Anti-VEGF injections for diabetic retinopathy Lucentis, Avastin, & Eyelea ...a leaflet for patients
Macular oedema shown in green by the arrow. Macular oedema affects the centre of the retina which is responsible for sharp vision, seeThe front of the eye is on the left, and the retina is shown in red
Lucentis, Avastin and Eyelea are anti-growth factor drugs (anti-VEGF). The drugs are given as injections into the vitreous cavity of your eye. Lucentis, Avastin, & Eyelea= Ranibizumab, Bevacizumab, Aflibercept
The drugs are used to reduce
- macular oedema, that is fluid at the back of the eye, occurs in diabetes, retinal vein occlusion. (Often abbrevaiated as DMO or DME, hat is diabetic macular oedema)
- reduce retinal new vessel growth in these conditions
- to reduce new vessel growth on the iris (rubeotic glaucoma)
- The drugs are also used to treat ARMD, but that is not discussed here.
injection in a very clean room.
The drugs are given as an injection usually in a clean minor surgery room. 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. Repeated injections are safe.
In the UK Avastin is not licenced, but it is the commonest drug used round the world.
If the macular oedema is greater than 400µ, the NHS funds treatment NICE.
Diabetes and other conditions damage blood vessels in the retina, and the damaged blood vessels then start to leak. The leakage makes the retina waterlogged, a bit like a sponge, as in the diagram above. This is part of 'diabetic maculopathy' (DME) or 'macular oedema' in retinal vein occlusion. animation. Text
The macula is the central area of the retina, responsible for your central or 'sharp' vision used for reading & watching TV.... our sharp & detailed vision. When the macula is swollen (oedema) the sight is reduced, and people cannot see details like faces and writing on TV, and bus numbers.
The retinal damage releases a chemical, VEGF (VEGF= vascular endothelial growth factor). The VEGF then causes adjacent retina to leak or grow 'new blood vessels' as below.
Macular oedema (DME) and response to Anti-VEGF treatment
Anti-VEGF treatment will reduce DME (diabetic macular oedema). They are unlikely to improve sight if there is no oedema. Rarely patients will notice a deterioration in vision,, due to more macular ischaemia.
The Anti-VEGFs are given by injection into the vitreous cavity of the eyeball details. The drugs last 4-8 weeks. There are different protocols.
- see details
- Starting with 3-5 injections a month apart.
- The 'treat and extend' plan. There is an OCT scan at each visit.
- If the leakage (macular oedema) reduces or stabilises the interval is extended.
- If the leakage (macular oedema) increases, the interval is reduced again.
A second effect of the VEGF is to make tiny blood vessels grow. These are called 'new' blood vessels, and an ophthalmologists calls these 'new vessels' see animation . This is proliferative retinopathy.
These new vessels are very delicate and very easily bleed, and this blood can damage your eye badly. This is 'proliferative retinopathy'. If the blood spreads in front of the retina, scar tissue can grow. The scar tissue can then shrink and pull the retina off, causing blindness.
New blood vessel growth must be stopped. Laser is the main treatment, but Lucentis and Avastin are new treatments that will generally be used IN ADDITION to laser. See the evidence also . Minella. Tonella. May work instead of laser DRCRnet 16.
When the blood vessels grow in the 'drainage meshwork, the aqueous humour produced in the eye cannot drain away. This leads to a very high pressure in the eye, called rubeotic glaucoma. Avastin is an excellent treatment for this, but the effect may be temporary. Rubeotic glaucoma is described in detail here with an animation here. See the evidence. Laser is usually needed as soon as the pressure has dropped.
normal flow of aqueous humour
drain blocked by 'new' blood vessels' aqueous trapped in eye, and this puts the pressure up
- The eye is cleaned.
- Anaesthetic drops are instilled.
- In the injection room the eye is cleaned again, and a drape is placed around the eye
- a couple of minutes later the nearly painless injection is given
- (steroid implant insertion can be a little more painful)
- Iodine is very effective at preventing injections. For patients 'allergic ' to iodine, we therefore recommend the continued use of iodine, but irrigate 2 minutes after iodine installation.
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. You may see the drug floating around your eye for the next few hours.
- 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. These disappears overnight.
- Minor problems are common such as a haemorrhage on the surface of the eye (subconjunctival haemorrhage).
- Also, patients with dry eyes may have intense pain the site of the injections...more lubricants should have been used before and after the injections, and more irrigation of the iodine.
- 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
(often with 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.
An infection... common symptoms Eye 12
- blurred vision........96%
- redness ...............50%
- lid swelling ...........10%
- discharge .............10%
Please tell your doctor is you are pregnant, and try and avoid getting pregnant for the 6 weeks following the injection. This is a new drug and is probably UNWISE IN PREGNANCY. In any respect, pregnancy makes active diabetic retinopathy MUCH worse. Retina 2012
There is a 1% risk of a retinal tear after this injection. Please seek attention (within 24 hours....the next day is usually OK) from an ophthalmologist if you develop the symptoms of a tear, that is (all of a sudden) a sudden shower of floaters and flashes of light. These may happen in the months after the injection.
Anticoagulants ...extra precautions
By keeping to these levels as much as possible (or lower still) you will be doing your best to stop your eyes getting worse. Occasionally by sticking to these targets your retinopathy will improve, even without laser. Review BMJ17
- 30-120 minutes exercise a day ,
- moderate alcohol consumption only,
- avoid obesity if possible,
- balanced diet including
- 9 portions of vegetables or fruit a day (9 for men, 7 for women), Lowers BP
- minimal of animal or 'hard' vegetable fats,
salt, see the evidence
Alcohol should be limited to one drink or unit a day, six days a week (Mukamal 2004). More than this leads to brain damage.
- Oily fish such as sardine, salmon, tuna, trout, at least twice a week (small amounts are fine...not a whole salmon!).
- Fibre and healthy fats in the diet slows down retinopathy. No transfats and minimal saturated fat.
- no (ultra) processed food Cell Metab 19 as this puts weight on and leads to inflamation throughout the body.
- generally 130/80 (see graph) or preferably less BMJ 16. Even less if well <120 BMJ17
- (120/75 ..home monitoring)
- 125/75 or less if protein in urine present (115/70.. home monitor)
- ACE inhibitors or Angiotensin Receptor Antagonists unless young/pregnant/very low blood pressure/poorly tolerated
- The lower the better in macular oedema, as long as you feel well.
- An ideal pressure is below 115 (systolic, first number) for healthy people. <120 is is only suitable for new/well diabetes patients 2012. Otherwise slightly higher as above.
- Home monitoring blood pressures should be 10mmHg (systolic) and 5mmHg (diastolic) lower see than these 'clinic' pressures.
- Depression & anxiety increase BP.
- 48-58 mmol/mol (6.5%-7.5%) or less (see graph) with very few or preferably no hypos. These (or slightly lower) levels are the best to prevent complications
- <58 mmol/mol (7.5%) for insulin users; <48 mmol/mol (6.5%) if not using insulin and have good health. Problems with intensive control. Target should be adjusted according to health and age. If you are a type 1 patient and cannot achieve good control, you need to checked for other conditions such as coeliac disease (anti-TTG antibodies), addisons, and thyroid.
- If hypos develop, seek expert advice from your diabetes nurse/doctor.
- if your HbA1c is high (say 97mmol/mol / 11%), then the next step may be to achieve 75 (9%)....in other words, and any improvement is helpful, gradually reaching lower levels above.
sudden decrease in HbA1c
- A sudden improvement in control (HbA1c drop of 33 mmol/mol/3% ) will lead to a temporary rapid increase in progression of retinopathy: laser may be needed.
- Good control is important in the longer term, that is after about 2 years. When people who control their diabetes well will be better off after this period. See
- A temporary increase in retinopathy is most common when starting insulin for the first time, especially if the diabetes is very badly controlled when you start the insulin.
- Individual targets Nice 16
cholesterol and statins
- <4.0mmol/l, and statins recommended for most adult patients with diabetes whatever the cholesterol.
- statins are recommended whatever the cholesterol, if well tolerated age>40y Statins reduce retinopathy EJO 20
- A fibrate such as fenofibrate may help if there a lot or exudates.
- LDL <2
- Avoid if pregnant, GFR <15, pancreatitis
- If GFR low but still >15, need a lower dose.
- smoking 20 a day triples/quadruples retinopathy
- passive smoking may double retinopathy: room-mates inhale at least 25%
- electronic cigarettes are much much safer and probably have a negligible effect on retinopathy debate BMJ 18
- even 'Just one cigarette a day seriously elevates cardiovascular risk ' BMJ18, so it is best to stop completely.
- type 1 patients and ideally type 2 patients using insulin with significant glucuose fluctuations, glucose sensors are ideal : Freestyle or Dexcom.
- Insulin pumps generally produce better control still, but are harder to use.
|Diabetes education courses|
- everyone with diabetes should attend an education course, Primary Care Trusts are obliged to send you on such a course, but very few patients have ever attended one. If you have not been on one, discuss this with your diabetic team.
sleep apnoea etc
- this contributes to macular oedema and loss of sight (Schwartz, 2006), and many serious problems.
- It is common in diabetes, particularly if you are overweight. Do you have sleep apnoea?
- see 15 Retina18 Retina19
- 5.0-7.2 mmol/l before meals
- <10.0 mmol/l after meals
- no serious hypos
- for patients who test their glucose levels and adjust insulin doses, the new glucose sensor is highly recommended and has transformed the lives of many patients. They are provided on the NHS for type 1 patients. I would recommned then for type 2 pateints using mulitple insulin injections, but they are not funded by the NHS (~£30/week)
- Rosiglitazone and pioglitazone should not be used if there is significant retinopathy, and certainly not if macular oedema is present, as they increase macular oedema and fluid retention. Case 49. Lirglutadite and Exenatide are drugs that can be used instead low also lower weight (they are injections.)
- insulin users need to avoid serious hypoglycaemia. Expert help is usually needed if episodes are severe/frequent. See
- 10% compliance if multiple treatment,
? 60% one tablets
type 2 at diagnosis
- need a test for Haemochromatosis