OBJECTIVES: Limited research has been conducted to evaluate the humanistic and economic burden of age-related macular degeneration (AMD). A multi-country, cross-sectional study was conducted to examine the burden of bilateral neovascular AMD (NV-AMD) on visual impairment, quality of life (QOL), and vision-related functioning (VF), and explore the relationship among these outcomes. METHODS: We surveyed 401 bilateral NV-AMD patients recruited from retina specialists and 471 elderly non-AMD (control) patients from general practitioners in France, Germany, Spain, UK and Canada. Patients completed a telephone survey including a set of validated instruments: the National Eye Institute Visual Function Questionnaire (NEI VFQ-25), the EuroQol (EQ-5D), and the Hospital Anxiety and Depression Scale (HADS). Physicians recorded visual acuity (VA) and treatment information. Multivariate regression models were utilized in the analysis. RESULTS: Based on their better eye VA, NV-AMD patients were categorized as having normal VA (>20/40, 13%), mildly impaired VA (20/40 to > 20/80, 21%), moderately impaired VA (20/80 to > 20/200, 28%), severely impaired VA (20/200 to > 20/400, 18%), and near blindness (<20/400, 19%). They reported a decremental mean VF (NEI VFQ summary scale score) from 62.4 (normal VA) to 39.4 (near blindness) and an incremental mean depression symptom (HADS depression subscale score) from 5.5 (normal VA) to 8.5 (near blindness) (p <0.001), while control subjects (all with better eye normal VA) reported substantially better VF (mean NEI VFQ score of 89.1) and fewer depression symptoms (mean HADS depression score of 4.1). However, no discernable trend was observed in EQ-5D (a general QOL measure) or HADS anxiety subscale scores across VA impairment level. CONCLUSIONS: Vision-specific QOL measures are important in capturing the relationship between vision loss and QOL in NV-AMD patients. Consistent with the literature, greater depression symptoms and lower VF were observed in AMD patients with more severe vision loss.