In this study, we aim to evaluate the efficacy and safety of an individualized dosing schedule comprising Aflibercept and RF-PDT in patients with polypoidal choroidal vasculopathy (PCV). The primary objective is to compare the polyp closure rate at week 12 between the 2 treatment groups. The secondary aims include comparing visual, anatomical, treatment burden and clinical biomarkers between each treatment group.

Age related macular degeneration (AMD) is one of the leading causes of blindness worldwide. In its exudative or wet form, choroidal neovascularization (CNV) causes an exudative maculopathy resulting in sudden loss of vision with severe effects on patients' quality of life. Intravitreal injections of anti-vascular endothelial growth factor agents (anti-VEGF) have become the mainstay of treatment for AMD CNV and has been shown to have favorable outcomes in most AMD CNV subtypes. In the Asian population, however, a particular subtype called polypoidal choroidal vasculopathy (PCV), which affects about 50% of exudative maculopathy, has been shown to have less favorable response to anti-VEGF therapy.

The best treatment option for PCV has remained unclear. Current best evidence is from 2 recent randomized controlled trials, the EVEREST II trial which compares the efficacy of ranibizumab with or without photodynamic therapy (PDT) for treatment of PCV and the PLANET trial which compares Aflibercept monotherapy against a rescue PDT when Aflibercept is deemed ineffective. Both trials have reported significant improvement in visual outcomes, however there remain significant unanswered questions and unmet needs regarding the use of Aflibercept and PDT as the best treatment for PCV.

In this study, we aim to compare the efficacy of combination Aflibercept with RF-PDT (at baseline) and Aflibercept monotherapy. This particular strategy has not been studies before and represents the amalgamation of unanswered questions from the best evidence to date for the treatment of PCV.

Inclusion Criteria:

• Patients aged over 50 years old at the time of informed consent.

• Provide written informed consent.

• Willingness and ability to comply with all scheduled visits and study procedures.

• Confirmed diagnosis of symptomatic macular PCV based ICGA.

• Activity of PCV confirmed by exudative activity involving the macula on OCT or Fluorescein Angiography (FA) or both.

  • Presence of intra retinal or subretinal fluid/blood as seen on OCT

  • Treatment naïve

    • NO previous treatment with intravitreal anti-VEGF agents, regardless of the indication
    • NO previous thermal laser in the macular region, or verteporfin photodynamic therapy (vPDT), regardless of indication
    • NO other previous treatment for neovascular AMD (nAMD), except oral supplements and traditional Chinese medicine

• An ETDRS BCVA of at least 4 letters (Snellen equivalent approximately 20/800 or better) in the study eye.

• Greatest Linear Dimension (GLD) of the total lesion area (BVN + polyps) <5400µm (~9 mucopolysaccharidoses (MPS) Disc Areas) as delineated by ICGA.

Exclusion Criteria: - Participant

• Medical condition that, in the opinion of the investigator, would preclude participation in the study (e.g. unstable medical status including blood pressure, cardiovascular disease, and glycemic control).
• Participation in an investigational trial within 30 days of enrollment which involves treatment with unapproved investigational drug.
• Known allergy to any component of the study drug.
• Blood pressure> 180/110 (systolic above 180 OR diastolic above 110 on repeated measurements). If blood pressure is brought below 180/110 by anti-hypertensive treatment, individual can become eligible.
• Myocardial infarction, other acute cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 4 months prior to randomization.
• Systemic anti-VEGF or pro-VEGF treatment within four months prior to randomization or anticipated use during the study.
• Amblyopia or blind in one eye Study Eye
• Eye with intra retinal or sub-retinal fluid due to other causes than PCV
• An ocular condition is present (other than PCV) that, in the opinion of the investigator, might affect intra or sub retinal fluid or alter visual acuity during the course of the study (e.g., Diabetic Macular Edema (DME), vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, etc.)
• Substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by more than three lines (i.e., cataract would be reducing acuity to worse than 20/40 if eye was otherwise normal).
• Any intraocular surgery within 1 month of enrollment
• Treatment with intra vitreal corticosteroids
• History of retinal detachment or surgery for retinal detachment
• History of vitrectomy
• History of macular hole
• Evidence of vitreomacular traction that may preclude resolution of macular edema &gt; 4 disc areas of intra/sub retinal hemorrhage
• Aphakia
• Exam evidence of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis

Other Eye

• Active intraocular inflammation
• History of uveitis