IVT in United States may be an abbreviation for intravitreal
treatment, not intravitreal triamcinolone as on this
website.
Introduction: Avastin, Bevacizumab
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
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)
reduce new vessel growth in these conditions.
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
The eye is cleaned.
Anaesthetic drops are instilled
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.
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,
DRRN , Byeon, India
it is unlikely to improve sight if there is no oedema
occasional patients will notice a deterioration in vision,
and such eyes are more likely to have more macular ischaemia
than the eyes that benefit
treatment needs to be OCT monitored: treatment should be
offered if there in increase in oedema.
treatment will be needed with monthly injections until oedema
has resolved, until there is no improvement in the oedema,
and after that injections are continued to maintain that level.
So if there is 400µ central macular thickness, injections
are carried out monthly until there is no extra response. In
such a patient oedema may reduce to 250µ. If a further
injection does not reduce the oedema, then 250µ would be
considered the best that can be achieved. After that injections
would be restarted if the thickness increases again. So if
the thickness increases, perhaps to 300µ, injections would
be restarted again so as to maintain 250µ.
Even with injections vision may not improve. Vision improves
in 50% patients, but oedema reduces in most (?~80%). So vision
is NOT a good indicator of whether Avastin is needed.....macular
thickness on the OCT must be used.The Restore
Study used Lucentis, but there is no reason to think Avastin
will not be similarly effective
Resistant cases may respond to intravitreal
steroids. Currently Triamcinolone is in regular use,
but this should probably be replaced with intravitreal steroid
implants
Avastin is rarely funded by the NHS.
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 evidencealso . 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
drain blocked by 'new' blood
vessels' aqueous trapped in eye, and this puts the pressure
up
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.
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
I have no detailed advice as yet, but generally your anticoagulant
dose should be reduced or carefully checked just before you have
the injection. You should remind your ophthalmic team you use
anticoagulants and ask for specific advice.
After the injection the anticoagulant dose can return to the
normal dose.
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.
low
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
damage in the brain.
Oily
fish such as sardine, salmon, tuna, trout, at least twice a week
(small amounts are fine...not a whole salmon!).
Home monitoring blood pressures should be 10mmHg (systolic) and 5mmHg
(diastolic) lower see than
these 'clinic' pressures.
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
Insulin pumps generally produce
better control still, but are harder to use.
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.
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.
