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Introduction: Anti-vascular endothelial growth factor (VEGF) therapy is the first-choice treatment for neovascular age-related macular degeneration (nvAMD); however, patients often are burdened physically, financially, and mentally. We investigated the relationship between mental status and feasibility of an intravitreal ranibizumab treat-and-extend (TAE) regimen for nvAMD., Methods: In this prospective, multicenter study, 75 patients with nvAMD received ranibizumab intravitreally in a TAE regimen. After two monthly injections, the injection intervals were extended step-by-step to 6, 8, 12, and 16 weeks in eyes with dry maculas on optical coherence tomography (OCT) and, if exudation persisted or relapsed, shortened by one step. The best corrected visual acuity (BCVA) measurement and OCT were performed at baseline and on the same days of the scheduled injections. At baseline, all patients completed a survey, the Hospital Anxiety and Depression Scale (HADS), regarding mental burden. At week 52, patients on the TAE regimen for 1 year completed the HADS and a questionnaire designated to assess treatment-associated mental status., Results: Fifty-one patients (68%) completed the 1-year TAE regimen; 24 eyes (32%) discontinued the TAE regimen because of the rescue treatment, difficulty in completing clinical visits, or financial burden. In 51 eyes on the TAE regimen for 1 year, the mean BCVAs improved from 64.3 letters at baseline to 71.6 letters at week 52. The mean anxiety and depression scores on HADS decreased significantly (p < 0.01) after the 1-year treatment. Women tended to have higher anxiety scores, possibly associated with fear of injection and recurrence, while some men had higher depression scores potentially associated with financial burden, difficulty in completing clinical visits, and subsequent interruption of the TAE regimen especially in eyes with low treatment efficacy., Conclusions: A TAE regimen of intravitreal ranibizumab injections preserves vision in eyes with nvAMD and reduces mental burden associated with disease relapse., Trial Registration: This clinical study was registered retrospectively on December 22, 2014 with the ClinicalTrials.gov identifier NCT02321839., (© 2022. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)