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New drug treatment for Neovascular ARMD: some notes  David Kinshuck 2008
'Low vision' section,
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RNIB page (link)
Hints & Coping
Macula degeneration: pathology
dry ARMD
wet ARMD

myopic macula degeneration

Macula degeneration: understanding
Risk simulation
Diabetic maculopathy (link)
Coping with poor sight in one eye
Magnification

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Walsall Eyes Newsletter
Macular Disease Society
New drugs..Lucentis, Macugen, Avastin  
A table comparing drugs
Studies published and in progress

Audio interview (NEJM)
Rehabilitation Centre
rnib.talkandsupport

Links
Abbreviations

education

Large diagram 1
Large diagram 2
Animation full size
Animation (link)
Case 1 macula for students: 400kb
Case 2 macula: hard drusen
Case CSR
Case 4: wet macular degn (CCNV)
Case 5: occult CNV
Case 6 soft drusen
Atlas...Bests, Haem
SWF file for laptops of light/macular animation: 1mb
epidemiology
US Aging Times Review

Genes
treatment advances

injection...prevention infection

Lucentis, Macugen, Avastin

These drugs which are given as injections into the vitreous cavity of the eye see. They are very effective treating most types of wet ARMD.

They are anti-growth factor drugs, and work by preventing the growth factor VEGF from working. VEGF stimulates the growth of the 'new blood vessels' involved in neovascular ARMD, so when its effect is blocked the vessels close and the leakage stops. The VEGF is released from damaged retina.

NICE have announced in provisional guidleines that Lucentis will be funded in the next few months. This is for both classic and occult wet-armd.

Research suggests Lucentis is the most effective. Macugen is less effective, and both have been approved by the FDA. Macugen . These drugs may be more effective if used in combination with PDT.

Many ophthalmologisst believe that Avastin (Moorfields)  is just as effective as Lucentis, either but it has to be given 'off label' in the UK; both are now approved in the US, but only Lucentis is licensed for use in the UK.Avastin is much cheaper than Lucentis, and is made by the same company. All the research has been carried out with Lucentis, not Avastin. It is likely that this is because the company has a conflict of interests, and there is much less profit to be made from Avastin. The company is withdrawing cheap Avastin from the US making it difficult for ophthalmologists to use.

Avastin is safe    studies of avastin   for a RAP    CNV ARMD    more studies

The benefits of Lucentis (Ranibizumab) are described in October 2006's NEJM in minimally classic/occult ARMD, and in classic . The financial aspects, and the debate as to whether ranibizumab (Lucentis) and bevacizumab (Avastin) are most effective, is discussed here . An audio interview is here.

Although these drugs are effective, 'dry' macula' changes still progress after treatment and sight can slowly deteriorate over years.

 

Current protocols
  1. Assess all patients eligible with FFA

  2. Patients have to have sight 6/60 or better (or equivalent)

  3. Lucentis injections monthly for 3 months

  4. assess with OCT at future visits..treat whenever there is a 100 micron increase in retinal thickness in foveal area.

  5. after 3 injections a 1 month check, if inactive may extend the next check from 4 to 6 months

  6. and so on...extending the intervals a few weeks if the condition remains inactive

  7. PDT or intravitreal steroids may be needed for certain cases


  8. treatment this improves sight in 40%

  9. another 50% 'will stabilise', but the sight may get 3 lines worse.

  10. the remaining 10% get much worse (particularly if smoking continues)

  11. 'classic' neovascular ARMD' responds much better.

  12. 'occult' neovascular ARMD, type 1' with a PED responds the worse, and occasionally the retina may 'rip', but they are still moderately effective. See the Marina study.

  13. They will also be effective against 'occult' neovascular ARMD, type 2 (without a pigment epithelial detachment). It is expected NICE will groups classic and occult CNV together

  14. Prior to NICE approval, many aresa of the UK do not have funding for Lucentis. In these areas many ophthalmologists are using Avastin instead of Lucentis, as it is so much cheaper. An informal survey at the Royal College meeting 2007 indicated that about 50% ophthalmologists are happy with Avastin, and this is nearly or as effective (perhaps 90-100%) as Lucentis.

  15. Risk factors must be addressed....smoking (stopped), blood pressure (low, <140/80), little salt, little transfats and saturated fat, a low cholesterol (helpful..consider statins), oily fish (twice/week), 5-9 portions vegetables/fruit a day (ie 2 salads and 4 fruits...vitamin tablets if this is not possible), exercise (walking/dancing/gardening 60 minutes/day, longer if overweight). Relations should take similar precautions.

  16. the Anchor and Marina study used monthly injections (Lucentis). Alternatively, without PDT.
    But the Pronto study, after the first 3 months of loading injections, involved monitoring progress and only gave repeat injections if their was a recurrence. A suggested regime would based on this,
    .....that is 3 x monthly injections for 3 months
    .....after that repeat injection if 5 letters were lost, or if OCT showed more than 100micron thickening;
    ...... or if there was haemorrhge present.
    In this way, based on the Pronto study, only 5 injections would be necessary (on average 5 in the first year. (After the first year, results are unclear). The Pronto study did not use PDT.

  17. Lucentis/Avastin treatment is far superior to no treatment or PDT alone for most patients.

  18. The PIER study treated at 0, 1, 2, 5, 8, 11 months...but results were not as good as ANCHOR.
 

Anchor study
This is is the main Lucentis and classic CNV study.

Marina study

This is is the main Lucentis and occult CNV study.

Abstract

Aisenbrey's study.

 


Anecortave acetate
This is a modified steroid that can be injected behind the eye. See See It does help to prevent progression of CNV, but is probably not as effective as the 3 drugs above.  

 


A flow chart

 

A very simplified ARMD treatment pathway (2008)


IVT: intravitreal triamcinolone
IVT is a steroid and can help reduce the size of CNV membranes. The procedure and risks are discussed here. With ARMD or CNV it is usually given in addition to PDT.

and here .  Concerning macular oedema in diabetes, Triamcinolone may reduce macular oedema more effectively.
 

 


Lucentis, Avastin, Macugen
intravitreal injections

The procedure is discussed here. (Triamcinolone has extra risks and is discussed here.) In ARMD or CNV they are usually given in addition to PDT. These drugs are not yet available for general NHS use. AvastinMacugen ,   infection..preventing

These drugs are given as an injection into the vitreous cavity of your eye. They are 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'.

 

 

Macular degeneration shown in green by the arrow.

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 red.

macular oedema / ARMD

 

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.

You may see the drug floating around your eye for the next few weeks.

intravitreal triamcinolone, lucentis, avastin, macugen


After the injection

After the injection you usually notice black swirls in the vision, which start to disperse gradually, but are a nuisance for a few weeks. By one month the drug should be working.

 

 


Risks etc
Triamcolone Triamcinolone has extra risks in addition to those on this page and is discussed here.
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. The eye must have a normal pressure before the patient goes home.
Days

About 1/1000 people will develop a serious eye infection.

The day after the injection your eye should be comfortable. 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 evenings

Risks are summarised See this summary.  There is a small chance these drugs will cause other serious problems. As these drugs have not yet passed clinical trials, the exact risks are not known.

Pregnancy Please tell your doctor is you are pregnant, and try and avoid getting pregnant for the 6 weeks following the injection. These drugs should not be given during pregnancy.
Anticoagulants ...extra precautions I have no detailed advice as yet, but generally your anticoagulant dose should be reduced or carefully checked, and you should remind your ophthalmic team you use anticoagulants and ask for specific advice.

 



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