Summary
A leading cause of blindness worldwide is age-related macular degeneration. This condition is characterized by progressive damage to the retina of the eye and irreversible blindness as a result. DHA is an crucial component of the retina of the eye, necessary for functioning of the cells that transduce light signal. Studies indicate that DHA supplementation may play a crucial role in the prevention of early age-related macular degeneration. 
 
Introduction
Age-related macular degeneration (AMD) is the leading cause of blindness in elderly individuals, affecting 21 million people worldwide. In this condition, different cell types and tissues of the eye are damaged, leading to visual impairments. AMD exists in the form of dry AMD (referred to as atrophic or non-exudative AMD) and wet AMD (referred to as neovascular or exudative AMD). Progression of dry AMD occurs in three phases: early, intermediate and late AMD, where the macula gets thinner with age. Wet AMD is a form of late AMD that typically causes a faster loss of vision than dry late/phase AMD. A multitude of factors ranging from risk genes to lifestyle are known to contribute to the development and progression of this disease. Amongst these, dietary intake of omega-3 fatty acids has emerged as an especially important factor of influence. Because no treatment options for AMD exist that can reverse vision loss, current focus lies on the prevention of AMD development and progression.

The retina of the eye are a tissue type with very high levels of DHA, which are concentrated in the photoreceptor cells (the cells that take up light) and retinal pigment epithelial cells (cells that support photoreceptor cell function and health). DHA is pivotal for the health and functional ability of these cells, which are targeted by AMD. As an inverse relation between DHA intake and early AMD risk has been established, science points towards a role of DHA in the prevention of AMD development and progression.    
 
Research findings
A 2011 study on 2167 individuals of 55 years and older aimed at assessing the effect of diet on AMD development found a positive effect of DHA intake (Ho et al., 2011). This research project assessed the dietary intake of omega-3 fatty acids such as DHA in a population that did not have AMD at the start of the study. The researchers found that dietary DHA/EPA intake was inversely correlated with reduced risk of early AMD, meaning that individuals who consumed more DHA/EPA overall had a lower risk of developing AMD. This effect was especially pronounced in persons that carried risk genes for the development of AMD.

A meta-analysis by Zhong and colleagues generated a dose-response effect of DHA on early and advanced AMD risk (Zhong et al., 2021). The 11 studies used for this analysis focused on dietary intake of fatty acids, such as the omega-3 fatty acids DHA and EPA. The results of this meta-analysis indicated that higher DHA/EPA dietary intake was associated with a decreased risk of early AMD development in a dose-dependent manner. Importantly, while DHA showed no clear dose-response effect on advanced AMD risk reduction in this analysis, EPA showed a trend towards a dose-response effect of advanced AMD risk increase.   

Studies conducted with omega-3 supplementation vary in concentration and composition of omega-3 fatty acids, as well as their confirmation. This has implications for the bioavailability and required dose for effect of these omega 3-fatty acids such as DHA, and has made it difficult to determine the specific mechanistic role of DHA in AMD development. In the search for a mechanistic explanation of the AMD-protective effect of dietary intake of DHA, Zanón-Moreno and colleagues examined the effects of DHA and Lutein oral supplementation on AMD development (Zanón-Moreno et al., 2020). Hundred healthy individuals aged 40-70 were given Lutein or Lutein + DHA for 3 months. Lutein is a carotenoid that supports photoreceptor function and health. Lutein supplementation on its own showed positive effects on AMD development risk reduction; this effect was strengthened in persons receiving both Lutein and DHA supplementation. The authors found that DHA supports the transport to and uptake of Lutein in the macula, thereby providing a possible explanation for the protective effects of DHA against early AMD development.
 
Conclusion 
Though publications on the effects of DHA supplementation alone on AMD development risk are lacking, dietary DHA intake has been shown to reduce the risk of early but not late AMD. Supplementation with DHA may therefore be beneficial for the prevention of AMD development, rather than progression. Furthermore, DHA has been shown to improve the bioavailability of Lutein in the retina, promoting health and function of the photoreceptor cells that are targeted in AMD. This is a possible explanation of the protective effects of DHA against AMD development.

Supporting the findings above, the EFSA (European Food Safety Authority) recognizes that DHA plays an important role in maintenance of eye health and function (EFSA Panel on Dietetic Products, Nutrition and Allergies, 2011). Accordingly, the EFSA states that 250mg DHA per day contributes to the maintenance of normal vision.
 
References
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). (2011). Scientific Opinion on the substantiation of health claims related to docosahexaenoic acid pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA Journal, 9(4), 2078. https://doi.org/10.2903/j.efsa.2011.2078

Ho, L., van Leeuwen, R., Witteman, J. C. M., van Duijn, C. M., Uitterlinden, A. G., Hofman, A., de Jong, P. T. V. M., Vingerling, J. R., & Klaver, C. C. W. (2011). Reducing the Genetic Risk of Age-Related Macular Degeneration With Dietary Antioxidants, Zinc, and ω-3 Fatty Acids: The Rotterdam Study. Archives of Ophthalmology, 129(6), 758–766. https://doi.org/10.1001/archophthalmol.2011.141

Zanón-Moreno, V., Domingo Pedrol, J. C., Sanz-González, S. M., Raga-Cervera, J., Salazar-Corral, J., & Pinazo-Durán, M. D. (2020). Feasibility Study of a Docosahexaenoic Acid-Optimized Nutraceutical Formulation on the Macular Levels of Lutein in a Healthy Mediterranean Population. Ophthalmic Research, 64(6), 1068–1076. https://doi.org/10.1159/000509439

Zhong, Y., Wang, K., Jiang, L., Wang, J., Zhang, X., Xu, J., & Yao, K. (2021). Dietary fatty acid intake, plasma fatty acid levels, and the risk of age-related macular degeneration (AMD): A dose–response meta-analysis of prospective cohort studies. European Journal of Nutrition, 60(6), 3013–3027. https://doi.org/10.1007/s00394-020-02445-4