A Phase 3 interventional study of Pars plana vitrectomy and Intravitreal 2 mg aflibercept will be injected at baseline then monthly for two further doses, then 2-monthly until month 12 in Eye Diseases, Macular Degeneration, Wet and Sub-Macular Hemorrhage, sponsored by King's College Hospital NHS Trust. Recruiting at 42 sites in 7 countries. Open to participants aged 50 Years to 120 Years. Per ClinicalTrials.gov, last updated 2026-09-11.
Sponsored by King's College Hospital NHS Trust · Phase 3, Interventional, and Treatment
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:
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:
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.
93 studies on the registry are indexed under Wet Macular Degeneration; 10 are open to participants now.
This study's planned enrollment of 210 is above the median of 101 across 74 interventional studies indexed under Wet Macular Degeneration.
Browse Wet Macular Degeneration studies →King's College Hospital NHS Trust is the lead sponsor of 171 studies on the registry; 56 are open to participants now.
Compared within Wet Macular Degeneration, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Eye Diseases. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
General
Males or females aged at least 50 years
Study eye
Exclusion Criteria:
General
Any other condition which, in the opinion of the investigator, would prevent the participant from granting or complying with the protocol, such as dementia, mental illness, or serious systemic medical disease.
Study eye
Intraocular surgery within 12 weeks of enrolment except for uncomplicated cataract surgery, which is permitted within 8 weeks of enrolment.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Surgery with aflibercept at the end of surgery, with post-operative review day 1 and week 1 (day 7)
Procedure: Pars plana vitrectomy · Drug: 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
Aflibercept monotherapy commencing at baseline.
Drug: Intravitreal 2 mg aflibercept will be injected at baseline then monthly for two further doses, then 2-monthly until month 12
Pars plana vitrectomy
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, Actilyse, Boehringer Ingelheim) up to a maximum of 25 micrograms in 0.2 mls.
Also known as: Actilyse (Boehringer Ingelheim)
Intravitreal 20% sulfahexafluoride (SF6) gas tamponade.
assessment of Early Treat of Diabetic Retinopathy Study (ETDRS) letters of best-corrected visual acuity (BCVA) in the study eye.
The primary outcome is the proportion of participants with a BCVA gain ≥10 ETDRS letters in the study eye at the 12 month visit.
Time frame: 12 months
Assessment of Early Treatment Diabetic Retinopathy Study (ETDRS) letter improvement in Best-Corrected Visual Acuity (BCVA) in the study eye
Change in ETDRS letters in BCVA in the study eye at the month 6 visit.
Time frame: 6 months
Mean ETDRS BCVA
Time frame: 6 and 12 months
Radner maximum reading speed
Time frame: 6 and 12 months
Area of scotoma size using Humphrey Field Analyser 10-2 or equivalent
Time frame: 6 and 12 month
National Eye Institute 25-item visual function questionnaire (NEI VFQ-25). composite score.
Time frame: 6 and 12 months.
EQ-5D-5L with vision bolt-on score.
Time frame: 6 and 12 months.
Presence/absence of subfoveal fibrosis and/or atrophy and area of fibrosis/atrophy using multimodal reading centre image analysis.
Presence or absence of subfoveal fibrosis and/or atrophy and area of fovea-involving fibrosis/atrophy assessed using multimodal imaging by an independent reading centre, combining spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF) and stereo fundus photographs.
Time frame: 12 months.
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