A Study to Learn How Well a Higher Amount of Aflibercept Given as an Injection Into the Eye Works and How Safe it is in People With Reduced Vision Due to Swelling in the Macula, Central Part of the Retina Caused by a Blocked Vein in the Retina (Macula Edema Secondary to Retinal Vein Occlusion)

Inclusion criteria

• Adult ≥18 years of age (or country's legal age of adulthood if the legal age is >18 years) at the time of signing the informed consent.
• Treatment-naïve macular edema involving the foveal center secondary to RVO (BRVO, HRVO, or CRVO) diagnosed within 16 weeks (112 days) before the screening visit in the study eye.
• Early Treatment Diabetic Retinopathy Study BCVA letter score of 73 to 24 (20/40 to 20/320) at screening and baseline visits in the study eye.

Decrease in BCVA determined to be primarily the result of RVO in the study eye.

• Mean CST ≥300 μm on optical coherence tomography (OCT) if excluding Bruch's membrane (e.g., Cirrus or Topcon) or ≥320 μm if including Bruch's membrane (e.g., Heidelberg Spectralis), confirmed by the reading center at the screening visit and by the site at baseline visit in the study eye.
• Capable of giving signed informed consent form (ICF) by study participant or legally acceptable representative, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
• US participants will be required to have a Health Insurance Portability and Accountability Act (HIPAA) authorization; in other countries, as applicable according to national laws.
• Women of childbearing potential (WOCBP) or men who are sexually active with partners of childbearing potential must agree to use highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 4 months after the last administration of study intervention. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for participation in clinical studies and fulfil the conditions set on Section 10.4.2.

Exclusion criteria

• Concurrent disease that causes substantial decrease of BCVA, is expected to limit BCVA recovery or is likely to require medical or surgical intervention during the study in the study eye.
• Presence or history of the following ocular conditions:

• Advanced age-related macular degeneration (neovascular AMD or geographic atrophy) in the study eye.
• Diabetic macular edema or diabetic retinopathy, defined in diabetic participants as diabetic retinopathy lesions outside the area of the vein occlusion in the study eye and anywhere in the retina in the fellow eye.
• Anterior segment neovascularization, vitreous hemorrhage, retinal detachment in the study eye.
• Vitreomacular traction, epiretinal membrane or structural damage to the macula that is considered by the Investigator to significantly affect central vision or preclude improvement in vision in the study eye.
• Macular hole of stage 2 and above in the study eye.
• Myopia of a spherical equivalent of at least 8 diopters prior to any refractive or cataract surgery in the study eye.
• Corneal transplant or corneal dystrophy in the study eye.
• Idiopathic or autoimmune uveitis in the study or in the fellow eye.
• Presence of the following ocular conditions at screening or baseline visit:

• Significant media opacities, including cataract, that interfere with BCVA, or imaging assessments (e.g., fundus photography [FP], OCT) in the study eye.
• Aphakia, or pseudophakia with absence of posterior capsule (unless it occurred as a result of a yttrium-aluminum-garnet [YAG] posterior capsulotomy performed more than 30 days before the screening visit), in the study eye.
• Uncontrolled glaucoma (defined as IOP >25 mmHg despite treatment with anti-glaucoma medication); or history or likely future need of glaucoma surgery in the study eye.
• Intraocular inflammation/infection (including trace, or above, cells in the anterior chamber and/or vitreous) within 12 weeks (84 days) of the screening visit in the study or in the fellow eye.
• Extraocular or periocular infection or inflammation (including infectious blepharitis, keratitis, scleritis, or conjunctivitis) in the study or in the fellow eye.
• Uncontrolled blood pressure (defined as systolic >160 mmHg or diastolic >95 mmHg) at the screening visit or baseline visit.
• Uncontrolled diabetes mellitus, defined by hemoglobin A1c (HbA1c) >12% at the screening visit.
• History of cerebrovascular accident or myocardial infarction within 24 weeks (168 days) before the screening visit or between screening and baseline visits.
• Renal failure requiring dialysis, or renal transplant at screening or potentially during the study.
• Any prior or concomitant ocular or systemic treatment (with an investigational or approved, anti-VEGF or other agent) or surgery for RVO in the study eye.
• Previous administration of systemic anti-angiogenic medications for any condition.
• Prior treatment of the study eye with any of the following drugs (any route of ophthalmic administration) or procedures:

• Anti-angiogenic drugs at any time including investigational therapy (e.g., with anti-angiopoietin/anti-VEGF bispecific monoclonal antibodies).
• Previous use topical steroids within 4 weeks (28 days) from the screening visit, or intraocular or periocular steroids within 16 weeks (112 days) from the screening visit, or steroid implants at any time.
• Previous treatment with intraocular or periocular implant, gene therapy, or cell therapy at any time.
• Treatment with ocriplasmin at any time.
• Vitreoretinal surgery (including scleral buckling) at any time.
• Any intraocular surgery, including cataract surgery, within 12 weeks (84 days) before the screening visit.
• Previous treatment with retinal laser photocoagulation.
• Prior treatment of the fellow eye with any of the following:

a. Gene therapy, or cell therapy in the fellow eye at any time.

• Participation in other clinical studies requiring administration of investigational treatments (other than vitamins and minerals) at the time of screening visit, or within 30 days or 5 half-lives of administration of the previous study intervention, whichever is longer.