OBJECTIVES: To estimate the cost of illness associated with diabetic macular edema (DME) in 13 countries, with a focus on diagnosis, treatment and cost of advanced disease. METHODS: A structured literature review to assess prevalence and cost of DME was conducted including Embase, Medline, government and professional association websites. Structured face-to-face or online interviews were conducted with 378 ophthalmologists experienced in managing DME to determine rates of diagnosis, use of drug and laser treatments and frequency of follow-up and monitoring visits. Countries were Belgium, Czech Republic, Finland, France, Germany, Ireland, the Netherlands, Poland, Portugal, Spain, Sweden, Switzerland and China. An excel model synthesizing data and estimated overall cost of illness was built; costs were converted to Euros at 2014 market rates. RESULTS: Across the 13 countries an estimated 5.3 million people have DME; physicians estimated 32-68% (range between countries) of DME patients are undiagnosed, a total of 3.1m people. Annual medical cost of DME was estimated to be €1.2bn, median medical cost per patient was €918, range from €46 (China) to €4,858 (Switzerland). Productivity loss due to poor vision  in DME patients costs €4.7bn, 71% of the total cost of illness. Other cost components were laser and drug treatments (mean across countries 17.9%, range 1.4-38.9%), follow-up visits (5.8%, 2.6-33.9%) and monitoring visits (2.9%, 0.3-15.9%). Diagnosis accounted for 0.3% of the total cost (range 0.1-0.9%). Some cost components could not be reliably estimated for all countries. CONCLUSIONS: Considerable variation was identified in screening, diagnosis and treatment between countries. Despite the availability of effective therapies, physicians reported that current practice fails to identify a substantial proportion of patients with DME. Poor vision due to DME results in economic loss that is much larger than current spending on therapy.  Limitations include use of expert opinion and incomplete data; results may not be generalisable outside the countries studied.