The primary objective of SCORE2 is to test for non-inferiority based on mean change from baseline in visual acuity letter score at Month 6 for eyes randomized to intravitreal bevacizumab every 4 weeks compared with eyes randomized to intravitreal aflibercept every 4 weeks using a non-inferiority margin of 5 letters.~Secondary objectives of SCORE2 are to:~compare the bevacizumab and the aflibercept groups with regards to central retinal thickness, as measured with spectral domain optical coherence tomography (SD-OCT), at Month 6 and change between baseline and Month 6;~assess Month 12 visual acuity and SD-OCT outcomes associated with different dosing strategies after Month 6 in participants who respond well to treatment;~assess Month 12 visual acuity and SD-OCT outcomes associated with alternative treatment strategies after Month 6 in participants who respond poorly to treatment;~compare area of retinal ischemia and rates of neovascular complications of CRVO in the bevacizumab vs. aflibercept groups;~add to our knowledge of the safety profile of these anti-vascular endothelial growth factor (VEGF) medications in the setting of eyes with macular edema secondary to CRVO;~conduct a cost effectiveness analysis comparing intravitreal bevacizumab to intravitreal aflibercept to assess the economic implications from a payor perspective using decision analytic methods.~Other exploratory aims of SCORE2 are to:~investigate the correlation of features identified through SD-OCT segmentation analysis, such as the inner segment-outer segment (IS-OS) junction (also known as the ellipsoid zone), with such characteristics as visual acuity and central retinal thickness;~investigate the correlation of area of peripheral retinal nonperfusion from widefield fluorescein angiography with visual acuity and central retinal thickness, and the prognostic value of baseline peripheral and central retina perfusion status in predicting disease course and treatment responsiveness;~investigate the correlation of features on adaptive optics imaging with such characteristics as visual acuity and central retinal thickness.
SCORE2 is a multicenter, prospective, randomized, phase III clinical trial in which all participants enrolled will be followed for up to 2.5 years. SCORE2 is designed as a non-inferiority trial, with study eyes randomized to intravitreal bevacizumab (1.25 mg) every 4 weeks vs. intravitreal aflibercept (2.0 mg) every 4 weeks. SCORE2 aims to determine if bevacizumab is non-inferior to aflibercept for the treatment of macular edema associated with central retinal vein occlusion (CRVO), with the primary outcome of visual acuity measured at Month 6.