Introduction

The causes

• genes
• healthy lifestyle & exercise
• smoking
• blood pressure & exercise & weight
• diet
• Vitamin supplements
• Oily fish
• cholesterol
• statins
• cataract surgery (another page)
• macular pigment

pathology

• invisible changes
• What does a person notice with these early changes

types of dry ARMD

• progression
• drusen
• soft drusen
• diagram..drusen
• Basal laminar drusen
• geographic      (separate page)
• mixed/retinal pigment epithelial hypertrophy
• foveomacular dystrophy

Distortion of vision and other symptoms:
dry ARMD changing into wet ARMD

• distortion of Vision
• Amsler grid test
• the other eye                               (separate page)

Notes

• links
• Macular Disease Society
• BMJ article   a slide show
  

• Coping / Low vision
  • Hints & Coping
  • Coping with one eye
  • Magnification
  • Low Vision Assessment
  • Low vision Gateway (US)
• Support
  • Rehabilitation & local services
  • Birmingham Focus (link)
  • Walsall Eyes Newsletter
  • Macular Society
  • Rehabilitation Centre
  • RNIB.talk and support
• Macular degeneration
  • Explanation (link)
  • Understanding
  • Pathology ARMD
• dry ARMD
  • hard drusen
  • soft drusen
  • geographic
  • AOFMD
• none-ARMD  macula
  • ERM
  • VMT
  • macular hole
  • Juvenile macular dystrophies
  • PFT parafoveal telangiecasia
  • Proliferative vitreoretinopathies
  • CSR
• PEDs
  • CSR
  • serous (avascular) PED, not CSR
  • drusenoid PED
  • vascularised PED
  • haemorrhagic PED
  • PCV
• wet ARMD & Lucentis
  • wet ARMD
  • Lucentis treatment program
  • Lucentis animation
  • myopic macular degeneration
  • Macular degeneration: understanding
  • Risk simulation
  • Diabetic maculopathy (link)
  • PDT program
  • New drugs..Lucentis, Avastin, Eylea
  • A table comparing drugs
  • Studies published and in progress
  • Audio interview (NEJM)
  • VMC
  • Screening for wet ARMD
  • deciding AVF is needed
• Types of wet ARMD
  • Occult type 1, PED
  • Occult type 2
  • Classic
  • Rip
  • Polypoidal (PCV)
  • RAP
  • extensive subfoveal haemorrhage
  • Peripapillary CNV
• Myopia
  • refraction
  • dry macula changes
  • wet macula disease (CNV)
• Abbreviations
• Animations etc
  • Large diagram 1
  • Large diagram 2
  • wet /dry ARMD full size
  • Lucentis
  • SWF file for laptops: ARMD animation: 1mb
  • Excellent animation..link
  • VMT vit-mac-traction
• Cases for students etc
  • 1 ARMD etc
  • 2 hard drusen
  • 3 Central Serous Retinopathy
  • 4 Wet macular degn (CCNV)
  • 5 Occult CNV
  • 6 Soft drusen
  • Case Pre-macula haem
  • Case Bests
  • 10 PDT
  • 11 rip
  • 12 CNV
  • 13 CSR & PED
  • 14 Dry/Occult
  • 15 polypoidal
  • 16 myopic early CNV
  • Atlas...Bests, Haem
  • 17 macula hole
  • 18 more fluid with oct
  • 19 fluid reaccumulates
  • 20 peds & nsd
  • 21 AOFVD
  • 22 AOFVD/ERM
  • 23 speckles
  • 24 VMT
  • 25 epiretinal membrane
  • 26 Juvenile retinoschisis
  • 
    
  • 27 early classic
• Further information
  • dry ARMD (link)
  • US Aging Times Review
  • Links
  • RNIB page (link)
  • epidemiology
  • Genes
  • biology of ARMD
  • OCT
• Lifestyle
  • Alcohol
  • Smoking
  • Diet
  • Blood pressure
  • exercise

ARMD is usually a progressive condition, affecting the center of the retina and the centre of the vision. Invisible early changes occur, then usually some type of dry ARMD, such as drusen or geographic atrophy.

Later, the dry changes may progress, usually slowly, to cause more atrophy and damege to the central retina. The dry changes are bascially aging, wearing out of the central retina.

Then in some people, wet changes develop, with blood vessel growth and leakage in the macular area. These wet changes can be slowed down with anti-VEGF drugs (see wet ARMD page).

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.

Dry ARMD is discussed on this page.

Age-related macular degeneration (ARMD) is one of the commonest causes of poor sight in developed countries. Whilst the causes are different in different people, certain factors may contribute. The main factor is age. 

contributes 32% overall, even passive smoking

cholesterol

a high fat diet 10% (2010)

alcohol

Excess alcohol is also related to ARMD, see 

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.

The lighter the skin or the least retinal macular pigment is related to risk.

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. Lack of exercise as we drive everywhere in Western countries will contribute.

click here for full size image

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. We will soon be able to work out who is at risk...the main genes have been found. Tsee

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

• Smoking, accounts for 32% of ARMD
  
• regular exercise,
  
• alcohol,
  
• a healthy diet
• reduces risk 70% (diet,exercise, not smoking)     Archives 2011
  

• Overall smoking accounts for 32% of ARMD. Even stopping at the age of 80 will reduce the risk of developing the disease.
  So if you have a relation with macular degeneration, try and stop as smoking may make it develop earlier.
  
  
• Smoking increases the risk of macular degeneration about 3 times. Macular degeneration occurs 10 years earlier in smokers.
  
  
• If you have macular degeneration, do try and stop. Even if you are 90 years old stopping smoking will help your eyes considerably.
  
  
• Passive smoking is also harmful: for instance, if your partner smokes cigarettes a day, you body receives 25% of the smoke, so that is equivalent to you smoking 5 cigarettes a day. 28000 cases a year in the UK.
  See 2002 report and 2003 study . Lithuania     Japanese  
  
  
• A new report here describes the risk of passive smoking (doubles the risk) and personal smoking (triples the risk) of both types of ARMD, that is geographic atrophy and neovascular.
  
  
  
• Each cigarette probably increases the progression rate or ARMD ~15%

larger

• 30 minutes a day at least, walking, or more active exercise for younger people,  reduces risk by 70%: 2006
• Exercise may help by preventing hardening of the arteries.
  30 minutes walking a day for example...regular walking, for example, three times a week will result in less than a third of the amount of neovascular ARMD compared to people who don't walk or exercise and who drive everywhere.
  
  
• A low blood pressure helps. A level of 140/85 or below is likely to be best. Blood pressure is written as '140/85', with the systolic/diastolic. Above 115 (systolic) the risk of heart disease increases. See the evidence and more. Macular haemorrhages are more likely with high blood pressure. More evidence Eye.
  
  
• Obesity is also a risk factor see. 
  
  
• A low salt diet is important Salt and more than 2 units of alcohol a day may cause blood pressure to rise.
  

Too much may contribute indirectly by increasing blood pressure, and is related to ARMD, see. Red wine may be healthier in small amounts).

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, drunk every day, will put the systolic blood pressure up (16 x 0.25=) 4mmHg.

enlarge

• This should include a variety of vegetables and fruit
  (at least 5-9 x 100gm portions/day) (2008)
• low fat only dairy food
• the minimum of trans and saturated fat
• the minimum of red meat, as part of a balanced diet
• oily fish ...2 small portions a week, Blue Mountain 2009, Australia 09 reduces aging
• 1-2 hours exercise a day
• A low salt diet is important
• Vitamin D reduces risk, (Vitamin D increases with sunilght)  Archives 2011      Vitamin D
• a Mediterranean or Japanese diet (as was 20years ago) will almost certainly protect. 
• Losing weight (if overweight) reduces risk
• Solid fats are harmful Eye 2011
• plants sterols lower cholesterol food.gov.uk,  which foods
• Zinc

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
5 is a minimum..best 9 for men, 7 women, 5 children, see.

The Guardian (2005) reviewed healthy diets etc, here, here , here , here and so on.

See some epidemiology

As the macula is the most metabolically active area in the body, with the greatest oxygen demand, it has been thought that antioxidants such as vitamins may play a critical role.
The retina contains the pigments carotenoids lutein, xeaxanthin, mesoxanthin. Lutein is in darg green leaves such as kale and spinach, and most of us do not eat enough. Xeaxanthin is in orange peppers, corn, nectarines and oranges (and other yellow/orange fruits/vegetable).
'Higher dietary intake of lutein/zeaxanthin was independently associated with decreased likelihood of having neovascular AMD, geographic atrophy, and large or extensive intermediate drusen' Seddon. These vitamins are in the 'AREDS2' supplements Lack of vitamins has been linked to macular degeneration.
If you are unable to eat this many vegetables, AREDS2 supplements may help, but too many vitamins may be harmful.  
See Micronurients 2013
ICap (Alcon), is available in pharmacies and optometrists. This has lutein and other vitamins in, and had been recommended by some ophthalmologists..

The AREDS1 vitamins reduce ARMD by 25%. It is not known whether or not they help patients who have a healthy diet.

Beta-carotene supplements are not recommended for smokers, as they may contribute to lung cancer. I Cap is similar to the AREDS vitamins that reduced ARMD risk by 28%. zeoxanthin , Against., BMJ
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.
If you have a healthy diet, ophthalmologists disagree. More details of food composition here.

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.  
This paper & another found no benefit, so it is difficult to be certain.

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. Statins may not help Retina 2013

Macular pigment density is inversely related to ARMD: the thicker the pigment the less likely the condition.

• this explains why the condition is much commoner in Caucasians with blond hair and lighter coloured retina
• increasing the pigment with lutein may delay the condition Acta 2012  Eye 2012
• ARMD is unusual in Afro-Caribbeans, and this may be because the 'elastin' layer is thicker.
• Especially in wet ARMD with CNV, the elastin layer acts as a barrier to the growing CNV (new vessels). Elastin is part of Bruchs membrane link.

Dry ARMD progresses over many years (this page). In some types of dry ARMD progression may be very slow, but it may be quicker in other types. Sight does deteriorate, but most people manage to cope well, although reading is difficult and life may be different.
Dry ARMD may progress to the 'wet type' .

Wet ARMD  begins as new vessels growth in the macular area, causing retinal leakage and swelling. Seepage. 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.

As we get older, changes develop in the retina. The bruchs membrane thickens and the choroidal blood vessels change. see diagram

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, Eye 2013

1. Deposits..basal linear deposit (a thin layer)
2. Deposits of waste products may develop, called drusen
3. the dry changes may convert to 'wet ARMD'
4. or drusen lead to geographic atrophy

In this process

• pigment changes develop
• changes in the choroid pseudodrusen / reticular drusen
• .....patches of extra thin retina develop, just as though the retina is 'worn out'. Often the patches of thin retina gradually get larger, reducing sight.
• drusen containinflammaory proteins, complement, fibrin, fibrin products, lipids, lipoproteins, glycoaminoglycans, amyloid, Eye 2013
• <50% drusen patients develop AMD Eye 2013

These changes are described with photos below. Inflammation plays a significant role, Eye 2013

• difficult seeing in dim light
• needing to read with extra light
• difficult seeing in bright light
• slow recovery in bright light
• poor central vision when you wake up

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).

• progression
• drusen
• soft drusen
• diagram..drusen
• geographic
• foveomacular dystrophy
• Choroidal Sclerosis
• mixed/retinal pigment epithelial hypertrophy

Once the invisible changes above develop, the dry changes develop.

1. drusen develop. These are deposits of various types of fatty (lipids) substances.
2. the drusen may may small and hard...in which case progression is slow
3. alternatively the drusen may soft, in which case the condition usually progresses
4. the soft drusen cause thinning of the retina and loss of sight
5. the degree of sight loss is very variable...depending on the amount of retina that becomes thin. If the very centre of the macula is affected (the fovea) the reading becomes a problem. Sometimes the fovea appears healthy, but the fovea is surrounded by thin 'atrophic' retina....reading may still be a problem as the images of letters that are being read fall  on the damaged non-seeing retina...so you can only see part of words at any one time.
6. the thinning of the retina is called 'geographic atrophy'. Atrophic changes are present in most of the of the 'dry' types of ARMD as below.
7. A number of patients with the dry geographic atrophy or soft drusen also develop wet  macular degeneration. Wet ARMD occurs when blood vessels grow under the macula, and leak and bleed.
   But in some ways it is best to consider wet and dry as different conditions, with different genetic and environmental 'causes'.
8. Eye 2011...risks should be addressed.

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.

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. The progression is a usually a very slow process taking years.

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.

see photo

Patchy vision in atrophic macular degeneration

Some types are non progressive, and not discussed here in detail (such as old macular holes). Every person is different, and often it is very difficult for your doctor to predict what will happen to your sight.Sometimes changes can occur more rapidly, and this would suggest that you are also developing the 'wet' type of ARMD as below. See www.macula.org

The appearance of the retina may be same in different patients (phenotype.) But in fact each person's condition (even though it looks the same to the doctor on the photographs or scans may have different factors such as different genes (genotype).
This is one of the reasons it is so difficult how each person's condition will progress. 2011: no treatment yet.

Dry types of macular degeneration usually progress slowly

• the same retinal appearance in different patients may have different 'causes'.
• it may help to consider wet and dry macular degeneration as 'different' conditions.
• whilst wet usually follows dry ARMD, only one out of three dry ARMD patients develop wet
• by addressing all the risk factors above, especially smoking, the progress of dry to wet may be stopped

There are different types of drusen. They are one of the signs of dry ARMD, and soft and pseudodrusen/reticular predisposed to wet ARMD..

• hard drusen
• soft drusen
• pseudodrusen / reticular drusen

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.

and another large one. another See hard drusen (right) & case.

enlarge...hard drusen with atrophic patches

enlarge...white arrow is pointing to one of the large soft drusens
(Soft drusen, 6/6. vision slight distortion, patient born 1936)

Drusen look like little white spots in the retina. See tiny drusen. 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 lipofuscin. This pigment will also slow down the passage of chemicals to and from the retina.

People with a lot of drusen in the central retina have slightly reduced sight. If there are a few drusen you may be said to have very early 'dry' macular degeneration.

Drusen are slightly related to cholesterol levels. It is logical that reducing the cholesterol will slow down drusen development and therefore slow macular degeneration.Drusen are linked to choroidal blood flow reductions Retina11

UK cholesterol target is 4.5mmol/l, and the World Health Organisation recommends less than 3.5 as ideal, although risks increase above 2.5.
DK therefore advises patients with drusen to try and reach these targets, even if that means using statins (as long as the patient can find a statin that without side effects [statins increase diabetes and cataract risk]). This is especially important for softer drusen as above.

Patients with large drusen: 20% risk or wet ARMD.

Pseudodrusen / reticular drusen

Reticular drusen/ pseudodrusen are vascular changes in the choroid, which appear as RPE changes on the OCT. However, this is an artefact...the changes are in the choroid risk.  Features BJO 2012

Such drusen may lead to wet ARMD: they are related to chromosome 10 gene differences,

See  Photo   Autofluoresence is helpful.

See types of drusen,  risks and epidemiology. Soft drusen are inherited: see CFH Y402H. Drusen come and go BJ0 2010   Types of drusen with photos BJO 2011.

Basal laminar drusen

• Basal laminar drusen OCT 2010
• complement gene

(on separate page)

Areas of thin retina develop, like the patterns of countries of the world. The areas get bigger over years, slowly causing more damage to the sight. Geographic atrophy is the main type of dry ARMD. See a photo

Geographic atrophy (GA) accounts for a third of ARMD, with new 12,000 cases a year in the UK. It is believed to be caused by retinal pigment epithelial atrophy leading to cell death. It is best examined with the autofluorescence technique but this is seldom available Retina 2010. There is no treatment available yet, although trials are in place. FAF photo. Atrophic myopic macular degeneration is usually similar.

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.

It is now clear that GA can lead to wet ARMD, particularly if the GA has an irregular outline ('lobulated'). There is a gene contribution from chromosome 10 genes. This is a more rapidly progressing form, with basal laminar deposits.

So GA is not one disease...it  is the end stage of many different types of 'dry' ARMD, and an intermediate type in others. It is still not known whether the primary priblem is in the retinal pigment epithelium, choroid, or photoreceptors. GA affects 1/3 people >75y.

Wet ARMD may develop, but anti-VEGF will not improve sight BJO 2012 (TTreatment may slow down visual loss.)

enlarge...white arrow is pointing to the geographic change. This progressed over 7 years. Just recently, sight deteroirated, and there are cnv (wet ARMD) which has just begun (blue arrow). Patient male, born 1932. (Only 7% of GA leads to cnv).

Autofluorescence can be used to predict the progression rate.
Lipofuscin deposits demonstrate autofluorescence, with the stressed affected retina showing up white, the atrophic retina black. Crystalline and soft drusen may turn into areas of GA.
Night vision, age, smoking, blood pressure etc can be used to predict progression. Rods tend to be affected first, then cones.

Changes may include thinning of the retina, drusen, pigmentation, or thickening of the retina. There is a variable outcome. ‘Prevention’ may help.

photo     photo    photo

This is a type of dry macular degeneration (ARMD). The damage is confined to the centre of the macula, the fovea. This is a very small central area, and has been described by Gass, and here. Generally the prognosis is good.

However, the retina does become thin in the affected area, and the sight may get slightly worse with age.
A few patients do eventually develop wet ARMD, or other problems. However, this is not part of the condition, and is really coincidental.

See  

• Case 21 for photos and scans
• photo  and  another
• Case 22
  Adult onset foveomacular vitelliform dystrophy / epiretinal membranes
• Adult onset foveomacular vitelliform dystrophy page alone

http://www.nei.nih.gov/health/maculardegen/armd_facts.asp

http://www.eyesight.org/Macular_Degeneration/Pictorials/pictorials.html     
( very helpful)

http://www.maculardisease.org       info@maculardisease.org 
The Macular Society
PO Box 1870
Andover
SP10 9AD
Tel: 01264 350551

ARMD web site http://www.armd.org.uk/index.html

thanks to