THE TIGER STUDY
About Macular Degeneration
Age-Related Macular Degeneration (AMD) is a common cause of sight loss in patients aged 50 and above. It affects the macula, which corresponds to the central part of vision, and is usually present in both eyes though they may not be affected to the same degree at the same time.
It comes in 2 forms:
- Dry AMD - the most common. This progresses slowly over time and is usually asymptomatic until late. There is as yet no proven treatment to prevent the progression of dry AMD.
- Wet AMD - this form progresses more rapidly, with bleeding and swelling of the macula at the back of the eye. Eye injections of medications called anti-vascular endothelial growth factor (anti-VEGF) such as ranibizumab (Lucentis®) and aflibercept (Eylea®) can slow down the progression of wet AMD and have become standard of care in many countries.
Why do the TIGER study?
Rarely, if a patient with wet AMD develops a large bleed at the back of the eye this blood can accumulate under the macula. This is called a submacular haemorrhage (SMH) and if untreated often leads to permanent vision loss.
A SMH will eventually clear on its own - however blood is harmful when in direct contact with the macula and may cause scarring and permanent central vision loss if left too long. Thus, keys to treat SMH are to stop further bleeding and help blood clear away faster (or at least to push it away from the macula).
It is not clear what the optimal treatment of SMH should be. Three recognised treatment options are:
- Injecting anti-VEGF medication directly into the eye per standard treatment for wet AMD - this prevents further bleeding, and relies on the the cells in the eye to clear the blood away.
- Injecting anti-VEGF medication AND a clot-busting drug called tissue plasminogen activator (TPA) with gas into the eye which dissipates over several weeks. The addition of TPA and gas is to liquefy the blood and push it away faster.
- Performing an operation called a vitrectomy, injecting TPA directly to the bleed, filling the eye with gas, and then giving regular injections of anti-VEGF. This essentially combines both of the above treatments in one controlled operation, and has the added benefit of ensuring the TPA is administered exactly where it needs to work.
About the TIGER study
It is not clear which of the above treatments is the most effective in improving vision in the long term. Furthermore, while TPA is widely used in healthcare it is not yet licensed for use within the eye. As such, a study is warranted to establish best care.
The TIGER study is a pan-European multi-hospital phase III, double-masked, randomised surgical trial investigating whether performing a Vitrectomy, injecting TPA and gas in addition to regular injections of anti-VEGF (in this case Eylea®) will improve vision over injections of anti-VEGF alone which is considered standard of care.
All patients enrolled on the study will receive regular injections of Eylea®but may also be allocated the above mentioned surgery at the time of recruitment on a 50% random basis.
The study is led by Professor Timothy Jackson. The study is funded by Fight for Sight and sponsored jointly by King's College London and King's College Hospital.
Clinicaltrials.gov identifier: NCT04663750
(https://www.clinicaltrials.gov/ct2/show/NCT04663750?cond=NCT04663750&draw=2&rank=1)
What are the Risks and Benefits of the TIGER treatments?
Patients on the surgical arm of the TIGER study will undergo a procedure called a vitrectomy wherein the central jelly within the eye (the vitreous) is removed. The clot-busting medication TPA is then injected underneath the retina adjacent to the bleed, then the eye is filled with gas and Eylea® is injected. If there is a cataract in your eye before surgery, we may also undertake cataract surgery at the same time, replacing the cataract with a clear artificial lens. The total procedure will take about 30-60 minutes, and you are then seen the day after surgery.
Patients on the non-surgical arm will receive Eylea® from the start of the study.
Thereafter all patients are followed up with monthly Eylea® injections for 3 months, then 2-monthly Eylea® injections for 9 months.
The risks of surgery include:
- Red eye and bruising
- Post-operative inflammation (controlled with steroid eyedrops)
- Post-operative low pressure OR high pressure (checked on Day 1 after surgery)
- Cataract (if cataract surgery has not been done before, and is not undertaken at time of surgery)
- Allergies to eyedrops or antiseptic used in surgery
Rare but potentially sight-threatening risks of surgery include:
- Infection
- Retinal Detachment
- Recurrent or worsening bleeding in or around the eye
Vision will be expected to be poorer than normal with gas in the eye after surgery - however if patients experience severe pain especially with increasing red eye, or sudden loss of vision on returning home or in the weeks following surgery they should contact the study team to be seen as soon as possible.
The main risk of the clot-busting medication TPA when used for heart attacks or strokes is increased risk of bleeding from any wound or injury - however as the volume given for the TIGER study is very small, and only used under the retina, it is unlikely patients will experience this risk.
The risks of Eylea® treatment are well recognised, and include:
- Red eye and bruising
- Inflammation
- High Pressure
- Retinal Detachment (very rare)
- Infection (very rare)
As with surgery, if patients experience severe pain especially with increasing red eye, or sudden loss of vision on returning home or in the weeks following any injection they should contact the study team to be seen as soon as possible.
How can I be referred / Refer a patient?
If you or a relative has a SMH of 15 days or shorter onset, you or your primary doctor/ophthalmologist can refer you to the nearest recruiting site.
If you have a patient you would like to refer for the TIGER Study please see which nearby sites may be recruiting (study-sites). Key inclusion criteria are as follows:
- Aged 50 and above
- Submacular haemorrhage secondary to AMD (with or without previous treatment) of 15 days or fewer onset (to the nearest estimation)
- Vision between count fingers (CF) and Early Treatment of Diabetic Retinopathy (ETDRS) visual acuity of 70 letters (~20/40 or ~6/12 Snellen)
Irrespective of the treatment delivered, timely assessment and treatment of SMH is key to prevent any permanent vision loss. To be included on the TIGER Study surgery must be delivered at a maximum of 18 days from SMH onset (7 days from screening if onset is unknown).
