Does Diet Play a Role in Glaucoma?

For the past 2 decades, vision researchers have evaluated the association of diet and nutrition with ocular diseases. In this issue, Mehta et al¹ (see pg. 565) describe secondary analyses of the Women’s Health Initiative Dietary Modification (WHI DM) trial exploring the relationship between diet and glaucoma. The WHI DM trial enrolled and randomized 48 835 women in 1993 to a low-fat diet with increased intake of fruits, vegetables, and grains or their usual diet.¹ The active treatment arm was supported by intense nutritional counseling. Adherence to the treatment of the low-fat diet was measured with self-reported food frequency questionnaires. The diagnosis of glaucoma was determined through linking the 28 954 participants in the WHI DM trial enrolled in Medicare with Medicare claims data (1993e2018). The results of this study demonstrated that there was no benefit from the dietary modification on the incidence of primary open-angle glaucoma (POAG). However, women who were in the lowest quartile for calorie intake from total fat at baseline had an increased risk of incident POAG regardless of age and sex.

Numerous researchers have demonstrated that a lower risk of glaucoma was associated with an increased dietary intake of various nutrients, including the family of B vitamins, omega-3 fatty acids, nitrates, and specific foods such as green leafy vegetables and fruits.² However, individuals consume a whole diet and not just isolated dietary components that possibly interact to provide the protective effects. Therefore, the field of nutrition research has focused more on dietary patterns such as the Mediterranean diet or the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, which combines the Mediterranean and Dietary Approaches to Stop Hypertension diet, than on the intake of individual nutrients. Better adherence to the MIND diet was found to be associated with decreased risk of dementia on follow-up of 1 year in the Rotterdam Study.³ The eye component of the Rotterdam Study also found that the higher adherence to the MIND diet was associated with a reduced risk of incident POAG.⁴ The food components that were important in this association included higher intake of green leafy vegetables, berries, and fish.

The question of dietary fat that is addressed in the current report on the WHI DM cohort was studied previously in an observational study of 2 cohorts: the Nurses’ Health study (n = 76 199 women) and the Health Professionals Follow-up Study (n = 40 206 men).⁵ This study of 2 cohorts found that the dietary intake of the major fats and their subtypes was not associated with POAG risk.⁵ However, there was a positive association of higher ratio of n-3 to n-6 polyunsaturated fatty acids with higher risk of POAG, especially for high-tension POAG. Given these results, it may not be surprising the secondary analyses of the WHI DM trial did not provide positive results for the use of the low-fat diet for incident POAG. In addition, a major limitation of the WHI DM trial was the particularly low compliance with the dietary intervention, making these data difficult to interpret, as noted by well-known nutritional experts.⁶ The finding from the WHI DM trial regarding the higher risk of POAG with diet modification in those participants with the lowest caloric intake is a post hoc subgroup analysis that needs to be replicated in other studies. In general, the totality of evidence from the literature would suggest that the role of nutrition may be important in glaucoma.

Nutrition in health and disease is considered a research priority as the National Institutes of Health launched the program “Precision Nutrition” to answer “what to eat to stay healthy” as part of the 2020–2030 Strategic Plan for National Institutes of Health Nutrition Research. This is to ensure rigor and consistency across the biomedical research studies that examine the role of diet in diseases in federally funded studies.⁷ Likewise, the White House hosted the “White House Conference on Hunger, Nutrition, and Health” to call for action for partners across all sectors to help end hunger and reduce diet-related diseases and disparities.⁸ Clearly, despite the lack of association in the current study of POAG in the WHI DM trial, there is interest in evaluating the role of diet more rigorously. There may be opportunities to consider prospective studies of diets in ocular diseases such as glaucoma and age-related macular degeneration, given the interest in food as medicine and its effects on the microbiome in treating chronic diseases that are the leading cause of blindness. This may be a new era in nutrition research.