ObjectiveTo preliminarily investigate the predictive value of volumetric fluctuation index (VFI) of different exudative lesions during anti-vascular endothelial growth factor (VEGF) loading treatment for retreatment requirements within 12 and 24 months in neovascular age-related macular degeneration (nAMD). MethodsA prospective cohort study. From January 1, 2022 to March 31, 2023, 46 patients with nAMD who visited State Key Laboratory of Ophthalmology of Sun Yat-sen University for the first time were included in the study. Among them, 35 were male and 11 were female; the average age was (65.61±7.22) years. All patients received a three-times loading treatment followed by on-demand treatment, and were regularly followed up for 2 years. Using optical coherence tomography (OCT), OCT angiography, and 3D Slicer software, three-dimensional reconstructions were performed for seven types of exudative lesions, including subretinal fluid (SRF), intraretinal fluid (IRF), strong reflective substances under the retina [SHRM, including vascular SHRM (vSHRM) and non-vascular SHRM (avSHRM)], and pigment epithelial detachment [PED, including serous (sPED), fibrovascular PED and hemorrhagic PED (hPED)]. Based on the volume data at baseline and 1, 4, 8, and 12 weeks after treatment, the short-term VFI of each lesion was calculated to evaluate its early fluctuation characteristics. According to whether re-treatment was needed within 12 and 24 months after the end of the loading period, the patients were divided into the supplementary treatment group and the stable group. The Mann-Whitney U test was used to compare the differences in VFI between the two groups; a multivariate linear regression model was used to analyze the independent influencing factors of the number of supplementary treatments. ResultsAmong 46 eyes at 12 months post-loading, 17 and 29 eyes were assigned to the retreatment and stable groups, respectively. SRF-VFI and total fluid-VFI were both significantly higher in the retreatment group than in the stable group (Z=3.221, 2.924; P=0.001, 0.003). At 24 months post-loading, 22 and 24 eyes were in the retreatment and stable groups, respectively; total fluid-VFI remained significantly higher in the retreatment group (Z=2.177, P=0.029). Linear regression analyses revealed that, after adjusting for sex, age, macular neovascularization subtype, anti-VEGF drug subtype, and baseline total lesion volume, total fluid-VFI (standardized β=0.382, 0.460) and IRF-VFI (standardized β=0.359, 0.495) were significantly associated with retreatment frequency within 12 and 24 months post-loading (P<0.05); SRF-VFI and sPED-VFI (standardized β=0.361, 0.392) were significantly associated with retreatment frequency at 12 and 24 months post-loading, respectively (P<0.05). Total SHRM-VFI and avSHRM-VFI (standardized β=?0.543, ?0.710) were significantly negatively correlated with retreatment frequency within both 12 and 24 months post-loading (P<0.05); hPED-VFI was significantly negatively correlated with retreatment frequency within 24 months post-loading (standardized β=?0.513, P<0.05). ConclusionsEarly volumetric fluctuation patterns can assess long-term treatment requirements in nAMD. Greater total fluid fluctuation predicts more frequent retreatments, while greater SHRM and hPED fluctuation predicts fewer retreatments.