AIM: To evaluate the therapeutic effects of ranibizumab on optic disc and macular microvascular perfusion in central retinal vein occlusion (CRVO) with macular edema (ME). METHODS: Optical coherence tomography angiology (OCTA) parameters, including optic disc vessel density (VD; including whole-disc VD, intra-disc VD, and peripapillary VD), superficial/deep capillary plexus (SCP/DCP) VD, and central macular thickness (CMT) were analyzed. Additional assessments included best-corrected visual acuity (BCVA) via Early Treatment Diabetic Retinopathy Study (ETDRS) chart and hemorheological profiling. CRVO patients received monthly intravitreal ranibizumab injections for three consecutive months. Pre- and post-treatment parameters were statistically compared. RESULTS: The study comprised 60 CRVO-ME patients (28 males; 32 females), aged 50–78y (mean 63.3±7.6y) and 60 age-/sex-matched healthy controls. As compared with participants exhibiting normal funduscopic findings, CRVO patients demonstrated significantly elevated levels of low-shear-rate whole blood viscosity (LSR-WBV), high-shear-rate whole blood viscosity (HSR-WBV), and aggregation index (AI, all P<0.05). In CRVO-affected eyes, vertical cup-to-disc (C/D) ratio and optic cup volume were significantly smaller, whereas retinal nerve fiber layer (RNFL) thickness was significantly greater, compared to both unaffected contralateral eyes and normal control eyes (all P<0.05). Following treatment, VD of the entire optic disc (P<0.05), intra-disc VD (P<0.05), and peripapillary VD (P<0.05) all increased significantly relative to baseline. CMT decreased significantly (P<0.05), whereas macular SCP-VD and macular DCP-VD showed non-significant slight reductions (P>0.05). At baseline, BCVA of CRVO eyes correlated with whole-disc VD (r=-0.276, P=0.033), intra-disc VD (r=-0.342, P=0.009), and peripapillary VD (r=-0.335, P=0.007), with intra-disc VD demonstrating the strongest association. Besides, BCVA improvement, after the treatment, correlated positively with whole-disc VD (r=0.342, P=0.008) and intra-disc VD (r=0.396, P=0.002). CONCLUSION: Optic disc blood perfusion is more closely associated with visual acuity than macular perfusion, suggesting intra-disc VD may serve as a potential biomarker for monitoring visual acuity changes in CRVO. Multiple ranibizumab injections significantly improve optic disc perfusion but may have exerted detrimental effects on the macula. CRVO patients shows higher hemorheological parameters than those with normal fundi. Reduced vertical C/D ratio and optic cup volume may be linked to CRVO incidence, potentially acting as susceptibility factors.