Correlations between SS-OCT and OCT angiography biomarkers in treatment-naïve neovascular AMD during aflibercept therapy: a prospective study.

BACKGROUND: Swept-source OCT (SS-OCT) and OCT angiography (SS-OCTA) enable high-resolution assessment of retinal and choroidal biomarkers in neovascular AMD (nAMD). However, prospective analyses and how these biomarkers correlate before and after therapy are limited. The aim of this study was to prospectively evaluate biomarker correlations following a loading dose of aflibercept using state-of-the-art, high-resolution imaging with SS-OCT and SS-OCTA over the course of a 4-month follow-up in treatment-naïve nAMD. METHODS: This prospective interventional case series study included 21 eyes from 21 treatment-naïve patients with nAMD. All eyes received three monthly intravitreal aflibercept injections. Patients were evaluated at baseline and one month after the loading phase (4-month visit). The biomarkers included the best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), macular neovascularization area (MNVA), vessel density (VD), and avascular area of the superficial plexus (AASP) and deep plexus (AADP). Pre (baseline) and posttreatment values were compared, and correlations were analyzed using Pearson’s or Spearman’s methods. RESULTS: Significant functional, structural, and vascular improvements in all the evaluated biomarkers except intraocular pressure were observed after treatment. The mean BCVA improved from 1.11 ± 0.47 to 0.56 ± 0.20 logMAR (p < 0.001). SS-OCT (CMT and CCT), and SS-OCTA (MNVA, AASP and AADP) metrics were significantly lower following treatment. Correlation analysis revealed multiple statistically significant associations among structural, functional, and vascular biomarkers. The baseline CMT showed a moderate positive correlation with the CMT posttreatment (r = 0.53; p = 0.013) and a very high negative correlation with CMT reduction (r = − 0.95; p < 0.001). The baseline CCT was highly correlated with CCT posttreatment (r = 0.87; p = 0.002). The BCVA correlated significantly with CMT at baseline and posttreatment. Notably, the baseline MNVA was moderately negatively correlated with the posttreatment CCT (r = − 0.51; p = 0.019). Significant correlations were also identified between the AADP and both the baseline CMT and CMT reduction, as well as between changes in AASP and CCT. These findings highlight complex and interdependent relationships among retinal thickness, choroidal structure, visual function, and OCTA-derived microvascular biomarkers following aflibercept therapy. CONCLUSIONS: In treatment-naïve eyes with nAMD, aflibercept loading therapy induces significant and coordinated functional, structural, and microvascular changes. The observed correlations demonstrate that baseline SS-OCT and SS-OCTA biomarkers not only reflect initial disease burden but are also closely associated with the magnitude and direction of anatomical and vascular remodeling after treatment. These findings support the value of integrated multimodal biomarker assessment for improving prognostic stratification and advancing individualized management strategies in treatment-naïve nAMD. These findings are novel and have not been previously reported in the literature. CLINICAL TRIAL NUMBER: Not applicable.