In the present study, investigators attempt to evaluate the short-term, detailed changes in choroidal morphology after three monthly injections of aflibercept in pachychoroid neovasculopathy. The association between these changes and clinical outcomes will be additionally investigated. The primary purpose of this study is to provide reference data regarding the aflibercept-related morphologic changes that implicate structural and functional choroidal alteration, and hence its clinical implications.

Pachychoroid neovasculopathy (PNV), is a recently proposed entity after advancements in retinal imaging, belonging to the pachychoroid spectrum of diseases. It is a prevalent subtype of neovascular age-related macular degeneration (AMD) in the Asian population (19.5%~41.6% among neovascular AMD), characterized by presence of type 1 macular neovascularization (MNV) without polypoidal lesion in an eye exhibiting pachychoroid features, although its pathogenesis is not fully understood. In addition, PNV can be distinguished from typical neovascular AMD by a relative absence of drusen or pseudodrusen, younger age of onset, and thickened choroid with pachyvessels. Although both neovascular AMD and PNV respond well to anti-vascular endothelial growth factor (VEGF) therapy, separate analysis of treatment outcomes in PNV merits further investigation targeting the different underlying pathologies.

It is well-known that anti-VEGF therapy influences choroidal structures, including choroidal thickness, choroidal vascularity index, and choroidal area. In general, decrease in choroidal thickness after aflibercept injection is more prominent than that after ranibizumab or bevacizumab injections. Some investigators postulated that this difference in the effect on choroid is responsible for the superior efficacy of aflibercept in polypoidal choroidal vasculopathy (PCV) over other anti-VEGF agents and influence the choice of anti-VEGF agent in real-world practice. To date, several investigators have demonstrated changes in choroidal thickness after anti-VEGF therapy in PNV. However, the detailed changes in choroidal morphology after aflibercept therapy and its clinical implications in pachychoroidal neovasculopathy remain to be elucidated.

In the present study, investigators attempt to evaluate the short-term, detailed changes in choroidal morphology after three monthly injections of aflibercept in pachychoroid neovasculopathy. The association between these changes and clinical outcomes will be additionally investigated. The primary purpose of this study is to provide reference data regarding the aflibercept-related morphologic changes that implicate structural and functional choroidal alteration, and hence its clinical implications.

Inclusion Criteria:

• Willing, committed, and able to return for all clinic visits and complete all study related procedures.

• Able to read, (or, if unable to read due to visual impairment, be read to verbatim by the person administering the informed consent or a family member) understand and willing to sign the informed consent form.

• Signed informed consent

• Patients aged 50 years or older

• Patients diagnosed with treatment naïve pachychoroid neovasculopathy

  • Diagnostic criteria of PNV

    1. Presence of type 1 MNV
    2. Subfoveal choroidal thickness ≥250 µm
    3. Focal or diffuse choroidal thickening
    4. Presence of dilated choroidal vessels (pachyvessels)
    5. Thinning or absence of choriorapillaris and Sattler's layer overlying pachyvessels
    6. Absence of drusen or pseudodrusen, except for pachydrusen

• ETDRS BCVA letter score ≥25 letters (approximately 20/320 or better) in the study eye

Exclusion Criteria:

• Any prior ocular (in the study eye) or systemic treatment or surgery for neovascular AMD except dietary supplements or vitamins.
• Prior treatment with anti-VEGF agents
• Known serious allergy to the fluorescein sodium for injection in angiography.
• Significant media opacities, including cataract, in the study eye that might interfere with visual acuity, assessment of safety, or fundus photography.
• Any concurrent ocular condition in the study eye which, in the opinion of the investigator, could either increase the risk to the patient beyond what is to be expected from standard procedures of intraocular injection, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety.
• Any ocular or periocular infection within the last 2 weeks prior to Screening in either eye.
• Any history of uveitis in either eye.
• Presence of definite chorioretional anastomosis
• Subretinal hemorrhage that is either 50% or more of the total lesion area, or if the blood is under the fovea and is 1 or more disc areas in size in the study eye. (If the blood is under the fovea, then the fovea must be surrounded 270 degrees by visible choroidal neovascularization.)
• Scar or fibrosis, making up > 50% of total lesion in the study eye.
• Scar, fibrosis, or atrophy involving the center of the fovea in the study eye.
• Presence of retinal pigment epithelial tears or rips involving the macula in the study eye.
• History or clinical evidence of diabetic retinopathy, diabetic macular edema or any other vascular disease affecting the retina, other than AMD, in either eye.
• Any concurrent intraocular condition in the study eye (e.g. cataract) that, in the opinion of the investigator, could require either medical or surgical intervention during the 76 week study period.
• Prior vitrectomy in the study eye
• Any history of macular hole of stage 2 and above in the study eye.
• Any intraocular or periocular surgery within 3 months of Day 1 on the study eye, except lid surgery, which may not have taken place within 1 month of day 1, as long as its unlikely to interfere with the injection.
• Prior trabeculectomy or other filtration surgery in the study eye.
• Uncontrolled glaucoma (defined as intraocular pressure ≥ 25 mmHg despite treatment with antiglaucoma medication) in the study eye.
• Active intraocular inflammation in either eye.
• Active ocular or periocular infection in either eye.
• Aphakia or pseudophakia with absence of posterior capsule (unless it occurred as a result of a yttrium aluminum garnet posterior capsulotomy) in the study eye.
• History of corneal transplant or corneal dystrophy in the study eye.