OBJECTIVES: The introduction of treatment with inhibitors of Vascular Endothelial Growth Factor (VEGF) has made possible the treatment of the Retinal Vascular Diseases (RVD) for which there was limited therapeutic resources, or even none. The objective of this study was to estimate the average annual cost in Italy incurred by the National Health Service (NHS) as well as society due to RVD in which there is an overexpression of VEGF. METHODS: We developed a probabilistic incidence-based cost of illness model to estimate an aggregate measure of the economic burden associated to RVD-induced diseases in terms of direct and indirect costs. A systematic literature review was performed in order to extrapolate epidemiological and direct cost data for total or partial blindness patient in Italy. Indirect costs were calculated as social security costs analyzing a specific database of the National Institute of Social Security (INPS). Data were analyzed considering the total services provided and the mean cost for two types of benefits: disability pension and attendance allowance. Furthermore, one-way and probabilistic sensitivity analysis with 5,000 Monte Carlo simulations was performed in order to test the robustness of results. RESULTS: RVD with overexpression of VEGF was estimated to affect 0.84% of the Italian population (501.128). Direct costs analysis is under review while the annual indirect cost per patient for the disability pensions amount to € 3,454 for total blindness patient and € 3,157 for partial blindness. For attendance allowance was estimated an average cost of € 10,350  for total blindness € 2.397 for partial blindness. CONCLUSIONS: This is the first study in which direct costs (incurred by NHS) and especially indirect costs (incurred by the Social Security System) were taken into account to estimate the overall burden associated with RVD with overexpression of VEGF in our Country.