Anti-vegf treatment for wet ARMD (neovascular ARMD)
Wet ARMD can now be treated easily. Wet ARMD is caused by the growth of a tiny network of blood vessels under the centre of retina (the macula), which grow and leak. The growing and leaking can be controlled with the new anti-VEGF drugs . This drugs stops the new vessel growth in 90% of patients.
what is happening in macular degeneration: anti-vegf treatment stops the blood vessel growth and leakage (action shown by red X) enlarge
The drugs are gven as an injections directly into the middle chamber of the eye. There are 3 drugs. Eylea & Lucentis are the drugs approved by NICE. Eylea very slightly more effective than Lucentis BMJ 14 BJO 15 .
Avastin is not approved by NICE but is used widely round the world. It is the cheapest and nearly as good as Eylea/Lucentis. Retina17 . We are now allowed to use it Avastin at last. We should use it much more and save £m Eye 19.
The drugs stop or slow down new vessel growth: the new vessels are called CNV, choroidal neovascularisation.
The risk of anti-VEGF treatment is small
- 1/1000 serious infection
- Small risk of other less serious problems such as cataract and retinal tears.
- 80% of people keep reasonable vision Retina 17
- 10% of patients develop macular atrophy Retina 18
- RCO guidelines 18
- systemic effects unusual BJO14
- we have to do better Eye 16
- service Eye 19
The drugs are given by injection into the vitreous cavity of the eyeball as below. The drugs last 4-8 weeks. There are different protocols, but the most recent is 'treat and extend'. Eye 20
All injectons now are offered as treat and extend
- For an average case type 1 'occult' or type 1 with ped or type 2 cnv, 3 injections with 4 week gap to start with.
- For a type 3 case (a 'RAP' type), or polypoidal 5 injections with 4 week gap.
- If at the last of the injections there is no fluid/leakage, the interval before the next injection can be extended by two weeks to make it 6 weeks.
- After 6 weeks there is another injection and OCT: once again, if at this time there is no fluid/leakage, the interval before the next injection can be extended by two weeks to make it 8 weeks, then to 10 weeks, with a maximum interval of 12 weeks.
- If at the time of an injection there is fluid/leakage present, the interval to the next injection is reduced by two weeks (to make the minimum interval 4 weeks).
- After a number of injections with a 12 week interval, usually about 3, injections may be stopped but OCT monitoring continued for about 6 months.
- But some CNV respond exceptionally well, such as those in myopes (1-3 injections in most cases), peripapillary CNV, (3 injections 80%). After the (1-3) injections, monthly OCTs are needed to confirm the condition stays dry.
- Even after one year of a 'dry' appearance, 25% of patients will notice a recurrence in the next 12 months. BJO 16
- At a recent meeting: discharge after 12 months (with injetions during this period) of being 'dry', that is no leakage or activity, treatment can be stopped. Another year of observation will be needed to check the condition remains dry. Reuccrence after this is 10% /year
- Polypoidal CNV and PEDs are more likely to need ongoing treatment in the second and subsequent years Retina 17.
- A very slightly longer interval between injections may be possible with Eylea.
- Fixed interval may help classic rather than occult BJO 20
Notes at BMEC,
- For bilateral cases if one eye dry (no injection needed for >6 weeks) and one wet please do not put in the treat and extend service as active eye may need 4 weekly injections till stable. For simultaneous Bilateral active eyes you can do treat and extend.
- Confusion and missed treatment has happened if the instructions in the management section of Medisoft are too long. Clearly write number of injections either eye at the top and then copy paste further details if you think they are needed. Injectors cross check with notes and Medisoft and their job is made easier if clear brief instructions are given at the top especially for nurse injectors.
- Medisoft is mandatory for any situation with injection request but as per departmental protocol instruction need to be written in the notes as in number of injection and site. If in a rare virtual clinic notes were not available that needs to be noted in Medisoft otherwise all decisions to inject need to be clearly written in the notes.
- Please ask patients about new cardiovascular events when listing for injections, this should be done for all face to face consultations as well as nurses need to document that in the virtual clinic and assessor needs to check that, as on two occasions patients were booked for injections with history of cardiovascular event in the preceding 4 weeks.
This treatment is being researched, (Oraya). It reduces the need for injections a little, but they are still needed. There is a 3% incidence of diabetic retinopathy. It will make diabetic retinopathy much worse and should not be used if diabetic retinopathy is present, or if the diabetes is badly controlled.
- confirm with FFA
- cnv less than 4 mm
- Oraya 2 days after first injection
- takes 10 minutes using a list lamp and contact lens in outpatients
- eye and head fixed..3 minutes fixed position
- still need next 2 injections
- Daily Mail 14
This may help some patients, page. But this is seldom available.
Out of 100 patients
- 10 of patients will get worse (this includes PED patients who may get a tiny rip in the retina)
- 40 will notice better sight
- Another 50 will have stable sight or a small reduction (but not get any improvement)
- 20 patients: the 3 injections will stop CNV permanently and more injections will not be needed (Eylea patients will still get 7 injections)
- Read the appropriate articles and booklets procedure
- Follow the advice, particularly not smoking.
- A healthy lifestyle & diet.
- Consider Lutein and Xeozanthin ‘vitamin’ supplements (10-20% benefit).
- Smoking...the treatment will be much less effective. Essentially wet ARMD patients have a choice, smoke or keep the central vision. Nearly all smokers will not have their central vision in 5 years.
- There is a lot of organisation in involved: if you think you have been forgotten about, contact the department. Patients having treatment generally need injections or scans every 1 (or Eylea every 2 months) .
- Check sight daily for distortion both eyes. If the other eye has good sight but starts to get distortion of vision, this eye needs a OCT scan to see if wet ARMD is present.
- After an injection, if the sight is misty, an check is needed right away to determine if there is an infection in the eyeball.
- Sometimes switching to another anti-VEGF may help Eye 14
- summer holidays Eye 15
- none respnders...PEDs (and some PCVs) BJO 14
- Treatment is effective if there is a haemorrhage Retina 2010
- Avastin is effective BMJ 2010 editorial 2010. NEJM 2011 AJO 2011 (College of Ophthalm statement 2011 IVAN 2013 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 is safe BMJ BMJ 2010 studies of avastin BMJ 2010 editorial 2010 for a RAP CNV ARMD more studies Avastin for CNV Myopic CNV myopic CNV Chan 09 Avastin dose (Wu 09) Wakabayashi 09 2010 Similar to Lucentis
- Refractory wet..change to Eyelea AJO 13
- Alflibercept may be more effective with persistent fluid BJO13 BJO14 BRI14 Eye 14 BJO 14, PED Eye 14 Retina13
- Safe on cells? BJO14
- Similar efects BJO14
- If sight does not improve but there is no 'fluid' and the macular is dry, there may be subretinal fibrosis, atrophy (thinning) of the retina, or a chronic disciform scar.
- resistant case, aflibercept Eye14 Retina 14
- choroidal secondaries Eye 14
- treat and extend Retina14
- drug resistant subretinal/intra-retinal fluid can be stabilized Retina 15
Old data: the most effective protocol is monthly Lucentis or Avastin (Catt 2 Study). As required treatment was not as effective. Enlarge
With treatment, vision does improve, then may get a little worse very slowly. Eylea should equal Lucentis.
Scarring of the macula will reduce sight Retina16.
Wet ARMD green (yellow 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.
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'.
- see 2018
- The eye is cleaned 5% polvidone iodine (this significantly reduces infections).
- Anaesthetic drops are instilled. Drops severeal minutes before and more 1 minute before the injection.
- and a few minutes later the nearly painless injection is given. 2 sets of installation are bst, first 15 minutes before the first cleaning (with the iodine); and a second just before the second cleaning before the injection itself.
- Injection generally 4mm behind limbus.
- The eye pressure may go up for a few hours, and extra treatment may be neede.d
- You may see the drug floating around your eye for the next few days.
- Reflux Retina 14
- Apraclonidine 0.5% /Iopidine may reduce pain Retina17., and given before the injection will reduce bleeding and lower pressure.
- Draping not essential, no post op antibiotics.
- Fewer infections if given superiorly.
- Gloves and face mask for injector.
- If the pressure goes up stays up very high a paracentesis may be needed.
- After the injection you usually notice black swirls/blobs in the vision, which start to disperse gradually, but are a nuisance for a few days. By one month the drug should be working.
- Post op carbomer tears makes the eyes more comfortable.
- Bubbles appear in the vision; they float around the eye. These come from then injection syringe, and the bubbles float to the top of the eye and appear in the lower vision. They can be very upsetting, but they are air bubbles, and always go. Most disappear by the next day, some take a little longer.
- The cleaning solution can make the eye very sore for 24 hours. The cleaning solution is strong and may burn the eye. We have found this problem much commoner for patients with dry eyes. Such patients are probably best using a lubricant after the injection itself, such as Viscotears or VitApos, or Xailin night.
- 10% of patients notice a red eye from a subconjunctival haemorrhage. This heals over 2-14 days. Bleeding may be related to aspirin or anticoagulant use.
A bubble after anti-vegf injection: shrinks and disappears after 1-2 days. The bubble is air from the syringe. Enlarge
a small haemorrhage after anti-vegf injections is common enlarge; sometimes the haemorrhage is large
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
- The cleaning solution can burn the surface of the eye, making it very sore during the night. There should be a full recovery over the next 1-2 days.
- There may be a small haemorrhage on the surface of the eye, and this should disappear over 1-2 weeks (subconjunctival haemorrhage).
- A bubble may appear in your vision, floating around: a bubble of gas may enter when the drug is injected.
- 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.and treatment
Anticoagulants ...extra precautions
Acetazolamide 500mg 1 hour beforehand helps to keep pressure down
- Poor response: BJO 19 with 'choroidal vascular hyperpermeability'.
- Early disease responds better and patients are more likely to keep good vision.
- "Thick Subretinal fluid and macular oedema on OCT may be characteristic of none-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
- "About 15% did not sufficiently respond to anti-VEGF treatment. Vitreo-retinal adherences were the only ophthalmologic factor which could be identified to be significantly correlated with insufficient response" BJO 2013.
- patients with poor sight will benefit if there is little atrophy and fibrosis Retina 15
- Technically recurrence rates are for
- peds 75%
- subretinal fluid 16%
- Intraretinal fluid only 0%
- Subretinal fibrosis 50%
- no relation of injections with macular atrophy BJO 19
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
Sight at the beginning is crucial: vision at presentation 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 enlarge
Y axis....6/9 is good vision, 6/36 is poor.
There is lots of stress on care-givers, who find the treatment program an ordeal. Eye 16