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Good Hope Hospital Eye Clinic

Wet age related macular degeneration (ARMD):
Lucentis and Avastin
D Kinshuck

Note:

  • USA: 66% Avastin Both drugs equal BMJ 2012   and here BMJ editorial 2012       Implications BMJ 2012
  • April 2011.it is now official, Avastin is just as good as Lucentis, NEJM 2011 editorial
  • in the Manchester area Avastin is being used replacing Lucentis. The information in this page applies equally to Avastin when used for ARMD. There are many studies in progress comparing the two drugs. Avastin is used twice as often as Lucentis AJO 2011, and is equally effective (College of Ophthalm. statement 2011).
  • This page is designed to be printed out. It summaries the NHS Lucentis treatment program at Good Hope.
  • There is some extremely important information on this page. Further details are available on our website, as below.
  • CNV= choroidal new vessels (the cause of wet ARMD)

Lucentis/Avastin pages

Professionals

Low vision & Macula Disease

Coping & low vision

Support

Macular degeneration

dry ARMD

none-ARMD  macula/retina

PEDs

wet ARMD & Lucentis

Types of wet ARMD

Myopia

Animations etc

Cases for students etc

Further information

Lifestyle

 

What is ARMD (age related macular degeneration)  

The retina lines the back of the eye, like the film in a camera. The macula  is the area in the centre of the retina.The macula is the part of the retina is responsible for detailed vision, that is seeing faces, reading, watching TV. If the macula is damaged central vision starts to become patchy or distorted. ARMD is one of the commonest types of macular damage, and is common in older people. AR MD does not cause blindness, but with reduced central vision life is more difficult

diagram of the macula area of the retina

enlarge

.There are two types of ARMD, dry and wet.

  • Dry ARMD progresses very slowly, over many years. It is essential 'wearing out' of the macula. There is no medical treatment.
  • Wet ARMD occurs when there is a leak under the macula. It progresses quickly. Lucentis dries the leak out, and this page discusses the new Lucentis treatment.

 

central vision is lost in ARMD

enlarge


Wet ARMD

Wet ARMD is a condition in which blood vessels grow under the retina. They grow under the central retina, in the area is called the macula. These growing blood vessels then start to leak and cause a type of blister, like a small 'hill'.When wet ARMD develops central vision starts to become patchy or distorted or bent, after months central vision may get much worse.

Before the wet ARMD develops, invisible aging changes develop over many years.

diagram of wet armd developing

 

Wet ARMD...2 years of activity

Without treatment the blood vessels grow and leak for an average 1-2 years. These leaky blood vessels that cause the 'blister' eventually scar. This leaves a big damaged area in the central retina, and this reduces all the central vision. During the active phase sight gets worse. But after that 1-2 years sight stabilises and often does not get any worse. By the end of 2 years many people have lost a lot of their central vision, and cannot read etc, ut others retain better sight. See animation. Treatment (e.g. Lucentis/Avastin) is needed during the active phase, and is of no help later. Lucentis treatment may be needed indefinitely, although at present few people have received itm ore han 2 years

diagram of macular damage

enlarge

 

VEGF and Lucentis/Avastin    (vascular endothelial growth factor)

VEGF (vascular endothelial growth factor) is one of the main chemical 'fertilizers' that stimulates blood vessel growth and leakage. VEGF is a chemical released by damaged macular cells...these cells are damaged by the aging process. Avastin and Lucentis are two 'anti-VEGF' drugs. They stops the blood vessels growing and leaking, by neutralising VEGF. Lucentis is the the 'anti-VEGF' drug passed by NICE (NICE is the English Government department that approves new drugs). We now know Avastin is just as good as Lucentis, NEJM 2011 editorialThese drugs are antibodies, and are large molecules. As they it cannot be eaten like a tablet, they have to be given by an injection into the eye.

wet armd shown with an angiogram

CNV ..the white patch enlarge

 

The results of Lucentis and Avastin

Lucentis/Avastin usually stops the blood vessel growth and leakage. Lucentis and Avastin make the central scar much smaller that it would have been without treatment. After 2 years treatment, patients may have lost some central vision, but they keep more sight than without the treatment.

The effect is very variable. Some people retain good central vision; some most of their central vision; and some will do badly. Smokers or those with high blood pressure are likely to get the worst results.

  1. treatment this improves sight in 40%
  2. another 50% 'will stabilise', but the sight may get 3 lines worse.
  3. the remaining 10% get much worse (particularly if smoking continues)
  4. unfortunately results are worse in older patients
  5. Different types of wet ARMD respond differently:
  6. official results

none-steroidal eye drops in addtion to anti-VEGF maj help Retina12

 

VEGF trap

This drug is likely to be very helpful.

 

Dry AMRD

There are many other types of ARMD, and most of these are dry. Lucentis/Avastin has no effect on these whatsoever. These dry types or ARMD changes are essentially thinning of the central retina ...'wear and tear' as people get older.

Indeed most patients with wet ARMD will have had dry ARMD changes previously. The wet changes develop as an 'extra'.

Even with successful Lucentis/Avastin treatment the dry changes will still progress, but these changes are extremely slow and take many years.

dry ARMD...drusen
(the creamy patches)
enlarge

dry armd

 

Results of Lucentis/Avastin better with a healthy lifestyle

To get the best results, it is

  • absolutely essential to stop smoking...each cigarette makes the condition 15% worse (proven link). 20 cigarettes increase the progression rate 360%
  • keep a blood pressure below 140 systolic (the top figure)
  • have regular exercise (if well 2 hours walking a day if overweight, 1 hour if thin)
  • keep a cholesterol below 4.5 mmol/l (below 3.5 even better) even if this means cholesterol tablets
  • have a healthy diet low in fat, very low in saturated and trans-fats
  • have 7-9 portions of vegetables/fruit day
  • have very little salt (this is in processed food)
  • pass this message on to the rest of the family...ARMD may run in families
  • vitamin supplements are advised if the diet is poor and you cannot eat the vegetables needed. Doctors disagree as to whether they are needed if you have a healthy diet.
  • ARMD is increased if overweight

smoking..graph..enlarge

UK tobacco companies, promote sales and many people with become blind as a result.

smoking quadruples macular degeneration risk

 

NICE ..eligibility
  1. the best-corrected visual acuity is between 6/12 and 6/96
  2. there is no permanent structural damage to the central fovea
  3. there is evidence of recent presumed disease progression (blood vessel growth, as indicated by fluorescein angiography, or recent visual acuity changes)
  4. lesion size is less than or equal to 12 disc areas in greatest linear dimension

 

The Lucentis/Avastin treatment program

Initially growing blood vessels stop growing for about 6 weeks after a Lucentis/Avastin injection. Later the vessels may stop growing for longer. Here is an outline of the treatment program.

Lucentis injections are given monthly for 3 months. Then monthly check ups are needed, and more Lucentis/Avastin is given each time there is some leakage.

Optometrist / patient suspect diagnosis
arrow
referral to rapid access macula clinic
arrow
diagnosis confirmed....vision measured, fluorescein angiogram +/- OCT scan carried out, eye examined by doctor

arrow

date for 3 lucent is injections given, about a month apart, with follow up one month later

arrow
follow up visits about every month for 2 years (see below), and may be after that. Repeat OCT and brief examination, if fluid present repeat injection
arrow
repeat injections, follow up appointment given
arrow
follow up, repeat injections if active

 

NICE ..results
  1. 'classic' neovascular ARMD responds much better.
  2. assess with OCT at future visits..treat whenever there is a 100µ increase in retinal thickness in foveal area.
  3. after 3 injections a 1 month check,
  4. Most experts advise... if inactive may extend the next check interval (this is a very controversial issue at present).
  5. PDT laser or intravitreal steroids may be needed for certain cases, in addition to Lucentis/Avastin.
  6. 'occult' neovascular ARMD, type 1' with a PED responds the least, and occasionally the retina may 'rip', but they are still moderately effective. See the Marina study.
  7. Lucentis/Avastin will also be effective against 'occult' neovascular ARMD, type 2 (without a pigment epithelial detachment).
  8. see NICE

 

Referral from Optometrists

Referral will be accepted from optometrists finding wet ARMD, that is ARMD with fluid and haemorrhage. Patients will be seen in the rapid access macular clinic

  • FAX number (will be written here when working, same number for Good Hope, Solihull, Heartlands) )
  • investigations will be carried out.
  • Patients with dry ARMD or ineligible patients will considered for the Low Vision Clinic and partial sight registration.
  • eligible wet ARMD patients will be given dates for the 3 'loading' injections and follow up clinic.

 

Low Vision Clinic

A full Low Vision service is available at Good Hope (and most Eye Departments). Patients can be referred by the GP at any time. In addition to specific help reading, we try and identify patients who need extra support or social contact in the community, and liaise with social services, help groups, and other community support groups. The clinic is for anyone who

  • cannot read properly
  • says their glasses are still not correct
  • with ARMD with visual difficulties
  • cannot drive their car or read n10
  • asks for LV appointment or a magnifier
  • any eye condition
magnification aids AND social  support needed...from the Low Vision team

 

Lucentis/Avastin, 3 injections to start

These are a requirement of the program because Lucentis/Avastin works best if given as 3 injections. These are a month apart, with no examination in between. Antibiotic drops are prescribed before and after the procedure.

 

Lucentis/Avastin: the injection

Lucentis/Avastin is given as an injection into the vitreous cavity of your eye. It is given in a clean room or an operating theatre. The injection procedure itself takes seconds and is usually feels like a tiny prick. You can go home later that day...this is a 'day case' procedure'.
Good Hope, Heartlands, and Solihull patients will be treated in their respective hospital when possible. Good Hope patients in the new Treatment Centre.

 Wet macular degeneration with fluid (green)
Macular degeneration affects the centre of the retina which is responsible for sharp vision.
The front of the eye is on the left, and the retina is shown in purple.For the Lucentis/Avastin injection, the eye is cleaned. Anaesthetic drops are instilled, and a few minutes later the nearly painless injection is given. The eye pressure may go up for a few hours, and extra treatment may be needed.

enlarge

diagram of lucentis intravitreal injection

 

Risks etc

Hours

The injection will put the eye pressure up for a few hours. It is therefore riskier is you have glaucoma, but this is generally not a major problem. There should not be much pain

Night

Days

About 1/1000 people will develop a serious eye infection. The day after the injection your eye should be comfortable, there should be very little pain. If your eye starts to get red, with misty vision (there may be no pain), perhaps 2-5 days after the injection, you should suspect an infection and attend your eye department urgently. In Birmingham this is the Birmingham and Midland Eye Centre Casualty at the
Birmingham & Midland Eye Centre, City Hospital, Dudley Road, Birmingham B18 7QH
Tel: 0121-554 3801. Avastin, infection..preventing.

Risks summarised

Summary  Rarely cataracts, retinal detachments, macular haemorrhages (BJO 2008), a rip Eye 2011.

Pregnant

Retina 2012

Anticoagulants ...extra precautions

See ..You should remind your ophthalmic team you use anticoagulants and ask for specific advice. Treatment is safe continuing the anticoagulents (Retina 2010).  Epidemiology 2010

Anticoagulants

If patients are using anticoagulants (warfarin) Lucentis is still safe:

  1. The INR should be less than 3.0
  2. If the INR is steady, with a test in the last 4 weeks, another test is not needed
  3. if your INR fluctuates it should be repeated.
  4. There is a slight increase in bleeding for warfarin patients, both on the surface of the eye, and into the cavity of the eye (vitreous haemorrhage). Such bleeds will not usually be serious.

 

Blepharitis

This is a low grade infection of the eyelids (see).

  1. In this condition there is a small risk that bacteria from the eyelids can cause enter the eyeball when the injection is given, producing a very serious infection as above (endophthalmitis)
  2. Patients with severe blepharitis need intensive treatment before the injection (see). Antibiotic drops, tablets, and lid cleaning.
  3. Patients with mild blepharitis should start lid cleaning.
  4. Intermediate severity...lid cleaning and possibly drops

 

Follow up clinics

Patients are required to have check ups every 4 weeks. This is a requirement of NICE and the funding Primary Care Trusts.

At these visits

  • patients will see the macular clinic nurse and have their vision measured
  • OCT examination
  • eye examined by doctor (not all patients)
  • later if the condition is stable appointments may have longer gaps
  • re-treatment is arranged if the OCT demonstrates a 100µ increase in retinal thickness in foveal area
  • retreatment is needed if the vision gets worse (and this is due to the CNV recurring)
  • vision usually gets worse about 4 weeks after this increase in fluid...if your vision changes, this does suggest fluid is accumulating and the new vessels have starting growing again
  • Treatment needs to be given as soon as possible after the 4 weekly scan. Delays can cause loss of sight Eye 2012 Action on AMD
  • Large areas of CNV will need more treatment, often with a little improvement with each injection. 6-12 may be needed before initial stabilisation.

healthy macula  OCT

a healthy OCT  (F = fovea, the centre of the macula)

OCT showing fluid due to CNV

fluid has accumulated...more Lucentis needed enlarge

Follow up visits

  • for the 6 months after an injection, every months
  • if there has bee no injection for 6 months, visits every ~6 weeks
  • 12 months after the last injections, every 3 months
  • if there is fluid at any follow up visit, generally 3 injections arranged

 

NICE ..stopping treatment
  1. Lucentis should be continued only in people who maintain adequate response to therapy.
  2. Treatment is stopped if there is a persistent deterioration in visual acuity with identification of anatomical changes in the retina that indicate inadequate response to therapy.

 

Wet ARMD and 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 below.

  • The atrophic or dry type usually does occur in both eyes, but remember this generally gets only slowly worse.
  • There may be a gap of years before the process begins in the second eye.
  • The neovascular or wet type can also affect the other eye, at an overall rate of 90% over the next 5 years.
  • 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.)

 

Distortion of Vision and other symptoms of 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

  • distortion of vision, where straight lines such as window frames appear bent as shown below
  • a feeling as though you are looking through water

We advise using 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. Good Hope patients should contact the Rapid Access Clinic contact team). The test is explained well here.Your ophthalmologist may recommend tests such as a fluorescein angiogram. This will demonstrate any new vessels, where they are, what type they are, and what type of treatment if any will help.

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.

 

The Macular Society

The main support and information group for ARMD patients is the Macular Society. http://www.maculardisease.org   
info@maculardisease.org 

The Macular Society
PO Box 1870
Andover
SP10 9AD
Tel: 01264 350551

 

More information

See our website (google Good Hope Eye clinic and ARMD), and the links opposite. The web address of this page is in the 'footer'. Additional treatment may be needed for some patients. These include

What to expect in the eye clinic

After your consultation you should be aware of the following. Ask for a second consultation if you would like one...at Good Hope a Low Vision appointment is offered and these issues are discussed a little again.

  1. you should be told the diagnosis...wet. dry etc
  2. something can be done even if there is no medical treatment (explanation, counselling, low vision support etc)
  3. be told about any local trials
  4. told the treatment options which should now be available in the NHS
  5. be told that the condition may progress...dry can convert to wet, wet can progress, severe wet  ARMD can lead to visual hallucinations (Charles Bonnet)
  6. be aware of low vision support with optical aids, computer access for reading etc; and be referred to low vision service even if not bad enough to be registered partially sighted
  7. if visual loss is severe be registered partially sighted etc
  8. aware of the importance of a healthy diet, regular exercise, and particularly the dangers of smoking
  9. aware of local agencies that can help, e.g. the Macular Disease Society and Birmingham Focus
  10. have a booklet explaining wet ARMD

 

References

References are placed in the appropriate section, but this is a list starting 2012.

 

Nurse Injection

In some departments nurses are carrying out these injections. Results are similar. (Moorfields and Exter in particular).

 

Symptoms of infection

Eye 12..these are the common symptoms that patients notice.

  1. blurred vision........96%
  2. pain/photophobia...73%
  3. redness ...............50%
  4. floaters................25%
  5. lid swelling ...........10%
  6. discharge .............10%


 

 

Apologies to visitors for all the site moves. It is now here www.goodhopeeyeclinic.org.uk/  and hopefully will not move again.

Eye website feedback -- Heartlands -- page edited June 2012 -- Public transport to Good Hope --