Since the original findings in 1994,97 the relationship between lutein and zeaxanthin in the diet or blood and AMD has been investigated in several populations. Higher intakes or blood levels of lutein or zeaxanthin have been associated with lower rates of some types of AMD in some studies15,90,97,100 but not in others.101- 104 Generally, the relationships between lutein and zeaxanthin and AMD have been more consistent among studies of later stages of AMD and among populations that have consumed higher levels of lutein and zeaxanthin. These inconsistent results might reflect the variability among individuals in the ability to increase macular pigment with dietary or supplemental xanthophylls, as discussed earlier. As we learn and adjust for the dietary, medical, and lifestyle attributes that affect macular pigment, independent of diet, these relationships may become clearer. We may also gain insights about relationships between lutein and zeaxanthin intake and progression of later stages of AMD from clinical trials in which subjects diets' are supplemented with foods or pills rich in lutein and zeaxanthin. To learn about the long-term effects of lutein and zeaxanthin on preventing earlier stages of AMD, we will look to long-term prospective studies after we better understand the other determinants of macular pigment levels. The Age-Related Eye Disease Study II, which is scheduled to begin recruitment in late 2006, will study the potential efficacy of lutein, zeaxanthin, and omega-3 long-chain polyunsaturated fatty acid supplementation on the progression of AMD. It is designed as a 2 × 2, factorial, placebo- controlled study, with one quarter of the cohort receiving placebo, one quarter lutein or zeaxanthin, one quarter omega-3 fatty acids, and one quarter a combination of the latter 2. The Age-Related Eye Disease Study I vitamin supplement, as the standard-of-care supplement formula, will be offered to all participants.