OBJECTIVES: To identify and summarise challenges to the economic modelling of macular oedema due to retinal vein occlusion (RVO) and diabetic macular oedema (DMO). METHODS: National Institute for Health and Care Excellence (NICE) technology appraisals (TAs) for RVO and DMO published before 1 June 2015 were reviewed to identify areas of uncertainty in submitted economic models. Evaluations were compared to assess whether, over time, these uncertainties have been addressed. RESULTS: Three completed NICE TAs were identified for RVO and two for DMO. The main area of uncertainty identified related to whether patients would be treated in their better-seeing eye (BSE), worse-seeing eye (WSE) or both eyes (bilateral), and consequently how this should be modelled. This had implications for the appropriate application of utility estimates for patients treated in the BSE, WSE or bilaterally and for the classification of patients as blind. Blindness is associated with high costs and low quality of life, which were incorrectly accounted for in one-eye models. Other areas of uncertainty included the relevance of the unlicensed comparator bevacizumab, the frequency and duration of treatment, and the extrapolation of visual acuity beyond short-term observed trial data. The trial evidence used ranged from 6 months to 3 years and included evidence for treatment in one eye only. Most TAs modelled one treated eye only, with crude adjustments applied to account for bilateral treatment. Only the most recent appraisal for aflibercept in central RVO modelled the visual acuity of both eyes. All other uncertainties were consistent throughout the identified TAs. CONCLUSIONS: The main uncertainties are in which eye(s) patients are treated in practice and the extrapolation of outcomes beyond trial data. Modelling is limited by short-term clinical trial evidence that provides evidence for the treatment of one eye only.