www.diabeticretinopathy.org.uk

  

Intravitreal Avastin (IVA)...a leaflet for patients

Introduction: Avastin, Bevacizumab

macular oedema
Macular oedema shown in green by the arrow.
Macular oedema affects the centre of the retina which is responsible for sharp vision, see
The front of the eye is on the left, and the retina is shown in red

Avastin (medical name Bevacizumab) is an anti-growth factor drug (anti-VEGF). Intravitreal Avastin (here called IVA) is an injection of the anti-VEGF drug Avastin into the vitreous cavity of your eye.

The drug is used to reduce

  1. macular oedema, that is fluid at the back of the eye, occurs in diabetes (or retinal vein occlusion or other macular disease such as ARMD)
  2. reduce new vessel growth in these conditions.
avastin injection to reduce macular oedema
Avastin is injected in a very clean room.

IVA is given as an injection usually in the operating theatre in the UK, or 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.

In the US the term 'IVT' means intravitreal 'treatment', which might be triamcinolone, Lucentis, Macugen, or Avastin. This page refers to Avastin (though the pages for Macugen and Lucentis are virtually identical).

In (January 2007) the UK Avastin is not licenced, which means that has not yet been approved by the NHS. Repeated injections appear safe.   VEGF levels drop after the injection.

The procedure

Leakage.....macular oedema etc

Diabetes and the 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' or 'macular oedema' in retinal vein occlusion. animation.

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.

Avastin blocks the effect of VEGF by binding to the VEGF receptors on the cells in the retina. This then reduces the leakage, and the sight may improve. See the evidence, also,   DRRNByeon, India

Avastin in diabetic retinopathy macular oedema:

 

New blood vessel growth

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 .

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 Avastin is a new treatment that will generally be used IN ADDITION to laser. See the evidence also . Minella. Tonella.

 

Rubeotic glaucoma

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
normal aqueous flow
drain blocked by 'new' blood vessels' aqueous trapped in eye, and this puts the pressure up
new vessels in trabecular meshwork

After the injection , benefits

By one month the drug should be working. Many people will notice some improvement in vision. Generally this improvement is temporary, and the injection may be offered again months later. The macular oedema reduces, with a maximum reduction at 2 weeks, and starts to wear off after 3 months (see). It gives a chance for laser treatment and lower blood pressure etc  to have their effect. Further injections may be needed, but as this treatment is new there is no definite treatment plan available.

 

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. Extra eye drops or tablets are given if the pressure stays up. 1-2 hours after the injection, the central retinal artery circulation may stop...this needs immediate attention.

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 Eye Centre Casualty, at the City Hospital.There is a very small chance that the drug will cause side effects outside the eye, such as aggravating heart disease, but no extra risk was found in a large safety survey.

Symptoms of infection

Eye 12..these are the common symptoms that patients notice.       

  1. blurred vision........96%
  2. pain/photophobia...73%
  3. redness ...............50%
  4. floaters................25%
  5. lid swelling ...........10%
  6. discharge .............10%

 

 

Months..sight

The drug will reduce the retinopathy, both the leakage and new vessel growth.Laser...if it has not been carried out already will be needed, on many occasionsRarely Avastin cause some loss of sight...there is no detailed information as to the exact risk.

Unlike a steroid, there should be no long term pressure effects.

Years

IVA may hasten cataract development.

Pregnancy

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 DANGEROUS IN PREGNANCY. In any respect, pregnancy makes active diabetic reitnopathy MUCH worse.

Retinal tears

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.

Extra Precautions

Anticoagulants

Dose generally not adjusted.

 

Targets to reduce retinal leakage

HbA1c and insulin advice applies to diabetes only; also,  for the non-diabetic, 140mmhg is the maximum recommended blood pressure.

lifestyle

blood pressure

HbA1c

  • 7.0-6.5% or less (see graph) with very few or preferably no hypos. These (or slightly lower) levels are the best to prevent complications.
  • If hypos develop, see expert advice.
  • if your HbA1c is high (say 11%), then the next step may be to achieve 9%....in other words, and any improvement is helpful

sudden decrease in HbA1c

  • A sudden improvement in control (HbA1c drop of 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. 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.

cholesterol

  • <4.5 mmol/l, and statins recommended for most adult patients with diabetes whatever the cholesterol.
  • statins are recommended whatever the cholesterol, if well tolerated age>40y
  • A fibrate such as fenofibrate may be advisable in every person with exudative maculopathy.They educe retinopathy progression 40% (Fenofibrate 200mg od) Field Study
  • a fibrate instead or in addition to statin if triglycerides high
  • LDL <2

smoking

  • smoking   20 a day triples retinopathy
  • passive smoking may double retinopathy: room-mates inhale at least 25%

insulin

education

  • everyone with diabetes should attend an education course, such as DAPHNE (insulin) , DESMOND (type 2 at diagnosis), or XPERT (type 2). Primary Care Trust 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

glucose level

  • 5.0-7.2 mmol/l before meals
  • <10.0 mmol/l after meals
  • no serious hypos

Glitazones

  • 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.

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