Embodiments of the present disclosure relate to computer storage, methods, and systems for the automatic optimization of accessible color themes. Systems and methods are disclosed that leverage the use of confusion lines to identify and highlight relationships between colors that may be inaccessible (e.g., indistinguishable) for a person with a vision impairment, such as a color vision deficiency. In some embodiments, a set of input colors can be automatically optimized for color accessibility using confusion lines. The set of input colors can be optimized utilizing an objective function, including at least one of a CVD alignment term, out-of-gamut term, distinguishability term, and faithfulness term.