www.goodhopeeyeclinic.org.uk/
====
Good Hope Hospital Eye Clinic
New treatment for Neovascular ARMD: some notes
David Kinshuck  
Low vision & Macula Disease

 

Lucentis (Ranibizumab), Avastin (Bevacizumab)

These anti-VEGF 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.

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. 

The benefits of Lucentis (Ranibizumab) are described in minimally classic/occult ARMD, and in classic. Monthly versus PRN

Catt 2012

Currently the best reponse is monthly injections (not as required), but 33% of patients do not need these (and it is impossible to identify which patient is in which group).
Anti-VEGF drugs

Avastin

Many ophthalmologists believe that Avastin (Moorfields)  is just as effective as Lucentis, 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 effective BMJ 2010 editorial 2010. Less frequent Avastin (every 12 weeks) is not as effective as frequent use Retina 2011.

It is now official, Avastin is just as good as Lucentis, NEJM 2011 editorial. Another comparison Biswas 2011. In the US, Avastin is used twice as often as Lucentis AJO 2011, and is equally effective (College of Ophthalm statement 2011).

Both drugs equal BMJ 2012   and here BMJ editorial 2012       Implications BMJ 2012      £84m saving with Avastin  Equal results Ophthalmology 2012    Equal BJO 2013
Avastin

 

Eyelea, (VEGF-trap, aflibercept)

Eyelea, (VEGF-trap, aflibercept) looks very promising, with 3 loading doese, then 2 monthly injections thereafter, with no interim OCTs needed. This will be a much easier protocol for many patients,

Some patients may manage with much less intensive treatment. At present we do not know how to identify such patients. Approved BJO 2012    VIEW 1 and VIEW 2.

  • Year one:     week 4, 8, 12, 20, 28, 36, 44, 52
  • (this schedule will overtreat some patients and undertreat others)
  • year two:     week 0, 12, 24, 36, 48  with interim PRN

 

Drugs combined with PDT etc   

 

Brachy/radiotherapy   

Radiotherapy with vitrectomy: Cabernet, Merlot

  • cost; technical; explanation; 
  • not suitable if diabetic;
  • does appear effective BJO 2012
  • A surgical probe is inserted with a radioactive tip, and help in postion so the xrays treat the macular area. A vitrectomy operation is needed first.

Stereotactic: Intrepid

  • Oraya
  • Larger area treated
  • reduces need for injections, but they are still needed
  • may be available in Birmingham 2014
  • 3% incidence of diabetic retinopathy

 

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. Early CNV..god vision is maintained Eye 11

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

  7. Lucentis injections monthly for 3 months see

  8. Then monthly visits with OCT assessment. Treat whenever there is a 100µ increase in retinal thickness in foveal area.

  9. after 3 injections a 1 month check,with on monthly OCT scans

  10. and so on... if the condition remains inactive after 6 months, extending the intervals a few weeks

  11. responding well...treat until dry or until 'plateau' reached

  12. not responding well (not dry, no plateau, vision getting worse), review diagnosis

  13. PDT may help polypoidal

  14. treatment this improves sight in 40%

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

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

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

  18. '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.

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

  20. 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 (i.e. 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.

  21. 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 100µ thickening;
    • or if there was haemorrhage 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.

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

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

  24. 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

  25. We have to note intraretinal cysts  Acta 2011

  26. Helpful even if vision good Retina 2012
  

 

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.

  

 

Comparision: Catt 2 study

comparision of anti-VEGF protocols

The most effective protocol is monthly Lucentis or Avastin (Catt 2 Study). As required treatment was not as effective. Enlarge

 

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.

 

Anti-VEGF 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.   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

 

Predictors of response
  • "Thick Subretinal fluid and macular oedema on OCT may be characteristic of non-responders and may be helpful for tailoring treatment for neovascular AMD". See   
  • Follow up Retina 2012
  • poor response Retina 2012
  • poor results are mainly due to disease progression, including that caused by fibrosis

subretinal fibrosis...a common cause of poor response to anti-VEGF treatment

subretinal fibrosis: subretinal fibrosis (red arrow) ...a common cause of poor response to anti-VEGF treatment. Treatment will reduce fluid but not the fibrosis. enlarge

 

 

Long term
Tufnail, 2012, national wet ARMD dataset
  • 2 female: 1 male
  • average age 79y
  • average 5 injections/year; 9 visits/year
  • sight does deteriorate slowly
  • natural course ~50:50
    disciform scar/fibrosis & geographic atrophy
  • age/genes
  • smoking 2-3x risk
  • areds vitamins ?25% benefit
  • diet ?12% contribution
  • a excellent paper BJO 2012
  • atrophy develops Retina 2013

 

lucentis: vision deteriorates slowly even with treatment

enlarge

Sight at the beginning is crucial:

vision at presentataion of wet ARMD is crucial...good vision at the onset is maintained, deteriorating just a little compared to initial presentation.

We must try and diagnose patients early.

 

vision at presentataion of wet ARMD is crucial...good vision at the onset is maintained, deteriorating just a little compared to initial presentation

enlarge

 

 

 

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 --