Good Hope Eye Dept
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Good Hope Hospital Eye Clinic
New drug treatment for Neovascular ARMD: some notes 
David Kinshuck 2008
Low vision & Macula Disease

 

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 now approved Lucentis will be funding, 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 . T

Many ophthalmologists 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 and funded 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.

Avastin is safe    studies of avastin   for a RAP    CNV ARMD    more studies   Avastin for CNV     Myopic CNV     myopic CNV Chan 09    Avastin dose (Wu 09)  Wakabayashi 09.    Avastin is just as effective as Lucentis Jyothi 2010

The benefits of Lucentis (Ranibizumab) are described 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.     Avastin is effective BMJ 2010 editorial 2010

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

Delays in use can cause visual problems.

  

 

Drugs combined with PDT
 

 

Current protocols (including NICE guidelines 2008)
  1. Assess all patients eligible with FFA

  2. the best-corrected visual acuity is between 6/12 and 6/96

  3. there is no permanent structural damage to the central fovea

  4. lesion size is less than or equal to 12 disc areas in greatest linear dimension

  5. there is evidence of recent presumed disease progression (blood vessel growth, as indicated by fluorescein angiography, or recent visual acuity changes)

  6. Lucentis injections monthly for 3 months see

  7. Then monthly visis with OCT assessment. Treat whenever there is a 100 micron increase in retinal thickness in foveal area.

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

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

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

  11. treatment this improves sight in 40%

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

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

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

  15. '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.

  16. They will also be effective against 'occult' neovascular ARMD, type 2 (without a pigment epithelial detachment).,and use is aproved by NICE.

  17. 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.

  18. the Anchor and Marina study used monthly injections (Lucentis).
    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.

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

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

  21. ranibizumab should be continued only in people who maintain adequate response to therapy. Criteria for discontinuation should include persistent deterioration in visual acuity and identification of anatomical changes in the retina that indicate inadequate response to therapy. It is recommended that a national protocol specifying criteria for discontinuation is developed. (NICE)

  22. Pegaptanib is not recommended for the treatment of wet age-related macular degeneration. (NICE)
  

 

Anchor study

Anchor is the main Lucentis and classic CNV study.

 

 

 graph showing Lucentis results (from Lucentis website)

 

Marina study

Marina is the main Lucentis and occult CNV study. 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 (2009)

 

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.) Avastin,   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
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.
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 evenings
Risks summarised
See this summary  Rarely cataracts or retinal detachments may occur. Macular haemorrhages may develop (BJO 2008) . A rip may develop.
Anticoagulants ...extra precautions
See ... you should remind your ophthalmic team you use anticoagulants and ask for specific advice.

 

 

 

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