Diabetic macular oedema (DMO) is the leading cause of vision loss associated with diabetic eye disease. The exponential increase in the diabetic population and thus, of DMO is an impetus for optimizing the management of DMO. One major challenge in DMO management is the discrepancy between treatment outcomes seen in clinical trials and the real world. Contrary to the homogeneity, better patient motivation and shorter study durations seen in randomised control trials, routine clinical practice is fraught with more diverse populations, undertreatment and variable compliance with long-term therapy. Under both circumstances, this review aims to compare efficacy outcomes and adverse events of DMO therapies within the scope of anti-vascular endothelial growth factor (anti-VEGF) medications, specifically the commonly used ones-bevacizumab, ranibizumab and aflibercept. Impediments and methods to achieve better treatment outcomes in the real world will be addressed to achieve better outcomes. Low- to lower-middle-income countries are faced with even more barriers which range from paucity of data on epidemiology and treatment response to scarce human and financial resources to poorer national level attention and then basic issues like transportation. Additionally, to address the lack of a global consensus in DMO treatment, this review generates and recommends, for clinical and research purposes, an up-to-date consensus algorithm for DMO management universally. Underpinned by results from clinical trials and recent guidelines, this therapeutic flowchart can be utilised in various resource settings including low- and lower-middle-income countries where affordability is a major deterrent to treatment access.