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Age Related Macular Degeneration (ARMD) pathology & treatment David Kinshuck & Monique Hope-Ross |
Contributing factors: aging, genes, diet, smoking, etc |
Age-related macular degeneration (ARMD) is one of the commonest causes of poor sight in developed countries. The main factor is age. Whilst the causes are different in different people, other factors contribute. |
| age | age is the main factor |
| smoking | contributes 29%, even passive smoking |
| diet | related up to 49% |
| blood pressure | high blood pressure damages the circulation...2008 target is 140 systolic in clinic, 130 systolic at home, but even lower is better. |
| exercise | via blood pressure effects; regular exercise reduces risk by 70% |
| genes | ~50% is directly due to the genes we inherit, see and Gene page |
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a high fat diet is probably directly related to this condition |
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| exercise | reduces progression tp neovascular ARMD by 70% |
| airbourne pollution | This has been found to cause cardiovascular disease, and therefore is likely to contribute to macular disease. In urban environments, ~8% of deaths are generally attributed to pollution. More definitive proof is awaited, but may take years to obtain, especially the contribution of pollution to ARMD specifically. |
We now know that alcohol excess is also related to ARMD, see |
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| sunlight | Sunlight exposure, especially the summer sun, contributes to ARMD; and sunglasses protect, see. Some sunlight exposure is important...gentle sun exposure increases vitamin D production, and this will reduce the risk of many conditions such as diabetes, osteoporosis, and prostate cancer. It is probably very bight sunlight that contributes to ARMD, not gentle exposure. |
| other | Other pro-inflammatory states can influence the condition, such as chlamydia |
| macular pigment | ARMD is much commoner in caucasians...the lighter the skin/least retinal macular pigment is related to risk. It is unusual in Afro-Caribbeans. |
Other countries |
Some communities in Japan did not develop macular degeneration as people aged, but as soon as they started eating Western food the condition started to occur. Similarly, when Japanese people move to Western countries, they develop the condition more frequently. These observations suggest that the high fat (and type of fats, such as saturated and trans-fats) in our diet, the lack of protective fats (omega 3s, from fish), and salt (by increasing blood pressure) increases the number of people with ARMD. |
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Genes |
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We inherit these from our parents. Genes are the genetic information that tells our body what chemicals to make. Overall, our genes may contribute to more than 50% of ARMD. This paper suggests that we will soon be able to work out who is at risk...the main genes have been found. See Gene page The genes that may cause macular degeneration probably control the way used-up chemicals are removed from the eye. Being long-sighted (hyperopic) is also a risk factor
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A healthy lifestyle |
| A healthy lifestyle helps to prevent age related macular degeneration. This is important for the younger relations of age related macular degeneration sufferers: |
Smoking |
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Blood Pressure & Exercise
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Alcohol Too much may contribute indirectly by increasing blood pressure, and is related to ARMD, see May be red wine (in small amounts) is healthier. Blood pressure rises after drinking (opposite...drinking 4 pints/bottle of wine). Each gram of alcohol puts systolic blood pressure up 0.24mmmHg, diastolic 0.16 mmHg. This means 1 pint of beer (2 units, each unit 8g alcohol) with 16gm of alcohol, if drunk every day, will put the systolic blood pressure up (16 x 0.25=) 4mmHg. |
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Diet Experts recommend a healthy diet.
Fruit/vegetables prevent 36-50% of ARMD see, see and see (fruit & vegetables lower homocysteine levels, and this improves blood flow). Pulses like beans are fine. Bread, pasta, rice and potatoes provide ‘energy’. Vegetarians have lower blood pressures and healthier lipid levels, see . A healthy diet reduces homocysteine levels, which are associated with ARMD . Certainly saturated fats increase the risk of ARMD; and fish and polyunsaturated fats halve the risk. Avoiding certain fats helps, with strong evidence here (explained more clearly here for heart disease). Nuts may help prevent ARMD (small amounts...they are fattening). |
5-9 portions of fruit/vegetables
a day, with portions of different colours The Guardian (2005) reviewed healthy diets etc, here, here , here , here and so on. See some epidemiology |
Vitamin supplements |
If you are unable to eat this many vegetables, low dose multivitamin tablets may help, but too many vitamins may be harmful. Lack of vitamins has been linked to macular degeneration Some research suggests that the pigments in vegetables, lutein, and two types of zeoxanthin might be helpful, as these are the pigments found in the healthy macula. Lutein is in most fruits and vegetables, one type of zeaxanthine is in corn, nectarines and oranges (and other yellow/orange fruits/vegetable), but one type is not normally present in the diet. However, some supplements include doses that are too high, so once again, these are probably best as part of a healthy diet. 'Ocuvite-Lutein' is one preparation that may help. One paper suggested
zinc may be helpful, but only in low dose, and is probably best
as part of a healthy diet. These supplements may not help (see),
as some experts advise that people with a healthy diet may be harmed
by taking vitamin supplements. A review (2006, Drug and Therapeutics
Bulletin, not free online) recommmeded a healthy diet including
green vegetables diet was preferable to supplements. |
The AREDS vitamins reduce ARMD by 25% if diet is not discussed. It is not known whether or not they help patients who have a healthy diet. Ocuvite-Lutein has the most logical formulation...but a healthy diet may be better still.
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Oily fish |
| Oily fish twice a week reduces ARMD by 40%, especially oily fish such as tuna, mackerel, sardines, herring, and salmon. A Japanese diet may be helpful as above. Other omega 3 fats are helpful. |  |
Statins |
ARMD is commoner in people with higher cholesterol levels. Atherosclerosis, caused by a high cholesterol, does contribute to ARMD, see Statin treatment reduces macular degeneration. See see,
Although statin tablets are not yet formally recommended by
all agencies, this author would recommend them for people with ARMD. Naturally all relatives of ARMD patients should address this issue of fat levels in the blood, sticking to a low fat diet with plenty of exercise, avoiding obesity, just as described on this page for ARMD patients. |
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Cataract surgery Cataract surgery leads to an extra 4-5 times risk of developing neovascular macular changes or dry ARMD (this is controversial). Certainly patients with early ARMD undergoing cataract surgery should be warned of symptoms, that is distortion or changes in central vision, and attention should be sought in a few days. Also |
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The pathology Age-related macular degeneration is explained in more detail on other web-sites, such as the RNIB and NIH. This is an excellent animation: www.eyesight.org. Below is a brief description. Age-related macular degeneration (ARMD) is usually a progressive condition. Dry ARMD progresses over many years. Sight does deteriorate, but most people manage to cope well, although reading is difficult and life may be different. In sime types of dry ARMD progression may be very slow, but it may be quicker in other types. Dry ARMD may progress to the 'wet type', but this is not always the case. Wet ARMD begins as new vessels growth in the macular area, causing retinal leakage and swelling. It progresses to cause a scar in the macular area. If the scar is small, sight is reasonable; if large, the sight can be very poor. Imagine your retina has five layers. Normally this retinal appearance stays constant even in old age, but changes may develop as you get older.
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Invisible changes |
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As we get older, changes develop in the retina. The bruchs membrane thickens and the choroidal blood vessels change. The thickened bruchs membrane prevents waste products leaving the retina (see animation and the link), and also prevents nutrients entering. This is thought to be a direct cause of the condition. Lipofuscin (type of fat) accumulates in the retinal pigment epithelium; this damages the pigment cells which eventually die. The choroidal circulation changes...the blood vessels become larger but fewer. This is probably mainly due to a 'hardening of the arteries' that happens elsewhere in the body, particularly with a Western diet. The invisible changes progress to cause dry ARMD,
These changes are described with photos below. |
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What does a person notice with these early changes ? |
If you notice these problems then you are probably at risk and need a check from an optometrist or ophthalmologist. If there are no visible changes, the author would strongly recommend a healthy lifestyle as prevention...it helps your general health in any respect. (This section: after Prof. Bird) |
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Drusen |
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Drusen may develop. These are accumulations of material, probably some waste products of the retinal cells. These are common, and do not usually affect the sight. The accumulation occurs as bruch's membrane becomes thicker and prevents the free flow of materials to and from the light or photoreceptors layer. Also, the retinal pigment cells accumulate liposfuscin .This pigment will also slow down the passage of chemicals to and from the retina. |
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| Some people with a lot of drusen do have slightly reduced sight. Hard drusen: If they are well defined
with a sharp edge, the
sight is likely to stay good. Soft drusen: If they are a little like cotton wool, they are more serious as they may lead to more serious disease with 'exudative changes' as below: prevention is most important (see above). Reference. Soft drusen are inheritied: see CFH Y402H. See types of drusen, risks and epidemiology. If there are a few drusen you may be said to have very early 'dry' macular degeneration.
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see
a retinal photo See hard drusen (right) & case. |
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Atrophic 'Dry' macular degeneration .. non-neovascular |
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The retina becomes very thin, just as though it is worn out. The patches of such thin retina do not 'see', so the central vision becomes patchy. Essentially it is a type of wear and tear. Atrophic changes are present in most of the of the 'dry' types of ARMD as below. Dry types of macular degeneration can get very slowly worse, but only affect the macular area. The rest of the retina, which helps you see at the sides so you can walk round the house, always stays good. This movie is excellent. If this wear and tear is mild you may be able to read and even drive, although it takes a little longer to adjust to different lighting. Often it is a little more severe, and reading is difficult, and driving is impossible. TV is not too bad if you sit close: this is discussed in Hints & coping. Dry ARMD may progress to cause more damage to the central retina';
this is a usually a very slow process taking years. Some types are
non progressive, and not discussed here in detail (such as old macular
holes). Sometimes changes can occur more rapdily, and this would suggest that you are also developing the 'wet' type of ARMD as below. See www.macula.org .
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Patchy vision in atrophic macular degeneration |
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Some types of 'dry' macular degeneration |
Geographic We now know here that the risk of passive smoking (doubles the risk) and personal smoking (triples the risk) of both geographic atrophy. See genes and here. Myopic macular degeneration is usually similar. |
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Very Central See a photo. |
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Mixed
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Choroidal Sclerosis The thin area actually looks white, and the thick choroidal blood vessels can be seen underneath. Photo. |
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Dry ARMD changing into Wet ARMD |
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Dry ARMD may develop into 'wet' ARMD (4%/year). In wet ARMD, leaks develop, and new vessels start to grow right through the retina. Occasionally wet ARMD develops without dry changes, although usually there is an area of retinal damage that triggers the process. Wet ARMD progresses 4 times faster (a 400% increase in progression rate) in smokers. |
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Wet ARMD (exudative/leaky) |
There are 3 main types of wet ARMD |
Fibrovascular retinal pigment epithelial detachment (PED): Occult CNV type 1 |
In a few unlucky people, the dry macular degeneration turns into this type. Occasionally, there may have been no obvious 'dry' changes visible before this develops. In this type the damaged area looks like a dome. Fluid leaks under the retina, hence the term 'wet'. Laser has been tried in this condition but is not helpful. Without the anti-VEGF drugs the condition tends to progress and central vision becomes very poor. Treatment (Lucentis, Avastin) often helps but is not always effective. Occasionally these drugs can cause the retina to 'rip', causing more loss of sight. See a case . There are 3 types of PED, reviewed here (avascular, occult, polypoidal), and here with OCT a photo. Generally ARMD with a PED is classified as 'occult' CNV, type 1. There is another type of PED without any vascular element. In younger patients this is usually part of Central Serous Retinopathy. In older patients it may be due to ARMD, but as there is no vascular element it cannot be treated. |
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‘Occult’ CNV type 2 (no 'PED') |
In this type of ARMD, there
are new blood vessels, but they are not clearly seen with the angiogram. ‘Occult’ CNV
is the term given to a specific ‘blotchy’ appearance of the
angiogram. Occult ARMD is probably an early phase of classic, see . The symptoms of this type of CNV are the same as 'classic CNV' . This type 2 occult CNV usually turns into classic CNV over the next months or years, to cause poor central vision. |
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Classic neovascular ARMD (also called ‘classic CNV’) |
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Some dry types of macular degeneration progress to form this type of wet ARMD. It is very difficult to predict whose dry ARMD will progress, but the risk factors include those mentioned above (soft drusen, high blood pressure, smoking, poor diet, lack of exercise). When blood vessels grow under the macula, this is termed choroidal neovascularisation (CNV or CCNV). When the new vessels are seen easily on a fluorescein angiogram, they are called 'classic CNV': They look like a net of blood vessels. See a photo, another , another , another (case 12) and a healthy fluorescein for comparison. When a doctor looks in the retina looks elevated, there may be tiny haemorrhages, a grey area, or exudates. This photo is a severe case. In milder cases vision may still be good. The condition may develop over days or weeks, with increasing distortion or blurred central vision. If this process is mild you can still read, but if it becomes severe reading with any magnifier is impossible. Treatment, if possible, will be include new ant-VEGF drugs. Laser may help (see details of the Verteporfin treatment program) but is becoming less important as it is not effective as the new drugs. If you notice the symptoms (central vision becoming distorted or blurred, sometimes like looking through water) you should have your eye checked: see distortion below. This is usually a very serious type of macular degeneration, serious because it can cause very poor sight. It never blinds in the sense that you cannot see light and dark, but in its serious form it can damage the central vision so you can only see fingers or even the movements of hands. Once again, the side vision will normally be good, so you should always be able to walk around the house. Surgery has not proved very helpful. The CNV grow at 20microns/day, reaching 3000 microns in 6 months.
They can be extremely difficult to see in early stages. Small membranes
gain, on average, 5 lines of vision with the Lucentis. The condition is occasionally unresponsive to treatment. Macugen is probably the least effective of the new anti-VEGF drugs, and even combined with laser may give a poor response. |
New vessels growing under the central retina in a 'classic' pattern: PDT treatment may help
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Polypoidal choroidal vasculopathy |
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Laser and anti-VEGF injection treatment |
Until recently the only treatment was laser treatment. If the classic new vessels (CNV) are not in the very centre of the retina, regular laser can help. (Laser is a very bright light that makes tiny burns at the back of the eye.) This appearance is called classic extra-foveal CNV. If the CNV were away from the fovea, regular laser may help. However, over the years laser burns expand and this can reduce central vision years later. This treatment is only suitable if the CNV are well away from the fovea. |
If the area of neovascular ARMD (CNV),
shown as the red area, is not under the very centre (the yellow
spot, called the fovea), regular laser may help. |
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Most people with neovascular ARMD have CNV in the centre of the retina. Regular laser cannot be used as it itself would destroy the central vision, so photo-dynamic laser (PDT) laser may help. But even with this treatment many people lose vision. Now Anti-VEGF drugs are being used, and success rates are much higher. They may be used in addition to PDT. This is discussed here. See a case.. The drugs are given by injections in the eye itself about 8 times a year. Traditionally after laser the CNV often return, and this may be the case with new drugs. We have to await further research results. Here is an up to date treatment plan, if the new anti-VEGF drug Lucentis is available see. There are other treatments for neovascular ARMD (CNV), such as surgery or transthermal laser, but these are not very successful and not in general use: |
If the area of CNV is under the very centre PDT laser may help. This appearance is called classic sub-foveal CNV. See a photo (angiogram) See PDT |
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| PDT | discussed here |
| Surgery | inpractical etc |
| drugs | new drugs anti-growth factor injections. |
| Feeder vessels | can be lasered, with/ without other treatments. |
| Macular haemorrhage | Intra-vitreal gas and TPA effective with a large fresh macular haemorrhage +/-laser later. |
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Scarring |
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Many types of macular degeneration progress to cause scarring. 'Dry' types usually progress more slowly, but occasionally can cause very poor central vision, but this is commoner in the 'wet types'. If your conditions is severe wet (example) scarring is likely. See a scar , another. another large |
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Distortion of Vision and other symptoms of ARMD |
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How would you know if you have the 'neovascular' type of age related macular degeneration? Some symptoms suggest you may be developing the problem
If you do develop distortion of vision you usually need to see your ophthalmologist reasonably soon. In the UK you may need to discuss this with your GP, or in a large city attend the Eye Emergency department. Your ophthalmologist may recommend tests such as a fluorescein angiogram. The angiogram tells the doctor if there are new vessels, where they are, what type they are, and what type of laser if any will help. |
Amsler grid test Patients should probably be given the Amsler Grid test to use every day, or at least once a week, at home. These authors recommend this test, although personally I have found that patients may still present late. Patients are given a grid, told to look at the central spot with their reading glasses on, using one eye at a time. If any of the adjacent lines become bent or wiggly or distorted, then CNV (blood vessels growing under the macula) may be present, and patients should see their ophthalmologist (in Birmingham attend the Eye Centre Casualty, City Hospital). The test is explained well here . |
Distortion of straight lines which may start to appear crooked over a few weeks usually means the ARMD is progressing. Sometimes this is due to the 'neovascular' ARMD developing, and you are advised to be checked in case laser may help. |
ARMD and risks for the other eye |
Unfortunately age related macular degeneration can affect
the other eye. See healthy lifestyle above:
this may help. If you do notice a change in your sight, see distortion above. See
a search . Risk
from drusen.
Concerning neovascular or wet type ARMD....
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Rip |
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Sometimes the retina in the macula area can tear and shrink. This is call a 'rip' of the pigment epithelium. It may occur spontaneously as part of CNV ARMD, but can occur after PDT. See a case, with reports a pigment epithelial rip (thanks to Ajith Kumar/BMEC). Even the new drugs can cause the retina to 'rip', , but the risks are only slightly increased. A rip causes significant loss of central vision. |
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Abbreviations |
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Here is a summary of some of the abbreviations ophthalmologists use in this condition: |
| CNV | choroidal new vessels (i.e. neovascular
macular degeneration, or 'wet'). Blood vesssels growing through the retina
under the macula. Also called CCNV. |
| CNVM or CNVm | a choroidal neovascular membrane, that is a network of CNV, although in practice this means the same thing as CNV |
| ARM | age-related macular disease |
| ARMD | age-related macular degeneration |
| PDT | photodynamic therapy (for classic sub-foveal neovascular ARMD ) |
| Occult CNV | hard-to-see neovascular ARMD (based on angiogram) |
| Classic CNV | easy-to-see neovascular ARMD (based on angiogram) |
| dry ARMD | thinning (and other changes) of the central retina |
| PED | pigment epithelial detachment, a type of wet ARMD |
| Rip | a pigment epithelial rip or tear |
| VEGF | Vascular endothelial growth factor...the main chemical that makes blood vessels grow in ARMD |
| Links | |
| some facts, USA, |
http://www.nei.nih.gov/health/maculardegen/armd_facts.asp |
| support, USA | Macula Degeneration Support Website |
| PDT (new laser) | http://www.visudyne.com/index.jsp ....for
patients (needs enrollment) |
| animation | http://www.eyesight.org/Pictorials/Pic-Wet/pic-wet.html ( very helpful) |
| anatomy | http://webvision.med.utah.edu/ |
| more facts, UK | Royal National Institute for the Blind |
| support, UK |
http://www.maculardisease.org info@maculardisease.org ARMD web site http://www.armd.org.uk/index.html |
| photos | Some useful photos http://eyephoto.ophth.wisc.edu/. |
| a review for professionals | Age-related maculopathy: features and new treatment modalities 2002 (abstract) |
| depression | this is common and can be prevented/treated See our LVA page |
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thanks to |
Photos thanks to Good Hope and BMEC photographers/staff |
----------------------Eye pages website feedback -----this page edited March 2008---------------------- |
