INTRODUCTION: Treatment burden of anti-vascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (AMD) can be reduced with the Observe-and-Plan (O&P) regimen, which allows for an individualized treatment while reducing the number of injections and assessment visits. In this study, we evaluate detailed characteristics of treatment interval adjustment through individual follow-ups and evaluate adherence to the O&P regimen in a real-world setting in one of the largest centers in Europe. METHODS: This was a retrospective cohort study of treatment-naïve eyes with neovascular AMD that were treated with intravitreal aflibercept 2 mg in an O&P regimen who had persisting exudation after completion of loading dose. We evaluated decisions on adjustment of treatment intervals and adherence to the O&P regimen from a total of 5 follow-up visits. Data from visits and decision on treatment intervals were extracted from a treatment database. RESULTS: A total of 561 eyes were eligible for this study. Treatment intervals gradually increased from a 4-weeks interval (loading dose) to a wide distribution of intervals from 4-weeks to 12-weeks, and at the 5th follow-up 24.9% were followed without any treatment. In total, 209 eyes (49.5%) at the 5th follow-up (of 422 eyes present at the 5th follow-up) adhered to the treatment algorithm. CONCLUSION: Aflibercept 2 mg in an O&P treatment regimen leads to a variety of treatment intervals, and some eyes may be overtreated. An important proportion of eyes deviate from the intended O&P treatment regimen. Our study contributes to understanding real-world implications of personalized treatment regimens.