AMD (Age Related Macular Degeneration) is the leading cause of severe visual loss and blindness registration in the UK . It is a disease which affects the retina (the nerve and blood vessel network at the back of the eye responsible for vision). Patients can suffer with severe visual loss and have difficulties with every day tasks such as recognising faces, reading & driving.

There are two variations of the disease, a 'dry' type & a 'wet' type also known as neovascular AMD (nAMD). In wet/nAMD new vessels grow from the blood supply underneath the retina, in part due to higher than normal levels of a protein called Vascular Endothelial Growth Factor (VEGF). Since the introduction of drugs which block VEGF, visual outcomes for patients with wAMD have dramatically improved.

There are 2 widely used treatments; ranibizumab and aflibercept. Whilst the majority of patients have a successful outcome with treatment, many patients experience suboptimal response. This study evaluated if these patients experience a benefit from a switch to a different antiVEGF drug treatment.

In this study nAMD patients who are showing no or poor to response to treatment with aflibercept were switched to ranibizumab to assess if there is any benefit in terms of treatment outcomes.

Patients visited the hospital clinic 8 times over the 7 - 8 month study period. Monthly ranibizumab injections were given for the first 3 months, then monthly as required for the next 3 months.

Inclusion Criteria:

• Best corrected visual acuity (BCVA) ≥23 ETDRS letters in study eye
• Evidence of active choroidal neovascularisation (CNV) involving the center of the fovea in study eye Patient subgroup specific inclusion criteria: - Group 1. Primary treatment failure
• Initiated treatment with aflibercept <130 days prior to the Screening Visit.
• No increase in BCVA (≥5 letters) since commencing treatment with aflibercept.
• Disease activity has never been controlled in the study eye after initiating aflibercept as defined by at least one of the following: evidence of unchanged or increasing retinal or subretinal fluid; new PED; unchanged or increasing size of preexisting PED.

Group 2. Suboptimal treatment response

• Aflibercept commenced ≥6 months prior to the Screening Visit.
• Received ≥3 aflibercept injections into the study eye within 6 months of the Screening Visit.
• Evidence of previous reduced disease activity (as defined by reduction of ≥50μm in Central Subfield Retinal Thickness on OCT) noted in the study eye after initiating aflibercept.
• At Screening Visit, disease activity has worsened (as defined by increasing retinal* or subretinal fluid, or new or increasing size of PED) in the study eye compared to prior visits.

Exclusion Criteria:

• History of cerebrovascular accident, transient ischemic attack or myocardial infarction within 3 months of the Screening visit.
• Uncontrolled blood pressure
• Evidence of bilateral active CNV during the Screening Period or at Baseline requiring bilateral antiVEGF injections.
• Prior intravitreal injection of ranibizumab or bevacizumab into the study eye and/or prior intravitreal injection of bevacizumab into the fellow eye.
• Cataract (if causing significant visual impairment), aphakia, severe vitreous hemorrhage, rhegmatogenous retinal detachment, proliferative retinopathy or choroidal neovascularization of any other cause than wet AMD (e.g. ocular histoplasmosis, pathologic myopia (≥8 dioptres)) at the time of Screening and Baseline.
• Irreversible structural damage involving the center of the fovea (e.g. advanced fibrosis or geographic atrophy) which in the opinion of the Investigator is sufficient to irreversibly impair visual acuity.
• Polypoidal choroidal vasculopathy (PCV), RPE tear, central serous retinopathy (CSR), or significant vitreomacular traction identified during Screening period or within 4 months of Baseline visit.
• Unable to obtain at Screening OCT images of sufficient quality to be analyzed