Vitrectomy, Subretinal Tissue Plasminogen Activator (TPA) and Intravitreal Gas for Submacular Haemorrhage Secondary to Exudative (Wet) Age-related Macular Degeneration (TIGER).

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 choroidalvasculopathy (IPCV) and retinal angiomatous proliferation (RAP).

3. SMH involving the foveal centre that measures at least 1 disc diameter in greatestlinear dimension.

4. Sub-neuroretinal haemorrhage at least 125 microns thick, measured at the fovealcentre 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 80or aflibercept.

3. Stroke, transient ischaemic attack or myocardial infarction within 6 months.

4. Participation in another interventional study within 12 weeks of enrolment orplanned to occur during this study.

5. Women who are breast feeding, pregnant, or planning to become pregnant during theclinical trial. Any sexually active women of childbearing potential must agreecontinued abstinence from heterosexual intercourse or to use highly effectivemethods of birth control for the duration up to 12 weeks after administration of IMPor the last administration of aflibercept on the trial. Men must also agree to use acondom if their partner is of child bearing potential, even if they have had asuccessful vasectomy. Females of childbearing potential are females who haveexperienced menarche and are not surgically sterilised (e.g. hysterectomy orbilateral salpingectomy) or post-menopausal (defined as at least 1 year since lastregular menstrual period). Highly effective methods of birth control are those witha failure rate of < 1% per year when employed consistently and correctly, eg.combined (oestrogen and progestogen containing) hormonal contraception associatedwith inhibition of ovulation via oral, intravaginal, and transdermal routes;progestogen-only hormonal contraception associated with inhibition of ovulation viaoral, injectable, implantable, intrauterine device (IUD), or intrauterinehormone-releasing system ( IUS); or vasectomised partner.

6. International Normalised Ratio (INR) greater than 3.5, unless it is anticipated thatthe INR can be brought below this level prior to vitrectomy, balancing the systemicrisks with those of intraocular haemorrhage*.

7. Unwilling, unable, or unlikely to return for scheduled follow-up for the duration ofthe trial.

8. Any other condition which, in the opinion of the investigator, would prevent theparticipant from granting informed consent or complying with the protocol, such asdementia, 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, asevidenced 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 theInvestigator, will preclude any improvement in BCVA following resolution of SMH,such as severe central macular atrophy or fibrosis, dense amblyopia, macular holeinvolving the fovea, or very poor BCVA prior to presentation with SMH (countingfingers or worse).

17. Inadequate pupillary dilation or significant media opacities, which will preventadequate clinical evaluation of the posterior segment or fundus imaging.

18. Intraocular surgery within 12 weeks of enrolment except for uncomplicated cataractsurgery, which is permitted within 8 weeks of enrolment.

• Applies only to participants receiving warfarin.