PURPOSE: To analyze retinal perfusion using ultrawide-field fluorescein angiography and optical coherence tomography angiography, in patients with central retinal vein occlusion treated by intravitreal injection of aflibercept. METHODS: Single-arm, multicenter, prospective, observational study. Treatment-naive eyes with central retinal vein occlusion initiated therapy with aflibercept. Ultrawide-field fluorescein angiography with correction of projection distortion and optical coherence tomography angiography were performed at baseline (M0), M3, M12, and M24. RESULTS: Fifty-six eyes were included. Visual acuity improved by 16 ETDRS letters at M12 ( P <
0.002), while mean central subfield thickness decreased from 801 µ m at M0 to 352 µ m at M12 ( P <
0.002). The ischemic index on ultrawide-field fluorescein angiography increased from 17% at M0 to 23% at M3, and to 36% at M24. Ischemic central retinal vein occlusion accounted for 18% at M0, 25% at M3, and 39% at M24 ( P <
0.05). Vascular leakage was only present in 21% of eyes at M12. The density of the superficial and deep capillary plexus remained stable, but the foveal avascular zone enlarged from 0.37 mm 2 at M0 to 0.61 mm 2 at M24 ( P = 0.02). No cases of reperfusion were observed. The mean number of injections at M12 was 7.0 ± 3.6. CONCLUSION: Changes in retinal perfusion were characterized by worsening perfusion in the periphery, while macular capillaries maintained a generally stable density at M24, even in ischemic central retinal vein occlusion. These findings support the need for regular monitoring of peripheral retinal perfusion in treated patients to detect silent progression of nonperfusion, which may lead to neovascular complications, while visual acuity is maintained over the long term, likely due to the preserved macular capillary density.