Intravitreal steroid implants (IVSI)
David Kinshuck
abbreviations
- VEGF = vascular endothelial growth factor
- IVA = Intravitreal Avastin
- IVT = Intravitreal triamcinolone
Introduction: IVSI, intravitreal steroid implants
IVSI are a new way of treating eye conditions, particularly macular oedema
in retinal vein occlusion, uveitis, and less commonly diabetic retinopathy
and other conditions. The steroid drug is prepared in a tiny capsule, and this
is inserted into the eye with a small injection.
The steroid is released slowly over the next few months. Details are
discussed on this page. There are 2 implants, Osurdex (dexamethasone) and Retisert. Osurdex will be he commonest implant used for the conditions here; Retisert will be used for uveitis, not discussed here in detail. IVSI are
used to reduce this leakage (macular oedema), that may occur in
Iluvien is likely to be helpful, as the benefit lasts nearly 9 months, and usually does not need to be repeated. It is not yet available for NHS UK use. As the drug causes cataracts, it is ideal if the diabetic macular oedema is in patients who have had cataract surgery. About 20% patients will need anti-glaucoma treatment afterwards, and of course there is ~100% cataract formation.
Macular oedema (diabetes, retinal vein occlusion, etc)
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
The macula is the central retina, the part of the retina
that is needed to read or watch television or see any details.
Macular oedema is waterlogging of this central area of the retina. It is caused
when the central retina is damaged and starts to leak fluid. (The fluid originates
from blood. Essentially the fluid is blood without the red blood cells.)
The leak causes poor sight, that is difficult reading,
watching TV. Your central or 'sharp' vision becomes blurred.
Laser remains part of the treatment, but IVSI will help if there is macular
oedema. Risk factors should be controlled (blood
pressure, smoking, cholesterol etc). IVSI will be particularly helpful if
the macular oedema is very central as laser would not so helpful. Oph 2011 Oph 14 Retina 17 Scarring etc BJO17
Macular oedema in uveitis
IVSI will be particularly helpful in posterior uveitis patients, particularly
in unilateral (or mainly unilateral) posterior uveitis. In addition
to reducing the leakage, the steroid reduces the inflammation itself. Retina 2013 Very helpful Retina15
Osurdex is a steroid implant that reduces macular oedema. A tiny capsule
of the drug is injected into the eye.
The procedure
- 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)
- if triamcinolone is used
- Triamcinolone 40ml, 0.1ml=4mg
- So need 2mg = 0.05mls, same volume as Lucentis and Eyela, same size syringe
- Shake first just before draw up as there would otherwise be an uneven distrribution of the drug
Iodine allergy
- an alternative is Chlorhexidine, but in this area several infections have developed following Chlorhexidine use
- we are therefore recommending the continued use of iodine, but irrigation the out after 2 minutes after iodine installation
After the injection
By one month the drugs 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 are usually
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. There should not be much pain. You may
see the drug floating around your eye for the next few hours.
Night
- 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.
Days
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.
A scratchy after injentiosn is normal; a painful achy eye may be infected.
Check pressure 4, 8, & 16 weeks after injection EJO15 .
Symptoms of infection
These are the common symptoms that patients notice Eye 12
- blurred vision........96%
- pain/photophobia...73%
- redness ...............50%
- floaters................25%
- lid swelling ...........10%
- discharge .............10%
Months..sight
The drugs 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 occasion. Rarely
the drugs will 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
IVL or IVA may hasten cataract development or to vitreomacular traction Eye 17.
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 UNWISE
IN PREGNANCY. In any respect, pregnancy makes active
diabetic retinopathy MUCH worse.Retina 2012
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.
Anticoagulants ...extra precautions
You should remind your ophthalmic team you use anticoagulants and ask for
specific advice. Treatment is safe continuing the anticoagulents (Retina
2010). Epidemiology
2010
Extra precautions for Triamcinolone (steroid) and steroid implants Osardex and Iluvien
Trivaris
is preservative free triamcinolone and may be safer than triamcinolone with preservative
Herpes simplek keratitis or uveitis
- The drugs are unsafe generally, as they are likely to cause a recurrence that is difficult to treat.
Months...Eye pressure
- Generally the drugs are usnssfe in glaucoma patients.
- About 50% of people develop a rise in eye pressure that
needs anti-glaucoma eye drops for a few months, or perhaps
longer. Retina17 Retina17
- 16% develop a significant pressure rise, needing drops
and diamox tablets (diamox is best avoided in renal failure
patients)
- in some studies 7% develop a serious pressure rise that
may require glaucoma surgery (this is about half of the 16%
above)
- sometimes the eye pressure is permanently raised, although
on some occasions it is just temporary
- the pressure rise may develop in a week (and is so is
likely to be troublesome). But it may not present until 4
weeks. If you have a normal or near-normal pressure at 4
weeks you are unlikely to develop severe glaucoma later.
- The pressure rise is not always related to the patient..we
have had one patient who had both eyes injected (on separate
occasions), but only one eye developed a pressure rise.
- The benefits
wear off if injections need to be repeated.
- See some
results...benefits may last 2 years. Other
results,
no long term gain.
- Expect a bigger pressure rise with the second eye
Renal Failure or Diamox
allergies
Diamox is a drug given to lower eye pressure, and
is generally not used in renal failure as it it can make some patients
very ill. If this drug cannot be avoided, you must take precautions..as
your your ophthalmic team may not realise you aware you have renal
failure. Occasionally the benefits will outweigh the risks, but discuss
this with your ophthalmic and renal team.
Naturally it should not be given if you are allergic to it....remind
your ophthalmic team.
Pre-existing glaucoma
As IVT may put up your eye pressure, IVT is a problem (and ideally
would be avoided) in glaucoma patients. However, on most occasions
the pressure rise can be treated.
Follow up Schedule
This is an idea of your follow up schedule if your eye pressure
(IOP, intraocular pressure) stays low: 4 weeks IOP, 12 week IOP & clinic, 6 months IOP , 12 months IOP, every 12 months IOP. The steroid effect wears off, and often the injections needs to be repeated.
Years
IVT hastens cataract development.
Pregnancy
Please tell your doctor if you are pregnant, and
try and avoid getting pregnant for the 6 weeks following the injection.
Glaucoma treatment is not ideal in pregnancy.
Types of IVSI implant
Osurdex (dexamethasone)
- see
NELM
- 1/1000 risk of infection
- the eye pressure often goes up so many patients will need glaucoma drops
- in 1% the pressure rise is severe so the glaucoma needs surgery
- safe and practical Eye 16
- lasts 20 weeks Eye 14: fixed 5 monthly injections may help Eye 15
- effective for macular oedema Retina16
- Steroid implants are risky in glaucoma patients, and usually should not be used. Sometimes, such as in uveitis , there is no choice, and then glaucoma surgery will be needed in addition.
- patient
information
- retinal vein occlusion Geneva 2010
- uveitis
- Diabetic retinopathy
- In a patient with diabetic macular oedema, anti-VEGF treatment is best to start with. It is generally best to wait 6 months before determining if there is a response to the anti-VEGF treatment, but personally I think if the oedema has been carefully measured, and there is no reduction whatsoever after one injection, then steroid implants should be considered. Such patients will have 'chronic' oedema: nearly everyone with recent onset oedema will get a good response to anti-VEGF injections.
- They not ideal for diabetic retinopathy if a patient has not had cataract surgery, due to cataract development, and Anti-VEGFs more appropriate. But if the cataracts have been removed, they may be more helpful.
Iluvien
- see Osardex above concerning indications and glauocma risks.
- Essentially this implant is like a long acting Osardex above.
- see also EJO17
- This treatment is an implant of Fluocinolone Acetonide, and is licenced for diabetic macular oedema DME and now approved by NICE.
- It lasts 3 years (with one injection).
- Use if not responsive to anti-VEGF. Traditionally, we are told to wait 6m (after 5 anti-VEGF injections) , but a recent meeting reported that if there is no reduction at all in DME 4 weeks after one anti-VEGF, then there is unlikely t be a good response to more, and therefore Iluvien will be ideal.
- NICE require the patient must have had cataract surgery (pseudophakia), .
- At present we offer this as cataract surgery with the implant 3 weeks later.
- There is overall a small improvement in vision. Studies: FAME
- FAME A... 20%. improvement in vision ....macular oedema > 3y
- FAME B minimal improvement in vision ..macular oedema < 3y
- It does reduce macular oedema by 33% in the first year, from 450um to 300um.
- Probably first choice in vitrectomised eye (poor repsonse to anti-VEGF).
- DME does reduce , but to different degree in different patients.
- This results are comparable with anti-VEGF treatment...but a lot more anti-VEGF injections needed to achieve the same result.
- Risks:
- 90% cataract formation if catract surgery has not been caried out
- 18% patients will need glaucoma medication
- 1/1000 or less ...a very serious infection
- 2% severe glaucoma needing lacuoma surgery
- Can use in IOHT, unsafe to use in glaucoma
- Concerning intraocular pressure, how can we identify which patients will get a pressure rise etc
- 33% population steroid response
- Of those 95% iop..rises 10
- 5% rises 30
- Poag (glaucoma) patients, 95% get a pressure rise
- 1st degree relative of poag. 60% get a pressure rise
- Older pt, myopes, age/6 y diabetic, connective tissue disease, get more pressure rise
- 10% ioht pt get poag in 5 y, risk halved if ioht treated with Slt
- measure pressure after implanting at 1 w, 1 m, 12 weeks
- at these visits IOP 21-25 no treatment, >30 treat, 25-30 consider treatment (eg is smokers/high blood pressure, disc changes etc)
- if pressure not controlled with 2 drugs, refer to glaucoma team
- Visual improvement is more related to DME if it has not been present for a long time. Longstanding macular oedema does not respond as well.
Vision depends on photoreceptors function, so it is important to treat early.
- If a patient has needed extensive topical or intraocular steroids and there has never been a pressure rise, then a pressure rise with this drug is much less likely Eye17. Conversely, if there was a pressure rise with steroids then a pressure rise is much more likely.
Retsert
- see
- will be useful for uveitis, not ideal for diabetic retinopathy, not discussed here.
Intravitreal Methotrexate
This is a new treatment proposed and being carried out at Moorfields Eye
Hospital. It is for uveitis, and looks exceedingly promising 2009.
- If you have posterior uveitis with macular oedema, mainly in one eye, discuss
this treatment with your ophthalmologist.
- Methotrexate Retina14
An example
Before on right, after Osurdex left. Haemorrhages have reduced and macular oedema has reduced. Vision improved from 6/18 to 6/9 so patient can drive (other eye was an amblyopic eye). Did develop glaucoma, controlled with drops. enlarge
