea to be broadly similar in their effectiveness and their side effect profile too.
At Bettersight we now have growing experience of offering Eyelea to our patients. We consider Eyelea in the following circumstances :
As a potential alternative to Lucentis in new cases of wet AMD
As a treatment switch from Lucentis in cases where Lucentis is showing a sub-optimal effect
As a treatment switch from Lucentis in patients who are finding the 4-6 weekly clinical monitoring overly burdensome. In such cases a switch to Eyelea could reduce the clinic visiting burden down to two monthly or even less in some cases.
- Avastin™ (BEVACIZUMAB)
Avastin was in fact the very first anti VEGF agent to be used in the UK for treatment of wet AMD both in the UK and across other parts of the world. However Avastin is licensed only as an anti-cancer drug and does not have a license for use in the eye. This does not mean Ophthalmologists cannot use it for management of wet AMD or other disorders – only that patients should be aware that use of Avastin is ‘off label’ also described as ‘off license’.
In Medicine ‘off label’ use of a drug is commonplace and quite routine. There has in fact been great debate within the Ophthalmology professsion about the use of Avastin for wet AMD in particular. This is because Avastin used for eye injection purposes is considerably less costly than either Lucentis or Eyelea but appears to have a very similar effect.
This debate has only intensified as a result of the publication of a landmark clinical trial – The USA National Eye Institute funded CATT trial. This trial showed conclusively that both treatment effect and side effects/risks were very similar between Lucentis and Avastin. This trial proved what Ophthalmologists have known for many years that Avastin is both safe and effective with broad similarity to Lucentis. The differences that were seen were so small they were not found to have reached the standard threshold for what doctors call ‘statistical significance’ – in other words the small differences seen could simply be down to chance findings. The study conclusion was that Avastin was equally effective to Lucentis for wet AMD treatment.
At Bettersight we generally prefer to recommend licensed treatments wherever possible. However in cirscumstances where the patient is self funding their treatment (perhaps due to non eligibility on NHS criteria) we have no hesitation in giving our patients the choice between a licensed anti VEGF agent and Avastin. It is of interest that in these situations many of our patients opt for the considerably less costly ‘off label’ Avastin treatment.
Its also worth noting that due to NHS regulations, at present Avastin is not used for treating wet AMD in the NHS though this position may change at some point in the future.
Alternative treatment options for wet AMD
At Bettersight we have been intimately involved in the anti-VEGF therapy revolution in wet AMD treatment having seen at first hand the enormous positive impact that anti-VEGF treatment has had on our wet AMD suffering patients since 2006 onwards. It is however worth bearing in mind that there are some other treatment options that can be considered in some patients with wet AMD.
We outline some important points about both Photodynamic Therapy (PDT) and ARGON laser photocoagulation.
- Photodynamic Therapy (PDT)
Photodynamic Therapy (PDT) was first introduced in the UK towards the very end of the 1990′s. In its time it represented a step forward for treatment of some cases of wet AMD. The treatment is still applicable in certain cases of wet AMD – but primarily as an ‘additional’ treatment in conjunction with anti-VEGF therapy.
The process of PDT involves intravenous injection of a special dye – called Verteporfin (VISUDYNE). Once in the blood stream this dye helps to sensitize some of the abnormal blood vessles that make of wet AMD to a very particular type of Laser. The Laser used is of very low power and does not heat the retina but works in combination with the dye injection to help seal up these abnormal blood vessels.
PDT is fairly effective at doing this but the vessels invariably start growing again and the treatment is often repeated on a three monthly basis for as long as it remains effective. The outcomes of PDT application in wet AMD were nowhere near as good as anti-VEGF therapy which is why it has been almost completely superseded by anti-VEGF therapy injections.
At Bettersight we do still occasionally consider PDT for wet AMD – but only really as combination treatment alongside anti-VEGF injections and only for very specific sub-types of wet AMD.
- Argon Laser for wet AMD
Prior to PDT becoming available in the late 1990′s – the only widely used treatment for wet AMD was argon laser treatment. This treatment first involves identification of the area of abnormal blood vessels (called a choroidal neovascular membrane – CNVM) in the macula by an angiogram test.
If the CNVM was relatively small and not involving the very central part of the macula AND if it had very specific characteristics then argon laser could be used to treat it.
Essentially argon laser is a heat generating laser – thus argon laser involves careful ‘cauterising’ of the membrane whilst minimising collateral damage. This was and is a highly skilled process!
Argon laser was generally only applicable in around 1 in 10 of all wet AMD cases but when it was deployed carefully it could sometimes be curative with just a single treatment session. The major downside is that laser treatment in this way does leave a dark patch near the centre of the vision and sometimes the area of cautery could be larger than intended. Also though some cases could be treated with a single treatment episode – there is still the prospect of a recurrent episode which may then not be suitable for argon laser.
At Bettersight – we still consider argon laser treatment only for very specific types of wet AMD and where the risks and benefits are appropriately balanced and where we feel there is a good prospect for one treatment session being sufficient.