NCT04663750: TIGER

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.

Recruiting now Phase 3 Last updated 13 May 2026

What this trial tests

Phase 3 trial testing Pars plana vitrectomy in Eye Diseases in 210 participants. Currently enrolling.

Timeline

16 April 2021

Primary endpoint
1 December 2028

1 December 2028

Quick facts

Lead sponsor	King's College Hospital NHS Trust
Phase	Phase 3
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	treatment
Enrollment	210
Start date	16 April 2021
Primary completion	1 December 2028
Estimated completion	1 December 2028
Sites	36 locations across Germany, Ireland, Poland, Switzerland, United Kingdom

Drugs / interventions tested

• 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) up to a maximum of 25 micrograms in 0.2 mls — full drug profile →
• Intravitreal 20% sulfahexafluoride (SF6) gas tamponade — full drug profile →

Conditions studied

• Eye Diseases — all drugs for Eye Diseases →
• Macular Degeneration, Wet — all drugs for Macular Degeneration, Wet →
• Sub-Macular Hemorrhage — all drugs for Sub-Macular Hemorrhage →

Sponsor

King's College Hospital NHS Trust

Who can join

Adults 50 to 120, any sex, with Eye Diseases or Macular Degeneration, Wet. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• assessment of Early Treat of Diabetic Retinopathy Study (ETDRS) letters of best-corrected visual acuity (BCVA) in the study eye.
  Time frame: 12 months
  The primary outcome is the proportion of participants with a BCVA gain ≥10 ETDRS letters in the study eye at the 12 month visit.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Vitrectomy, subretinal Tissue plasminogen activator and Intravitreal Gas for submacular haemorrhage secondary to Exudative Age-Related macular degeneration (TIGER): study protocol for a phase 3, pan-European, two-group, non-commercial, active-control, observer-masked, superiority
   Jackson TL, Bunce C, Desai R, Hillenkamp J, et al · · 2022 · cited 27× · PMID 35101110 · DOI 10.1186/s13063-021-05966-3
2. Comparison of treatment methods for submacular hemorrhage in neovascular age-related macular degeneration: conservative versus active surgical strategy.
   Mun Y, Park KH, Park SJ, Cho HJ, et al · · 2022 · cited 9× · PMID 36050401 · DOI 10.1038/s41598-022-18619-5
3. Vitrectomy, subretinal Tissue plasminogen activator and Intravitreal Gas for submacular haemorrhage secondary to Exudative Age-Related macular degeneration (TIGER): update to study protocol and addition of a statistical analysis plan and health economic analysis plan for a random
   Lee CN, Desai R, Ramazzotto L, Wafa H, et al · · 2025 · cited 2× · PMID 40229856 · DOI 10.1186/s13063-025-08727-8