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Treatment for bleeding in the eye due to wet macular degeneration

Vitrectomy, Subretinal Tissue Plasminogen Activator and Intravitreal Gas for Submacular Haemorrhage Secondary to Exudative Age-Related Macular Degeneration (TIGER): a Phase 3, Pan-European, Two-group, Observer-masked, Superiority, Randomised Controlled Surgical Trial.

Phase 3 Interventional King's College Hospital NHS Trust · NCT04663750

This study is testing if a new surgical treatment combined with injections can help older adults with bleeding in the eye from wet macular degeneration see better than the usual injections alone.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment210 (estimated)
Ages50 Years to 120 Years
SexAll
SponsorKing's College Hospital NHS Trust Academic / other
Locations36 sites (Bonn and 35 other locations)
Trial IDNCT04663750 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to compare the effectiveness of a surgical approach combined with anti-VEGF injections against the current standard treatment of anti-VEGF injections alone for patients suffering from submacular hemorrhage (SMH) due to wet age-related macular degeneration (AMD). The study will involve participants aged 50 and older who have been diagnosed with SMH and will assess visual outcomes following treatment. Participants will undergo a series of interventions including vitrectomy, subretinal tissue plasminogen activator (TPA) injection, and intravitreal gas tamponade, alongside regular anti-VEGF injections. The goal is to determine if this combined approach leads to better visual recovery compared to standard care.

Who should consider this trial

Good fit: Ideal candidates are males or females aged 50 and older with submacular hemorrhage secondary to treatment-naive or previously treated exudative AMD.

Not a fit: Patients with serious allergies to fluorescein or indocyanine green, or those with hypersensitivity to the study medications will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve vision recovery for patients with submacular hemorrhage due to wet AMD.

How similar studies have performed: There have been no large, published randomized controlled trials evaluating treatments for submacular hemorrhage, making this approach relatively novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

General

1. Males or females aged at least 50 years

   Study eye
2. SMH, comprising sub-neuroretinal haemorrhage with or without sub-RPE haemorrhage, that occurs secondary to treatment naïve, or previously treated exudative AMD, including choroidal neovascularisation (CNV), idiopathic polypoidal choroidal vasculopathy (IPCV) and retinal angiomatous proliferation (RAP).
3. SMH involving the foveal centre that measures at least 1 disc diameter in greatest linear dimension.
4. Sub-neuroretinal haemorrhage at least 125 microns thick, measured at the foveal centre using spectral-domain optical coherence tomography (SD-OCT).
5. BCVA between counting fingers and an Early Treatment of Diabetic Retinopathy Study (ETDRS) letter score of 70, inclusive.

Exclusion Criteria:

General

1. Serious allergy to fluorescein or indocyanine green (ICG).
2. Hypersensitivity to alteplase, gentamicin, arginine, phosphoric acid, polysorbate 80 or aflibercept (Eylea).
3. Stroke, transient ischaemic attack or myocardial infarction within 6 months.
4. Participation in another interventional study within 12 weeks of enrolment or planned to occur during this study.
5. Women who are breast feeding, pregnant, or planning to become pregnant during the clinical trial. Any sexually active women of childbearing potential must agree continued abstinence from heterosexual intercourse or to use highly effective methods of birth control for the duration up to 12 weeks after administration of IMP or the last administration of aflibercept on the trial. Men must also agree to use a condom if their partner is of child bearing potential, even if they have had a successful vasectomy. Females of childbearing potential are females who have experienced menarche and are not surgically sterilised (e.g. hysterectomy or bilateral salpingectomy) or post-menopausal (defined as at least 1 year since last regular menstrual period). Highly effective methods of birth control are those with a failure rate of \< 1% per year when employed consistently and correctly, eg. combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation via oral, intravaginal, and transdermal routes; progestogen-only hormonal contraception associated with inhibition of ovulation via oral, injectable, implantable, intrauterine device (IUD), or intrauterine hormone-releasing system ( IUS); or vasectomised partner.
6. International Normalised Ratio (INR) greater than 3.5, unless it is anticipated that the INR can be brought below this level prior to vitrectomy, balancing the systemic risks with those of intraocular haemorrhage\*.
7. Unwilling, unable, or unlikely to return for scheduled follow-up for the duration of the trial.
8. Any other condition which, in the opinion of the investigator, would prevent the participant from granting informed consent or complying with the protocol, such as dementia, mental illness, or serious systemic medical disease.

   Study eye
9. SMH that is known or estimated to have been present for longer than 15 days, as evidenced by history, pre-trial clinical documentation, or fundus appearance.
10. SMH due to eye disease other than exudative AMD.
11. Current active proliferative diabetic retinopathy.
12. Current intraocular inflammation.
13. Current ocular or periocular infection other than blepharitis.
14. Current or known former high myopia (\>6 dioptres).
15. Aphakia.
16. Other current or pre-existing ocular conditions that, in the opinion of the Investigator, will preclude any improvement in BCVA following resolution of SMH, such as severe central macular atrophy or fibrosis, dense amblyopia, macular hole involving the fovea, or very poor BCVA prior to presentation with SMH (counting fingers or worse).
17. Inadequate pupillary dilation or significant media opacities, which will prevent adequate clinical evaluation of the posterior segment or fundus imaging.
18. Intraocular surgery within 12 weeks of enrolment except for uncomplicated cataract surgery, which is permitted within 8 weeks of enrolment.

    * Applies only to participants receiving warfarin.

Where this trial is running

Bonn and 35 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Eye DiseasesMacular Degeneration, WetSub-Macular Hemorrhage
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.