Good Hope, Heartlands, and Solihull Eye Clinics

Age Related Macular Degeneration (ARMD) pathology & treatment

David Kinshuck

ARMD introduction

ARMD is an aging change or wearing out of the central retina. It causes loss of central vision. This makes reading and driving difficult. Later, if it gets more severe, it becomes difficult seeing faces, crossing roads, and cooking. The peripheral or side vision always remains, so even if the central vision is poor, it is always possible to see and get round the house and see to the side.

ARMD is usually a progressive condition. Invisible early changes occur, then usually some type of dry ARMD, such as drusen. Later, the dry changes may progress, usually slowly, to cause geographic atrophy and thinning of central retina. These are all termed part of 'dry' ARMD. Treatment for geographic atrophy is awaited.

A secondary change may then develop in some people, as the body tries to 'heal' the changes. Blood vessels may start to grow in the centre of the retina in the macula area. The blood vessel growth causes leakage and scarring, and is termed 'wet' ARMD. These wet changes can be slowed down with anti-VEGF eye injections (wet ARMD page).

This page summarises our current knowledge. Age-related macular degeneration is explained in more detail on other web-sites, such as the RNIB and NIH. An excellent animation: www.eyesight.org.

 

Contributing factors: aging, genes, diet, smoking, etc

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. 

"By age 85, 57.4% of [people have] AMD. Age, smoking, plasma HDL cholesterol, BMI, and female sex are associated with AMD. Elevated HDL cholesterol is associated with GA development."  .Oph 14

 

age Age is the main factor.
smoking Contributes 32% overall, even passive smoking. BJO 17
diet related up to ~30%; a high cholesterol from an unhealthy diet or genes Klein (2010); Toothbrushing helps. (tooth decay promotes conditions such as rheumatoid arthritissummary  BJO16  
blood pressure High blood pressure damages the circulation...target is 140 systolic in clinic, 10 lower for diabetes. 10 lower at home. 120 at home for diabetes. Best below 120    2 medications often required.
exercise

;reduces progression to neovascular ARMD by 70%     AJO17

genes ~50% is directly due to the genes we inherit Gene page
cholesterol a high fat diet 10% (2010)
airbourne pollution This causes cardiovascular disease, and will contribute to macular disease. In urban environments, ~8% of deaths are generally attributed to pollution BMJ 14
alcohol Excess alcohol is also related to ARMD, see 
sunlight Strong sunlight contributes to ARMD; and sunglasses protect, see.  But gentle sun exposure increases vitamin D production, and this will reduce the risk of many conditions such as diabetes, osteoporosis, and prostate cancer. Retina16
inflammation Chlamydia  high CRP, dental caries, each contribute
macular pigment Light skin increases risk Eye 2012.
obstructive sleep apnoea Untreated obstructive sleep apnea hinders response to bevacizumab in age-related macular degeneration  Retina 16     BJO 17
Oral Bisphosphonates AJO 16     2-4x risk
Choroid BJO 17

 

Other countries

pie chart illustrating factors contributing to ARMD

enlarge

 

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, the lack of protective fats (omega 3s, from fish), and salt (by increasing blood pressure) increases ARMD. Lack of exercise as we drive everywhere in Western countries will contribute.

 

Genes

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. The main genes have been found. Gene page.   For example, these genes control the way used-up chemicals are removed from the eye. Being long-sighted (hyperopic) is also a risk factor

 

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

smoking increase the risk or ARMD 3-4 times

 

the risk of smoking and passive smoking and ARMD

larger

  • 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 receive 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    China  
  • Passive smoking doubles the risk  ,  personal smoking triples the risk of both geographic atrophy and neovascular ARMD.
  • Each cigarette increases the ARMD progression rate ~15%.

 

Blood Pressure & Exercise

dancing and all other forms of exercise delay ARMD

 

  • 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 (regular walking) three times a week will reduce ARMD risk by one third, 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.

Alcohol

 

after 8 units of alocohol blood pressure rises for 2 days

enlarge

Too much may contribute indirectly by increasing blood pressure, and is related to ARMD, see.

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.

 

Diet

Experts recommend a healthy diet.

fruit and a healthy diet will sigificantly reduces the risk of developing ARMD

7 portions of vegetables a day and 2 portins of fruit, with portions of different colours

 

 

Fruit/vegetables prevent 36-50% of ARMD see, see and see (fruit & vegetables lower homocysteine levels, and this improves blood flow) BMJ 15. 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).

Vitamin supplements

Age-Related Eye Disease Study--Results

Lutein and Zeoxanthin  supplements slow down progression on average 10%, AREDS 2, 20% if diet is poor.

As the macula is the most chemically 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 dark 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.  No need Cochrane 2017.

References

 

Oily fish

oily fishes reduces ARMD  ~40%

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. See

 

Cholesterol & statins, patient and relatives

Statins

Statins benefit

no benefit

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. DK recommends 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. Statins may not help

 

 

Macular pigment

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.

 

Cataract surgery and Vitreous changes

cataract

One paper suggests cataract surgery leads to an extra 4-5 times risk of developing neovascular macular changes or dry ARMD. Another states this is not so AREDS 25. 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.

If the vitreous is separated from the macular the risk of CNV is significantly reduced AMJO 09.

 

The retinal changes in ARMD

Invisible changes

These are the different layers of the retina:

retinal layers

the different retinal layers

As we get older, changes develop in the retina. The bruchs membrane thickens and the choroidal blood vessels change. diagram. The thickened bruchs membrane prevents waste products leaving the retina (animation) , and also prevents nutrients entering. Lipofuscin (type of fat) accumulates in the retinal pigment epithelium (RPE); this damages the pigment cells which eventually die. The choroidal circulation changes...the blood vessels become larger. This is probably mainly due to a 'hardening of the arteries' that happens particularly with a Western diet.

thickening of bruchs membrane with age in macular degeneration, diagram

 

Unfortunately these invisible changes tend progress, and this process is called 'dry ARMD' Eye 2013, leading to

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

In this process

  • Pigment changes develop; pseudodrusen / reticular drusen. develop in the choroid.
  • Drusen contain inflammaory proteins, complement, fibrin, fibrin products, lipids, lipoproteins, glycoaminoglycans, amyloid, Eye 2013  Inflammation Eye 2013.
  • Patches of extra thin retina develop, just as though the retina is 'worn out'. These patches enlarge reducing sight (geographic atrophy),.
  • <50% drusen patients develop AMD Eye 2013.

 

What does a person notice with very early dry ARMD?

You may notice difficult seeing in dim light, needing to read with extra light, difficult seeing in bright light, slow recovery in bright light, and 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. A healthy lifestylewill delay or prevent AMD and other health problems.

 

Types of 'dry' macular degeneration

As the dry changes progress, sight is affected. Detailed vision is worse, so it becomes harder to read, hard to see details on television, and later harder to drive. Optometrist are able to detect the macula changes, which are described here:

 

Drusen

Drusen look like little white spots in the retina. 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 flow of chemicals to and from the 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.

See diagram types of drusen  after Eye 17

 

Hard and soft drusen:

If they are well defined with a sharp edge, the sight is likely to stay good for a long time.

If the white spots look a little like cotton wool, they are termed soft drusen. these are more of a problem as they may lead to geographic atrophy (thin retina) or wet AMRD.

 

hard drusen

enlarge...hard drusen with atrophic patches

 

soft drusen...see white arrow

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

 

drusen

drusen (in between hard and soft)

 

Drusen are slightly related to cholesterol levels. It is logical that reducing the cholesterol will slow down drusen development and therefore slow macular degeneration. 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).

Pseudodrusen / reticular drusen

pseododrusen = reticular drusen: predispose to wet ARMD

 

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 2012See  Photo   Autofluorescence is helpful

 

Basal laminar drusen

An unusual type of drusen, sometimes linked to the conditions.

Geographic atrophy (GA)

geographic macular degeneration, diagram

Geographic atrophy (GA): patchy areas of thin retina (atrophy) in the macula area

Separate page.  GA is very common indeed. Patches 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, with very patchy central vision. GA 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 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 GA and wet ARMD. Genes and here.

 

geographic ARMD with cnv

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

 

GA small print

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 problem is in the retinal pigment epithelium, choroid, or photoreceptors. GA

  • affects 1/3 people >75y.
  • causes 26% of uk blindness 
  • Incidence quadruples each decade 
  • 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. New treatment
  • Eye 17.. link with renal function

Concerning the change for GA dry arm to wwet

  • Bilateral ga less likely than unilateral to get cnv
  • cnv are more likely if the GA has an irregular outline ('lobulated').

 

Mixed

mixed macular degeneration, diagram

Mixed type of dry AMD: drusen, pigmentation, and atrophic patches.

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

Thickening of the retina is termed 'retinal pigment hypertrophy'.

Adult Bests,
previously termed Adult onset foveomacular vitelliform dystrophy (AOFVD),

macular degeneration of gass, diagram

A pale are develops in the central retina (the fovea) is affected, leading to problems with central vision.

 

This is a type of dry macular degeneration (ARMD), now know as adult onset Bests disease. 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. Only a few patients do eventually develop wet ARMD, or other problems.

adult best oct and photo

OCT: drusenoid PED..vision 6/24, very little change in the last 2 years

See  

 

Summary; progression of 'dry' macular degeneration, but staying dry

dry AMRD

phagocytosis of tips ...normally tips of photoreceptors (rod outer segments) are repaired every night

phagocytosis of tips of photoreceptors (rod outer segments).

phagocytosis efficiency of RPE reduces

debris accumulates, such as drusen & thickened basement membrane

inflammatory component

atrophy

VEGF > wet

After the invisible changes above develop, dry changes may 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.
  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.

 

 

atrophic macular degeneration

atrophic patches see photo

 

patchy central vision is a symptom of macular degenerationPatchy vision in atrophic macular degeneration

 

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.

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.

Some types of dry ARMD are none 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.   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 ARMD may progress to wet

As above, some types of ARMD do not progress. Most progress slowly to give areas of atrophy. These areas may enlarge to cause GA In some types of dry ARMD progression may be very slow. Sight does deteriorate, but most people manage to cope well, although reading is difficult and life may be different.

But occasionally dry ARMD may progress to the 'wet type' : essentially the body tries to 'heal' the damaged area, and a network of blood vessels starts to grow in the central retina (Wet ARMD) . Dry types of macular degeneration usually do progress slowly:

  • it may help to consider wet and dry macular degeneration as 'different' conditions.
  • whilst wet usually follows dry ARMD, only one third of dry ARMD patients develop wet
  • by addressing all the risk factors, especially smoking, the progress of dry to wet may be stopped

 

Wet ARMD (exudative/leaky)

Wet ARMD

retinal damage

VEGF
(vascular endothelial growth factor)

blood vessel growth

leakage..blood and fluid

give anti-VEGF drug

leakage stops for a while

In wet ARMD, new vessels grow under the central retina in the macular area, causing retinal leakage and swelling. (CNV..choroidal neovascularisation). The blood vessel frowth seems to be part of the eye's 'healiing' response to ack of oxggen/damage. The damaged retina releases a chemical VEGF (Vascular endothelial growth factor). The VEGF stimulates blood vessel growth, to produce the different types of wet ARMD. In addition, the new blood vessels leak, causing fluid under the retina in these condition.

The network of blood vessels usually progresses to cause a scar in the macular area. If the scar is small, sight is reasonable; but if large, the sight can be very poor. 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). This is described below.

There are different types of wet ARMD

Type 2 CNV (formally termed 'classic CNV')

 

early cnv (macular degeneration)

New vessels growing under the central retina in a 'classic' pattern: Anti-VEGF treatment needed.  enlarge  Photo (case 12)

 

When blood vessels grow under the macula, this is termed choroidal neovascularisation (CNV). When the new vessels are seen easily on a fluorescein angiogram, they are called 'classic CNV': they look like a net of blood vessels.

When a doctor looks in the retina looks elevated, there may be tiny haemorrhages, a grey area, or exudates. Severe . 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 early you can still read, but if it becomes severe reading with any magnifier is impossible. Treatment is based on anti-VEGF drugs,  although other treatment are available

This is usually a serious type of macular degeneration, serious because it can cause very poor central vision. 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.

ARMD progression rate and relative risk of smoking geographic neovascular
active smoking x 3.4 x 2.5
passive smoking x 2

see

 

'Occult' CNV type 1 (no PED)

type 1 CNV ('occult')

type 1 cnv

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 . Occult and classic patterns can occur together. Anti-VEGF drugs generally help. The symptoms of this type of CNV are the same as 'classic CNV', except the condition takes longer to develop. Without treatment, this type 2 occult CNV usually turns into classic CNV over the next months or years, to cause poor central vision.

  • Large occult membranes can develop haemorrhages with anti-VEGF treatment (BJO 2008).
  • photo   another   another..occult/mixed    another   flash   another    large diagram
  • The term occult is not really used now: the condition is a subtype of wet armd sometimes termed type 1 cnv.
  • Sometimes there is a hyper-reflective material which is related to prognosis, and to pachychoroidopathy (= thickened choroid).
  • Sometimes there is fluid, but if the fluid is stable injections don't seem to help.
  • This is similar to the type 1 cnv below, the difference being there is no ped

CNV type 1

type 1 cnv

type 1 CNV

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. This type of CNV probably an early phase of classic, see . Occult and classic patterns can occur together. Anti-VEGF drugs generally help. The symptoms of this type of CNV are the same as 'classic CNV', except the condition takes longer to develop. Without treatment, this type of CNV usually turns into classic CNV over the next months or years, to cause poor central vision.

  • Large type 1 CNV membranes can develop haemorrhages with anti-VEGF treatment (BJO 2008).
  • photo   another   another..occult/mixed    another   flash   another    large diagram
  • The term occult is not really used now: the condition is a subtype of wet armd sometimes termed type 1 CNV.
  • Sometimes there is a hyper-reflective material which is related to prognosis, and to pachychoroidopathy (= thickened choroid).
  • Sometimes there is fluid, but if the fluid is stable injections don't seem to help.
  • This is similar to the type 1 CNV below, the difference being there is no PED

CNV type 1 with a vascularised PED

In this ttype of CNV there is a PED (pigment epithelial detachment)

 

 

occult cnv with a PED (a type of macular degenerationa PED..pigment epithelial detachment, with CNV (choroidal neovascularisation): type 1 with a PED. This condition usually progresses, but progression rates are very variable.

 

In this type of wet ARMD the damaged area looks like a dome, but in addition fluid leaks under the retina, hence the term 'wet'.

Anti-VEGF drugs generally help. The PED may reduce in size with treatment, and treatment will reduce intraretinal and subretinal fluid. Retina 2011. Occasionally the retina may 'rip', causing more loss of sight Eye 2011. Overall, 15% of PEDs rip, but the risk is proportional to the PED size, so a large PED is much more likely to rip. About of 8% of patients may develop worse sight with treatment Retina 17. The rip typically occurs 2 months after starting treatment. The rip may not cause that much visual loss initially, but central vision may get worse over time.

 

a vascularised PED (a type of wet ARMD)

November, 7 months later, a PED has developed, with a retinal haemorrhage. Also, intraretinal and subretinal fluid.

Patient, age 86, April, reasonable vision 6/24 Photo / OCT show drusen, hard and soft enlarge

Professionals

  • ARMD with a PED is classified as 'occult' CNV, type 1.  Outcomes Eye 11
  • Look for polyps,    see   PCV.
  • photo  case 9 r/l     left     case.
  • There are 3 types of PED, reviewed here (avascular, occult, polypoidal). 
  • photo avascular PED
  • intraretinal cysts indicate a poorer response BJO14
  • combined with geographic atrophy BJO 14
  • treatment helps stabilize/improve SIO 15
  • fluid fluctuates with injections every 2 months
  • serous PEDs respond better Retina 16; switich antiVEGF if response poor.
  • incomplete response to antiVEGF AJO 16    Vriable response  Retina 17

 

 

Polypoidal choroidal vasculopathy

This is another type of CNV. The condition is seen as a branching choroidal network of vessels with vascular dilatation.

  • more common in Chinese and Afro-Caribbeans.
  • The choroidal neovascularisation often occurs with a serous haemorrhagic PED.  
  • Polypoidal choroidal vasculopathy page.   
  • multiple PEDS, subretinal haemorrhages, visible polyps: deep orange lesions
  • lipid exudates, subretinal fluid, RPE atrophy, peripapillary lesions
  • classic & occult cnv, peripheral lesions: Features see
  • distinguishing polypoidal choroidal vasculopathy from typical neovascular age-related macular degeneration based on spectral domain optical coherence tomography Retina16
  • Wilki
  • type 1 and type 2 IOVS

 

 

Other types of wet ARMD

 

Pigment epithelial detachments (PED), summary

PEDs are present in different types of ARMD, but the caues are slighty different. The treatment depends on the cause. The PED is a dome of fluid under the pigment layer of the retina.

Hereare the different types of PED, some of which were discussed above:

 

Serous (avascular) PED

This is another type of PED, without any vascular element. In younger patients this is usually part of Central  Serous Retinopathy. In older patients this is usually part of 'dry' ARMD, and there may have been obvious 'dry' changes visible before this develops. Anti-VEGF treatment is not helpful (Eye 2010). Perhaps a serous PED in an older patient is better thought of as half way between dry and wet ARMD.

However, if the other eye has had wet ARMD, then such an eye is at very high risk of wet ARMD itself. Eye 2012  . It is probably safer for such a patient to have regular OCT examinations, perhaps every 3 months: as yet there is no evidence to prove that this will help, but logically it will help by detecting very early disease that is much easier to treat.

The PED is a dome of fluid under the pigment layer of the retina. there is a 'PED' only, no leak
enlarge

'PED', with a leak under the retina (shown here) or in the retina

  

 

 

 

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

How would you know if you have the 'neovascular' type of age related macular degeneration? Some symptoms suggest you may be developing the problem:

  • best to continue Retina 17
  • distortion of vision, where straight lines such as window frames appear bent as shown below
  • a feeling as though you are looking through water
  • distortion only occurs in 10-50% of patients
  • 7/8 patients have no symptoms in the early stages  BJO 2011
  • amsler helps with training Eye 2012
  • Amsler helpful Eye14
  • strategies for early detection CO14
  • need to detect early BJO 16

If you do develop distortion of vision you usually need to see your optometrist or ophthalmologist and have an OCT scan within a few days. See the amsler test below.  Your ophthalmologist will recommend an OCT scan, and this shows the wet ARMD immediately.

In addition 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 treatment if needed.

Wet ARMD progresses 4 times faster (a 400% increase in progression rate) in smokers. 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. photos  There may be a trigger factor such as inflammation, that triggers the conversion of dry to wet. (For example. teeth decay bacteria have been implicated.)

 

Amsler grid test

distortion of sight

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.

Patients should 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 (this is a major problem). 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 optometrist, ophthalmologist (or in Birmingham attend the Eye Centre Casualty, City Hospital).  The test is explained well here . home device  another Ophth14

Unfortunately visual changes follow changes that can be detected by OCT scans BJO 2011  CNV are detected

  • 1/8 when the patient notices changes generally
  • 1/3 when there are changes in the amsler grid
  • 1/3 by reduced vision acuity reading a chart as compared with OCT. Monthly OCTs are necessary to detect recurrences!
  • late presentation is common and linked to social deprivation BJO14
  • a home device may be best Eye 16  see

 

ARMD and the other eye, risks

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. Risk from drusen

  • The atrophic or dry type usually does occur in both eyes, but remember this generally gets only worse slowly.
  • There may be a gap of years before the process begins in the second eye.
  • If one eye has had wet ARMD, and the other eye has a PED, then screening with regular OCTs may help.
  • If you notice the symptoms (central vision becoming distorted or blurred, sometimes like looking through water) you should have your eye checked with an OCT scan: see distortion.

Concerning neovascular or wet type ARMD:

  • The neovascular or wet type can also affect the other eye, at an overall rate of ~50% over the next 5 years. BJO 17
  • High blood pressure, one large drusen near the fovea, 5 drusen in the macular area, and retinal pigment epithelial changes each contribute to this 90%.
  • So if you have only one of these risk factors, such as 5 drusen and a low blood pressure and don't smoke, then the progression rate is 90/4, that is about 23% over a 5 year period . If you have 2 risk factors, 45%.
  • But if you have 2 risk factors (45% 5 year risk) and your partner smokes 20/day, your risk is 45 x2 = 90% over 5 years...see immediately below.
  • The figure is 4 times higher for smokers, and twice as high for passive smokers. (If smoking at 20 cigarettes/day.)
  • the active phase may last 3-12 months, with the sight deteriorating during this time, and after that they may be little change. Treatment (laser & drugs) is needed during the active phase, and is of no help later. Anti-VEGF treatment may be needed for 2 years.

 

Aspirin and anticoagulants

Thanks to colleagues

  • aspirin and anticoagulants can lead to more aggressive wet ARMD etc, JAMA 2013
  • Secondary prevention: there is strong evidence that its benefits of aspirin and anticoagulants outweigh the risks
  • Primary prevention: risks and benefits. In patients who, under current guidelines, are eligible for treatment because of their 10-year risk of myocardial infarction or stroke, "the presence or absence of strong risk factors for neovascular AMD might tilt treatment decisions in one direction or the other."
  • Other uses of aspirin: be cautious in recommending long-term aspirin to other patients, such as those requiring pain control.

 

Some other features of ARMD

Scarring

macular scar diagram ARMDScarring in ARMD
photo

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 scarring is likely.

 

Rip / tear

Sometimes retina in the macula area can tear and shrink. This is call a 'rip' or a 'tear' of the pigment epithelium. It may occur spontaneously as part of wet ARMD, but can occur after PDT or anti-VEGF treatment, particularly if there is a large PED. A rip may cause significant loss of central vision see. but the risks are only slightly increased.

The chances of rip depend on how elevated the PED is (the retinal pigment epithelial detachment). For instance, an 840μ elevation has a 50% chance of ripping. A 500μ elevation has a 10% chance of ripping. Gelsiken 2009   A Case.   Rip: separate page for printing.

 

Abbreviations

Here is a summary of some of the abbreviations ophthalmologists use in this condition:

anti-VEGF / injection drugs that reduce growth and leaking from the new blood vessels under the retina in ARMD, or on the retina in diabetes etc. They are given by injection into the eye. Avastin, Lucentis, Eyela.
ARM age-related macular disease = age-related macular degeneration = ARMD
ARMD age-related macular degeneration
Classic CNV easy-to-see neovascular ARMD    (based on angiogram) blood vessels growing under the retina and leaking
CNV choroidal new vessels (i.e. neovascular macular degeneration, or 'wet'). Blood vessels 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
CSR central serous retinopathy
drusen a type of aging change of the retina...tiny white spots/areas
dry ARMD thinning (and other changes) of the central retina
FFA fluorescein angiography
Fovea the very centre of the macula
GP general practitioner
ICG indocyanine green angiography
IRF, irf intraretinal fluid (an OCT scan finding)
macula the centre of the retina that sees detailed vision like faces and reading
neovascularisation similar meaning to wet armd
NSD, nsd Neurosensory detachment
OCT / scans optical coherence tomogram: a 3 dimensional photograph of the macula, called a scan
Occult CNV hard-to-see neovascular ARMD (based on angiogram) blood vessels growing under the retina and leaking (but the leakage is late) (type 1 CNV)
PCV Polypoidal choroidal vasculopathy
PDT photodynamic therapy (for classic sub-foveal neovascular ARMD )   
PED pigment epithelial detachment, a type of wet ARMD
RAP, rap retinal angiomatous proliferation (type 3 cnv)
Rip a pigment epithelial rip or tear
SRF subretinal fluid (not subretinal fibrosis)
Subretinal fluid fluid under the retina typically type 2 cnv (or part of other types)
VEGF Vascular endothelial growth factor...the main chemical that makes blood vessels grow in ARMD
VMC Virtual macular clinic..patients attend for an OCT and the scan is interpreted later, and the patient contact if another anti-vegf injection is needed
wet (armd) wet age-related macular degeneration, with CNV as above (blood vessels growing and leaking under the retina, usually under the macula)

 

Links

 

support, USA Macula Degeneration Support Website
animation http://www.eyesight.org/Macular_Degeneration/Pictorials/pictorials.html   (helpful)
anatomy http://webvision.med.utah.edu/book/part-ii-anatomy-and-physiology-of-the-retina/
more facts, UK Royal National Institute for the Blind
support, UK http://www.maculardisease.org       info@maculardisease.org 

The Macular Society
PO Box 1870
Andover SP10 9AD
Tel: 0300 30 30 111

ARMD web site http://www.armd.org.uk/index.html
depression this is common and can be prevented/treated   See our LVA page
thanks to Photos thanks to Good Hope and BMEC photographers/staff