Early Fluctuations of Exudative Lesions as Predictors of Two-Year Clinical Outcomes in Neovascular Age-Related Macular Degeneration

Purpose: To investigate how early fluctuations of exudative lesions correlate with 2-year outcomes in neovascular age-related macular degeneration (nAMD). Methods: This prospective study included 92 treatment-naïve nAMD eyes treated with anti-vascular endothelial growth factor (anti-VEGF) therapy using a 3+PRN regimen over 2 years. Volumes of seven exudative lesion types were measured: subretinal fluid (SRF); intraretinal fluid (IRF); vascular and avascular subretinal hyperreflective material (vSHRM and avSHRM, respectively); and serous, fibrovascular, and hemorrhagic pigment epithelial detachment (sPED, fvPED, and hPED, respectively). Four fluctuation parameters were calculated during the 3-month loading phase. Relationships between these early fluctuations and clinical outcomes, including best-corrected visual acuity (BCVA) and injection frequency, were analyzed. Results: A total of 92 eyes (92 patients) were included, with a mean age of 65.65 ± 7.20 years. After adjusting for baseline characteristics, fluctuations in both vSHRM and avSHRM were identified as independent predictors of 2-year BCVA prognosis, with greater fluctuations associated with poorer visual outcomes (vSHRM Stdβ range, 0.671-0.797; avSHRM Stdβ range, 0.722-0.856; all P ≤ 0.001). However, only IRF fluctuation metrics were found to be independently associated with injection frequency over 2 years (Stdβ range, 0.327-0.532; all P < 0.05), with greater fluctuations correlating with more frequent injections. Conclusions: SHRM fluctuations during the loading phase predict 2-year visual outcomes, and IRF variations correlate with injection frequency in nAMD. Translational Relevance: Early fluctuation patterns of exudative lesions can serve as predictive biomarkers to guide personalized anti-VEGF treatment strategies and optimize long-term visual outcomes in nAMD patients.