At a glance
- What the study gets you
- Access to the study treatment being tested
- Type of study
- Interventional (receives a drug or procedure)
- Time in hospital
- In-person visits at study sites — visit count not specified by the sponsor
- Drug or intervention
- Pars plana vitrectomy (procedure), Intravitreal 2 mg aflibercept will be injected at baseline then monthly for two further doses, then 2-monthly until month 12 (drug), subretinal injection of recombinant TPA (Alteplase) up to a maximum of 25 micrograms in 0.2 mls (drug), Intravitreal 20% sulfahexafluoride (SF6) gas tamponade (drug)
- How long the study runs
- Study runs about 92 months (dates as stated)
- About the drug or intervention
- Pars plana vitrectomy — procedure: Pars plana vitrectomy · Intravitreal 2 mg aflibercept will be injected at baseline then monthly for two further doses, then 2-monthly until month 12 — drug: Intravitreal 2 mg aflibercept will be injected at baseline then monthly for two further doses, then 2-monthly until month 12. · subretinal injection of recombinant TPA (Alteplase) up to a maximum of 25 micrograms in 0.2 mls — drug: Subretinal injection of recombinant TPA (Alteplase, Actilyse, Boehringer Ingelheim) up to a maximum of 25 micrograms in 0.2 mls. · Intravitreal 20% sulfahexafluoride (SF6) gas tamponade — drug: Intravitreal 20% sulfahexafluoride (SF6) gas tamponade.
- Patient visit burden
- Not specified by the sponsor
In plain English
This trial, called TIGER, looks at a possible treatment for bleeding under the central part of the retina (the macula) caused by wet age-related macular degeneration. The treatment being studied involves eye surgery (vitrectomy), an injected medicine called tissue plasminogen activator (TPA) that helps break down the blood, and a gas bubble placed in the eye. It is sponsored by King's College Hospital NHS Trust.
Who can take part
- Adults aged 50 or over, male or female.
- Bleeding under the macula caused by wet age-related macular degeneration, including some related eye conditions (choroidal neovascularisation, idiopathic polypoidal choroidal vasculopathy, and retinal angiomatous proliferation).
- The bleed covers the centre of the macula and is at least the size of one optic disc across.
- The bleed under the retina is at least 125 microns thick at its centre, measured with a detailed eye scan.
- Vision in the study eye is between counting fingers and a score of 70 letters on a standard vision chart.
Who may not be able to
- A serious allergy to fluorescein or indocyanine green (a dye used in eye tests).
- An allergy to certain medicines used in the trial (alteplase, gentamicin, arginine, phosphoric acid, polysorbate 80 or aflibercept).
- A stroke, mini-stroke or heart attack in the last 6 months.
- Taking part in another treatment study in the last 12 weeks, or planning to during this trial.
- Being pregnant, breastfeeding, or planning a pregnancy during the trial. People who can have children and their partners must use highly effective contraception for a period during and after the trial.
- A blood clotting measure (INR) above 3.5, unless it can safely be lowered before surgery.
- Being unable or unlikely to attend follow-up visits for the whole trial.
- Any other condition that would make it hard to give informed consent or follow the trial, such as dementia or serious illness.
- The bleed having been present for more than about 15 days.
- The bleed being caused by something other than wet age-related macular degeneration.
- Active severe diabetic eye disease, inflammation in the eye, or an eye or eyelid infection (other than mild eyelid inflammation).
- Being very short-sighted (more than 6 dioptres), past or present.
- Having no natural lens in the eye (aphakia).
- Other eye problems that would stop vision improving even if the bleed cleared, such as severe scarring or thinning of the macula, a lazy eye, or a macular hole.
- Pupils that will not widen enough, or cloudy areas in the eye, that would stop clear eye examinations or photographs.
- Eye surgery in the last 12 weeks (simple cataract surgery is allowed if it was at least 8 weeks ago).
What taking part involves
- • Vitrectomy: surgery to remove the clear gel from inside the eye.
- • Injection of a medicine called tissue plasminogen activator (TPA) under the retina to help break down the blood.
- • A gas bubble placed inside the eye.
- • Aflibercept may also be given as part of the trial (it is listed among the trial medicines).
Time commitment: Not stated — ask the trial team.
Plain-English summary (AI-generated) from registry data. Not eligibility advice — only the trial team can confirm whether you can take part. Use the eligibility checker to see how your health profile matches this trial.
- Type of study
- Testing a treatment
- Ages
- 50 Years to 120 Years
- Who
- All
- Number of participants
- 210
- Started
- 2021-04-16
- Last checked
- 2026-07
Plain English Summary
What is this study?
- • Testing a new treatment for eye diseases
- • Phase3 - 210 participants
- • The centre of the retina (macula) at the back of the eye contains cells that give us our central vision that we use for reading and recognising faces
Who can take part?
- • Ages 50 Years to 120 Years
- • Diagnosed with eye diseases
Where?
- • Chelmsford - Mid and South Essex NHS Foundation Trust
- • Canterbury - Kent & Canterbury Hospital (East Kent University)
- • London - King's College Hospital NHS Foundation Trust
- • Edinburgh - The Princess Alexandra Eye Pavilion
- • +22 more UK sites
This is a simplified summary. Always discuss with your doctor before making any decisions.
About This Trial
The centre of the retina (macula) at the back of the eye contains cells that give us our central vision that we use for reading and recognising faces. These cells can be damaged by a disease called wet age-related macular degeneration (AMD), where new abnormal blood vessels grow through the macula and leak fluid. This can affect vision. In some cases, wet AMD can also cause a bleed under the macula, known as a submacular haemorrhage (SMH), which can lead to marked and persistent loss of vision in the eye. The current standard treatment for wet AMD is to give injections containing 'anti-VEGF' drugs into the eye. Anti-VEGF drugs reduce the leakage of fluid so that the macula can become dry again and sight can improve. Anti-VEGFs are also the current standard of care for SMH, mainly because there is no licensed treatment for the SMH itself (patients with SMH were excluded from most wet AMD studies). The purpose of this study therefore is to compare two treatments: 1. Standard treatment for wet AMD (anti-VEGF injections). 2. Standard treatment above plus surgery. This study will find out if having surgery alongside anti-VEGF injections can improve vision further over the current standard treatment of anti-VEGF injections alone.
More detail
SMH is a rare but devastating complication of wet AMD. Untreated, SMH typically leads to permanent and severe loss of vision, ranging from 6/30 (approximately 20% normal vision) to only being able to perceive light versus dark (no useful vision). There are no large, published, randomised controlled trials (RCTs) evaluating treatments for SMH. Hence there is no widely-accepted treatment approach. Some patients are managed by observation, others with drugs (anti-VEGF) injected into the eye, others with eye surgery (vitrectomy, subretinal TPA, gas) and combinations thereof. From a regulatory perspective the standard treatment is with anti-VEGF injections alone, since these are licensed for the treatment of wet AMD (and there is no treatment licensed for SMH). This study will test the hypothesis that surgery with anti-VEGF injections for SMH due to wet AMD is superior to the current standard of treatment with anti-VEGF injections alone. The results will help guide future clinical practice to maximise the visual outcomes for patients with SMH. Most potential participants will present or be referred to the clinics of the investigators who provide routine care for wet AMD. Referrals may arise from research networks, family physicians, optometrists or ophthalmologists. After confirming the diagnosis of SMH, informed consent will be obtained and potential participants will be asked to sign a consent form. Following this, baseline screening will occur, including a clinical examination and a series of vision tests to confirm eligibility to take part in the study. Once successfully screened, each participant will be randomly allocated to one of the two study groups: 1. Standard current treatment with anti-VEGF injections: participants will be given their first injection into the study eye at the screening/baseline visit, or otherwise within a few days. Following this, each participant will receive another injection at month 1, another at month 2 and thereafter one injection every two months until the end of the study (month 12). Anaesthetic eye drops will be given to numb the eye before each injection. 2. Standard current treatment with anti-VEGF injections plus surgery: participants will be given their first injection into the study eye at the time of surgery and then all other injections as per the schedule above. During the surgery, the clear gel (vitreous) that fills the inside of the eye will be removed and a clot-busting drug (TPA) will be injected into the eye to help break up the blood clot. The inside of the eye will then be filled with gas to help push the dissolved clot away from the macula. Various options for anaesthetic will be discussed with each participant before surgery, including (i) local anaesthetic only, (ii) local anaesthetic with some sedation, to reduce any anxiety or (iii) general anaesthetic so the participant is asleep during the surgery. If the participant also has a cataract or is likely to develop one, the surgeon will discuss the option of having cataract surgery as part of the same operation. After the surgery, participants will be asked to keep their heads forward, to enable the gas bubble to move the blood clot away from the macula. This should be done for 50 minutes out of every hour for the first five days. During the 10-minute breaks, participants will be encouraged to move around and be active. At night, participants will be asked to sleep on the side of the operated eye, i.e. with the operated eye lowest. The gas is expected to disappear from the eye around 4-8 weeks after surgery. Participants who have had surgery will be instructed to return for follow up the day after surgery and also one week later. All participants will also have a clinical examination at 6 and 12 months that will include tests of their vision. They will also attend regularly for anti-VEGF injections: every month for the first three visits, then every two months until the study is completed at month 12.
How this trial compares with your answers
Answer 2 more questions to improve match
What we know so far
Still need:
- • Tell us your age for better matching
- • Tell us your sex for better matching
Preliminary match based on your answers. Full eligibility requires on-site assessment including medical history, physical exam, and lab tests. This does not guarantee enrolment.
Eligibility at a Glance
Key info
- Age: 50 Years - 120 Years
- Who can join: All genders
What the study is looking for
- ✓General
- ✓Males or females aged at least 50 years
- ✓Study eye
- ✓SMH involving the foveal centre that measures at least 1 disc diameter in greatest linear dimension.
- ✓Sub-neuroretinal haemorrhage at least 125 microns thick, measured at the foveal centre using spectral-domain optical...
Who cannot take part
- ✗General
- ✗Serious allergy to fluorescein or indocyanine green (ICG).
- ✗Hypersensitivity to alteplase, gentamicin, arginine, phosphoric acid, polysorbate 80 or aflibercept.
- ✗Stroke, transient ischaemic attack or myocardial infarction within 6 months.
- ✗Participation in another interventional study within 12 weeks of enrolment or planned to occur during this study.
See the full criteria
Where Is This Study? (26 UK sites)
Mid and South Essex NHS Foundation Trust
Chelmsford CM1 7ET, United Kingdom
Kent & Canterbury Hospital (East Kent University)
Canterbury CT1 3 NG, United Kingdom
King's College Hospital NHS Foundation Trust
London SE5 9RS, United Kingdom
The Princess Alexandra Eye Pavilion
Edinburgh EH3 9HA, United Kingdom
Sunderland Eye Infimary
Sunderland SR2 9HP, United Kingdom
Hull Royal Infirmary
Hull HU3 2JZ, United Kingdom
Belfast Health and Social Care Trust
Belfast BT9 7AB, United Kingdom
University Hospitals Sussex NHS Trust
Brighton, United Kingdom
Bristol Eye Hospital
Bristol BS1 2LX, United Kingdom
Royal Devon and Exeter Hospital
Exeter, United Kingdom
Gartnavel General Hospital
Glasgow, United Kingdom
Leicester Royal Infirmary
Leicester, United Kingdom
Royal Liverpool University Hospital
Liverpool L7 8 XP, United Kingdom
Barts Health NHST trust - Whipps Cross University Hospital
London E11 1NR, United Kingdom
Moorfields Eye Hospital
London EC1V 2PD, United Kingdom
Imperial College Healthcare NHS Foundation Trust (The Western Eye Hospital)
London NW1 5QH, United Kingdom
Maidstone and Tunbridge Wells NHS Trust
Maidstone ME16 9QQ, United Kingdom
Manchester Royal Eye Hospital
Manchester, United Kingdom
James Cook University Hospital, (South Tees NHSFT)
Middlesbrough, United Kingdom
Royal Victoria Infirmary
Newcastle upon Tyne NE1 4LP, United Kingdom
Nottingham University Hospitals
Nottingham, United Kingdom
Oxford University Hospitals NHS Foundation Trust
Oxford OX3 9DU, United Kingdom
University Hospitals Plymouth NHST
Plymouth, United Kingdom
University Hospital Southampton NHS foundation Trust
Southampton SO16 6YD, United Kingdom
Torbay and South Devon NHS
Torquay TQ2 7AA, United Kingdom
New Cross Hosp, Royal Wolverhampton NHST
Wolverhampton, United Kingdom
How to Get in Touch
Riti Desai, M.Sc.,M.Phil.
Sponsor contactCONTACT
Lisa Ramazzotto, M.Pharm
Sponsor contactCONTACT
