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This prospective study aimed to explore the effect of medical intraocular pressure (IOP) reduction on structural and capillary vessel density (VD) change by optical coherence tomography (OCT) angiography in early glaucoma. Patients with newly diagnosed glaucoma and a follow-up of ≥6 months were enrolled. An ocular examination that included slit-lamp bio-microscopy, pneumatic tonometry, gonioscopy, standard automated perimetry, and OCT angiography was performed. Quantitative OCT angiography parameters were assessed using a linear mixed model that was adjusted for inter-eye correlation. The correlations between IOP changes and OCT angiography parameter changes were analyzed using Spearman's correlation test. In total, 52 eyes of 36 participants, including 33 glaucoma eyes of 17 participants and 19 healthy eyes of 19 participants served as the case and control groups, respectively. The IOP of the case group decreased from a baseline mean of 20.4 ± 0.8 mmHg to 15.7 ± 0.5 mmHg at 3 months (p < 0.001) and to 16.1 ± 0.5 mmHg at 6 months (p < 0.001). For the subgroup with an IOP reduction of >20%, the deep macula VD was negatively correlated with baseline IOP and significantly decreased at 3 months follow-up. Additionally, change in retinal nerve fiber layer (RNFL) was positively correlated with a change in IOP at 6 months. In conclusion, the deep-layer macula VD was correlated with baseline IOP and influenced by the reduction in IOP in the short term. The changes in VD revealed the vulnerability of the deep vascular complex. The OCTA parameters provide in vivo monitoring information during medical treatment for early glaucoma. [ABSTRACT FROM AUTHOR]