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Anti-VEGF injections

What is Vascular Endothelial Growth Factor, VEGF?

Vascular Endothelial Growth Factor (VEGF) is a chemical that is normally present in all parts of the body, including the retina.

In many diseases there is an excess that can either lead to leakiness of retinal capillaries or the growth of abnormal blood vessels from the choroid (choroidal neovascularisation or CNV) or from the retina itself (at the optic disc – NVD or elsewhere – NVE). Anti-VEGF injections are now the mainstay of many retinal treatments.

The first treatment commonly used in the eye working against VEGF was bevacizumab (Avastin™), which is an antibody that sticks onto VEGF molecules and prevents them from attaching to cells. This prevents the VEGF from having the effects described above. Bevacizumab is approved by the TGA for use in chemotherapy for bowel cancer. In these patients it is injected into patients’ veins in a dose 400 times more than is injected into the eye and has been found to increase their risk of stroke and heart attack. This has not been demonstrated with intravitreal injections, but is, at least, a theoretical risk.

The two newer anti-VEGF drugs are ranibizumab (Lucentis™) and aflibercept (Eylea™) and are now available on the PBS for most of the conditions in which they have been shown to work well. Along with bevacizumab, they have completely revolutionised the treatment of conditions that previously were either guaranteed paths to blindness or sever visual loss.

In this article, each of the anti-VEGF drugs is described along with the conditions for which they are used. While it has been argued that the newer drugs are ‘better’, little difference between them has been shown in most studies, with a few exceptions. Dr Chauhan’s selection of drug for your condition will be based on which drugs are available on the PBS, which have been shown definitely to work better for your condition and which have a better theoretical safety profile.

Bevacizumab (avastin™)

Bevacizumab IS AN OFF-LABEL TREATMENT, which means that it has not been formally approved for use in the eye.

Bevacizumab is used for age-related macular degeneration (AMD) more throughout the world than ranibizumab and aflibercept, which were specifically developed, licensed and approved for use in the eye. This is because bevacizumab is cheaper; in Australia ranibizumab and aflibercept is almost completely subsidised by the government and the opposite is true. These drugs appear to work equally as well.

Bevacizumab is used in treating many other conditions in which VEGF is implicated. These include:

Ranibizumab (lucentis™)

Ranibizumab is currently being studied in many research trials across the world for all of these applications.

In Australia ranibizumab is approved for use in treating CNV due to age-related macular degeneration that is under the fovea. This covers most, but not all, patients with AMD. Those not covered are treated with bevacizumab as the financial burden of self-funded monthly intravitreal injections of ranibizumab is beyond almost everyone and the two drugs appear to be equally effective and safe.

Additionally, as of 2015 ranibizumab is approved for use in other conditions such as macular oedema due to diabetic retinopathy and retinal vein occlusion (central and branch).

Aflibercept (eylea™)

Aflibercept was released in Australia in 2013, seven years following the introduction of ranibizumab. It has since found wide spread adoption within ophthalmology practices and subsidised for treatment of similar retinal conditions as ranibizumab. This includes CNV due to age-related macular degeneration that is under the fovea, macular oedema due to diabetic retinopathy and retinal vein occlusion (central only).

The safety and efficacy profile has been found to be similar also to both ranibizumab and bevacizumab.

Anti-vegf Injections

Anti-VEGF drugs are either complete or partial antibodies that block the action of VEGF. This is a chemical that is normally present in all parts of the body, including the retina. In many diseases there is an excess that can either lead to leakiness of retinal capillaries or the growth of abnormal blood vessels from the choroid (choroidal neovascularisation or CNV) or from the retina itself (at the optic disc – NVD or elsewhere – NVE).

SOME OF THESE TREATMENTS ARE OFF-LABEL, which should be discussed with your retinal specialist.

  • Anti-VEGF drugs are used in treating many other conditions in which VEGF is implicated. These include:
  • CNV due to age-related macular degeneration, myopic macular degeneration, trauma and inflammation
  • Macular oedema due to diabetic retinopathy and retinal vein occlusion
  • Abnormal new vessels in the retina (NVD or NVE) due to ischaemic conditions like diabetic retinopathy and retinal vein occlusion
  • Abnormal new vessels in the front of the eye (NVI or NVA) and the high intraocular pressures (IOP) that result from these (neovascular glaucoma)

How Are Intravitreal Injections Given?

The intravitreal injection (injection straight into the vitreous of the eye) is given in a clean environment in order to reduce the risk of infection. Most patients are concerned about 4 issues:

Will it hurt?

No. You will have anaesthetic drops instilled into your eye about three times about ten minutes apart by a nurse or orthoptist. At this stage your eye would already be numb enough for a cataract operation.  The injection itself is extremely quick and you will feel a sudden and split-second feeling of pressure. Almost every patient has a “is that all there is to it”? response after their first injection.

How will I keep my eye open for the operation?

Your eye will be held open gently with the gloved fingers of the injecting doctor.

How will I keep my eye still for the injection?

You will be asked to look at a particular point on the ceiling. This will keep your eye still.

Will I be able to see the needle?

No. The injection is done from the side and you will not see it at all.

The nurses will test your vision immediately after the injection and will then apply ointment and an eye pad. You may then go home, usually about an hour and a half after entering the clinic. The eye pad should stay on, untouched, for 4 to 6 hours and should then be removed at home. You should then put the gel that you’re given in your injected eye every 1 to 2 hours until you go to sleep. When you wake up the next day, your eye should be comfortable.

You will be provided with the gel before you leave. You will also be given instructions and several contact telephone numbers in case of problems.

What Are The Risks Of Intravitreal Injections?

Before you are treated, you need to know the risks and benefits so you can make an informed decision.
Side effects are uncommon with intravitreal injections. Some are related to the injection itself, and some due to the drug itself.

Chances of injection-related risks:

  • Infection: less than 1/2000*
  • Severe bleeding into the eye: less than 1/1000*
  • Retinal detachment: less than 1/1000*
  • Persistent high pressure in the eye: less than 1/100*
  • Cataract: less than 1/1000*
  • Allergy: less than 1/1000*
  • Inflammation: less than 1/1000* (* for each injection)

Intravitreal drug-related risks:

As is true for any new drug, unknown and potentially serious or life-threatening side effects could occur with anti-VEGF injections. There are two such drugs readily available for these treatments and should be discussed with your retinal specialist, but it is the opinion of most retinal specialists that the two drugs appear to be equally effective and safe.


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