What is the role of macular pigment density measures in future clinical studies of age-related macular degeneration (AMD)? Measuring and following macular pigment optical density (MPOD) in clinical studies of AMD is intriguing, given reported associations between lower values and increased odds of macular degeneration, potential mechanisms of protection, including blue light filtering and free radical neutralization, the presence of lutein and zeaxanthin in the retina, and availability of lutein and zeaxanthin supplements.1 Studies have shown that supplementation with lutein and zeaxanthin in healthy volunteers as well as in those with early or late AMD has resulted in increases in serum concentrations of lutein and zeaxanthin and macular pigment density.2 A post hoc secondary analysis of an Age-Related Eye Disease Study 2 (AREDS2) subgroup with the lowest dietary intake of lutein and zeaxanthin suggests a protective effect of lutein and zeaxanthin supplementation in reducing the risk of progression to advanced AMD.3 To my knowledge, studies have not established the value of MPOD or change in MPOD as a valid surrogate for measuring risk of progression to advanced AMD, and the optimal dose and duration of lutein and zeaxanthin supplementation remains unanswered.