Human eyes is important sensory organ to maintain healthy lifestyle which owned 80% of our sensory inputs by playing a vital role in overall maintaining well-being and healthy lifestyle. Nevertheless, present digitalized era led to deteriorating eye health due to unavoidable and required uses of digital and screen-mediated devices. So, the risk of eye diseases is tangential soared due to various age-related ocular pathogenesis e.g. hypertension, thyroid problems, menopause and menopause. These ocular diseases are reported ophthalmic pathogenesis like macular degeneration, diabetic cataract, diabetic retinopathy, preterm birth retinopathy, lazy eyes, nyctalopia, xanthopsia, xerophthalmia, ocular surface diseases (OSD), dysfunctional tear syndrome (DTS), kerato-conjunctivitis, dry eye syndrome and dry eye diseases. So, protecting our eyes is mandatory via opting healthy dietary habits including dry fruits, fresh fruits, leafy vegetables, prescribed vitamin-minerals supplements that can be helpful to reduce vision loss. Sufficient dose of vitamin and minerals supplements are considered a good step to improve ocular health. So that, we need to take these supplements under ophthalmologists’ supervision as according to patient health conditions and their family medical history. Hence, this discrete and stipulated review will might be helpful to aware general public about improving healthy eyesight. Furthermore, it will also strengthen their clinical knowledge about the nutritional role of leafy green vegetables, fruits and super foods containing minerals and vitamin supplements to cure our priceless ocular health and maintaining healthy vision.

Keywords: macular degeneration, cataract, ocular health, selenium, glaucoma, healthy vision

In present era, we need to extra careful about our ocular health due to long-term stress exposure and poor dietary habits that induce free radical damage at cellular level. Due to this, ophthalmic and ocular pathogenesis became main cause to deteriorating quality of life, mental health that imparted societal and health burden globally. So, we should take care ourself to improve our eye health by including super food (fresh fruits and green-leafy vegetable) and safe dose of supplements like vitamin A (retinol), Vitamin E (tocopherol) and vitamin C (ascorbic acid), minerals (Omega, lutein, zinc), carotenoids (β-Carotene, Lycopene) and essential fatty acids like EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid).^1-4 Many ophthalmologists have recommended effective dose of lutein and zeaxanthin to treat ocular pathogenesis like glaucoma, age-related macular degeneration and cataract that diagnosed in eye patients to improve vision. They also advised to use sunglasses, clear UVR-blocking spectacles or contact lenses to patients that are still under experimental validation.^5-9 Excessive use of digital devices has become main cause for an ocular conditions termed Digital eye strain.^10-12 Excessive gazing at a digital screen is found to harmful because it emits high-energy visible called blue light. If our eyes got long-term exposure of blue light with these omnipresent digital screens that will led to increase the risk of many lethal ocular problems at early as well.^13-17 Combinations of super foods, fruits and vegetables containing antioxidants e.g. anthocyanins aglycons (cyanidin, delphinidin, pelargonidin, peonidin, petunidin, malvidin), carotenoids, flavonoids and β-carotene. Flavonoids, lutein and zeaxanthin are found to neutralize lethal effects of macular degeneration and chronic ocular inflammations. Hence optometrists, ophthalmologist and ocular researchers are working synergistically to revamp medical management of ophthalmic pathogenesis like ophthalmitis, diabetic retinopathy, xerophthalmia, ocular surface diseases (OSD), keratoconjunctivitis, diabetic cataract, diabetic retinopathy, preterm birth retinopathy, nyctalopia, dysfunctional tear syndrome (DTS), xanthopsia and dry eye diseases. Hence, this review can might be helpful for ophthalmologists and ocular scientist to compute safe and effective concentrations of nutritional diets including vitamins A (retinol), vitamin E (tocopherol) vitamin C (ascorbic acid) and nutraceuticals for prescribing to ocular patients to delay onset of various ophthalmic pathogenesis.

Vitamin A (Retinol)

Therapeutic role of vitamin A (retinol) was explored so much to improve visual impairments belong to nyctalopia (night blindness) in ocular patients and found to induce repair of chromophore; rhodopsin protein followed by decreasing accumulation of toxic byproducts called N-retinyl-N-retinylidene ethanolamine.^17-24 Nevertheless, diabetic retinopathy, glaucoma and age-related macular degeneration (ARMD) can be cured to reduce vision loss in elderly patients. Multi-factorial eye disease are reported to be caused by genetic, age related pathogenic conditions (preterm babies, hypertension, diabetes and obesity) and environmental factors (aging, excessing drinking, smoking).^25-28 Demarcated thickening of the Bruch’s membrane is reported in age-related macular degeneration that effect permeability of nutrients and removal of cell waste. It les to deposit cell debris between retinal pigment epithelium (RPE) and the Bruch’s membrane degrading the efficiency of photoreceptors.^29,33 Moreover, vitamin A deficiency is found to confirmed dietary source to prevent blindness globally and but also help in maintaining the ocular functioning by strengthen the coverings and linings of the eyes to minimize ill effects caused by xerophthalmia (dry eyes). So that sufficient intake of vitamin A containing food and supplements can help to stop the progressive corneal damage and reduce the instances of blindness in suspected patients.^34-36

Vitamin C (ascorbic acid)

Vitamin C was subjected to study its well-known potent antioxidant properties that has significant role in maintaining the integrity of ocular blood vessels and healthy eye function to prevent cataracts.^37-39 Replacing cataractous lens with artificial polymeric lens was considered effective to restores eyesight. However, accountability is also studied that progression of cataract can be delayed by 10 years by adopting healthy vitamin intake especially in combination of vitamin A with vitamin C. It was most common seen in diabetic cataract that is attributed due to accumulation of sorbitol and initiate osmotic stress that resulted in swelling of lens fibre cell ocular tissue liquefaction.^40-44 A previous intervention clinical trial study was carried out for dosage of vitamin C intakes of 250 mg/day found to reduce symptoms of cataracts in a three-month.^45,46 Deficiency of vitamin C was found to main cause of ocular collagen loss and affect mucous membrane that exaggerated eye discomfort, eye redness and a gritty feeling. Therapeutic role vitamin C role is found to effective in maintaining ocular health by strengthening the mucous membranes that produce tears for proper eyes lubricating to counteract oxidative stress which makes ocular tissues more vulnerable to damage.^47-49

Vitamin E (tocopherol)

Pivotal role of Vitamin E (tocopherol) has been reported to improve eye health as safeguard for ocular lens to neutralize the deleterious effects of various ocular diseases (uveitis, conjunctivitis, or dry eye syndrome) due to oxidative stress especially reducing the risk of progression of cataracts.^50-52 ARED study was proposed for interpreting role of vitamin E as anti-inflammatory agent that can reduce chronic eye inflammation to maintain prolonged ocular health.^53,54 15mg/day of vitamin E supplements is recommended for regular intake by Food and Nutrition Board of the Institute of Medicine.⁵⁵ Ocular findings were validating for interpreting various clinical studies done for the intake of effective and required doses of vitamin E including B vitamins (B6, folate, and B12) supplements that reduce early progression of ocular diseases in patients of age-related macular degeneration (AMD).^56,58

Vitamin B total

Total vitamin B [thiamine (B₁), riboflavin (B₂), niacin (B₃), pantothenic acid (B₅), pyridoxine (B₆), biotin (B₇), folate (B₉), and cobalamin (B₁₂)] are proposed for various clinical studies to validate respective nutritional role to maintain good ocular health.^58,59 Reported age-related eye disease studies (AREDS) were confirmed by optometrists and ophthalmologists for prescribing safe and effective intake of vitamin B supplements. They found to have positive ocular effect in elderly patients. Vitamin B² (riboflavin) has especially prescribed clinically with conventional ophthalmic therapeutic measures to improve ocular health by reducing retinal damage and progression of diabetic cataract.^60,61

Lutein and zeaxanthin

Lutein and zeaxanthin are known natural occurring plant pigments produced by plants of xanthophyll family. They were studied for their potential in treating many ocular diseases to study etiologic patients’ history of age-related macular degeneration.^62-65 George Wald was first carried out ocular studies in 1945 to confirm macular pigment (MP) contains lutein, zeaxanthin and mesozeaxanthin, that impart yellow colour.^66-69 The distribution of lutein and zeaxanthin in the retina of the eye varies. However, zeaxanthin followed by lutein are found to be as dominant xanthophyll carotenoids.^70-75 It may affect significantly in maintaining healthy human serum levels including retinal tissue in age-related macular degeneration (AMD) patients inhibiting chronic progression of AMD and ocular impairment.^76-79

Omega-3 fatty acids

Past clinical studies are validated for safe and effective intake of omega-3 essential fatty acids enriched diet including super foods, fruits, vegetables and nutraceutical supplementation found to improve ocular health of ocular patients who seeks ophthalmic care. Hence, they are termed “essential” because they cannot be synthesized in the body and have to obtain from diet. Diet enriched with omega-3 fatty acids are observed to have long-term ocular benefits to support various ophthalmic treatments of chronic ocular inflammations like dry eye syndrome and macular degeneration.^80-83 Dry eye syndrome is found to cause due to loss of tear film homeostasis and drop in potential balance to maintain ocular surface integrity. This ocular syndrome is found to impose significant clinical burden worldwide. So, optimal dietary intake of omega-3 fatty acids is well notable clinically to reduce the symptoms of dry eye syndrome symptoms followed by reducing ocular surface inflammation and ameliorating tear-lipid profiles.^84-88 Previous ocular studies, optometrists and ophthalmologists have recommended omega-3 fatty acid enriched diet (fish oil supplements) for improving ocular health in age-related macular degeneration (AMD) patients.^89,90

Selenium

Clinical and nutritional aspect of selenium are studied for its protective role in ophthalmic diseases e.g. cataract, macular degeneration, age-related ocular diseases, and retinitis pigmentosa. Selenium is known to have physiological role as selenocysteine residue key part of selenoenzymes geometry whose deprivation found to induce cataract in mice studies. However high dose of selenium is found to be toxic in proposed animal experimental studies. Clinical evidences are confirmed that dietary reference intakes of 55 microg/day of selenium found effective to prevent ocular diseases.^90-92 Oxidative stress has critical role to increase the chances of developing chronic ocular pathogenesis like cataract, age-related macular degeneration and diabetic retinopathy. Hence, antioxidant mechanism of selenoproteins may found to have positive synergistic effect on medical management of various ocular diseases and ophthalmic pathogenic conditions.⁹³

Zinc & anthocyanin

Risk of macular degeneration are found to reduce by the intake of antioxidant-rich superfoods and nutraceutical supplements containing carotenoids, flavonoids, anthocyanins, and vitamins. Zinc has been reported as essential element in high concentration to improve human ocular health due to key part of retina-choroid complex of eyes. The highest amount of zinc is reported in the retinal pigment epithelium (RPE) of RPE-choroid, 292 ± 98.5 µg g⁻¹ dry tissue followed by the retina of 123±62.2 µg g⁻¹ dry tissue. Due to ageing, ocular zinc concentration was found to decreasing that later become cause of onset of various ocular and ophthalmic pathogenesis.^94,95 Anthocyanin-rich bilberry extract have been counted as most potent plant-derived antioxidant that improve ocular health. Its protective effect studies were done on animal model to confirm to treat endotoxin-induced uveitis (EIU) and impairment of photoreceptor cell; rhodopsin function and reduce retinal inflammation.⁹⁶ Hence a functional soup containing anthocyanin-rich ingredient called “Anthaplex” is proposed for clinical study to interpret its its role in targeting cognitive improvement including ocular health. These findings were positive for the studying protective effect to treat dry eyes syndrome.⁹⁷

Good ocular health and healthy eyesight are key challenges of this modern, swift and digitalized era. Hence, this brief and juncture review is more focused on last bygone decade finding of various eye diseases studies worldwide. It may be helpful to aware readers to see purpose of maintaining eye health care. It can be take away to achieve clinical goal for proposing eye diseases studies that to be carry based on intake of antioxidants enriched diets decrease the risk of various ocular diseases like age-related macular degeneration, diabetic cataract, diabetic retinopathy, preterm birth retinopathy, nyctalopia, xanthopsia, xerophthalmia, ocular surface diseases (OSD), dysfunctional tear syndrome (DTS), kerato-conjunctivitis, dry eye syndrome, ophthalmitis and dry eye diseases. A revolutionary clinical initiative must be heading to next level by optometrists, ophthalmologist and clinical researchers to strengthen safety profile of human ocular health through boosting confidence to recommend clinical dietary recommendations via validating various multi-ethnic and multi-center trials.

I would like to express my cordial appreciation to Amity University Uttar Pradesh, Noida (India).

The author declares that there is no conflicts of interest.

1. Brown NA, Bron AJ, Harding JJ, et al. Nutrition supplements and the eye. Eye (Lond). 1998;12(Pt 1):127–133.
2. Edwards G, Olson CG, Euritt CP, et al. Molecular mechanisms underlying the therapeutic role of vitamin E in age–related macular degeneration. Front Neurosci. 2022;16:890021.
3. Yargiçoğlu P, Yaraş N, Ağar A, et al. The effect of vitamin E on stress–induced changes in visual evoked potentials (VEPs) in rats exposed to different experimental stress models. Acta Ophthalmol Scand. 2003;81(2):181–187.
4. Eve H, Coleman, Anne LC, Teutsch S. Eye health needs to be a population health priority. Am J Ophthalmol. 2016;173:7–8.
5. Cohen SY. Vitamins for prevention of age related macular degeneration: efficacy and risk. Bull Soc Belge Ophtalmol. 2006;(301):33–36.
6. McCusker MM, Durrani K, Payette MJ, et al. An eye on nutrition: the role of vitamins, essential fatty acids, and antioxidants in age–related macular degeneration, dry eye syndrome, and cataract. Clin Dermatol. 2016;34(2):276–285.
7. Hunter JJ, Morgan JIW, Merigan WH, et al. The susceptibility of the retina to photochemical damage from visible light. Prog Retin Eye Res. 2012;31(1):28.
8. Ivanov IV, Mappes T, Schaupp P, et al. UV–radiation oxidative stress affects eye health. J Biophotonics. 2018;11(7):e201700377.
9. Hagan J, Khazova M, Price LLA. Low-energy light bulbs, computers, tablets and the blue light hazard. Eye 2016;30(2):230.
10. Kaur K, Gurnani B, Nayak S, et al. Digital eye strain– a comprehensive review. Ophthalmol Ther. 2022;11(5):1655–1680.
11. Sheedy JE, Hayes JN, Engle J. Is all asthenopia the same? Optom Vis Sci. 2003;80(11):732–739.
12. Sheedy JE, Gowrisankaran S, Hayes JR. Blink rate decreases with eyelid squint. Optom Vis Sci. 2005;82(10):905–911.
13. Fong DS, Aiello L, Gardner TW, et al. Retinopathy in diabetes. Diabetes Care. 2004;27(Suppl 1):S84–S87.
14. Khalik EA, Hatem M, Nermeen MB, et al. Effects of diabetes mellitus on the eye. Menoufia Med J. 2015;28(4):15.
15. Erdinest N, London N, Lavy I, et al. Vision through healthy aging eyes. Vision. 2021;5(4):46.
16. Gollapalli DR, Rando RR. The specific binding of retinoic acid to RPE65 and approaches to the treatment of macular degeneration. Proc Natl Acad Sci USA. 2004;101(27):10030–10035.
17. Gamble MV, Mata NL, Tsin AT, et al. Substrate specificities and 13–cis–retinoic acid inhibition of human, mouse and bovine cis–retinol dehydrogenases. Biochim Biophys Acta. 2000;1476(1):3–8.
18. Radu RA, Mata NL, Nusinowitz S, et al. Treatment with isotretinoin inhibits lipofuscin accumulation in a mouse model of recessive Stargardt’s macular degeneration. Proc Natl Acad Sci USA. 2003;100:4742–4747.
19. Carazo A, Macáková K, Matoušová K, et al P. Vitamin A update: forms, sources, kinetics, detection, function, deficiency, therapeutic use and toxicity. Nutrients. 2021;13(5):1703.
20. Marzęda P, Łuszczki JJ. Role of vitamin A in health and illness. J Pre Cli Clin Res. 2019;13(3):137–142.
21. Zielińska MA, Wesołowska A, Pawlus B, et al. Health effects of carotenoids during pregnancy and lactation. Nutrient 2017;9(8):838.
22. Omenn GS, Goodman GE, Thornquist MD, et al. Risk factors for lung cancer and for intervention effects in CARET, the beta–carotene and retinol efficacy trial. J Natl Cancer Inst. 1996;88(21):1550–1559.
23. Albanes D, Heinonen OP, Huttunen JK, et al. Effects of alpha–tocopherol and beta–carotene supplements on cancer incidence in the alpha–tocopherol beta–carotene cancer prevention study. Am J Clin Nutr. 1995;62(6 Suppl):1427S–1430S.
24. Chew EY, Clemons TE, Sangiovanni JP, et al. Secondary analyses of the effects of lutein/zeaxanthin on age–related macular degeneration progression: AREDS2 report No. 3. JAMA Ophthalmol. 2014;132(2):142–149.
25. Sommer A. Vitamin A deficiency and clinical disease: an historical overview. J Nutri. 2008;138(10):1835–1839.
26. Summary report of the dietary reference intakes. 2020.
27. Armento A, Ueffing M, Clark SJ. The complement system in age–related macular degeneration. Cell Mol Life Sci. 2021;78(10):4487–4505.
28. Redmond TM. RPE65 takes on another role in the vertebrate retina. Proc Natl Acad Sci USA. 2017;114(41):10818–10820.
29. Lee Y, Hussain AA, Seok JH, et al. Modulating the transport characteristics of bruch’s membrane with steroidal glycosides and its relevance to age–related macular degeneration (AMD). Investig Ophthalmol Vis Sci. 2015;56(13):8403–8418.
30. Chong NH, Keonin J, Luthert PJ, et al. Decreased thickness and integrity of the macular elastic layer of Bruch’s membrane correspond to the distribution of lesions associated with age–related macular degeneration. Am J Pathol. 2005;166:241–251.
31. Spraul CW, Grossniklaus HE. Characteristics of Drusen and Bruch’s membrane in postmortem eyes with age–related macular degeneration. Arch Ophthalmol. 1997;115(2):267–273.
32. Crabb JW, Miyagi M, Gu X, et al. Drusen proteome analysis: An approach to the etiology of age–related macular degeneration. Proc Natl Acad Sci USA. 2002;99(23):14682–14687.
33. Nguyen CT, Fraser RG, Tan R, et al. Longitudinal changes in retinotopic rod function in intermediate age–related macular degeneration. Investig Ophthalmol Vis Sci. 2018;59(4):AMD19–AMD24.
34. Schick T, Ersoy L, Lechanteur YTE, et al. History of sunlight exposure is a risk factor for age-related macular degeneration. Retina. 2016;36(4):787.
35. Tomany SC, Cruickshanks KJ, Klein R, et al. Sunlight and the 10-year incidence of age-related maculopathy: the Beaver Dam Eye Study. Arch Ophthalmol. 2004;122(5):750.
36. Chambial S, Dwivedi S, Shukla KK, et al. Vitamin C in disease prevention and cure: an overview.. Indian J Clin Biochem. 2013;28(4):314–328
37. World health organisation. Blindness and vision impairment prevention. 2020.
38. Hodge WG, Whitcher JP, Satariano W. Risk factors for age–related cataracts. Epidemiol Rev. 1995;17(2):336–346.
39. Age related eye disease group. Risk factors associated with age–related nuclear and cortical cataract: a case–control study in the age–related eye disease study, AREDS report no. 5. Ophthalmology. 2001;108(8):1400–1408.
40. Klein BE, Klein R, Wang Q, et al. Older–onset diabetes and lens opacities: the beaver dam eye study. Ophthalmic Epidemiol. 1995;2(1):49–55.
41. Brian G, Taylor H. Cataract blindness–challenges for the 21st century. Bull World Health Organ. 2001;79(3):249–256.
42. Kinoshita JH. Mechanisms initiating cataract formation. Proctor Lecture. Investig Ophthalmol. 1974;13(10):713–724.
43. Kinoshita JH. Cataracts in galactosemia. The Jonas S. Friedenwald memorial lecture. Investig Ophthalmol. 1965;4(5):786–799.
44. Rautiainen S, Lindblad BE, Morgenstern R, et al. Vitamin C supplements and the risk of age–related cataract: a population–based prospective cohort study in women. Am J Clin Nutr. 2009;91(2):487–493.
45. Group TR, Chylack LT, Brown NP, et al. The Roche European American cataract trial (REACT): a randomized clinical trial to investigate the efficacy of an oral antioxidant micronutrient mixture to slow progression of age–related cataract. Ophthalmic Epidemiol. 2002;9(1):49–80.
46. Traber MG, Stevens JF. Vitamins C and E: beneficial effects from a mechanistic perspective. Free Radic Biol Med. 2011;51(5):1000–1013.
47. DePhillipo NN, Aman ZS, Kennedy MI, et al Efficacy of Vitamin C supplementation on collagen synthesis and oxidative stress after musculoskeletal injuries: a systematic review. Orthop J Sports Med. 2018;6(10):2325967118804544
48. Hyon JY, Han SB. Dry eye disease and vitamins: a narrative literature review. Appl Sci. 2022;12(9):4567.
49. Lobo V, Patil A, Phatak A, et al. Free radicals, antioxidants and functional foods: impact on human health. Pharmacogn Rev. 2010;4(8):118–126.
50. Kaur A, Gupta V, Christopher AF, et al. Nutraceuticals in prevention of cataract – an evidence based approach. Saudi J Ophthalmol. 2017;31(1):30–37.
51. Schmölz L, Birringer M, Lorkowski S, et al. Complexity of vitamin E metabolism. World J Biol Chem. 2016;7(1):14–43.
52. Patel JK, Rouster AS. Infant nutrition requirements and options. 2023.
53. Buscemi S, Corleo D, Di Pace F, et al. The effect of lutein on eye and extra–eye health. Nutrients. 2018;10(9):1321.
54. Institute of Medicine (Us) Panel on dietary antioxidants and related compounds. Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. Washington, DC: National Academies Press. 2000.
55. Lloyd JK. Lipoprotein deficiency disorders. Endocrinol. Metab. 1973;2(1):127–147.
56. Edwards G, Olson CG, Euritt CP, et al. Molecular mechanisms underlying the therapeutic role of vitamin E in age–related macular degeneration. Front Neurosci. 2022;16:890021.
57. Bishara S, Merin S, Cooper M, et al. Combined vitamin A and E therapy prevents retinal electrophysiological deterioration in abetalipoproteinaemia. Br J Ophthalmol. 1982;66(12):767–770.
58. Seddon JM, Gensler G, Klein ML, et al. Evaluation of plasma homocysteine and risk of age–related macular degeneration. Am J Ophthalmol. 2006;141(1):201–203.
59. Zampatti S, Ricci F, Cusumano A, et al. Review of nutrient actions on age–related macular degeneration. Nutr Res. 2014;34(2):95–105.
60. Huang P, Wang F, Sah BK, et al. Homocysteine and the risk of age–related macular degeneration: a systematic review and meta–analysis. Sci Rep. 2015;5:10585.
61. Pinna A. Zaccheddu F, Boscia F, et al. Homocysteine and risk of age–related macular degeneration: a systematic review and meta–analysis. Acta Ophthalmol. 2018;96(3):e269–e276.
62. Age–related eye disease study 2 research group. Lutein + zeaxanthin and omega–3 fatty acids for age–related macular degeneration: the age–related eye disease study 2 (AREDS2) randomized clinical trial. JAMA. 2013;15(19):2005–2015.
63. Huang YM, Dou HL, Huang FF, et al. Effect of supplemental lutein and zeaxanthin on serum, macular pigmentation, and visual performance in patients with early age–related macular degeneration. Biomed Res Int. 2015;2015:564738.
64. Wolf–Schnurrbusch UE, Zinkernagel MS, Munk MR, et al. Oral lutein supplementation enhances macular pigment density and contrast sensitivity but not in combination with polyunsaturated fatty acids. Investig Ophthalmol Vis Sci. 2015;56(13):8069–8074.
65. Huang YM, Yan SF, Ma L, et al. Serum and macular responses to multiple xanthophyll supplements in patients with early age–related macular degeneration. Nutrition. 2013;29(2):387–392.
66. Akuffo KO, Nolan JM, Howard AN, et al. Sustained supplementation and monitored response with differing carotenoid formulations in early age–related macular degeneration. Eye. 2015;29(7):902–912.
67. Akuffo KO, Beatty S, Peto T, et al. The impact of supplemental antioxidants on visual function in nonadvanced age–related macular degeneration: A head–to–head randomized clinical trial. Investig Ophthalmol Vis Sci. 2017;58(12):5347–5360.
68. Arnold C, Winter L, Frohlich K, et al. Macular xanthophylls and omega–3 long–chain polyunsaturated fatty acids in age–related macular degeneration: A randomized trial. JAMA Ophthalmol. 2013;131(5):564–572.
69. Sawa M, Shunto T, Nishiyama I, et al. Effects of lutein supplementation in Japanese patients with unilateral age–related macular degeneration: the sakai lutein study. Sci Rep. 2020;10(1):5958.
70. Beatty S, Chakravarthy U, Nolan JM, et al. Secondary outcomes in a clinical trial of carotenoids with co antioxidants versus placebo in early age–related macular degeneration. Ophthalmology. 2013;120(3):600–606.
71. Ma L, Yan SF, Huang YM, et al. Effect of lutein and zeaxanthin on macular pigment and visual function in patients with early age–related macular degeneration. Ophthalmology. 2012;119(11):2290–2297.
72. Ma L, Liu R, Du JH, et al. Lutein, zeaxanthin and meso–zeaxanthin supplementation associated with macular pigment optical density. Nutrients. 2016;8(7):426.
73. Weigert G, Kaya S, Pemp B, et al. Effects of lutein supplementation on macular pigment optical density and visual acuity in patients with age–related macular degeneration. Investig Ophthalmol Vis Sci. 2011;52(11):8174–8178.
74. Thurnham DI, Nolan JM, Howard AN, et al. Macular response to supplementation with differing xanthophyll formulations in subjects with and without age–related macular degeneration. Graefe’s Arch Clin Exp Ophthalmol. 2015;253(8):1231–1243.
75. Garcia–Layana A, Recalde S, Alaman AS, et al. Effects of lutein and docosahexaenoic acid supplementation on macular pigment optical density in a randomized controlled trial. Nutrients. 2013;5(2):543–551.
76. Garcia–Layana A, Recalde S, Hernandez M, et al. A randomized study of nutritional supplementation in patients with unilateral wet age–related macular degeneration. Nutrients. 2021;13(4):1253.
77. Sabour–Pickett S, Beatty S, Connolly E, et al. Supplementation with three different macular carotenoid formulations in patients with early age–related macular degeneration. Retina. 2014;34(9):1757–1766.
78. Murray IJ, Makridaki M, van der Veen RL, et al. Lutein supplementation over a one–year period in early AMD might have a mild beneficial effect on visual acuity: The clear study. Investig Ophthalmol Vis Sci. 2013;54(3):1781–1788.
79. Lawrenson JG, Downie LE. Nutrition and eye health. Nutrients. 2019;11(9):2123.
80. Rand AL, Asbell PA. Nutritional supplements for dry eye syndrome. Curr Opin Ophthalmol. 2011;22(4):279–282.
81. SanGiovanni JP, Chew EY. The role of omega–3 long–chain polyunsaturated fatty acids in health and disease of the retina. Prog Retin Eye Res. 2005;24(1):87–138.
82. Stapleton F, Alves M, Bunya VY, et al. TFOS DEWS II epidemiology report. Ocul Surf. 2017;15(3):334–365.
83. McDonald M, Patel DA, Keith MS, et al. Economic and humanistic burden of dry eye disease in Europe, North America, and Asia: a systematic literature review. Ocul Surf. 2016;14(2):144–167.
84. Patel VD, Watanabe JH, Strauss JA, et al. Work productivity loss in patients with dry eye disease: an online survey. Curr Med Res Opin. 2011;27:1041–1048.
85. Craig JP, Nichols KK, Akpek EK, et al. TFOS DEWS II definition and classification report. Ocul Surf. 2017;15:276–283.
86. Bron AJ, de Paiva CS, Chauhan SK, et al. TFOS DEWS II pathophysiology report. Ocul Surf. 2017;15(3):438–510.
87. Sullivan BD, Cermak JM, Sullivan RM, et al. Correlations between nutrient intake and the polar lipid profiles of meibomian gland secretions in women with Sjogren’s syndrome. Adv Exp Med Biol. 2002;506(Pt A):441–447.
88. Walter SD, Gronert K, McClellan AL, et al. ω–3 tear film lipids correlate with clinical measures of dry eye. Investig Ophthalmol Vis Sci. 2016;57(6):2472–2478.
89. Lawrenson JG, Evans JR. Advice about diet and smoking for people with or at risk of age–related macular degeneration: a cross–sectional survey of eye care professionals in the UK. BMC Public Health. 2013;13:564.
90. Flohé L. Selenium, selenoproteins and vision. Dev Ophthalmol. 2005;38:89–102.
91. Xu B, Liu Z, Zhao J, et al. Selenium intake help prevent age–related cataract formation: evidence from NHANES 2001–2008. Front Nutr. 2023;10:1042893.
92. Khoo HE, Ng HS, Yap WS, et al. Nutrients for prevention of macular degeneration and eye–related diseases. Antioxidants. 2019;8(4):85.
93. Al–Bassam L, Shearman GC, Brocchini S, et al. The potential of selenium–based therapies for ocular oxidative stress. Pharmaceutics. 2024;16(5):631.
94. Khoo HE, Ng HS, Yap WS, et al. Nutrients for prevention of macular degeneration and eye–related diseases. Antioxidants. 2019;8(4):85.
95. Nolan J, Gilbert R, Peto T, et al. Zinc nutrition and inflammation in the aging retina. Mol Nutr Food Res.2019;63(15):1801049. 
96. Miyake S, Takahashi N, Sasaki M, et al. Vision preservation during retinal inflammation by anthocyanin–rich bilberry extract: cellular and molecular mechanism, Lab Invest. 2012;92(1):102–109.
97. Wattanathorn J, Tong–un T, Thukham–mee W, et al. A randomized, double–blind, placebo–controlled study of an anthocyanin–rich functional ingredient on cognitive function and eye dryness in late adulthood volunteers: roles of epigenetic and gut microbiome modulations. Nutrients. 2023;15(16):3499.