Eye Info

Anti VEGF treatment for wet age-related macular degeneration

Summary: Designed to help you understand more about your eye condition, this guide has been written by our experienced eye health team.

• Availability of anti-VEGF treatment
• Introduction
• How the eye works
• What happens in wet age-related macular degeneration?
• What is Anti-VEGF medication?
• Will I be suitable for treatment?
• How is anti-VEGF treatment given?
• What are the complications?
• What tests are done?
• What is the possible outcome?
• What next?
• Useful contacts
• About this guide

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Availability of anti-VEGF treatment

At the moment provision of anti-VEGF treatments varies greatly across the country. People in Scotland receive treatment on the NHS as long as their clinician thinks they will benefit. However, in England, Wales and Northern Ireland, individual Primary Care Trusts and Local Health Boards have to decide whether or not to provide treatment on the NHS and what if any, restrictions to access to apply. In some areas, patients have to prove that they are exceptional cases to be treated; in others, they only receive treatment if they have already lost sight in one eye; and in yet others, treatment depends on the level of sight loss experienced. In most areas, treatment is available privately but for many people the cost is prohibitive. To find out if anti-VEGF treatment would help your eye condition and if it is available in your area, please speak to your eye specialist. If you are eligible for treatment and have problems obtaining it on the NHS, please contact RNIB's Helpline number (0845 766 9999 or 020 7388 2525).

Find out about RNIB's campaign for improved treatment of wet AMD.

Introduction

Wet age-related macular degeneration (AMD) is the less common type of AMD. Around 10 per cent of people diagnosed with AMD will have the wet form and approximately 90 per cent will have the dry form. Wet AMD occurs when new blood vessels start growing under the 'photographic film' (retina) in or around the macula (the central part of the retina responsible for detailed and colour vision). These new fragile blood vessels (called choroidal neovascularisation) leak fluid and blood which if untreated, can then lead to scarring in the macula and irreversible sight loss.

Anti vascular endothelial growth factor (anti-VEGF) medications are a group of drugs used in the treatment of wet type AMD. These drugs work by blocking the effects of a growth factor that blood vessels need in order to form and keep leaking and are most effective when used in the early stages of the condition. The anti-VEGF drugs stop the growth of new blood vessels, thereby reducing the risk of scarring and further sight loss.

How the eye works

We need light to see what is around us and its colour. Light bounces off the objects we look at. Different objects reflect different amounts of light.

Light rays enter the front of our eye through the clear cornea and lens. It is very important that both the cornea and lens are clear as this allows the light to pass directly through the front of the eye to the retina.

The cornea and lens bend light so that it can focus on the retina at the back of our eye. This gives us a clear, precise image. The cornea focuses the light towards our retina. The lens fine tunes the focussing of this light

Our tears form a protective layer at the front of the eye and also help to direct the light coming into our eye. The iris, the coloured circle at the front of our eye, changes the size of the pupil which allows different amounts of light into our eye. The pupil is the dark hole in the middle of the coloured part of our eye. The pupil gets smaller in bright conditions to let less light in. The pupil gets larger in dark conditions to let more light in.

The middle of our eye is filled with a jelly-like substance called the vitreous. The vitreous is clear and allows light to pass directly from the front to the back of our eye.

The retina at the back of the eye is a light-sensitive layer which consists of rod and cone cells. These cells collect the light signals directed onto them and send them as electrical signals to the optic nerve at the back of our eye. Rod cells are concentrated around the edge of the retina. They help us to see things that aren’t directly in front of us, giving us a rough idea of what is around us. They help us with our mobility and getting around by stopping us from bumping into things. They also enable us to see things in dim light and to see movement. Cone cells are concentrated in the centre of our retina where the light is focused by the cornea and lens. This area is called the macula. Cone cells give us our detailed vision which we use when reading, watching TV, sewing and looking at people’s faces. They are also responsible for most of our colour vision.

The optic nerve is made up of thousands of nerve fibres. These fibres pass the electrical signals along to our brain where they are processed into the image we are looking at.

Seeing can be likened to the process of taking pictures on a film with a camera which you then get developed. The retina is like a camera film which stores an image of what we are looking at. The image directed onto the retina is then sent along to the brain where it is processed, like developing a camera film. Therefore, we actually 'see' in our brain with the light information sent to it from our eyes. This whole process happens very quickly so that everything we see is in focus.

What happens in wet age-related macular degeneration?

In 'wet' type macular degeneration, blood vessels start growing in the macula from the layer under the retina, called the choroid, when there is a lack of oxygen in the cells. The body responds in a helpful way by trying to deliver more oxygen and nutrients to the cells by growing these new blood vessels. Unfortunately, this has the opposite effect since these new blood vessels are unstable, tending to leak fluid and blood under the retina which causes more damage. The abnormal leaking blood vessels, leaked fluid and blood is called the 'wet AMD lesion'. This pattern of leakage and vessel growth (called 'lesion' type) is determined by a test called fluorescein angiography. The lesions (on angiography) are either classified as ‘classic’ or ‘occult’. It is possible and not uncommon to have both lesion types in an eye, when it will be referred to as a ‘mixed lesion’. If the mixed lesion consists of more than 50 per cent classic composition, it will be called ‘predominantly classic’, and if less than 50 per cent ‘minimally classic’. The type of lesion you have can determine what treatment would be most effective for you.

What is Anti-VEGF medication?

The term 'anti' means against and 'vascular' refers to blood vessels. Anti vascular endothelial growth factor medications (Anti-VEGFs) are substances that stop blood vessels from forming or growing. Anti-VEGFs refer to a category of drugs which work by targeting a protein that is needed when new blood vessels form. Blocking VEGF can reduce the growth of new blood vessels, slow their leakage and slow down vision loss. There are currently three drugs that have been used in the treatment of wet macular degeneration: Macugen, Lucentis and Avastin.

Macugen

Macugen was approved by the European Medicines Evaluation Agency (EMEA) in Feb 2006 following extensive trials to show that it is safe and effective. Macugen stabilises sight in approximately 70 per cent of cases and has been shown to improve sight in 20 per cent of patients who have been diagnosed early on in the disease process. It can be used for all lesion types in wet AMD. Treatment consists of an injection into the eye every six weeks, usually for a minimum of two years.

Lucentis

Lucentis gained EMEA approval in Jan 2007. Again, this is based on extensive trials to show it is safe and effective. It can be used for all lesion types in wet AMD. The trials have shown it to stabilise sight in more than 90 per cent of cases and improve sight in up to 40 per cent of cases. The license lays down a treatment plan which starts with three injections at four weekly intervals followed by further injections based on the consultant's assessment of the patient. Patients need to be monitored every four weeks. In practice, patients receive on average eight injections in the first year and six injections in the second year.

Avastin

Has not been approved by the EMEA for the use of treatment in the eye as it has not gone through proper clinical trials to determine safety and how effective it is. Avastin has been approved as a treatment for colon and rectal cancer and is therefore readily available. When used for colon and rectal cancers, the drug is given into the vein of an arm. When Avastin is used for the treatment of wet AMD, it is given into the eye.

Ophthalmologists worldwide have been using Avastin off-label for AMD (‘off label’ refers to prescribing medications for purposes for which they are not licensed). Avastin has been showing success in stopping new blood vessel growth, and small studies and clinical observation suggest that the side effects may be similar to those observed in Lucentis and Macugen. However, since no large-scale long-term randomised controlled trials of Avastin have taken place, it is not possible to say with certainty whether Avastin has a similar safety and effectiveness profile as the other anti-VEGF treatments. Clinical trials have therefore been set up in the UK to compare Avastin with Lucentis. It is uncertain at this time how often Avastin injections are given.

Will I be suitable for treatment?

Not everyone with wet AMD will be suitable for anti-VEGF treatment. Anti-VEGF medication is most effective when treating blood vessels that are 'active' or 'leaking'. If wet AMD was diagnosed sometime ago, and there has been 'maturing' of blood vessels, then it is unlikely that a person will be suitable for treatment. This is because the process of fluid and blood leakage from new blood vessels occurs for a while, and then dries up, eventually leading to scar tissue formation (similar to what happens when a skin wound heals). Scar tissue in the macula causes permanent vision loss and will not respond to any current treatment.

After examining your eye, the consultant will undertake further tests such as a fluorescein angiogram to determine the lesion type, location and extent of bleeding. A technician or photographer will take photographs of the back of your eye after a trained member of staff injects a yellow dye (called fluorescein) into your arm. The dye travels through the body, including the blood vessels at the back of the eye, and a series of photos of the retina are taken. Prior to the angiogram, you will be given eyedrops to dilate your pupil so that a clear image of the retina can be viewed. The photos will show the consultant where the leaking blood vessels are located under the retina. Angiogram photographs are supplemented by Optical Coherent Tomograms (OCT) of the back of the eye (see below) and are used to compare the retina at the start of treatment and on subsequent visits.

How is anti-VEGF treatment given?

The ophthalmologist may give you antibiotic eye drops to use for a few days before the treatment to help prevent infection. Alternatively, the ophthalmologist may give an antibiotic drop into the eye just prior to the first treatment.

Anti-VEGF drugs are given as an injection into the vitreous (the jelly-like substance inside the eye). However, the injection will enter through the sclera (the white part of your eye). It may be done in an operating theatre or a room set aside for treatments like this one. The needle used is very sharp, small and short. The injection itself only takes a few seconds and feels like a tiny scratch.

Eyedrops will be administered into your eyes to dilate your pupils. This will allow the back of the eye to be examined more easily. Local anaesthetic eye drops will be placed into the eye which is to be treated so that the injection itself will be painless.

The eye and skin around it will be cleaned to prevent infection, and your face and the area around the eye will be covered by a drape to keep the area sterile. A small clip (a 'speculum') will be used to keep the eye open. Further anaesthetic drops are put into the eye to numb it and prevent you feeling pain. A few minutes later, the injection is given.

Your eye pressure will be measured approximately 30 minutes following treatment. The eye pressure may go up for a few hours and, if it remains high, treatment may be required. Your vision may be blurry for several hours afterwards due to the dilating eyedrops but this should improve by the next day.

You will be given antibiotic eyedrops to use for a few days following your treatment to prevent infection. Your eye may be red where the injection was given but that should disappear in a few days. Your eye will feel comfortable by the next day and you may notice black swirls in your vision for a few weeks.

What are the complications?

Most of the side effects involve the eye and are due to the injection procedure. These include:

• Endophthalmitis (infection of the eye): symptoms include burning sensation, eye pain, increased blurring of vision, light sensitivity and redness. Studies have shown that the chance of getting an infection is 0.1 per cent and this is why antibiotics are given prior and following treatment.

• Elevated Eye Pressure: this is usually temporary and due to an increase of fluid entering the eye.

• Retinal Detachment, Bleeding and Cataract Formation: these are unusual complications occurring in less than 1 per cent of patients in trial studies.

Other side effects not related the eye include high blood pressure, nose and throat infection and headache. There is a theoretical increased risk of strokes with anti-VEGF, however the actual risk of stroke with anti-VEGF is unknown.

What tests are done?

The ophthalmologist will order tests to be done following treatment. One of these tests may include a further fluorescein angiogram.

In some hospitals, optical coherence tomography is used to see if there is still fluid in the macula. This special photograph shows the layers of the retina in a cross section. Any fluid or inflammation can be seen using this photograph as well as the thickness of the retina. There is no dye or injection required for this type of photograph. Your visual acuity (how well you are able to read the chart) should also be checked at this time. This combination of checking for leaking fluid and visual acuity would be used to determine if additional treatments are required.

What is the possible outcome?

In various trials using Macugen and Lucentis, it was found that vision had stabilised, maintained or improved. In fact with Lucentis, there was a 33-40 per cent chance of achieving a clinically significant visual improvement. This means that up to 40 per cent of patients in the study trial had an improvement in vision with a gain of 15 letters or more (approximately three lines) on the eye chart following treatment with Lucentis compared to before starting the trial.

What next?

Talk to someone

The RNIB Helpline can:

• put you in touch with an RNIB specialist advice service such as welfare benefits and rights, education, employment, legal rights, emotional support, daily living help and residential care
• send you free information and leaflets
• give you details of support groups and services in your area.

Call us Monday to Friday 9.00 am – 5.00 pm on 0845 766 9999 or 020 7388 2525 (some callers may find it cheaper to call a landline, so we have detailed both 08 prefixed numbers and landline equivalents where available).

Get information

RNIB's guide to Adapting to sight loss offers ideas for people with sight problems on making life easier and ways of getting the most out of life.

You may also find the following useful:

• Find a Low Vision or Hospital Information service near you
• Education
• Employment
• Friends and family.

Useful contacts

The Macular Disease Society also provides information and support for people dealing with macular degeneration and related retinal diseases.

The Macular Disease Society
PO Box 1870
Andover
SP10 9AD
Telephone: 0845 240 2041
Email: info@maculardisease.org

RNIB is part of an organisation called AMD Alliance International whose role is to promote awareness of age related macular degeneration - the leading cause of blindness in the western world.

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About this guide

Updated Feb 2008
Copyright © RNIB

Content author: eyehealth@rnib.org.uk

Last updated: 08/04/2008 18:39