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PURPOSE.: More than 90% of blindness worldwide exists in the developing world, but information on the social and economic burden and the cost-effectiveness of treatment in these settings is often limited or nonexistent. We demonstrate the use of computer modeling to simulate the current and future epidemiology, outcomes, and treatment of primary open-angle glaucoma in high-incidence populations of the developing world. METHODS.: A previously validated vision model was modified to simulate the incidence progression and social and economic outcomes of glaucoma in Barbados, which was the source of epidemiology data, and Ghana, which has similar propensity for glaucoma but lower socioeconomic development. We then assessed the cost-effectiveness of hypothetical case-finding and treatment scenarios, including U.S. guideline-level care and one-time laser surgery. RESULTS.: Barbados incurs relatively greater social and economic burden from glaucoma than Ghana. In Barbados, population screening followed by U.S. guideline levels of care appears to be highly cost-effective. Because of a younger population with higher mortality at younger ages, glaucoma appears to cause less visual impairment and blindness in Ghana than in Barbados, resulting in lower per capita disability and productivity losses. Population screening or guideline-level treatment scenarios were generally not cost-effective in Ghana, but treating self-referring patients with a hypothetical one-time laser surgery was highly cost-effective relative to World Health Organization willingness to pay thresholds. CONCLUSIONS.: The social and economic burden of glaucoma is higher in developed nations because of increased life expectancy, an older population age profile, and higher per capita gross domestic product. Similarly, lower mortality rates and higher per capita gross domestic product increase the relative cost-effectiveness of screening and treatment interventions intended to mitigate glaucoma burden