Abstract:AIM: To explore the feasibility of optical coherence tomography angiography (OCTA) in the early detection of syphilis and syphilitic chorioretinopathy. METHODS: Patients with newly diagnosed syphilis were enrolled from September 2022 to November 2023. All the participants underwent serological examinations including rapid plasma reagin (RPR) test and treponema pallidum particle agglutination (TPPA) test, as well as macular OCTA scanning. Quantitative indicators including macular vessel flow density (VFD), vessel length density (VLD), and foveal avascular zone (FAZ) were measured and analyzed. RESULTS: A total of 44 participants were recruited in this study, including 24 patients in the syphilis group (14 males, mean age: 30.83±9.59y) and 20 healthy individuals in the control group (6 males, mean age: 29.6±11.86y). Compared with the control group, the syphilis group presented significantly higher macular VLD and VFD (P<0.05), as well as an increased FAZ perimeter. Subgroup analysis was performed based on RPR titers, with patients divided into the low-titer subgroup (1:2–1:4) and high-titer subgroup (1:8–1:128). Both subgroups showed elevated VLD and VFD (excluding inner VFD) relative to controls (all P<0.05). Moreover, significant elevation of VFD was only observed in the high-titer subgroup. Receiver operating characteristic analysis identified outer VLD as the optimal indicator for distinguishing syphilis patients from controls, with an area under the curve of 0.802 (95%CI: 0.667–0.937). CONCLUSION: Syphilis patients with either low or high RPR titers show increased macular VLD and VFD in the absence of obvious visual impairment, indicating the potential of OCTA microvascular parameters for early auxiliary diagnosis of syphilitic ocular lesions.