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Age-related Macular Degeneration

Age-related macular degeneration (ARMD) is the most common cause of vision loss in those aged over 50. It causes a gradual loss of central (but not peripheral) vision. Central vision is needed for detailed work and for things like reading and driving. The disease does not lead to complete blindness. Visual loss can occur w ithin months, or over many years, depending on the type and severity of ARMD. There are two main types of ARMD 'wet' and 'dry'. 'Wet' ARMD is most severe but more treatable. Visual loss caused by ARMD cannot normally be reversed. New drugs are an excitin g development for wet ARMD as they may halt or delay the progression of visual loss.

Understanding the back of the eye

The retina is made up of two main layers. There is an inner layer of 'seeing cells' called rods and cones. These cells react to light and send electrical signals down tiny nerve fibres (which collect into the optic nerve) to the brain. The outer layer - the retinal pigment epithelium(RPE) - is a layer of cells behind the rods and cones. The RPE is an insulating layer between the retina and the choroid. These cells help to nourish and support the rods and cones. They pass nutrients from the blood vessels in the choroid to the rods and cones. They also take waste materials from the rods and cones to the blood vessels in the choroid. The RPE can be thought of as a filter, determining what substances reach the retina. Many components of blood are harmful to the retina and are kept away from it by a normally functioning RPE. The rods and cones are responsible for vision in different conditions. There are many more rods than cones, and rods are smaller cells than cones. o The cone cells ('cones') help us to see in the daylight, providing the basis for colour vision. o The rod cells ('rods') help us to see in the dark - 'night vision'. The macula is a small but vital area of the retina at the back of your eye. It is about 5 mm in diameter. The macula is the part of the retina that is the most densely packed with rods and cones. The macula is essential for central vision. In the middle of the macula is an area called the fovea, which only contains cones. The choroid is a layer of tissue behind the retina which contains many tiny blood vessels. These help to take oxygen and nutrients to the retina. Bruch's membrane is a thin membrane which helps to form a barrier between the choroid and the delicate retina.

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The sclera is the outer thick white layer of the eye.

When you look at an object, light from the object passes through the cornea, then the lens, and then hits the retina at the back of the eye. The light from the object focuses on the macula. You need a healthy macula for detailed central vision.

What is age-related macular degeneration?

ARMD is a condition that occurs when cells in the macula degenerate. This occurs with partial breakdown of the RPE and the cells become damaged and die. Damage to the macula affects your central vision which is needed for reading, writing, driving, recognising people's faces and doing other fine tasks. The rest of the retina is used for peripheral vision - the 'side' vision which is not focused. Therefore, without a macula you can still see enough to get about, be aware of objects and people, and be independent. However, the loss of central vision will severely affect normal sight. There are two types - 'dry' and 'wet' ARMD - described below.

Who gets age-related macular degeneration?

ARMD is the most common form of macular degeneration and develops in older people. There are other rare types of macular degeneration which occur in younger people. ARMD can affect anyone. It is the most common cause of severe sight problems (visual impairment) in the UK, and indeed in the developed world. It becomes more common with increasing age, as the name suggests. It is rare under the age of 60. If you develop ARMD in one eye, you have a high chance (about 6 in 10) that it will also develop in the other eye. About 1 in 100 people aged 65-75, and about 1 in 8 people aged over 85 have ARMD severe enough to cause serious visual loss. About twice as many women over the age of 75 have ARMD compared with men of the same age.

The two types of age-related macular degeneration

Dry ARMD This is the most common form and occurs in 9 in 10 cases. In this type the cells in the RPE of the macula gradually become thin (they 'atrophy') and degenerate. This layer of cells is crucial for the function of the rods and cones which then also degenerate and die. Typically, dry ARMD is a very gradual process as the number of cells affected increases. It usually takes several years for vision to become seriously affected. Many people with dry ARMD do not totally lose their reading vision. Wet ARMD Wet ARMD may also be called neovascular or exudative ARMD. It occurs in about 1 in 10 cases. However, it is likely to cause severe visual loss over quite a short time - sometimes just months. Very occasionally, if there is a bleed (haemorrhage) from a new blood vessel, this visual loss can occur suddenly, within hours or days. In wet ARMD, in addition to the retinal pigment cells degenerating, new tiny blood vessels grow from the tiny blood vessels in the choroid. This is called choroidal neovascularisation. The new vessels break through Bruch's membrane and into the macular part of the retina. These vessels are not normal. They are fragile and tend to leak blood and fluid. This can damage the rods and cones, and cause scarring in the macula, causing further vision loss.

Both wet and dry ARMD are further classified according to severity. Early, intermediate or advanced types refer to the degree of damage to the macula. 6 in 10 cases of intermediate/advanced ARMD are due to wet ARMD.

What causes age-related macular degeneration?

In people with ARMD the cells of the RPE do not work so well with advancing age. They gradually fail to take enough nutrients to the rods and cones, and do not clear waste materials and byproducts made by the rods and cones either. As a result, tiny abnormal deposits called drusen develop under the retina. In time the retinal pigment cells and their nearby rods and cones degenerate, stop working and die. This is the dry type of ARMD. In other cases, something also triggers new blood vessels to develop from the choroid to cause the wet form of ARMD. The trigger is not known. It may be that some waste products which are not cleared from the RPE may stimulate new blood vessels to grow in an attempt to clear the waste. The exact reason why cells of the RPE stop working properly in people with ARMD is not known. Certain risk factors increase the risk of developing ARMD. These include: y Smoking tobacco. y Possibly, high blood pressure (inconclusive evidence). y A family history of ARMD. (ARMD is not a straightforward hereditary condition. However, your risk of developing ARMD is increased if it occurs in other family members.) y Sunlight. This has yet to be proven, but laboratory studies suggest that the retina is damaged by UVA and UVB rays (sunlight rays). ARMD seems to be more common in people from Caucasian (white) racial backgrounds than from other racial groups.

What are the symptoms of age-related macular degeneration?

y The main early symptom is blurring of central vision despite using your usual glasses. In the early stages of the condition you may notice that: o You need brighter light to read by. o Words in a book or newspaper may become blurred. o Colours appear less bright. o You have difficulty recognising faces. One specific early symptom to be aware of is visual distortion. Typically, straight lines appear wavy or crooked. For example, the lines on a piece of graph paper, or the lines between tiles in a bathroom, or the border of any other straight object, etc. A 'blind spot' then develops in the middle of your visual field. This tends to become larger over time as more and more rods and cones degenerate in the macula. Visual hallucinations are common in people with severe visual loss of any cause. Visual hallucinations (also called Charles Bonnet syndrome) can occur if you have severe ARMD. People see different images, from simple patterns to more detailed pictures. The experience can be upsetting but is less frightening if you are aware that it can happen in ARMD. Importantly, it does not mean you are developing a serious mental illness. If you do develop visual hallucinations they typically improve by 18 months but in some people they last for years.

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ARMD is painless. Symptoms of dry ARMD tend to take 5-10 years to become severe. However, severe visual loss due to wet ARMD can develop more quickly. Always see a doctor or optometrist promptly if you develop visual loss or visual distortion This .

is not only the case if you are worried about ARMD. Other sight-threatening conditions can occur suddenly with visual loss, such as a detached retina. Peripheral vision is not affected with ARMD and so it does not cause total blindness. Note: if the vision of one eye only is affected, you may not notice any symptoms, as the other good eye often compensates. When both eyes are affected you are more likely to notice symptoms. Older people should have regular eye checks to check each eye separately for early ARMD (and to check for other eye conditions such as glaucoma).

How is age-related macular degeneration diagnosed?

If you develop symptoms suggestive of ARMD, your doctor or optometrist (optician) will refer you to an eye specialist (ophthalmologist). This should be done urgently, especially if there is any suggestion of wet ARMD. The ophthalmologist may ask you to look at a special piece of paper with horizontal and vertical lines to check your visual fields. If you find that any section of the lines is missing or distorted, then ARMD is a likely cause of the visual problem. The ophthalmologist will examine the back of your eye with a slit lamp microscope. This is a magnifying piece of equipment where the ophthalmologist examines your retinae through what look like binocu lars. Digital photographs can be taken of the retinae. The ophthalmologist will look for the typical changes that occur with dry ARMD and wet ARMD. If wet ARMD is diagnosed or suspected, then a further test called fluorescein angiography may be done. For this test a dye is injected into a vein in your arm. Then, by looking into your eyes with a magnifier and taking pictures with a special camera, the ophthalmologist can see where any dye leaks into the macula from the abnormal leaky blood vessels. This test can give an indication of the extent and severity of the condition. Another test called ocular coherence tomography is becoming more commonly used. This is a noninvasive test that uses special light rays to scan the retina. It can give very detailed '3D' information about the macula, and can show if the macula is thickened or abnormal. This test is useful when there is doubt about whether ARMD is the wet or dry form. It is also a useful test to assess and monitor the results of any treatment.

Is there any treatment for age-related macular degeneration?

y For the more common dry ARMD, there is no specific treatment yet. There are, however, certain things that can be done to maximise the sight you do have and to improve your eye health. Low vision rehabilitation and low vision services are offered by hospital eye departments and information can be found from the Macular Disease Society and the Royal National Institute of Blind People (RNIB). Stopping smoking and protecting the eyes from the sun's rays by wearing sunglasses are important. A healthy balanced diet rich in antioxidants may be beneficial, as may the addition of dietary supplements (see below for details). Remember that in this type of ARMD the visual loss tends to be gradual, over 5-10 years or so. For the less common wet ARMD, treatment may halt or delay the progression of visual loss in some people. Newer treatments may even be able to reverse some of the visual loss. Treatments which may be considered include treatment with anti-vascular endothelial growth factor (anti-VEGF) drugs, photodynamic therapy and laser photocoagulation.

Anti-VEGF drugs In recent years a group of drugs (medicines) called anti-VEGF drugs has been developed. Vascular endothelial growth factor is a chemical that is involved in the formation of new blood vessels in the macula in people with wet ARMD. By blocking the action of this chemical, it helps to prevent the formation of the abnormal blood vessels that occur in wet ARMD. Anti-VEGF drugs are also called anti-angiogenic drugs meaning that they act against substances that promote new blood vessel growth. Anti-VEGF drugs include ranibizumab (Lucentis), pegaptanib (Macugen), and bevacizumab(Avastin). Others are being developed but, due to the new technologies involved, these drugs are very expensive (estimated at between 2,000 and 9,000 per year per patient). The National Institute for Health and Clinical Excellence (NICE) appraised these therapies in August 2008 and gave approval to ranibizumab. Ranibizumab (and other anti-VEGF drugs) are injected using a fine needle directly into the vitreous humour of the eye. Ranibizumab injections are needed every four weeks. But, very specific criteria have been set out by NICE to determine which patients are eligible for treatment. The rationale is that new medicines, particularly very expensive ones, should only be given in circumstances where there is medical evidencefor their effectiveness. Such evidence comes from medical trials of drugs, comparing them with each other and with existing treatments. Anti-VEGF drugs are an exciting new development in the treatment of wet ARMD. Ranibizumab will improve vision in about 1 in 3 people treated. However, treatment in most people willmaintain vision and prevent the condition from getting worse. About 1 person in every 10 treated, will not respond at all. Clinical (drug) trials are ongoing and involve other anti-VEGF drugs but, at present, NICE does not recommend them. Photodynamic therapy This is a technique that was developed in the late 1990s. A drug called verteporfin is injected into a vein in the arm. Within a few minutes the verteporfin binds to proteins in the newly formed abnormal blood vessels in the macula. A light at a special wavelength is then shone into the eye for just over a minute. Verteporfin is a photosensitive drug. This means that when light is shone at the blood vessels coated with verteporfin, the verteporfin activates and causes damage, destroying the abnormally growing blood vessels (neither damaging the nearby rods and cones, nor any normal blood vessels). Photodynamic therapy is only suitable for some cases. It depends on exactly where the new blood vessels are growing and their extent. It does not work in all cases although the success rate in treated people is high. Success means that the visual loss is prevented from getting worse - it does not restore any lost vision. Treatment usually needs to be repeated every few months to continue to suppress newly growing blood vessels. The main advantage that this method has over laser photocoagulation is that there is less damage to the normal retina. Laser photocoagulation This is a technique where a fine laser is 'fired' at the tiny new blood vessels that are forming. This destroys the developing new blood vessels which helps to prevent the condition from getting worse.

People undergoing this treatment will develop a permanent black or grey patch affecting their vision and no sight is restored. Laser photocoagulation is only suitable for a small number of cases. It depends on exactly where the new blood vessels are growing, as the laser may also damage the rods and cones. N blood ew vessels growing very close to the fovea may not be suitable because of the risk of severe visual loss arising from laser damage or scarring due to laser treatment. Other treatments Treatments such as radiation therapy, other drugs, and surgery to the retina are being investigated. For example, a surgical technique where a part of the peripheral retina is grafted into the diseased macular area is being investigated. The value of these newer treatments is not clear. The treatment of macular degeneration is an active area of research and treatment may well improve in the near future.

Diet, dietary supplements, and age-related macular degeneration

Certain groups of people with ARMD (both wet and dry types) can benefit from vitamin and mineral supplements. These supplements can slow down the progression of ARMD. They are thought to be most beneficial in certain groups of people, such as people with either advanced ARMD or with vision loss (due to ARMD) in one eye. Various products are available to buy over-the-counter (OTC). These supplements are not licensed medicines and generally are not available on prescription. Some primary care trusts (PCTs) may fund them, but have policies in place, such that they can only be prescribed on specialist advice. A specific combination of high-dose vitamins and minerals has been tested and found to be most effective. The mixture includes: vitamin C 500 mg, vitamin E 400 IU, beta-carotene (vitamin A) 15 mg (25,000 IU), zinc oxide 80 mg and cupric oxide 2 mg daily. Only two products in the UK contain all of these, in the stated quantities - Viteyes Original and Bausch and Lomb PreserVision Original tablets. (Other marketed products, e.g. ICaps, contain similar constituents but either in different proportions, or with additional ingredients.) There is some concern that the high doses of vitamins and minerals needed may lead to side -effects in some people. Certain vitamins are linked with specific diseases. Beta-carotene has been found to increase the risk of lung cancer in smokers, so these supplements are not advised in either exsmokers or current smokers. Vitamin E has been linked with an increased risk of heart failure in people with diabetes or vascular (blood vessel) disease. Zinc may increase the risk of developing bladder and kidney problems. Because of these potential problems, you should talk to your GP or ophthalmologist before starting these supplements.

Practical help
When your vision becomes poor, it is common to be referred (by your ophthalmologist) to a low vision clinic. Staff at the clinic provide practical help and advice on how to cope with poor and/or deteriorating vision. Help may include:

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Magnifying lenses, large print books, and bright lamps which may assist reading. Gadgets such as talking watches and kitchen aids which can help when vision is limited. Being registered as partially sighted or blind. Your consultant ophthalmologist can complete a 'Certificate of Visual Impairment'. You may then be entitled to certain benefits.

What else can I do?

y If you smoke, try to stop. If you are are smoker, there are numerous health benefits to quitting. Smoking is a risk factor for many illnesses, including ARMD. The NHS can provide help, support and medicines to assist stopping smoking. The NHS website provides further information on the services available: http://smokefree.nhs.uk/ Eat a healthy balanced diet to try to make sure you get plenty of the types of vitamins that may help in ARMD. Stay safe with regards to driving. If you are registered with sight impairment you should not drive and should notify the DVLA. The DVLA website (www.dvla.gov.uk) provides detailed guidance on fitness to drive and minimum standards with regard to sight. This includes being able to read, wearing your normal glasses, a vehicle number plate at a distance of 20 metres. Consider regular sight tests as you get older. You should visit an optometrist every two years, even if there is no change in your vision. An eye test can often pick up the first signs of an eye condition before you notice any change in your vision. Your optometrist can advise you how often you need to have an eye check-up, depending on your general health, age, family history and other medical conditions. Early detection of problems often allows more effective treatment.

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