Nutrients for Eye Health and Disease Management

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Joobin Khadamy, MD, FEBO

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Joobin Khadamy, MD, FEBO

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Introduction & Background

In today's health-conscious society, individuals are increasingly seeking guidance from medical professionals regarding nutrition and its impact on their well-being. The understanding that diet and nutrition are fundamental to overall health has been acknowledged for centuries, echoing the words of Hippocrates, the father of medicine, who stated, "Let food be thy medicine and medicine be thy food". Recent years have seen a growing recognition of the intricate relationship between nutrition and ocular health. From rare genetic disorders to common metabolic or age-related conditions, it has become evident that dietary interventions can have a substantial effect on the progression and management of various eye diseases.

On a broader scale, prevalent eye conditions like dry eye disease (DED), cataracts, glaucoma, diabetic retinopathy (DR), and age-related macular degeneration (AMD) are integral parts of the broader narrative concerning nutrition's role in eye health.

Less common conditions like Stargardt disease, Bassen-Kornzweig syndrome, Refsum disease, gyrate atrophy (GA) , and cystinosis often intersect with dietary interventions. For example, the connection between vitamin A supplementation and the acceleration of lipofuscin pigment accumulation in the retinal pigment epithelium (RPE) is a fascinating aspect of Stargardt disease. Additionally, genetic mutations in RHO1 and ABCA4 raise questions about which patients may benefit from such supplementation.

Ophthalmologists and nutritionists should be the trusted sources for providing nutritional guidance in these cases. Consequently, ophthalmologists must stay updated with the latest information to address inquiries related to nutrition effectively. Understanding the evolving landscape of dietary considerations in eye health and disease management is essential for delivering holistic patient care.

To unravel the nutritional requirements, a profound understanding of the eye's biochemical composition, the visual cycle, eye physiology, the aging process, neuroprotective factors, antioxidants, phytochemicals, and neuroplasticity is essential.

This all-encompassing review article explores the crucial role of nutrients, phytochemicals, antioxidants, and neuroprotective in the preservation of vision. It covers the role of nutrients in the management of a wide array of conditions including the manifestations of vitamin deficiencies, common inflammatory, metabolic, and degenerative diseases such as DED, DR, AMD, cataracts, and glaucoma, as well as rare genetic diseases and dystrophies.

Review

Materials and Methods

A narrative review was conducted using English-language literature available on PubMed up to October 2023. Relevant articles were identified through keyword searches encompassing topics related to diet, nutrition, supplements, food, nutrients, and various aspects of eye health, including ocular health and specific eye conditions discussed in this review. Additionally, manual searches of references in relevant studies and reviews within the field were conducted to complement the search strategy. Prioritization for inclusion of research articles followed a hierarchy, with preference given to systematic reviews and meta-analyses, followed by randomized controlled trials (RCTs), human observational studies, and case series. In instances where human studies were unavailable, consideration was extended to animal studies and in vitro research.

Decoding the science: from biochemistry and metabolism to nutritional guide

Nutritionists draw insights from molecular biology, biochemistry, and genetics to understand the impact of nutrients on the body, requiring a deep knowledge of the biochemical, cellular, and biological composition of various eye components. A wide array of metabolic processes, cofactors, vitamins, and minerals are integral to maintaining ocular structures such as the iris, retina, choroid, photoreceptors, lens, cornea, and vitreous humor. While precise breakdowns are challenging, a general overview is provided below.

The tear film is primarily water-based, containing electrolytes, proteins, lipids, and mucins. The cornea is abundant in collagen fibers, the sclera mainly comprises collagen type I, and the vitreous humor consists mostly of water, hyaluronic acid, and collagen fibrils. Additionally, collagen fibers play a key role in providing structural support to blood vessels, including those in the retina and choroids.

Collagen synthesis relies on the support and regulation of various nutrients. Amino acids, such as lysine and proline, are crucial in forming collagen fibers. Lysine, in particular, is essential for collagen cross-linking, which contributes to the cornea's structural integrity. Vitamin A, for instance, plays a role in reducing the expression of matrix metalloproteinases and stimulating collagen production. Vitamin C is crucial for collagen synthesis as it's involved in the hydroxylation of proline and lysine, which also requires oxygen and ferrous iron. Additionally, magnesium (Mg) and zinc (Zn) are necessary for the translation process associated with collagen formation , while Cu activates lysyl oxidase, facilitating cross-linking in the maturation of collagen molecules. However, it's important to exercise caution in supplement intake, as excessive levels of selenium (Se) and vitamin E, despite their essential antioxidant functions, may potentially hinder collagen synthesis . Maintaining a balanced approach to nutrition is key to supporting healthy collagen production.

The aqueous humor is mainly water, containing electrolytes, vitamin C (high concentration of ascorbic acid), and growth factors. The lens primarily consists of lens fibers and crystallin proteins that ensure transparency, benefiting from antioxidants like glutathione and vitamin C. The retina houses various neuron layers and maintaining its structure and function needs carotenoids like lutein, zeaxanthin, and omega-3 fatty acids from leafy greens and fatty fish.

Taurine, a sulfur-containing amino acid structurally akin to the neurotransmitters glycine and GABA, plays a crucial role in the body, being the most abundant free amino acid in the retina and the second most prevalent in the central brain after glutamate. Taurine functions as an osmoregulator, essential for maintaining the balance of water and ions in retinal cells, and crucial for proper visual signal processing. Moreover, it possesses antioxidant and neuroprotective properties, shielding cells, especially neurons, from oxidative stress and potentially influencing brain function. Ongoing scientific research continues to unveil the exact mechanisms and functions of taurine in various physiological processes. It can be found in various dietary sources, with seafood like shellfish and fish, dairy products like cheese and milk, and energy drinks being notable rich sources.

The RPE comprises pigmented cells with melanin which supports photoreceptors, while the choroid contains blood vessels and connective tissue. Melanin is vital, found in several eye structures, providing defense against oxidative stress, neutralizing free radicals, reducing lipid peroxidation, and absorbing different types of light. Essential vitamins and minerals support melanin production. Tyrosine is a substrate, and Cu is a co-factor for tyrosinase. Vitamin C aids in conversion and safeguards melanocytes. Vitamin B6 is involved, and vitamin E offers antioxidative protection. Vitamin A indirectly promotes melanin production, Zn plays a role in biosynthesis , Se defends against oxidative damage, and iron upregulates melanogenesis genes. Se-containing carbohydrates can inhibit melanin synthesis.

B vitamins support energy metabolism and ocular structures. Many vitamins contribute to optic nerve health, including B1, B2, B3, B6, B12, folate, C, E, D, A, and K, aiding nerve function, energy production, and protection from oxidative damage.

Arginine is involved in the production of nitric oxide (NO), a molecule that regulates blood flow to the eye. Proper blood flow is crucial for nourishing the ocular tissues and maintaining healthy intraocular pressure.

Coenzyme Q10 (CoQ10) is a fat-soluble compound belonging to the quinones category. It serves as an antioxidant and plays a vital role in cellular energy production. Although the primary source of CoQ10 is endogenous synthesis, it can also be obtained from dietary sources or supplements. COQ10 controls ROS levels. CoQ10 are molecules that have neuroprotective, antioxidant, and anti-inflammatory properties, and their use could have a beneficial effect in ocular pathologies including DR, RP, Leber’s hereditary optic neuropathy (LHON), and AMD. CoQ10 has been proposed as a potential neuroprotective agent in glaucoma. Foods like fatty fish, organ meats, whole grains, soybean and canola oils, nuts and seeds, and select vegetables contain CoQ10. While dietary sources contribute to overall intake, the primary source remains endogenous synthesis within the body.

Furthermore, the biochemical analysis of human milk can be a valuable tool for guiding the appropriate supplementation of nutrients crucial for eye health, thereby contributing to the optimal development of an infant's visual system. Lutein and zeaxanthin concentrations in human milk are highest during early milk production and significantly differ among populations. Studies show an inverse correlation between maternal human milk consumption and retinopathy of prematurity (ROP) incidence.

The interplay of oxidative stress and eye health, from intrinsic defenses to supplements

Oxidative stress results from an imbalance between the production of reactive oxygen species (ROS) and the body's antioxidant defenses.These conditions can be influenced by genetic factors, environmental exposures, and lifestyle choices.

The anterior segment of the eye is particularly susceptible to oxidative stress due to constant exposure of the eye to radiation, atmosphere oxygen, environmental chemicals, and physical abrasions. The retina is considered one of the highest energy-demanding and oxygen-consuming tissues of the body, exceeding even that of the brain. The susceptibility of the choroid to oxidative stress can be attributed to several factors including the choroid's high vascularity, located beneath the retina, which exposes it to constant oxygen and reactive oxygen species (ROS) via a rich network of blood vessels supplying the outer retinal layers, and the choroid's role in light regulation and the intricate interplay with the retinal pigment epithelium can lead to ROS generation when exposed to light, contributing to oxidative stress.

Oxidative stress is a significant contributor to various eye diseases. Some of these conditions include AMD, cataracts, DR, DED, Fuchs' endothelial corneal dystrophy, glaucoma, keratoconus (KC), ROP, RP, and uveitis.

The eyes possess intrinsic antioxidant systems to shield against oxidative stress and damage from reactive oxygen species. Melanin acts as a natural UV filter and antioxidant, helping to protect the eye from harmful UV radiation and oxidative stress.

Essential vitamins like A, C, E, and beta-carotene, in combination with a network of enzyme systems found in various cellular compartments, including mitochondria (housing superoxide dismutase (SOD) and glutathione peroxidase), peroxisomes (home to catalase), and the cytosol (containing SOD, glutathione peroxidase, ferritin, and ceruloplasmin), work in concert with crucial minerals such as Se, Cu, and Zn, to uphold the eye's defense mechanisms against oxidative stress and maintain overall health. A balanced diet rich in antioxidants is vital for supporting these natural defense mechanisms.

Several eye supplements are recommended to bolster eye health and reduce the risk of age-related eye conditions. These supplements contain antioxidants and other nutrients beneficial for the eyes. They include vitamins C and E, lutein, zeaxanthin, Zn, Se, omega-3 fatty acids, vitamin A, bilberry extract, Ginkgo biloba, alpha-lipoic acid (ALA), CoQ10, and N-Acetyl Cysteine (NAC). However, individual needs and effectiveness may vary. Overall, understanding the role of oxidative stress and the protective mechanisms within the eyes is crucial for maintaining eye health and preventing eye diseases.

Glutathione

Glutathione, a potent antioxidant, is naturally present in the eye's aqueous humor, lens, and cornea, composed of three amino acids: glutamine, cysteine, and glycine. Certain vitamins and minerals are crucial for glutathione production and maintenance, including cysteine, glutamate, glycine, Se, vitamin C, vitamin E, and Zn, obtained from various dietary sources. Glutathione's vital role in eye health involves protecting the lens from oxidative damage and cataract formation, supporting retinal health, reducing eye inflammation, and potentially slowing the progression of AMD and other degenerative eye conditions.

Glutathione peroxidase

This enzyme helps reduce hydrogen peroxide and lipid peroxides in the eye, protecting various eye structures from oxidative damage. Glutathione peroxidase 4 (GPx4) is an important antioxidant enzyme for maintaining redox status and protecting corneal endothelial and conjunctival cells from oxidative stress.

Superoxide dismutase (SOD)

SOD is a crucial enzyme in the eye responsible for converting harmful superoxide radicals into oxygen and hydrogen peroxide, thus preventing oxidative damage to the lens and retina. Its effectiveness relies on specific nutrients like Cu, which activates and stabilizes Cu-Zn SOD and extracellular SOD, and Zn, which maintains the structural integrity of Cu-Zn SOD. Manganese is essential for the production of mitochondrial manganese SOD2, guarding cells against oxidative stress during energy production. While not a direct co-factor, Se supports SOD's activity by enhancing overall cellular antioxidant defenses.

N-acetylcysteine (NAC)

NAC is a supplement under study for its potential antioxidative impact on eye health. It acts as a precursor to cysteine, a crucial element of the antioxidant glutathione. Investigations have delved into NAC's antioxidative role in various eye conditions, including cataracts, glaucoma, AMD, ROP, and RP, showing promise in slowing their progression. Furthermore, it shows potential for enhancing the management of conditions like dry eye syndrome and filamentary keratopathy by promoting tear film stability through the breakdown of disulfide bonds in mucus.

Cystatin C

Cystatin C, a widespread cysteine protease inhibitor produced by all nucleated cells, is involved in a wide range of physiological processes and exhibits potential neuroprotective and antioxidant properties. Its role in conditions like glaucoma, AMD, and neurodegenerative diseases is an area of active research, with the potential therapeutic applications of Cystatin C being a subject of ongoing investigation.

Roles of lipids and lipid-soluble molecules in vision and ocular health

Lipids play a vital role in maintaining eye health and visual function. Essential lipids contribute to the formation and stability of cell membranes in the eyes, ensuring the integrity of ocular tissues. Phospholipids, such as those found in the tear film, provide lubrication and protect the corneal surface. Lipids also support the absorption of fat-soluble vitamins, like vitamin A, which is crucial for proper vision. Cholesterol, although often associated with health concerns, is essential for the formation of cell membranes in the retina and the development of photoreceptor cells.

In addition to the usual lipid classes like glycerophospholipids, sphingolipids, fatty acids, and sterols, lipid-soluble molecules, specifically retinoids, bisretinoids, and carotenoids, are vital players in both ocular physiology and the development of ocular diseases.

The tear film lipid layer (TFLL) covers the cornea, preserving its clarity and hydration. This layer contains distinctive wax esters and cholesteryl esters with extended hydrocarbon chains. Disruption of TFLL stability can result in DED. Additionally, docosanoid-dependent signaling plays a role in corneal nerve regeneration, tear formation, and wound healing.

The ocular lens stands out due to its unique characteristics. It possesses a unique lipid, dihydrosphingomyelin, with a notably high cholesterol-to-phospholipid ratio of 10:1. An imbalance in the lipid structure of the lens can result in the aggregation of proteins and clouding of the lens, leading to cataracts.

The photoreceptor cells in the retina have specialized membranes that contain lipids, particularly in the outer segments of rods and cones. The presence of lipid-rich membranes is crucial for the process of phototransduction. Within the membranes of retinal photoreceptor outer segments, docosahexaenoic acid (DHA), a significant omega-3 long-chain polyunsaturated fatty acid (LCPUFA) obtained from the diet, plays a major role as a structural lipid. The biophysical and biochemical characteristics of DHA can impact photoreceptor membrane function through changes in lipid phase properties, thickness, permeability, and fluidity. The DHA levels in tissues influence retinal cell signaling during phototransduction. DHA engages in signaling pathways, activating membrane-bound retinal proteins and aiding rhodopsin regeneration. Enzyme-facilitated DHA release from glycerophospholipids contributes to generating neuroprotectin D1 (NPD1) and resolvin RvD6i. These substances trigger the production of growth factors, aiding in the regeneration of corneal nerves and easing neuropathic pain. Additionally, DHA creates neuroprotective docosanoids. The expression of ELOVL4, limited to select organs like the retina, brain, skin, testes, and Meibomian gland, demonstrates tissue-specific profiles of very-long-chain polyunsaturated fatty acids (VLC-PUFA) and very-long-chain saturated fatty acids (VLC-SFA). Mutations in the ELOVL4 gene, responsible for fatty acid elongation, lead to autosomal dominant Stargardt-like macular dystrophy (STGD3) and brain disorders.

Among lipid-soluble molecules, retinoids are essential for retinal function, with 11-cis retinaldehyde forming crucial visual pigments in photoreceptor cells to facilitate vision. The visual cycle, a complex process, involves the conversion of all-trans retinol into 11-cis retinaldehyde and utilizes various enzymes and proteins. RPE-retinal G protein-coupled receptor (RGR) and retinoid isomerase (RPE65) play key roles in the regeneration of visual pigments. Some all-trans retinaldehyde can lead to the formation of bisretinoids, which are not only fluorescent but potentially harmful.

Additionally, carotenoids such as lutein and zeaxanthin found in the retina affect eye health from early development to aging, impacting conditions like ROP and AMD.

The optic nerve is surrounded by a myelin sheath, which is composed of lipids. The myelin sheath acts as an insulating layer that facilitates the rapid transmission of visual information from the eye to the brain. Proper myelination relies on the essential role of sphingolipid metabolism, as sphingolipids play a critical role in the synthesis and maintenance of the myelin membrane.

Fatty acids, serving as an energy source for photoreceptor cells, and their oxidative metabolites also influence eye diseases. Sterols, primarily cholesterol, are crucial for maintaining retinal homeostasis. Sphingolipids have a role in determining cell survival and have implications for eye conditions such as AMD, uveitis, and DR. Lipid metabolism defects contribute to the development of DR, with discussions on lipid-lowering medications, dietary lipids, and the significance of omega-3 fatty acids. The involvement of fatty acids, cholesterol, sphingolipids, and PPARα in DR is also explored.

Excessive lipid intake, metabolism disruptions, or lipid exudation or accumulation from vessels can result in lipid accumulation in various parts of the eye, giving rise to a spectrum of eye-related manifestations and conditions. These can include the development of xanthelasma, xanthomas, corneal xanthoma, Schnyder corneal dystrophy , corneal arcus, or lipid keratopathy, as well as conditions like cholesterosis bulbi, asteroid hyalosis, atherosclerosis, central retinal artery occlusion (CRAO), and the buildup of lipid exudates within the retina, which is particularly associated with conditions such as DR and AMD, and coat's disease.

Lipid metabolism is intricately linked to the health of various eye structures, and maintaining the balance of these important lipids is paramount in preserving good eye health and sustaining optimal vision.

The glycation and aging process

The aging process involves glycation, a non-enzymatic chemical reaction between sugars and proteins or lipids that forms advanced glycation end-products (AGEs). While their natural production is part of a physiological process, excessive levels contribute to oxidative stress and inflammation, marking aging and various degenerative diseases. Factors like high-temperature cooking methods, sedentary lifestyles, and diets rich in processed foods elevate AGE production, intensifying these compounds' impact.

This glycation process contributes to various ocular changes. They may cause changes in cornea, lens, retina, and choroid contributing to diseases like diabetic keratopathy, keratoconus , cataracts, posterior capsule opacification after cataract, glaucoma, AMD, DR, and diabetic optic neuropathy.

A diet focused on minimizing glycation and reducing AGEs involves choosing low-glycemic Index (GI) foods, antioxidant-rich options, healthy fats, and herbs and spices like turmeric. It is recommended to avoid processed or charred foods and emphasize gentle slow cooking methods to reduce AGE formation. Additionally, a diet rich in fruits, vegetables, and antioxidants aids in preventing AGE accumulation, offering potential benefits against these civilization's diseases. While no clear treatment exists to reduce AGEs in healthy individuals, compounds in unprocessed diets show potential in reducing AGE accumulation in tissues.

The significance of neurons in ocular conditions and the potential of neuroprotective nutrients

The role of neurons is crucial in various eye diseases, including dry eye, DR, glaucoma, RP, and optic neuropathies. Neurons, particularly specialized photoreceptors, can be damaged in these conditions. In dry eye syndrome, corneal nerves are vital for tear production and ocular surface health, while DR affects both blood vessels and retinal neurons. RP and degenerative retinal diseases involve the progressive degeneration of photoreceptor cells, and optic neuropathies, whether caused by glaucoma or other factors, damage retinal ganglion cells and their axons. Across these eye diseases, preserving neural tissues emerges as a primary focus in treatment and management, recognizing the significant impact of neuronal involvement in their pathogenesis.

Neurotrophic factors are vital for the survival and function of neurons in the eye. Ongoing research explores the use of various neurotrophic factors and related compounds in ophthalmology. These factors and compounds hold promise in supporting the health and function of neurons in the eye.

Some of these factors and their potential applications include Nerve Growth Factor (NGF) in dry eye syndrome, Brain-Derived Neurotrophic Factor (BDNF) in glaucoma and optic neuropathy, Ciliary Neurotrophic Factor (CNTF) may protect photoreceptor cells in RP and macular degeneration, and Glial Cell Line-Derived Neurotrophic Factor (GDNF) may have neuroprotective effects on retinal ganglion cells in glaucoma and optic neuropathy.

Pigment Epithelium-Derived Factor (PEDF) may have neuroprotective and anti-angiogenic properties in DR and AMD, Fibroblast Growth Factor (FGF) and basic FGF (bFGF) may stimulate corneal healing and repair, Insulin-Like Growth Factor-1 (IGF-1) may promote retinal neuroprotection, Platelet-Derived Growth Factor (PDGF) effectively prevents photoreceptor degeneration by inhibiting apoptosis, offering a promising therapeutic approach to mitigate photoreceptor loss without the adverse effects of inducing retinal angiogenesis.

Tauroursodeoxycholic acid (TUDCA) is a bile acid, which is a category of chemical compounds found in the body. It is not typically obtained from dietary sources but is synthesized in the liver. TUDCA is available as a dietary supplement and is sometimes used for its potential health benefits, including its role in liver health and reducing endoplasmic reticulum stress. TUDCA is a promising neuroprotective agent in ophthalmology. It is being studied for its potential to support retinal neurons, particularly in conditions like glaucoma and RP. TUDCA works by reducing endoplasmic reticulum stress, inhibiting cell apoptosis (cell death), and modulating various cellular pathways that promote neuroprotection.

Specific nutrients and supplements may indirectly increase neurotrophic factor levels, maintaining overall good health and proper nutrition is essential for supporting neurotrophic factor activity and overall neuronal health. Key nutrients and supplements that indirectly support neural health include omega-3 fatty acids, antioxidants, B vitamins, vitamin D, curcumin, resveratrol, lutein, zeaxanthin, CoQ10, ALA, and NAC.

The production of neurotransmitters plays a significant role in eye health, and these essential compounds can be obtained from specific nutritional sources. Neurotransmitters are chemical messengers that transmit signals in the nervous system, including the visual pathways. Key neurotransmitters related to eye health include dopamine, acetylcholine, and glutamate.

Neuroplasticity, the brain's remarkable capacity to forge new neural connections throughout one's life, plays a critical role in shaping and maintaining the visual system. Dopaminergic foods, influencing dopamine levels, contribute significantly to this process. During childhood, neuroplasticity fine-tunes visual processing, and specific dietary choices rich in tyrosine (such as lean meats, fish, eggs, dairy products, and certain nuts and seeds) and certain fruits and vegetables (like bananas and leafy greens) have the potential to promote enhanced visual development and combat conditions like amblyopia. Dopamine, a pivotal neurotransmitter, wields its influence over various aspects of visual function, including contrast sensitivity and color perception. In cases of visual impairment, the harnessing of neuroplasticity is feasible through visual rehabilitation programs that consider dietary support.

Other neurotransmitters including indoleamines, a group of organic compounds that encompass melatonin, play a pivotal role in regulating circadian rhythms and the sleep-wake cycle, indirectly contributing to eye health by facilitating proper rest and minimizing the risk of eye strain and fatigue. This is vital for sustaining optimal eye function and overall visual well-being. Although melatonin is chiefly produced by the body, certain foods from fungi to animals and plants, with eggs, fish, and nuts emerge as some of the richer melatonin sources. Other sources include cherries, grapes, strawberries, tomatoes, walnuts, and almonds contain trace amounts of melatonin, though their dietary impact is relatively modest. Consumption of melatonin-rich foods has been associated with a significant increase in melatonin levels in human serum. Furthermore, melatonin exhibits promise in addressing specific eye conditions like glaucoma, accompanied by documented benefits for the immune system, inhibition of angiogenesis, cancer cell apoptosis induction, potent antioxidant effects, cardiovascular protection, anti-diabetic and anti-obesity properties, neuroprotection, and anti-aging attributes. One cohort study found that melatonin use was associated with a decreased risk of developing age-related macular degeneration (AMD) and a slower progression from nonexudative to exudative AMD, supporting further research into melatonin's potential as a preventive therapy for AMD. Clinical trials, including those focusing on advanced uveal melanoma stages, have delivered encouraging results while maintaining low toxicity levels. Given its diverse potential advantages, minimal associated risks, and wide accessibility, melatonin presents itself as a promising complementary therapy for individuals dealing with conditions like uveal melanoma.

Nutrients

A well-balanced diet offers the fundamental components necessary to uphold the structural integrity of ocular tissues and facilitate optimal eye function. This includes vitamins, minerals, essential fatty acids, amino acids, antioxidants, and neuroprotective factors, all of which are key in promoting overall eye and vision health. Together, these elements collaborate to protect the intricate mechanisms that form the foundation of our vision. This review examines the significance of these nutrients from an ophthalmological standpoint.

Water balance and ocular health

Given the eye's unique high-water content and fluid regulation system, systemic hydration status effects on ocular health. Dehydration, for instance, may contribute to dry eye syndrome, cataracts, alterations in vision and refraction, and retinal vascular issues. Conversely, excessive hydration can also be linked to certain eye diseases. Tear fluid osmolarity emerges as a potential marker for assessing systemic hydration status. Recent research suggests that the chronic activation of the renin-angiotensin-aldosterone system plays a role in DR and glaucoma development, offering a potential therapeutic target. The hydration status of the entire body not only impacts the biomechanical properties of the cornea, potentially altering measurements in individuals with keratoconus according to Singh et al., but it may also play a role in influencing the progression of thinning. There is speculation about a potential connection between dehydration and the occurrence of vitreous detachment, leading to subsequent retinal tear and retinal detachment. In light of these results, evaluating hydration status may be a crucial factor in managing patients with chronic eye conditions or those undergoing eye surgery. Further investigations into the impact of acute and chronic hydration changes in individuals with and without ocular diseases are needed to expand our understanding in this area.

Vitamins:

Fat-soluble vitamins, including vitamins A, D, E, and K, and water-soluble vitamins such as vitamin C and various B vitamins, each have distinct yet harmonious roles in the preservation of eye health. Notably, fat-soluble vitamins, particularly vitamin A, are indispensable for the production of the light-sensitive pigment rhodopsin in the retina, which is critical for both low-light and color vision. In contrast, water-soluble vitamins like vitamin C play a vital role in promoting the health of blood vessels in the eyes, potentially reducing the risk of conditions like cataracts. The collaborative synergy among these vitamins is central to maintaining the overall well-being of the eyes, underscoring the significance of a well-rounded diet that encompasses both fat-soluble and water-soluble vitamins to support diverse aspects of eye function and health.

Vitamin A

Vitamin A, found in both animal and plant-based foods as retinol and carotenoids respectively, fulfills the body's needs through various dietary sources. Animal products offer preformed vitamin A like retinol, while plants contain provitamin A carotenoids such as beta-carotene that can convert into active vitamin A. Typically, a well-balanced diet provides sufficient vitamin A.

This essential nutrient is crucial for ocular health, with its deficiency leading to various eye symptoms impacting the conjunctiva, cornea, and retina. Among its vital roles, maintaining healthy vision, especially in low-light conditions, stands out due to its role in rhodopsin, a key protein for night vision.

Vitamin A plays a critical role in supporting the proliferation and differentiation of ocular surface epithelium, contributing to the reduction of apoptosis in corneal epithelial cells and facilitating corneal wound healing. Moreover, it stimulates the synthesis of eicosanoids, leading to the expression of mucin MUC16. This specific mucin forms a protective barrier characterized by a moist surface on both the corneal and conjunctival epithelium, effectively preventing keratinization of the ocular surface. Additionally, Vitamin A enhances tear production and improves the quality of the tear film, making it a valuable treatment for DED.

Vitamin A holds multiple vital roles within the body. It plays a crucial part in immune system support, bolstering the body's defenses against infections. Furthermore, it regulates gene expression, fostering the growth and differentiation of diverse cell types throughout the body. Vitamin A also governs genes associated with the mammalian biological clock, influencing the body's responses to both day and night cycles and seasonal physiological adjustments. The synchronization of the human body and sleep cycle has a positive impact on eye health. This synchronization aids in optimal visual pigment regeneration and the regeneration of the ocular surface during sleep, highlighting the significance of well-coordinated body rhythms.

Vitamin A finds application in the treatment of various conditions, such as peripheral vision loss associated with RP, AMD, and ocular surface diseases like Superior Limbic Keratoconjunctivitis (SLK). Additionally, it is associated with genetic eye disorders like Cone-Rod Dystrophy and Stargardt Disease. However, current knowledge doesn't universally recommend vitamin A for all mutation types. Moreover, vitamin A plays a role in preventing conditions like intracranial hypertension, characterized by increased skull pressure, and papilledema, which involves optic nerve head swelling, which can significantly impact vision.

Vitamin A deficiency (VAD) is a major global health concern primarily associated with malnutrition or malabsorption. Its impact is especially profound in developing regions like Africa and South-East Asia, significantly contributing to instances of blindness. Inadequate nutrition, often aggravated by chronic gastrointestinal infections, particularly affects young children and pregnant women in resource-poor areas. On the contrary, in developed countries, VAD is linked to pancreatic, liver, and intestinal disorders. Clinical indicators of VAD include night blindness, xerophthalmia fundus, conjunctival and corneal xerosis, Bitot spots, corneal ulcers, and scarring. Severe complications like keratomalacia progress swiftly and can result in blindness if not promptly addressed.

Isotretinoin, a vitamin A analog, is prescribed for keratinization disorders, severe nodular acne, and psoriasis, but its use is connected to various ocular manifestations. Reported problems encompass sensitivity to light, reduced or blurry vision, reversible and permanent compromised adaptation to darkness, reversible and permanent color perception changes, changes in refractive errors (temporary myopia), and alterations in the visual field, reversible post corneal refractive surgery complications like keratitis and opacities. Conjunctival problems include blepharoconjunctivitis, keratoconjunctivitis sicca, blepharitis, and subconjunctival hemorrhages. Increased intracranial pressure and ON, are associated with isotretinoin. Reported retinal abnormalities involve alterations in retinal nerve fiber layers, premacular hemorrhages, photoreceptor damage, and pigment disturbances. Isotretinoin may increase the risk of thrombosis, and while rare, lens opacities, meibomian gland dysfunction, lacrimal gland atrophy, and changes in sebaceous gland secretions are also linked to its use. Previously, FDA guidelines state that isotretinoin is a contraindication for LASIK refractive surgery, and new findings suggest those guidelines should be reconsidered.

Vitamin D:

Vitamin D, obtained from sunlight exposure and specific foods, interacts with the cornea's vitamin D receptor (VDR), converting to calcitriol and reducing inflammation and oxidative stress, supporting corneal barrier function, influencing systemic calcium absorption, correlating with tear production and dry eye symptoms, and potentially contributing to dry eye disease (DED), with promising results in supplementation for DED improvement; additionally, topical and ophthalmic vitamin D solutions have shown effectiveness in enhancing ocular surface health and aiding healing in DED patients and post-cataract surgery.

Research suggests an association between vitamin D and various eye conditions like myopia, AMD, DR, and DED. Yet, evidence regarding other ocular diseases like glaucoma, thyroid eye disease (TED), and retinoblastoma (RB) remains scarce.

Low levels of 25 (OH) D in the initial days of life could potentially link to the development of retinopathy of prematurity and the need for treatment in premature infants.

Patients with progressive keratoconus have lower serum vitamin D levels compared to the general population. Lower levels of serum 25(OH)D were associated with longer axial length (AL) and a higher probability of myopia in young children, seemingly independent of outdoor exposure, indicating a possible direct role for 25(OH)D in myopia development. This correlation suggests a possible link between vitamin D and calcium, and their relationship to the rigidity of the sclera/cornea. This could present a promising avenue for tackling or preventing high myopia or keratoconus.

Maintaining adequate Vitamin D levels appears linked to improved inflammatory outcomes in multiple sclerosis (MS). However, incorporating vitamin D into standard disease therapy did not significantly impact the thickness of the retinal nerve fiber layer (RNFL) or macula in patients with ON.

Vitamin E (Tocopherol):

Vitamin E, which encompasses a group of eight fat-soluble antioxidants, is essential for protecting cell membranes from oxidative damage. α-tocopherol is the most significant in the human body. While α-tocopherol loses its antioxidant capacity upon neutralizing a free radical, other antioxidants like vitamin C can regenerate it. Its primary role is to combat free radicals, prevent lipid oxidation, and preserve cell membrane integrity, particularly important for the fatty-acid-rich retina.

Vitamin E contributes to antioxidant defense on the ocular surface and potentially benefits individuals with DED. Studies have indicated that vitamin E, particularly when combined with CoQ10, can aid in corneal wound healing, recovery of corneal subbasal nerve plexus, and stabilization of the ocular surface after cataract surgery.

Additionally, it impacts immune and inflammatory cell activities, inhibits platelet aggregation, and enhances vasodilation, which is beneficial for eye health.

Vitamin E also contributes to maintaining a healthy retina, essential for vision, and may reduce the risk of cataracts by shielding the eye's lens from oxidative damage. Additionally, when combined with other antioxidants, it could help lower the risk of AMD. However, further studies are needed to understand the specific effects of vitamins C and E independently.

Vitamin E can be sourced from a variety of foods, including nuts, seeds, vegetable oils, green leafy vegetables, fortified cereals, and fruits. The recommended daily intake of Vitamin E depends on age, sex, and life stage, but for adults, it's typically around 15 milligrams per day. However, intake levels often fall short of this recommendation, with the average intake in the US being around 8.6 mg/day for men and 7.3 mg/day for women over 50.

Vitamin K:

Vitamin K is important for blood clotting and may indirectly affect the vascular health of the eye. Vitamin K is also involved in the synthesis of myelin, the protective sheath around nerve fibers. Proper myelination is crucial for the health of the optic nerve.

Vitamin B Complex (B1, B2, B3, B6, B9, B12):

The Vitamin B Complex, comprising eight water-soluble vitamins, plays a critical role in safeguarding overall eye health and reducing the risk of conditions like cataracts and glaucoma. These vitamins act as coenzymes and are particularly relevant for ocular well-being. For example, Vitamin B1 (thiamine) possesses antioxidative properties and supports nerve function, they play a critical role as coenzymes for various enzymatic reactions. Vitamins B1, B6, and B12, called neurotropic vitamins, are essential to maintain the health of the nervous system, including the optic nerve. Vitamins B1, B2, B6, and B12 have functions that include antioxidative properties, immune system regulation, and the promotion of nerve survival and regeneration. These vitamins mainly function as coenzymes and are instrumental in maintaining ocular surface equilibrium and preventing DED. Several micronutrients in the Vitamin B group are associated with DED, particularly DED related to neuropathic ocular pain (NOP). Studies have shown promising results in improving tear secretion and DED symptoms through the supplementation of vitamins B1 and B2. Nebulization, oral supplementation, and topical application of Vitamin B complexes have demonstrated positive effects on tear secretion, corneal staining scores, nerve density, and the ocular surface environment. More research is needed to understand the specific effects of each B vitamin on DED, but these findings underscore the potential of Vitamin B supplementation, especially in cases associated with neuropathic ocular pain.

The Blue Mountains Eye Study reported a higher prevalence of posterior subcapsular cataracts among users of high-dose thiamine and pyridoxine (vitamin B6) supplements; however, the use of other B-vitamin supplements was associated with a reduced prevalence of nuclear and cortical cataracts.

Vitamin B1 (Thiamine):

Thiamine is essential for nerve function and plays a role in energy metabolism. A deficiency can lead to vision disturbances and eye muscle weakness, possibly contributing to conditions like optic neuropathy. Studies have shown mild ophthalmoparesis and bilateral symmetric vestibular loss in thiamine deficiency.

Vitamin B2 (Riboflavin):

Riboflavin is involved in energy production, metabolism, and the activation of other vitamins. It helps maintain healthy corneas and can guard against conditions like keratoconus. Deficiency may result in photophobia and eye discomfort, often associated with skin and mucous membrane issues.

Vitamin B3 (Niacin):

Niacin plays a vital role in energy production and DNA repair, crucial for overall eye health; its deficiency may lead to pellagra, marked by dermatitis, diarrhea, dementia, and ocular issues like photophobia and blurred vision. Nicotinamide adenine dinucleotide (NAD+) decline with age is associated with age-related diseases, although its role in retinal health remains poorly understood, despite its impact on retinal degenerative conditions. Recent studies propose that nicotinamide, a Vitamin B3 form, could preserve retinal and optic nerve function in glaucoma. By boosting cellular energy and curbing oxidative stress, nicotinamide offers a potential avenue for glaucoma therapy. It may also boost nitric oxide production, aiding in increasing aqueous humor outflow, regulating eye blood flow, reducing intraocular pressure, and safeguarding the optic nerve. Nicotinamide differs from niacin in that it doesn't typically induce flushing as it doesn't act as a vasodilator. Additionally, while niacin effectively manages dyslipidemia, it's crucial to acknowledge reported cases of niacin maculopathy in patients undergoing treatment for hyperlipidemia.

Vitamin B6 (Pyridoxine):

Pyridoxine is involved in amino acid metabolism and neurotransmitter production. It is essential for the normal development and function of the nervous system, including the visual pathways. According to findings from the Blue Mountains Eye Study, individuals using high-dose thiamine and pyridoxine (vitamin B6) supplements had a greater occurrence of posterior subcapsular cataracts. In contrast, the consumption of other B-vitamin supplements was linked to a decreased prevalence of nuclear and cortical cataracts.

Vitamin B9 (Folate or Folic Acid):

Folate is vital for DNA synthesis, repair, and cell growth. Adequate folate levels are important for the overall health of the retina and the optic nerve. Supplementing with folic acid could serve as a protective therapy for individuals with retinal vascular conditions characterized by elevated homocysteine or glucose levels.

Vitamin B12 (Cobalamin):

Vitamin B12 plays a crucial role in red blood cell formation, DNA synthesis, and neurological function. Its deficiency can lead to anemia, affecting blood circulation to the eyes and optic nerve. Studies suggest a link between its shortage and neurosensory issues, contributing to DED, which can be effectively addressed through supplementation to alleviate ocular neuropathic pain. Additionally, Vitamin B12 supplementation in diabetic rats has shown benefits in reducing retinal hypoxia, excessive VEGF expression, and cell death in the retina. However, it's worth noting that excessive intake of vitamin B12 may potentially contribute to the development of glaucoma.

Vitamin C (Ascorbic Acid):

Vitamin C, a crucial water-soluble antioxidant, plays a vital role in supporting overall eye health by supporting collagen synthesis, essential for blood vessels, cornea, and vitreous structural integrity. Abundant in the aqueous humor, it shields ocular structures like the lens, and cornea from oxidative damage, regenerating vitamin E for enhanced antioxidant effects. Present in human tears, it bolsters antioxidant and anti-inflammatory defenses on the ocular surface and aids in corneal wound repair, reducing edema and inflammation in injuries caused by factors like ultraviolet B exposure, corneal alkali burns, or infectious keratitis. The recommended dietary allowance (RDA) for vitamin C is 75 mg/day for women and 90 mg/day for men, but some individuals may fall short, risking conditions like scurvy, with ocular symptoms such as subconjunctival hemorrhages and light sensitivity.

Minerals:

Zinc (Zn):

Zinc, a vital trace mineral, is crucial for retina health and preventing AMD, playing diverse roles in eye function. It serves as a structural element in retinal enzymes and proteins, supports antioxidant defense against oxidative stress (present in SOD), aids immune function, promotes wound healing, contributes to night vision, and in combination with vitamins C and E, may reduce AMD risk. However, it's worth noting that excessive Zn intake or exposure can impair immune function, lead to digestive issues, cause color vision deficiency decrease contrast sensitivity and eye irritation, and disrupt the balance of Cu in the body, which is essential for protecting the eyes from sunlight. Maintaining an adequate but not excessive intake of Zn is crucial for maintaining retinal health and supporting eye well-being. Patients who are deficient in Zn are highly vulnerable to optic neuropathy. Zinc-rich foods include a variety of legumes like black-eyed peas, kidney beans, and lima beans, as well as oysters, lean red meat, poultry, and fortified cereals. Zinc absorption is lower in individuals consuming vegetarian diets; it is recommended that the Zn requirement for this group be twice as much as for nonvegetarians.

Selenium (Se):

Selenium, crucial for cell protection, especially in the eyes via glutathione peroxidase, is vital for thyroid health and potentially aids in managing thyroid eye disease by reducing associated inflammation. It might moderate the immune response targeting eye tissues in TED. Dietary sources include Brazil nuts, fish, poultry, and whole grains, with supervised supplements if intake is insufficient. The European Group on Graves Orbitopathy explores selenium's role in TED, suggesting benefits for mild Graves' orbitopathy. However, while selenium plays a role in various selenoenzymes, excess amounts beyond what's necessary can be toxic and lead to cataracts in animals. Clinical evidence supporting selenium's protective role in ocular diseases is lacking due to suboptimal selenium intake not causing relevant deficiencies in the eye. Thus, there's no current basis to expect benefits from selenium supplementation beyond daily dietary reference intakes of 55 micrograms/day in the context of ocular diseases.

Copper (Cu):

Copper plays a vital role in eye health, contributing to collagen formation, vascular maintenance, neurotransmitter synthesis (dopamine, norepinephrine, and serotonin), and the structural integrity of ocular tissues. Additionally, it is involved in melanin production, affecting pigmentation in the iris and RPE, providing UV radiation protection. Cu deficiency, as observed in Menkes disease, can lead to depigmentation of the iris and hair. Cu's presence in SOD supports antioxidant activity, safeguarding retinal cells from oxidative damage, which is particularly relevant in preventing conditions like AMD. However, maintaining proper Cu balance is crucial, as excessive levels can be detrimental, emphasizing the importance of a balanced diet that includes Cu-rich sources like whole grains, legumes, nuts, and seafood.

The accumulation of excess copper, whether due to a foreign body or Wilson's disease, can lead to deposition in different eye regions, resulting in tissue softening in the sclera, the development of a Kayser-Fleischer ring in the cornea, a greenish hue in the iris, sunflower cataracts in the lens, granular deposits in the vitreous, cellular alterations, and copper buildup in the retina. These effects contrast with iron-induced changes and are less prone to causing degenerative retinopathy.

Iron (Fe):

Iron deficiency, identified by signs like a pale appearance of the lower eyelid linings and an elevated vulnerability to eye infections, can indirectly affect eye health. Iron plays a role in the upregulation of genes related to melanin production, as mentioned previously regarding the significance of melanin in the eye.

Iron plays a crucial role in the cornea's health, participating in processes like the citric acid cycle, ATP production, and DNA synthesis. However, excess iron can lead to the formation of harmful oxygen-free radicals. Two key iron-related proteins in the tears are lactoferrin and ferritin, which are involved in iron transport, reducing oxidative damage, and bolstering antibacterial defenses. Iron lines observed in the cornea, such as the Hudson-Stahli Line, Fleischer's Ring, Stocker's Line, and Ferry's Line.

Iron overload can lead to conditions like hemosiderosis bulbi, which is the accumulation of iron deposits in the anterior chamber.

Iron's involvement in cataractogenesis is also noted, particularly in cases of ocular siderosis and a genetic syndrome known as hereditary hyperferritinemia cataract syndrome (HHCS), which is linked to elevated ferritin levels. Iron-catalyzed reactions and the formation of L-ferritin deposits within cataracts are considered potential mechanisms.

In the retina, iron plays a crucial role in phototransduction but can also lead to toxicity if it accumulates excessively. Iron deposition in the retina can contribute to retinal degenerative diseases. Excess iron is also thought to contribute to AMD, a degenerative disease of the central retina that can result in vision loss. AMD involves oxidative damage and inflammation, and increased iron levels have been detected in the retinas of AMD patients. Hereditary iron overload conditions such as aceruloplasminemia and hereditary hemochromatosis are also associated with retinal pathology, further suggesting the role of iron in retinal diseases.

Diseases of the optic nerve, including ON, ischemic optic neuropathy, traumatic optic neuropathy, and glaucoma, can lead to retinal ganglion cell death, often through apoptosis and the generation of ROS. While a direct link between excess iron and optic neuropathies is not established, iron's ability to produce highly reactive ROS may play a role in its pathogenesis. Glaucoma, for example, is linked to increased oxidative stress and glutamate neurotoxicity, which may involve iron-related proteins.

Potential therapies for these eye diseases include antioxidants, iron chelators, and dietary iron limitation. Antioxidants, such as those found in the Age-Related Eye Disease Study, have shown promise in slowing the progression of AMD. Iron chelators like deferiprone and deferasirox are being investigated for their potential to treat iron overload conditions and reduce iron-induced oxidative damage. Additionally, dietary iron limitation is being explored as a way to decrease lifetime iron stores and potentially reduce the risk of retinal degeneration.

Magnesium (Mg):

Magnesium is a versatile mineral crucial for a wide range of physiological functions, including its participation in over 300 enzyme systems responsible for processes such as protein synthesis, muscle contraction, and nerve function. It plays a pivotal role in energy production and nucleic acid synthesis, contributing to cellular well-being. In the context of eye health, Mg is mainly found in eye structures like the cornea, lens, retina, vitreous body, and anterior chamber, where it helps maintain structural integrity and function. It is also associated with a reduced risk of cataract formation and potential prevention of glaucoma. Moreover, Mg is vital for cardiovascular health, influencing blood flow and offering neuroprotective effects. Its role in maintaining nerve function, including the transmission of visual signals from the eye to the brain via the optic nerve, underscores its significance for overall eye health. Mg-rich foods like nuts, seeds, and leafy greens are valuable dietary sources to support these functions.

Calcium (Ca):

While calcium deficiency doesn't have a direct influence on eye health, severe deficiencies may be associated with the development of cataracts. Changes in calcium levels play a crucial role in cataract development, potentially linked to modifications in Ca2+ signaling within lens epithelial cells. In conditions like hypoparathyroidism, cataracts tend to form in the posterior subcapsular region due to low calcium levels in the aqueous humor, leading to membrane damage, inhibition of the lenticular Na+/K+ pump, and subsequent swelling of lens fibers along with dystrophic calcification.

Band-shaped keratopathy affects the cornea, causing calcium and phosphate buildup, resulting in whitish or grayish bands that hinder vision. Elevated blood calcium levels, particularly in conditions like systemic hyperparathyroidism and Vit-D toxicity, including hyperparathyroidism affecting the parathyroid glands, are associated with this condition and contribute to heightened calcium levels in the body.

Pseudoxanthoma elasticum (PXE), a genetic condition impacting connective tissues, especially elastic fibers, involves calcium in abnormal mineralization, leading to deposits in diverse tissues and characteristic changes in the skin, eyes, and cardiovascular system. The unclear mechanisms behind calcium's role in PXE relate to disrupted calcium metabolism, highlighting the necessity for comprehension to devise precise therapies and ongoing exploration of associated molecular and cellular pathways. Adjusting calcium levels within the Bruch membrane might offer potential treatments to mitigate Bruch membrane disruption and decrease the occurrence of choroidal neovascularization (CNV) in conditions such as myopia, PXE, or AMD.

In Cancer-associated retinopathy, the calcium-binding protein recoverin is pivotal, while in ocular melanoma, the reduction of the pro-apoptotic calcium-binding protein ALG-2 contributes to pathogenesis. Calcium-based materials show potential in boosting anti-cancer immunity. Disruption in maintaining calcium homeostasis in photoreceptors results in retinal dysfunction and the onset of pathologies leading to blindness.

Additionally, calcium plays a role in transmitting optic nerve signals, including those along the optic nerve. This may play a role in glaucoma pathogenesis.

Phytonutrients

Phytochemicals, synthesized by plants as a defense against fungi, bacteria, and plant viruses, and consumed by insects and animals, are categorized into different subclasses, each offering specific benefits for ocular health. Carotenoids, responsible for the red, orange, and yellow hues in fruits and vegetables, serve as antioxidants and supply vitamin A. Meanwhile, lutein and zeaxanthin, found in high concentrations in the retina, shield against high-energy light, decreasing the risk of cataracts and AMD. Polyphenols, encompassing flavonoids, phenolic acids, and polyphenolic amides renowned for their antioxidant traits, are found in food items like tea, berries, and dark chocolate. Certain flavonoids, like quercetin and rutin, deliver antioxidant and anti-inflammatory advantages, reducing the risks associated with cataracts and AMD. Anthocyanins present in dark fruits improve night vision and promote general eye health. Glucosinolates in cruciferous vegetables shield the eyes from oxidative harm, while phenolic acids like chlorogenic acid, found in coffee, might lower the risk of eye ailments. Terpenes containing essential oils in herbs such as rosemary and thyme enhance blood circulation and offer protection against oxidative stress. Saponins and plant sterols sourced from legumes aid in lowering LDL cholesterol levels and contribute to eye health, while tannins present in tea and red wine act as antioxidants and anti-inflammatories, offering protection for the eyes. Alkaloids like caffeine, found in coffee and tea, enhance retinal blood flow, promoting better eye health. Phytochemicals have also shown significant potential in eradicating bacterial biofilms without causing substantial harm to mammalian fibroblast cells. This promising trait suggests a potential solution for combating multidrug-resistant bacterial infections. Incorporating these phytochemical-rich foods into one's diet can significantly enhance eye health and potentially reduce the risk of eye-related conditions such as cataracts, glaucoma, and AMD, though further research is needed.

Carotenoids

Beta-Carotene (β-Carotene)

Beta-carotene recognized as a precursor to vitamin A and an antioxidant with potential eye health benefits, is renowned for its role in diminishing the likelihood of cataracts and age-related eye conditions. This compound undergoes conversion into retinol within the eye, promoting optimal night vision. The notable AREDS1 trial presented compelling evidence of its favorable effects when combined with vitamins C and E, Zn, and Cu, leading to a reduced risk of advanced AMD. Cohort studies additionally endorse the consumption of specific vitamins and carotenoids in mitigating the risk of age-related cataracts. While a higher dietary intake of beta-carotene is widely regarded as safe, it is advisable to exercise caution when exceeding typical dietary levels, particularly for individuals at risk of lung cancer. Notably, in smokers, substantial beta-carotene supplementation has been unexpectedly linked to an increased risk of lung cancer, ascribed to its pro-oxidant effects in an oxidative stress environment characteristic of a smoker's lung.

Lutein and zeaxanthin

Lutein and zeaxanthin are the only carotenoids found in the human lens and retina, with high concentrations in the macula of the retina, where they serve as both antioxidants and optical filters, safeguarding the retina from the harmful effects of high-energy light, including blue and ultraviolet light. Their association with a reduced risk of cataracts and AMD underscores their protective role for the macula, potentially benefiting individuals with diabetic macular edema. These carotenoids are prominently found in leafy greens such as spinach and kale. It's important to emphasize that individuals who reach the 95th percentile among women and the 99th percentile for lutein/zeaxanthin intake among men are the ones associated with reduced AMD risk through their dietary levels. This underscores the advantages of supplementation.

Astaxanthin

Astaxanthin, a xanthophyll, and member of the carotenoid group, is known for imparting red and pink colors to aquatic animals, birds, and microorganisms. It serves as a potent natural antioxidant with anti-inflammatory and anti-apoptotic properties, making it valuable in cancer prevention and eye disease protection. It stands out by working throughout the cellular membrane, offering defense against oxidative stress from reactive oxygen species in both inner and outer membrane layers. Clinical trials have shown its potential in enhancing eye health, yielding promising results in conditions like dry eye syndrome, keratitis, cataracts, DR, AMD, high intraocular pressure, and glaucoma.

Crocin

Crocin, a water-soluble carotenoid and a primary compound in saffron is responsible for the spice's distinct red color. It possesses antioxidant properties, protecting eye cells and tissues from oxidative stress and inflammation. These properties make it a candidate for reducing the risk of eye conditions such as AMD and cataracts. Saffron also contains other carotenoids like zeaxanthin and lycopene, contributing to its potential benefits for eye health. Although saffron is commonly used in cooking, it can also be taken as a dietary supplement for its potential eye health advantages, with further research needed to establish its full effectiveness.

Lycopene

Lycopene, a natural carotenoid found in red fruits and vegetables like tomatoes and watermelon, provides their distinctive red color. It serves as a potent antioxidant with potential health benefits, including supporting eye health and reducing the risk of AMD and cataracts.

Phenolic compounds

Phenolic compounds are a specific class of phytochemicals. They are characterized by the presence of a phenol group in their chemical structure. This group includes compounds like flavonoids, lignans, and stilbenes. Phenolic compounds are known for their antioxidant and anti-inflammatory properties and are found in a variety of plant-based foods, such as fruits, vegetables, tea, and whole grains. They are often associated with the health-promoting effects of a diet rich in fruits and vegetables.

Cinnamaldehyde

Cinnamon contains cinnamaldehyde, a key component responsible for its flavor and potential health benefits. This natural organic phenolic compound, along with other compounds like cinnamic acid and cinnamyl alcohol, contributes to cinnamon's unique aroma. Studies have examined cinnamon leaf oil and its antioxidant properties, as well as its ability to inhibit metabolic enzymes like carbonic anhydrase II (hCA II), acetylcholinesterase (AChE), and α-amylase, which are linked to conditions such as diabetes, Alzheimer's disease, cataracts, and glaucoma.

Polyphenols

Flavonoids

Certain flavonoids like quercetin and rutin have antioxidant and anti-inflammatory properties that can benefit eye health by reducing the risk of cataracts and AMD, along with conditions such as DED and uveitis. Certain flavonoids display promising antiviral properties.

Flavonoids function as antioxidants through a variety of molecular mechanisms. Firstly, they directly interact with free radicals, utilizing their free hydroxyl group(s) to neutralize these harmful molecules. Secondly, flavonoids serve as chelators for redox-active transition metal ions like Cd2+, Fe2+, and Cu2, which have the potential to generate ROS. These metal-binding sites within flavonoids are typically located near their hydroxyl and ketone side groups. Lastly, flavonoids play a role in regulating multiple cellular antioxidant systems, helping to restore the cellular redox balance following periods of oxidative stress. Beyond their antioxidant properties, flavonoids also influence inflammation by modulating key mediators such as AP-1, NFκB, STAT3, and nitric oxidases, particularly iNOS and nNOS. Additionally, they exhibit anti-proliferative and anti-apoptotic effects through pathways like HGF/SF-Met signaling, the MAPK pathway, and the PI3K-Akt pathway.

Quercetin, a natural flavonol antioxidant found in various plant sources, has shown therapeutic potential for treating various eye-related issues due to its antioxidant, anti-inflammatory, and anti-fibrosis activities. It may help with conditions like KC, TED, DED, ocular surface problems, cataracts, glaucoma, retinoblastoma, and other retinal diseases.

Oral administration of forskolin and rutin can contribute to improved intraocular pressure control in patients with limited responsiveness to multiple treatments. Flavonoids also aid in maintaining healthy blood vessels in the eyes, crucial for preventing DR. Anthocyanins, a type of flavonoid found in dark-colored fruits like blueberries and grapes, have unique antioxidant properties that can enhance night vision and overall eye health. Bilberry, rich in anthocyanins, offers antioxidant, genoprotective, anti-cancer, anti-inflammatory, and cardioprotective effects, making it valuable in preventing age-related conditions such as cardiovascular disease and cancer, managing type 2 diabetes, and lowering lipid levels. It has a traditional use for promoting eye health, potentially benefiting cataracts, retinopathy, macular degeneration, and night vision. Bilberry also exhibits impressive antimicrobial properties, which are significant in the context of growing antibiotic resistance. While bilberry's anthocyanins hold promise for overall health improvement, comprehensive exploration of their potential across various health domains requires further research, especially through controlled human trials. Common dietary sources of flavonoids include tea, citrus fruits, berries, red wine, apples, and legumes.

Curcuminoids

Curcuminoids, a polyphenolic class present in turmeric's rhizome, notably curcumin or diferuloylmethane, boast diverse pharmacological traits like antioxidative, anti-inflammatory, antimicrobial, and anticancer effects. Its potential extends to significant eye conditions such as corneal neovascularization, wound healing, DED, conjunctivitis, pterygium, glaucoma, cataracts, AMD, DR, and anterior uveitis, as explored in various studies. The main constraint of curcumin lies in its limited bioavailability, with only a minimal fraction of the substance reaching the bloodstream in a biologically active form.

Resveratrol

Resveratrol, a polyphenol found in grapes, red wine, grape juice, peanuts, cocoa, and certain berries, though a minor component in red wine compared to other polyphenols, has garnered attention in eye research. Studies highlight its diverse positive effects, including antioxidative, anti-apoptotic, anti-tumor, anti-inflammatory, anti-angiogenic, and vasodilatory properties. These traits have been examined concerning eye conditions like glaucoma, cataracts, AMD, and DR. Yet, further research is necessary to better understand its clinical benefits.

Terpenes

Terpenes, plant-based compounds responsible for unique scents and flavors, play a vital role in cannabis and its therapeutic effects. While smoked marijuana can temporarily reduce eye pressure, the effects are brief, requiring frequent use for continuous reduction. Specific terpenes like myrcene, with its peppery scent, aid in pain relief and relaxation. Caryophyllene, found in pepper and cloves, shows promise in reducing inflammation, anxiety, and depression. Terpenes like alpha-pinene and limonene, reminiscent of pine and citrus, respectively, exhibit anti-inflammatory properties and potential benefits for eye conditions like glaucoma. However, oxidation products of terpenes, such as limonene, may contain irritants contributing to reported eye and airway issues indoors. Ginkgo biloba extract (GBE), containing flavonoids and terpenoids, demonstrates antioxidant properties, potentially protecting eye cells from oxidative stress. Research indicates its potential in addressing various eye conditions like AMD, retinal diseases, and glaucoma by supporting retinal health, reducing damage, and enhancing blood flow. While generally well-tolerated, caution and professional guidance are advised for GBE use due to potential side effects and interactions, necessitating further research for a comprehensive understanding of its benefits in eye health.

Organosulfur compounds

The presence of organosulfur compounds in certain foods has been linked to improved eye health, attributed to their antioxidant and anti-inflammatory properties. Vegetables belonging to the Brassica genus, such as broccoli, contain sulforaphane, a potent antioxidant that may reduce the likelihood of developing AMD. Allium species, including garlic, contain alliin and allicin, two organosulfur compounds that exhibit both antioxidant and anti-inflammatory activities. Protein-rich foods often contain sulfur-containing molecules, such as glutathione and methionine, which contribute to antioxidant defenses and protect the sensitive cells of the lens and retina. Additionally, taurine, an amino acid found in many animal products, has been shown to mitigate oxidative stress within the retina. S-adenosylmethionine (SAMe), a naturally occurring sulfur-bearing compound, plays a regulatory role in various biochemical processes vital to eye health. The accumulation of evidence suggests that a diet rich in sulfur-containing compounds may decrease the incidence of debilitating eye diseases, such as cataracts, glaucoma, and AMD, underscoring the importance of incorporating sulfur-abundant foods into one’s diet for optimal ocular health.

Alpha-lipoic acid (ALA)

ALA, also known as lipoic acid, is a vital antioxidant organosulfur compound, involved in energy production and is sourced from various foods like organ meats, spinach, and broccoli. ALA can be obtained through oral supplementation and intravenous injection and has shown promise in managing conditions such as diabetes, neuropathy, and ischemic-perfusion injury. It has demonstrated potential in preventing DED by reducing matrix metalloproteinase-9 expression and maintaining ocular surface antioxidant status. Furthermore, ALA can protect against DR by inhibiting various factors and alleviating oxidative stress. ALA has also been linked to improved near-visual acuity by reducing disulfide bonds in lens proteins and enhancing the dynamic refractive power of the lens during accommodation.

The impact of habitual indulgence in coffee, tea, and alcohol on eye Health

Habitual indulgence in certain substances (coffee, tea, alcohol, and cigarette smoking) can have both positive and negative effects on eye health. Individual habits should be moderated to prevent potential negative effects.

Tea and Coffee

Habitual tea drinking can have varying effects on eye health. The type of tea, toxin presence, and consumption level are all factors. Green tea, rich in antioxidants (rich in catechins, particularly epigallocatechin gallate (EGCG)), can reduce the risk of cataracts and macular degeneration. Some studies even suggest caffeine might protect against dry AMD and enhance overall eye function. Herbal teas, like chamomile and calendula, help with hydration, benefiting DED. They may also have anti-inflammatory properties, helpful for conditions like Meibomian Gland Dysfunction (MGD) and DED.

Consumption of coffee and tea, particularly 2-3 cups of coffee and more than 4 cups of tea per day, is associated with increased macular retinal nerve fiber layer (mRNFL) thickness, suggesting potential neuroprotective effects that warrant further investigation into causal links and mechanisms.

However, high caffeine intake from teas like black or green tea can lead to dehydration and potentially increase intraocular pressure, a glaucoma risk. Caffeine can act as a diuretic, potentially causing fluid loss and increased urination. Caffeine-sensitive individuals should choose caffeine-free herbal teas or decaffeinated versions and maintain overall hydration.

A moderate dose of caffeine enhances rapid eye movements' kinematics, such as saccade velocities and quick phases of optokinetic nystagmus, in unfatigued individuals, without affecting pursuit eye movements or visual perception, suggesting that caffeine's influence on oculomotor control may be mediated by changes in central catecholamines even in non-fatigued conditions.

Teas may contain trace amounts of heavy metals, but high-quality teas in moderation usually don't pose a significant eye health risk. In summary, moderate tea consumption, especially green tea with its antioxidants, can benefit eye health, reducing AMD and cataract risk. Still, excessive caffeine-rich tea consumption should be avoided. Quality and toxin presence in tea should be monitored.

Alcohol

The effects of alcohol, including red wine, on eye health and associated conditions vary. While some compounds in red wine may have potential benefits for conditions like AMD, it's crucial to maintain moderation in alcohol consumption to reduce the risk of negative eye-related effects.

Alcohol intoxication, whether from binge drinking or moderate consumption, primarily affects the central nervous system and can lead to visual disturbances, including impaired color perception, decreased contrast sensitivity, and abnormal eye movements. It can also result in subclinical changes in eye movements, such as prolonged fixation latency and increased saccades.

Fetal Alcohol Syndrome (FAS) is associated with ocular findings that serve as markers for teratogenesis. Fully developed FAS cases often exhibit more pronounced ocular manifestations. Alcohol's impact on the eye involves transcription factors like Pax6 and Otx2, retinoic acid signaling, and oxidative and nitrogen signaling. Ocular abnormalities in FAS include various physical characteristics like short palpebral fissures, epicanthus, and microphthalmia, as well as optic disc hypoplasia and retinal vasculature tortuosity. Ocular examinations are crucial for diagnosing and managing eye conditions in FAS cases, and ion channel modulation is being explored as a potential treatment.

Alcohol consumption can have mixed effects on eye health. It's associated with an increased risk of AMD due to oxidative pathways and reduced intake of protective nutrients like Zn and vitamins. The relationship between alcohol and DR is still unclear, with some studies showing conflicting results. Alcohol consumption can also impact retinal vein occlusion (RVO), possibly through factors like hyperviscosity and dehydration. Central serous chorioretinopathy (CSCR) can be linked to alcohol consumption, affecting choroidal blood vessels. Chronic alcohol intake may lead to optic neuropathy characterized by central or cecocentral scotomas and color vision defects, which can be managed by reducing alcohol intake and providing vitamin supplementation.

Alcohol's relationship with glaucoma remains a topic of debate, with some studies suggesting an association and others hinting at a potential protective effect. Heavy alcohol consumption increases the risk of age-related cataracts, likely due to the generation of free radicals and disturbances in lens calcium levels. Alcohol can also affect the ocular surface, with some studies suggesting a link to DED and increased tear osmolarity, while others show contradictory results. A recent meta-analysis indicates that alcohol consumption can increase the risk of DED, possibly due to ethanol-induced inflammation in ocular surface cells. Chronic alcoholism can lead to vitamin A deficiency, contributing to keratinization and DED.

Additionally, alcohol, particularly red wine, can trigger ocular migraines, causing temporary vision disturbances. It is also a common trigger for rosacea flare-ups, a skin condition that can affect the eyes, leading to redness and irritation.

Choosing nutritional sources: natural supplements and healthy eating vs. multivitamins and minerals

Choosing between natural supplements and a balanced diet, or multivitamins and minerals, involves a trade-off between customization and convenience. Natural supplements and a balanced diet offer the advantage of targeting specific nutrients, minimizing additives, and enabling customization to individual nutritional needs, but they may require more planning and potentially cost more. In contrast, multivitamins and minerals provide a simplified, cost-effective means of obtaining a wide spectrum of essential nutrients but may deliver unnecessary elements and exhibit variability in quality.

Obtaining therapeutic levels of essential nutrients for eye health through a balanced diet can be challenging due to the need for large food quantities, which can have adverse effects from other components. For instance, achieving high doses of omega-3 fatty acids solely from fish could lead to excess mercury intake, so omega-3 supplements with controlled doses are a safer option. Similarly, for vitamin D, supplements can be more reliable than trying to get therapeutic levels through excessive sun exposure, which may increase the risk of skin damage.

The use of chemical compounds in medication doesn't imply an unnatural approach. Instead, it involves isolating the active substance in a precise dosage, which helps prevent side effects resulting from excessive consumption of other potentially unnecessary or toxic ingredients. Many pharmaceutical drugs have their origins in natural and herbal sources, and the utilization of chemical compounds in medications represents a focused and refined approach to harnessing their therapeutic properties. For instance, metformin, a widely prescribed medication for managing type 2 diabetes, finds its roots in the French lilac plant (Galega officinalis). It has been developed to help regulate blood glucose levels effectively. Atropine, derived from the deadly nightshade plant (Atropa belladonna), has been employed for its anticholinergic properties and is used in ophthalmology to dilate the pupil for various diagnostic and treatment purposes. These drugs exemplify how modern medicine can draw from the natural world while ensuring precise dosages and minimizing potential side effects associated with consuming the whole plant or herb. This approach combines the best of both worlds by integrating the benefits of herbal remedies with the rigor of pharmaceutical science.

Mediterranean diet

The Mediterranean diet (MD) is renowned for its substantial health benefits and environmental sustainability. It has consistently shown a strong association with increased longevity and a reduced risk of various age-related ailments, including cancer, dementia, and cardiovascular diseases. Although the precise definitions of the MD may exhibit slight variations, they all emphasize core elements: a generous consumption of plant-based foods such as vegetables, nuts, cereals, fruits, and legumes, with olive oil as the primary source of dietary fat. Additionally, the diet encourages moderate intake of dairy products, poultry, red wine, and fish, while discouraging the consumption of red meat and sweets. The combined impact of these dietary components, with their synergistic effects and interactions, is believed to underlie the MD's profound positive effects on eye health. The MD can help prevent chronic age-related eye diseases, including cataracts, glaucoma, AMD, DR, and DED.

More isn't always better: ocular manifestations of excessive intake of multivitamins and minerals

While multivitamin and mineral supplements are generally safe and provide vital nutrients that can promote overall well-being, including eye health, it's important to be cautious about excessive or prolonged consumption of certain vitamins and minerals in these supplements, which can potentially result in side effects affecting the eyes. For instance, consuming too much vitamin A can lead to a condition known as hypervitaminosis A, associated with intracranial hypertension and papilledema. Symptoms of vitamin A toxicity may encompass blurred vision and double vision (6th nerve palsy). Certain antioxidants like anthocyanins and xanthophylls have not shown adverse health effects, while others, such as β-carotene, must be consumed cautiously. Provitamin A carotenoids offer a safer alternative. Despite having provitamin A activity, the upper limit for β-carotene remains inconclusive. High doses of B-vitamin supplements have been linked to an elevated risk of cataracts. Excessive intake of vitamin E may increase the risk of bleeding disorders, which, while not directly impacting the eyes, can lead to increased eye bleeding following an injury. Similarly, excessive Zn intake can disrupt Cu absorption, potentially causing reduced Cu levels in the body. Cu is essential for the production of melanin in the eyes, which safeguards them from sunlight. A deficiency in Cu can result in light sensitivity and a heightened risk of eye damage from exposure to ultraviolet (UV) light. Moreover, excessive iron intake carries the potential for oxidative damage, with increased iron accumulation believed to contribute to AMD. Excess Cu levels may manifest in Wilson's disease (WD), characterized by Kayser-Fleischer rings, sunflower cataracts, disruptions in retinal function, and effects on visual systems and eye mobility. Among other vitamins, vitamin C has the lowest toxicity, although excessive consumption can impact gastrointestinal and renal function. While Se can offer benefits, chronic exposure can lead to toxicity, primarily affecting endocrine and neurological functions.

There is limited evidence to suggest that multivitamin use has a cancer-preventive effect, except for colon cancer, in both men and women participating in the NIH-AARP Diet and Health Study. However, in men, increased multivitamin use was associated with slightly higher risks of overall, prostate, and lung cancer, as well as leukemia. Additionally, women showed a higher risk of oropharyngeal cancer with greater multivitamin use. Establishing tolerable upper intake levels and recommended daily intakes for vitamins and minerals to safeguard against complications is necessitated.

Nutritional recommendations tailored for specific diseases

Nutritional recommendations serve as a potent tool for preventing and managing a range of eye diseases, ultimately contributing to the enhancement and preservation of one's vision. We have compiled prevalent nutritional and supplement guidelines for addressing different conditions that impact eye and vision health.

Age-Related Macular Degeneration (AMD)

Adherence to a Mediterranean diet has been linked to a reduced risk of AMD progression. In contrast, an Oriental diet pattern is associated with a lower prevalence of AMD, while a Western diet pattern is linked to a higher prevalence. Consuming a diet rich in vegetables with carotenoids and fatty fish containing omega-3 fatty acids can be beneficial for individuals at risk of AMD. On the other hand, it's advisable to minimize the consumption of vegetable oils and animal fats rich in omega-6 fatty acids, as well as red and processed meats, to lower the risk of AMD progression. High-glycemic index diets and excessive alcohol intake, exceeding two drinks per day, are also associated with an increased risk of AMD. It's essential to recognize that the quality of one's diet and food choices plays a pivotal role in AMD, highlighting the importance of providing appropriate nutritional advice to individuals at risk.

Prominent large clinical trials in eye health, primarily focused on AMD, include the Age-Related Eye Disease Study (AREDS) and its subsequent study, AREDS2, as well as the Nutritional AMD Treatment 2 (NAT2), and National Eye Institute (NEI)-supported AMD studies, collectively enhancing our knowledge of the influence of supplements, nutrients, vitamins, and minerals, notably in the context of AMD.

These supplements typically include antioxidants like vitamins C and E, Zn, and Cu, as well as the carotenoids lutein and zeaxanthin. The AREDS studies have shown that these supplements can slow the progression of AMD in some individuals and are often recommended as part of a comprehensive approach to managing the condition.

Cataracts

Cataracts can be influenced by factors such as metabolic diseases, nutrition, diet, and specific vitamins and minerals. The original AREDS formulation did not provide protective effects against cataract development, and beta-carotene has been associated with increased risks of lung cancer in smokers and hip fractures in women. Protective nutrients include antioxidants (like vitamin C, vitamin E, and Zn), found in foods such as citrus fruits and nuts, lutein and zeaxanthin in leafy greens, omega-3 fatty acids in fatty fish, and vitamin A sourced from carrots and sweet potatoes. Conversely, saturated and trans fats, excessive alcohol, high-sugar and high-glycemic-index foods, and metabolic diseases like diabetes and obesity can increase cataract risks, making proper management through diet, exercise, and medication vital for risk reduction.

Glaucoma

Several supplements exhibit potential in managing glaucoma. These compounds leverage various mechanisms, including antioxidant, anti-inflammatory, and anti-apoptotic properties. Baicalein, forskolin, marijuana, ginsenoside, resveratrol, and hesperidin have proven capable of reducing intraocular pressure. Ginkgo biloba, Lycium barbarum, Diospyros kaki, Tripterygium wilfordii, saffron, curcumin, caffeine, anthocyanin, CoQ10, and vitamins B3 and D have displayed neuroprotective effects on retinal ganglion cells. Omega-3 fatty acids found in fish oil supplements possess anti-inflammatory attributes, potentially improving ocular blood flow and decreasing intraocular pressure. Antioxidants like vitamin C protect the optic nerve, while vitamin E shields retinal ganglion cells from oxidative stress. Magnesium supplements aid in blood vessel relaxation and circulation, showing promise in preventing ganglion cell loss and serving as a potential candidate for glaucoma management. Additionally, extending citicoline treatment for up to 8 years has shown potential in stabilizing or enhancing glaucomatous visual function, hinting at citicoline's neuroprotective effects in glaucoma. Nevertheless, extensive future studies are needed to ascertain the efficacy and safety of natural products as alternative therapies for glaucoma.

Emerging research indicates that nicotinamide, a form of vitamin B3, shows promise in managing glaucoma. Nicotinamide's neuroprotective properties have gained attention for their potential to safeguard retinal ganglion cells and optic nerve function, both commonly compromised in glaucoma. By enhancing cellular energy production and reducing oxidative stress, nicotinamide may offer a valuable avenue for preserving vision in glaucoma patients, representing a novel and promising aspect of glaucoma therapy. It plays a role in regulating intraocular pressure in the eye through its potential complex interaction with nitric oxide, a crucial signaling molecule affecting blood vessel dilation. In the context of ocular health, nitric oxide can influence eye pressure regulation. Studies have suggested that niacin may enhance nitric oxide production, contributing to improved blood flow and a potential reduction in intraocular pressure. This suggests that nicotinamide may hold promise as a supplement for individuals with conditions like glaucoma, where elevated eye pressure can be a concern. However, further research is required to fully comprehend the mechanisms and therapeutic implications.

On the other hand, it's worth noting that high caffeine intake may lead to a slight increase in intraocular pressure (1-2 mmHg) in individuals with glaucoma, making it advisable to limit caffeine consumption. It's important to emphasize that, while these supplements hold promise, they should not replace conventional glaucoma treatments prescribed by healthcare professionals.

Diabetic Retinopathy (DR)

In addition to traditional treatments for diabetic patients, research is exploring the potential advantages of particular dietary approaches and supplements to prevent, manage, or delay the advancement of DR. Emphasis is placed on the use of antioxidants such as vitamins C and E, omega-3 fatty acids, and Zn. Furthermore, dietary plans like the Mediterranean diet and low-glycemic diets are being investigated and recommended as potential strategies in this context.

Dry Eye Disease (DED)

Nutrition plays a significant role in ocular surface health, particularly concerning dry eye syndrome. Several nutrients have protective effects on the ocular surface, such as omega-3 and omega-6 fatty acids for reducing inflammation, vitamin D for dry eye risk reduction and recovery enhancement, vitamin A supporting the corneal epithelium, vitamin B12, and citicoline improving ocular surface health, vitamin C protecting the eye's tear film, and vitamin E for oxidative stress reduction and corneal healing. Herbal teas like chamomile and calendula contribute to hydration and possess anti-inflammatory properties. Conversely, excessive caffeine and alcohol consumption can lead to dehydration and worsen dry eye symptoms, while high salt intake and excessive vitamin A supplementation can have adverse effects. Diets rich in saturated and trans fats are associated with a higher risk of dry eye syndrome, emphasizing the importance of a balanced diet for maintaining ocular surface health.

Meibomian gland dysfunction (MGD)

The well-being of meibomian glands, the small oil-producing glands in the eyelids, is crucial for maintaining a stable tear film and preventing dry eye syndrome. Although nutrition may not directly impact these glands, specific dietary habits and nutrients can indirectly benefit the meibomian glands. Omega-3 fatty acids can enhance meibomian gland function, while vitamin A supports the entire ocular surface, including the meibomian glands. Notably, vitamin A deficiency (VAD) is linked to chalazion in young children. Exposure to 13-cis retinoic acid (13-cis RA), a vitamin A metabolite, is one of the risk factors for meibomian gland dysfunction (MGD), although the precise mechanisms are not fully understood. It is hypothesized that 13-cis RA may hinder cell proliferation, promote cell death, alter gene and protein expressions, and diminish cell survival pathways in human meibomian gland epithelial cells. Additionally, oral vitamin D supplementation has been shown to enhance meibomian gland expressibility in MGD patients with vitamin D deficiency. While nutrition can contribute to meibomian gland health, it's worth noting that high-fat diets may harm meibomian gland function.

Superior limbic keratoconjunctivitis (SLK)

Using vitamin A eye drops has demonstrated moderate effectiveness in managing SLK. However, the role of systemic vitamin A and Se in the management of SLK remains uncertain and has not been established definitively.

Corneal stromal melt

For cases involving stromal melting that do not respond to standard treatment, including doxycycline and medroxyprogesterone, healthcare providers may recommend the use of NAC and a daily oral vitamin C (1,000 mg) supplement.

Thyroid Eye Disease (TED)

Selenium has been investigated for its potential role in managing TED. Multiple studies have indicated that Se supplementation could potentially benefit the condition, though the precise mechanisms remain incompletely understood. It is essential to avoid excessive iodine intake, commonly found in iodized salt and seaweed, as it can exacerbate thyroid disorders, including TED.

Idiopathic intracranial hypertension (IIH)

Obesity is a well-established risk factor in developed countries, and diets contributing to obesity may lead to nutritional deficiencies associated with the clinical symptoms of Idiopathic Intracranial Hypertension (IIH). Some vitamin A metabolite levels differ in IIH patients compared to obese individuals. Intracranial pressure (ICP) elevation and ON have been linked to the use of isotretinoin. Acetazolamide, a proven IIH therapy, appears to affect vitamin A metabolism. Limited data exists on dietary modifications for IIH treatment, but limiting vitamin A-rich foods like tomatoes, carrots, sweet potatoes, leafy greens, fish, and eggs may be beneficial. Patients with IIH or unexplained optic disc swelling should be screened, investigated, and treated for possible deficiencies in vitamins A, B1, and B12. Weight loss interventions for IIH should focus on improving nutrition alongside calorie restriction. Patients should also avoid tyramine-rich foods such as beer, wine, pickled items, aged cheeses, and meats.

Retinopathy of prematurity (ROP)

The use of vitamins, supplements, and nutrients in preventing ROP is a vital area of research. Vitamin A supplementation has been effective in reducing the risk of Type 1 ROP. Omega-3 fatty acids, lutein, zeaxanthin, resveratrol, quercetin, bilberry extract, and caffeine have shown potential benefits, possibly through anti-angiogenic, anti-inflammatory, and anti-oxidative mechanisms. However, more research is needed to clarify their mechanisms of action, safety for long-term use, means of delivery, and their effects on functional, neuronal, and behavioral outcomes in ROP infants. This approach may offer a non-invasive and natural way to complement existing treatments for ROP, but further investigation is necessary.

Retinitis pigmentosa (RP)

In the case of RP, it is advised to avoid vitamin E supplementation. Consideration of vitamin A supplementation should be guided by genetic testing, with caution, particularly for individuals with ABCA4 mutations, despite potential benefits for those with RHO1 gene mutations. Presently, the evidence, drawn from the results of three RCTs, does not strongly support the use of vitamin A, docosahexaenoic acid (from fish oil), or their combination in RP patients. These interventions did not significantly impact visual field, electroretinogram (ERG) amplitudes after one year, or visual acuity after five years of follow-up.

Given the limited applicability of the trials' exclusion criteria to many RP patients, it's unlikely that future trials will include such individuals. Therefore, it's crucial to carefully consider the findings from the reviewed trials in managing RP patients who meet these exclusion criteria. The potential systemic side effects or toxicity associated with long-term, high-dose vitamin A supplementation remain uncertain. Inherited retinal disorders, including RP, are aggravated by oxidative stress, making antioxidants like ALA and CoQ10 the focus of ongoing research for their potential benefits.

Stargardt disease

The inclusion of vitamin A supplementation in Stargardt disease might hasten the buildup of lipofuscin pigments within the RPE. However, current research on the effects of vitamin A in STGD1 lacks depth and consensus. The limited and inconclusive nature of existing data emphasizes the necessity for further investigations to reach a clearer understanding. Currently, advice to refrain from dietary vitamin A supplementation is mainly based on theoretical concerns. While animal studies suggest that replenishing vitamin A could potentially be a therapeutic avenue to hinder vision loss in STGD1, conducting additional clinical trials is crucial to confirm and validate these observations.

Cone-rod dystrophy

There isn't a targeted treatment for cone-rod dystrophy, but certain patients have received prescriptions for lutein, zeaxanthin, and omega-3 fatty acids. For broader support, employing general strategies like low vision aids and reducing exposure to phototoxicity, akin to those used for rod-cone dystrophies, should be taken into account as appropriate.

Gyrate atrophy (GA)

To manage GA, a successful method involves following a stringent diet that drastically reduces arginine intake. Supplementing with vitamin B6 (pyridoxine) can support this approach, potentially halting or slowing retinal degeneration, especially when started in childhood or at a young age.

Cystinosis

Individuals diagnosed with cystinosis might discover advantages in a treatment regimen incorporating both cysteamine and vitamin D supplementation.

Homocystinuria

Homocystinuria presents ectopia lentis as its main ocular feature, caused by altered fibrillin-1 properties due to homocysteinylation. This weakens zonules, leading to bilateral lens dislocation in most cases, prevalent from infancy to later years. Various ophthalmic studies highlight the importance of early diagnosis and control of the condition, as lens complications persist even with tight biochemical control. The ocular manifestations include myopia, high degrees of refractive errors, retinal degeneration, detachment, and secondary glaucoma. Treatment controversies exist, with a need for vigilant monitoring and often surgical intervention for persistent complications like lens dislocation and retinal issues. Treatment primarily involves pyridoxine supplementation, with doses ranging from 10-40 mg for pyridoxine-responsive patients and up to 200 mg/day for partially responsive cases. However, for pyridoxine-unresponsive patients, dietary restriction of methionine is suggested. Continual treatment throughout life is vital, as loss of biochemical control in later stages can lead to severe complications. Early diagnosis, typically confirmed through various tests including blood and genetic examinations, is crucial for initiating dietary modifications that can halt the progression of complications associated with homocystinuria.

Hypertyrosinemia

Eye symptoms include sensitivity to light and increased tear production due to pseudodendritic keratitis, induced by the accumulation of tyrosine crystals on the cornea. Managing hypertyrosinemia requires dietary restrictions on tyrosine and phenylalanine intake. These restrictions can help alleviate the severity of corneal and systemic changes, including cognitive impairment. It is crucial to maintain phenylalanine levels within the normal range. Some patients may also benefit from vitamin C supplementation.

Alkaptonuria

Bilateral bluish-dark scleral lesions present in the interpalpebral areas, located near the nasal and temporal perilimbal regions close to the rectus muscle insertion (known as Osler's sign). Additionally, there are "oil drop-like" spots observed in the cornea at the level of Bowman's membrane, which may advance with time. Vitamin C is utilized in managing the arthropathy linked to Alkaptonuria. However, clinical studies on its effectiveness in reducing pigmentation have yielded inconclusive results.

Fabry disease

The primary treatment for ocular symptoms arising from Fabry disease, caused by alpha-galactosidase A deficiency, involves using agalsidase alpha or beta (Fabrazyme). This approach effectively alleviates conditions such as cornea verticillata, conjunctival aneurysms, periorbital edema, posterior subcapsular cataracts, retinal vessel tortuosity, neuropathic pain, and angiokeratomas. Additionally, Beano, a dietary supplement containing alpha-galactosidase-A, can relieve gas, bloating, and discomfort caused by gas-producing foods while also addressing the deficiency associated with Fabry disease.

Bassen-Kornzweig syndrome (abetalipoproteinemia)

The ocular presentation varies: at times, it manifests as diffuse or sporadic pigmentary alterations termed atypical retinitis pigmentosa. Alternatively, it may resemble retinitis punctata albescens, displaying perivascular white spots across the peripheral retina. Those diagnosed with Bassen-Kornzweig syndrome (abetalipoproteinemia) are recommended to adhere to a regimen incorporating vitamin supplementation (A, D, E, K) and uphold a low-fat diet.

Refsum disease

Individuals with Refsum disease benefit from a low phytanic acid diet, crucial in slowing down its progression. It's vital to address vitamin D deficiency through dietary means. A decade-long observation showed stability in cardiac, pulmonary, and renal symptoms, while visual and auditory impairments persisted during this period.

Lowe syndrome (oculocerebral syndrome)

In Lowe syndrome, a rare condition marked by congenital and disciform cataracts, hypotonia, high intraocular pressure, acidosis, and developmental delay among other symptoms and signs, managing vitamin D deficiency is a crucial aspect of comprehensive care.

Leber’s hereditary optic neuropathy (LHON)

Individuals with LHON may benefit from supplementation with vitamin C, vitamin E, and vitamin B12. In approximately half of the cases, idebenone, a synthetic variant of CoQ10, has demonstrated effectiveness. Research is ongoing to explore the potential of strategies such as CoQ10 and citicoline in promoting optic nerve health.

Squamous Cell Carcinoma (SCC)

Vitamin A and carotenoid consumption are linked to a lower risk of cutaneous squamous cell carcinoma, suggesting a protective role against its development.

Ocular surface squamous neoplasia (OSSN)

Retinoic acid, either alone or combined with IFNα-2b, has been used in treating ocular surface squamous neoplasia (OSSN). However, as most studies used it alongside IFNα-2b, assessing retinoic acid's independent impact on OSSN remains challenging.

Melanoma

The rising incidence of melanoma, despite sun protection measures, prompts an exploration of dietary factors in melanoma development. Various nutrients, including caffeine, vitamins A, D, C, and E, polyunsaturated fatty acids, and flavonoids, are studied for their associations with melanoma risk. While caffeine displays promise in protecting against melanoma, inconsistencies in research findings for other nutrients may result from differences between animal and human studies and variations in nutrient intake definitions, necessitating further investigation into their effects on melanoma progression and treatment. Additionally, the significance of antioxidant-rich foods, vitamin D, omega-3 fatty acids, beta-carotene, and lycopene in supporting skin health and potentially safeguarding against UV radiation is highlighted.

Resveratrol, a natural polyphenol found in various sources like grapes, exhibits anticancer effects by inducing apoptosis in cancer cells and supporting immune surveillance. It has also shown promise in protecting the skin from sun damage. However, its bioavailability remains a challenge. Vitamin A and vitamin A-like compounds have demonstrated potential in inhibiting melanoma development and influencing melanoma cell behaviors. Vitamin C, acting as both an antioxidant and pro-oxidant, impacts immune homeostasis and exhibits anti-melanoma properties. Vitamin E and its various forms have shown photo-protective and anti-oxidative properties in animal studies, but the epidemiological evidence is less clear. Vitamin D's role in melanoma prevention is complex, with potential anti-proliferative effects on melanoma cells. Flavonoids, a group of polyphenolic compounds found in vegetables, have been studied for their antioxidant, anti-inflammatory, and anti-proliferative properties, with potential benefits in melanoma prevention and treatment. Dietary lipids, such as omega-3 polyunsaturated fatty acids, may affect melanoma risk, with PCB exposure showing a potential association with melanoma risk. Further research is needed to better understand the impact of these dietary compounds in melanoma prevention and treatment.

In the context of adjuvant therapy for choroidal melanoma, melatonin, a hormone that regulates sleep-wake cycles, has shown potential. Melatonin, primarily produced by the body, can also be found in various foods. Consuming melatonin-rich foods has been linked to a notable rise in melatonin levels in the bloodstream. Some studies suggest that melatonin when used alongside traditional treatments, may help slow the progression of choroidal melanoma by inhibiting tumor growth. This hormone's antioxidant properties and ability to modulate the immune system make it an interesting candidate for further investigation in the context of choroidal melanoma treatment. However, more research is needed to establish its effectiveness and safety as an adjuvant therapy for this specific type of melanoma.

Retinoblastoma

There's uncertain evidence linking retinoblastoma development to insufficient folic acid utilization during a crucial stage in tumor formation. Conflicting data exist regarding the role of folic acid in this context.

Refractive surgery

Previously, FDA guidelines regarded isotretinoin as a contraindication for LASIK and PRK refractive surgery. Recent findings propose a reconsideration of these guidelines. To potentially decrease haze post-PRK, a regimen of oral vitamin C at 1000 mg/day for one week before and two weeks after surgery, coupled with avoiding UV exposure, may be beneficial.

Plastic surgery

Nutrition plays a critical role in wound healing, with proper dietary supplements essential for preventing complications and expediting the healing process, particularly for surgical patients. Malnutrition can lead to surgical complications, infection, and reduced wound healing. A balanced pre-surgery diet with high protein content, plenty of water, and specific vitamins and amino acids can enhance wound healing and immune function. Adequate protein intake, including lean meats, poultry, fish, eggs, legumes, and tofu, is crucial for tissue repair. Balanced amino acid ratios ( like arginine, glutamine, and glycine ) are necessary for healthy skin and collagen production. Omega-3 fatty acids support wound healing by reducing inflammation. Vitamins (A, C, E) and minerals (Zn, iron, Cu, Mg) promote collagen synthesis and skin health. Vitamin K-rich foods, such as leafy greens, support healthy blood clotting, an important consideration in plastic surgery. Certain foods and supplements like garlic, ginger, Ginkgo biloba, turmeric, high-dose omega-3 fatty acids, high-dose vitamin E, and excessive alcohol should be avoided before surgery due to their anticoagulant effects. Prior to surgery, it's advisable to undergo preoperative nutritional assessments to achieve optimal outcomes. Consulting a dietitian is recommended, particularly for patients with systemic illnesses, to ensure they receive the best nutritional support. Although ocular surgeries are typically categorized as minor and have been excluded from previous studies examining the correlation between malnutrition and postoperative complications in hospitalized surgical patients.

Nutritional guidelines are lacking

A holistic approach to eye and visual health includes nutritional guidelines. Nutritional guidelines hold the potential to alleviate the economic burden on eye healthcare in an aging population by serving as preventive measures, slowing disease progression, reducing comorbidities, preventing falls and injuries, enhancing quality of life, promoting early detection, and lessening the economic impact through workforce productivity preservation in inherited diseases and caregiving reduction. Currently, there is no national or international guideline focusing on promoting eye health at the population level.

Nutritional guides help prevent a wide range of eye health issues. For patients with pre-existing eye conditions, dietary adjustments can be crucial. Patients with diabetes, for example, need to monitor their carbohydrate intake. Patients with moderate to advanced AMD may need supplementation. Nutrition plays a significant role in the healing process in post-refractive surgeries or after chemical burns. Certain foods can interact with medications or coagulation.

Delivering well-balanced nutritional guidance to patients, ideally substantiated by robust evidence from randomized clinical trials, poses challenges. These trials necessitate extended monitoring to evaluate gradual impacts and need controlling variables rooted in participants' diverse dietary habits. Ethical considerations may hinder randomized trials that require some participants to follow potentially unhealthy diets for comparative purposes. The inconsistencies in adherence, blinding complications, and resource-intensive demands further add complexity to the research. Consequently, researchers often turn to observational data, which, although informative, falls short of establishing causation as effectively as clinical trials, leading to a role for epidemiological studies in providing some evidence of effectiveness. Further clinical trials are needed to define specific recommendations for intake and supplementation

For patients with AMD, it is advisable to increase the consumption of green leafy vegetables and fatty fish, at least twice a week. A Mediterranean diet can offer additional benefits beyond AMD. Patients with moderate or advanced AMD should consider using AREDS-based supplements, but those who are current or ex-smokers should avoid formulations with beta-carotene. If patients are unsure of their dietary lutein intake, they can use lutein/zeaxanthin AREDS-based supplements, as they have shown minimal side effects in most trials. Those with a normal or high dietary lutein intake can opt for the modified beta-carotene-free AREDS formulation. These dietary changes can potentially delay the onset and slow the progression of AMD, although supplementation does not prevent its development. Such a nutritional intervention may help reduce the prevalence of early-stage AMD, decrease the incidence of advanced AMD, and ultimately lessen the associated healthcare burden.

There is growing interest in the role of neuroprotective treatments in managing glaucoma, and several clinical trials are underway to investigate their potential benefits. These trials, including the Glaucoma Nicotinamide Trial, Nicotinamide riboside as a neuroprotective therapy for glaucoma, Nicotinamide in Glaucoma Trial, and Targeting Metabolic Insufficiency in Glaucoma Trial, aim to evaluate various aspects of glaucoma management and neuroprotection in patients with primary open-angle glaucoma (POAG) and related conditions. It's important to note that participants in these trials will continue to receive their regular intraocular pressure-lowering glaucoma medications alongside these investigational interventions.

Besides tracking the results of RCTs and anticipating the release of national and international guidelines, eye care practitioners can utilize current knowledge. They can contribute to patient education and promote healthy dietary choices by displaying an instructive "M'eyeDiet" chart alongside traditional eye charts in various healthcare and public settings. This visual resource serves as a daily nutrient intake reference and enhances awareness of the relationship between nutrition and eye health, serving as a population-level educational tool.

In a world where one in seven people faces hunger, it's important to recognize the financial obstacles involved in accessing healthy diets like the Mediterranean diet and eye supplements, even though they offer potential benefits for ocular health. The increased cost of these dietary patterns and supplements creates barriers for individuals with limited incomes, which could impede their ability to afford and maintain these beneficial dietary practices, potentially affecting their overall eye health.

Conclusions

The increasing burden of eye care in an aging global population calls for innovative preventive and adjunctive therapies, with vitamins and supplements being convenient and well-received by patients. Extensive research has emphasized the connection between nutrition and the management, prevention, and deceleration of age-related eye conditions, although the intricate nature of nutrition's impact on ocular health leads to variations in individual responses, further complicated by genetic diversity. While conducting large-scale studies, particularly RCTs, is challenging, prioritizing epidemiological research is a promising initial step. The importance of addressing oxidative stress, exploring antioxidants, and lipids' role in visual health, maintaining balanced hydration, and moderating indulgent substance consumption remains significant.

For the general population, adopting natural dietary sources and healthy eating habits is advised, with the Mediterranean diet showing promise. In cases of disease, supplementation may be considered, but appropriate dosages require further investigation, mindful of potential risks associated with excessive multivitamins and mineral intake, especially regarding cancer risk. Consultation with a dietitian is recommended for individuals with systemic illnesses.

As our understanding of how nutrients influence ocular health is in its early stages, further epidemiological studies, genetic assessments, breast milk composition analysis, and biochemical assessments of retinas and choroids are crucial for uncovering relationships between dietary patterns, nutrients, and their impact on various eye conditions. Phytochemicals and plant-based compounds play a significant role in promoting eye health. Large-scale RCTs are pivotal for evaluating the clinical implications of findings from epidemiological, in vitro, and in vivo research. National and international nutritional guidelines concerning eye health, have yet to be published.