For a growing number of people, experiencing the deterioration of eyesight, or more extreme loss of vision can be frightening and overwhelming. The loss of vision in its later stages is a detriment to one’s independence and quality of life, and as more recent research shows, to areas of health beyond the visual system, such as mental health, cognition, and social function.

According to a simulation model created by the U.S. Centers for Disease Control and Prevention (CDC) and Research Triangle Institute (RTI), the combined economic costs from disability, loss of productivity, and comorbidities associated with the sum of age-related macular degeneration (AMD), glaucoma, cataracts, and diabetic retinopathy is roughly $51.4 billion lost annually, in addition to the many costs that one can’t put a dollar value on.

In addition to the many other measures we can take to protect our eyes in the long run, such as wearing sunglasses on bright days, avoiding risky behaviors such as smoking, maintaining a normal blood pressure, and keeping up a good diet, there are a number of specialty nutrients and non-nutritive ingredients supported by compelling evidence to help protect vision. 

Even beyond avoiding metabolic issues such as type 2 diabetes, hypertension, and inflammation, all of which are associated with potential vision loss, many ingredients are heavily concentrated in the eye and are shown to protect the structure and function of it.

While, conventionally, the consumer base for eye health products has been U.S. adults reaching their greying years at about 55 and older, evidence is mounting that promoting the structural integrity of one’s eyes is all about prevention; for most conditions, damage can be impossible to reverse and difficult to bring to a halt. For these reasons, the consumer base for eye health ingredients is skewing toward younger, more proactive demographics. Some ingredients with a primary function of preserving eye health are becoming more commonplace in everyday supplements. Further, the newer generation of consumers is more likely to skew toward natural products than older generations, and is more likely to be open to the concept of ingestible eye care products than older cohorts, according to Golan Raz, head of the global health division at Lycored, makers of the lycopene and lutein formula Lyc-O-InVision.

The leading supplement ingredients most likely to be used in an eye health formula are lutein and zeaxanthin, flavonoids, antioxidants, and omega-3 fatty acids, and a number of vitamins and minerals, though there are some ingredients currently seeing early clinical substantiation regarding their role in preserving vision. Compared to portfolios associated with other health benefits supplement companies pursue, however, the selection of nutrients well-qualified by research to assist in slowing down the progression of vision loss is comparatively set-in-place. There still remains plenty of motivation for researchers and developers to find ways to optimize the activity and availability of the ingredients used, and to seek out new clinical endpoints and benefits for a broader demographic range.

Natural Marketing Institute (NMI), a market researcher specializing in dietary supplements, broke down some of the needs and aspirations associated with the target consumers for eye health supplements. According to NMI’s research, one fifth of global consumers surveyed are managing some type of eye health or vision issue, with thrice as many consumers saying they are concerned about preventing vision issues in the future. Despite this, lutein and zeaxanthin, two of the most efficacious ingredients in the eye health space, are only used by a sliver of the overall supplement user population.

With a growing number of factors contributing to declines in population-wide eye health, the current eye health supplements market is valued somewhere between $1.5 and $2.5 billion, according to market research firms (depending on inclusion criteria), and is slated to grow at a CAGR of well over 6% over the next five years by most projections.

One leading driver for product growth within this category, according to Market Study Report, will be cost, as eye health supplements tend to be fairly expensive in comparison to some other categories. Additionally, the company cited that, alongside the growing prevalence of eye diseases, a rising number of ophthalmologists choosing to adopt these products into their eye care recommendations is fueling both the sales growth and perceived validity of nutritional products for the eyes.

On the product formulation front, success is driven by incorporating multiple ingredients into one product. Scientific evidence overwhelmingly supports that antioxidants, plant-based compounds, omega-3s, and other ingredients have an entourage effect better able to protect the many sensitive components of the eye than one standalone ingredient.

Because eye health issues and risks are often closely intertwined, Sevanti Mehta, president of Unibar, said that companies should pursue an ingredient or formula which checks many boxes.
“Supplement developers should be aiming to create a product that delivers holistic benefits,” he said. This means looking for an ingredient that not only protects the eye from blue light and increases macular pigmentation, but that should also optimize the levels of intraocular pressure and thereby reduce the risk of irreparable damage. Additional benefits to look for would be an ingredient that has positive effects against eye fatigue, inflammation, and dry eyes that occur from increased screen time.”

Market research dictates that consumers tend to seek more conventional delivery formulas for their eye care nutrients, such as liquids, softgels, powders, capsules, and tablets, rather than more innovative vehicles that veer into the functional foods and beverages category, Market Study Report said.

Blue Light
According to NMI, the amount of blue light-emitting device users worldwide is slated to reach 5 billion people. Light on this end of the spectrum, along with some invisible light rays including ultraviolet, can induce eye strain and fatigue, or in extreme exposures such as snow-blindness, cause something resembling a sunburn on the cornea.

While the eye is extremely effective at protecting the retina from UV light (though only sunglasses with 100% UV protection can prevent the type of damage that leads to cataracts), it is extremely inefficient at blocking blue light, causing oxidation throughout the most sensitive areas of the eye such as the retina, where the greatest concentration of photoreceptor cells exists. Blue light tends to cause more damage to eyes than other colors because it travels at shorter and smaller wavelengths, which causes it to scatter more than any other color as it reflects off of surfaces, including those beyond the cornea.

“When UV and HEV [high-energy visible radiation] penetrate the eye, a chain of reactions is set off,” said Raz. “Oxidants, such as free radicals and other reactive oxygen species, are formed, causing damage to cells in the eye. Most retinal diseases, including AMD, are mediated by inflammatory reactions, and oxidative stress is known to contribute to the inflammatory pathogenesis. An inverse relationship exists between the incidence of AMD and the amount of macular pigments, like lutein, in the macula.”

Raz said that other concerns involved in preventing eye damage can include work-related conditions, such as long-term exposure to white fluorescent light bulbs still common in office settings, or simply overworking, in addition to poor diet.

Certain nutrients with potent antioxidant properties are especially concentrated in the eye, and are more likely to cross the blood-eye barrier, a wealth of research shows. Not only do certain nutrients most prevalent in plant-based food sources mitigate the oxidative damage that may occur within the eye, but it is theorized that they physically act as a filter to block damaging rays from reaching the retina and its central region, the macula.

To the detriment of our vision, even on cloudy days and during the night, we willingly stare at sources of blue light for hours on end, on TVs, smart phones, computers, and virtually anything with a screen. The LED back-light technology used in today’s screens, which offers enhanced brightness and clearer images, packs an even bigger blue-light punch. Each year, the average American consumer spends consecutively more time in front of a screen than before. While natural blue light throughout the day helps to regulate circadian rhythm, memory, and cognitive function, unhealthy exposure to blue light (especially at night) is also associated with sleep deprivation, mood disorders such as depression, a condition known as digital eyestrain syndrome, and even greater risks of metabolic disorders.

Growing scientific evidence supports the idea that blue light damage prevention should be something to keep in mind beginning at an early age. While anatomical development of the eye is complete by age 4, visual development continues until 14 years of age, and until adulthood, the lens is more transparent than that of adults. Additionally, many of these blue-light related nutrients may have a role in cognitive function and development, a link highlighted by studies on children and adolescents.

“This means that the eyes of infants and children are more susceptible to oxidative damage by pass-through light that would otherwise be filtered by macular pigment,” said Brian Appell, customer marketing director of OmniActive Health Technologies. “There is growing evidence that macular pigment optical density (MPOD) can be used as a relevant biomarker of lutein levels in the brain. Increasing MPOD is correlated with better cognitive function, suggesting the positive role of macular carotenoids in cognition. Indeed, in children 4 to 13 years there is a positive correlation between MPOD and several aspects of cognitive performance. In young adults, increased MPOD is related to faster visual processing speed.”

Appell pointed to the BLUE (Blue Light User Exposure) Study, which was the first to demonstrate the supportive role that macular carotenoids play in supporting visual function and reducing symptoms such as sleep quality, eye strain, fatigue, and headache frequency. A six-month study in which young, healthy subjects supplemented daily with Lutemax 2020, showed that the blend of macular carotenoids improved subjects’ MPOD, the aforementioned symptoms, and visual performance indicators such as contrast sensitivity, disability glare, photo-stress recovery, and visual processing speed, all improved significantly.

The From-Home Era
COVID-19 is clearly exacerbating the tolls that blue light takes on our vision, even as media consumption reached an all-time high in 2019. Across all age groups, market research company Nielsen suggested that screen time since the onset of the pandemic has increased by 60% from February to March and has remained largely unchanged, meaning that the average American spends 13 hours per day staring at a TV, phone, tablet, computer, or some other kind of Internet-connected device. Nielsen reported that the uptick in screen time is similar to that which has been observed during other crisis events such as blizzards, hurricanes and more.

“While vision products have typically targeted ‘aging eyes’ and the resulting ailments, the year 2020 and the COVID-19 pandemic has upended the typical lifestyle for many people—adults, teens, and children alike,” said Melanie Bush, director of science for Artemis International. “As a result, time spent staring at screens has dramatically increased, making ‘eye fatigue’ a significant issue for people of all ages […] the dry, weary eyes are only the start of it, as related issues of headaches, blurry vision, and even neck and shoulder stiffness are also common symptoms of excessive eye strain. There are also ramifications on attention span among children and the ability to focus and concentrate. The potential long-term effects are still not clearly defined, but chronic stress—in any form—is not good for overall health.”

When analyzing the impact in children, the results are especially jarring. According to ParentsTogether, a non-profit which conducts reporting and commentary on children’s issues, screen time is up by a whopping 500% in some American children ages 18 or younger, as school transitions to a virtual setting rather than in-person learning and the confinement induced by social distancing causes children to substitute time normally spent engaged in healthy play with media consumption. ParentsTogether reported 85% of parents are worried about the increase in the amount of time their kids spend online. Meanwhile, the World Health Organization recommends that parents limit sedentary screen time for young children to one hour as a means of preventing myopia (nearsightedness) later in life.

Additionally, “a study from Global Myopia Awareness Coalition (GMAC) showed that children’s screen time has doubled since before the pandemic, and most parents agree it is harmful to their eyes,” said Appell. “Working and schooling from home, entertainment, and staying socially connected is increasing user rates faster than ever before. Post-COVID, these trends are expected to transform into lasting behaviors.”

Beyond the serious health consequences of remaining sedentary and in front of a screen, a review published in the American Journal of Ophthalmology projected that the increased digital device usage will cause a surge in cases of myopia years down the line, a serious collateral impact that comes as a result of tech-enabled virtual learning.

Many in the eye nutrition space believe that, even prior to the pandemic, the attention given to digital screen usage, especially in children, was scarce, and now emphasize through research, product development, and forms of outreach and advertising that taking care to preserve one’s vision is a requisite in the digital environment in which society now functions.

“It’s always better to reduce the risk of damage than to try to reverse it,” said Raz. “So in the same way we can balance the effects of environmental factors on our skin through ingestible skin care, we should be looking to nourish our eyes and support their ability to cope with oxidative damage.”

The constantly growing dependence on digital devices will likely cause a whole host of endemic health conditions later down the line, though, warned Julia Diaz, head of marketing for Pharmactive, whose products are distributed by Gencor. 

“Excessive screen time can significantly limit a child’s opportunity to experience the distinctive day-to-day activities, which can cause narrowing of their general interests regarding off-screen matters. In other words, a child who is extensively exposed to the virtual world on screens generally spares less time for playing, exercising, or interacting with friends and family in real life, which in turn, results in issues related to the eyes.”

Another clear demographic that needs to be targeted to maintain eye health is those who play video games, a media form which surged in popularity as a COVID-safe means of both entertainment and socializing, said Mehta. Excessive gaming is a surefire way to develop myopia, especially when using high blue light-emitting monitors for lengthy sessions, opening up the gate for a host of even worse conditions later down the line.

“Nutraceuticals can provide both protection from excessive digital screen time and enhancement to a gamer’s ability to see and react,” he said. “There is also great potential with millennials because many of them are looking to be proactive and take better care of their health now, so that they have less to worry about in the long run. By offering holistic eye health solutions they can get the best of both worlds by improving eye performance and attaining long-term care for their vision.”

“Americans already spent large amounts of time before the pandemic in front of digital screens, and this drastic increase is posing a serious health risk,” he added. “High myopia can be linked to an increased risk of various progressive eye disorders such as cataract, glaucoma, and age-related macular degeneration.” Children should also be wary of dry eye syndrome, inflammation, and eye fatigue, he said.

The combined increases of stress and screen time associated with the COVID pandemic may also be attributable to increased rates of high intra-ocular pressure, another physiological condition known to cause vision problems. “Without regular visits to an optometrist, heightened intraocular pressure can often go unnoticed until it is too late,” Mehta said. “Fear and agony of the COVID-19 pandemic is also leading to more stress, which affects the facial muscles, the extraocular and orbital eye muscles, and increases the production of aqueous fluid inside the eye, which has been shown to cause increases of IOP.”

Macular Mainstays
Two clinical trials, AREDS (Age-Related Eye Disease Study) and AREDS 2, which were sponsored by the National Eye Institute (NEI), were defining clinical trials for the eye health category, considered doctrines to follow for those seeking to create more conventional eye health formulations. In fact, the multi-ingredient formula used in the trial is sought after for its exact specifications, largely because of how significantly long-term supplementation reduced age-related macular degeneration among a sizeable portion of individuals.

AREDS, a trial with an average duration of 6.3 years for thousands of participants, found that a cocktail of antioxidants including vitamins C and E, beta-carotene (a form of vitamin A), zinc, and copper was able to reduce the average risk of age-related macular degeneration progressing to its advanced stages by 25%. AREDS 2, a five-year study which tested the original AREDS formulation with the addition of omega-3s, and the carotenoids lutein and zeaxanthin, didn’t find any differences in the level of protection compared to the AREDS formula. However, those who substituted beta-carotene for lutein and zeaxanthin still experienced the same level of protection against advanced AMD as the original formula, suggesting that these nutrients still play a role and, for the purposes of protecting against advanced AMD, can be substituted for beta-carotene. This substitution is important to keep in mind for consumers who smoke, as NEI found that high levels of beta-carotene increased smokers’ risks of developing cancer.

These trials set optimized parameters for a multitude of ingredients when it comes to eye health. They also established age-related macular degeneration as the key target for formulators, which continues to lead the pack of issues for which prevention is sought out, along with inflammation, dry eye syndrome, cataracts, and more. Nonetheless, preliminary trials targeting other ocular issues such as glaucoma, diabetic retinopathy, and others are on the rise as the eye health market continues to grow in interest.

Lutein and zeaxanthin have perhaps the most fleshed-out scientific understanding when it comes to their protective mechanisms. In addition to acting as a filter for blue light, the most damaging frequency, as pigments themselves they also increase the levels of pigmentation within the center of the retina in an effect that prevents retinal cells from being damaged.

Of the omega-3s, DHA is more predominantly associated with the eye health category. Making up about 30% of brain matter, in vitro and in vivo studies show that this compound is crucial to the development of the eye and ocular nerve. One clinical trial showed that DHA significantly reduces the buildup of a toxic molecule called A2E which accumulates in the back of the eye over time, leading to retinal cell death, including macular degeneration, one Harvard Medical School study found.

While the evidence is still mixed, some clinical studies also suggest that DHA may play a role in preventing dry eyes because of its propensity to reduce inflammation. The clear challenge for omega-3s in the eye health market appears to be getting them to cross the blood-brain barrier. Aker BioMarine, for example, is seeking collaborators for research into combining EPA and DHA with a compound called LPC, which was recently identified in a breakthrough study to be the primary transporter of DHA across the blood-brain barrier, a promising sign that a solution to the bioavailability problem is possible.

Newer Contenders
More recently, clinical research efforts have been inclined to demonstrate that the AREDS formula is a good summation of primary prevention-based eye care nutrients, but that there’s much more to this nutritional category as well for more performance-based benefits. While managing blue light damage is largely preventative, there are a number of short-term physiological stressors on the eyes, such as oxidative and endoplasmic reticulum stress.

“Eye health has essentially been predominated by AREDS formulas because it has been a category for consumers managing age-related vision problems—a market for prevention,” said Appell. “But that is shifting as more science and circumstances highlight the importance of ingredients like lutein and zeaxanthin isomers (RR-zeaxanthin and meso-zeaxanthin) play in vision health. The science shows they are not only important for prevention but also performance—how our eyes adapt to help us view and navigate our world daily.”

For these reasons, OmniActive formulated Lutemax 2020, which incorporates a more complete picture of macular carotenoids (all of the carotenoids actually found in the eye), containing lutein with zeaxanthin isomers in a balanced 5:1 ratio after seeing “greater emphasis on the role certain nutrients like lutein and the macular carotenoids play during the critical stages of development and growth. So even though nutrients like lutein and zeaxanthin isomers originally found their footing among the older demographics, their role has evolved to meet the modern needs of younger demographics who are experiencing issues related to digital device use and looking to optimize the health and development of their children,” Appell said.

He also pointed to a number of carotenoids typically understood for their role in eye health, noting that these carotenoids are also the most abundant in the developing brain. “It is important to note that these carotenoids are concentrated in areas of active learning and development. As such, these regions of the brain are susceptible to oxidative stress and damage,” Appell said.

Astaxanthin, another carotenoid that causes a reddish color in several types of seafood, is one of the most potent antioxidants in its class. While other antioxidants supporting eye health tend to function as a filter in the macula to protect against light damage, astaxanthin appears to be most concentrated within the muscles of the eye. Early clinical studies suggest that astaxanthin functions by removing free radicals from the working eye muscles, which could improve dynamic focus and close-up vision, and potentially reduce symptoms of eye strain. Other studies show that this antioxidant could potentially increase blood flow to the eye, which could dampen the effects of ocular aging on both the eye and the optic nerve.

Capsanthin, a carotenoid responsible for the reddish hue in hot peppers, is also revealing itself in preliminary clinical trials to have broad-ranging benefits in ocular protection. Unibar, the maker of a capsanthin-based eye health ingredient called CapsiClear, has been conducting clinical trials over roughly eight years, substantiating a number of eye health benefits that extend past those offered by the competing lutein; in addition to increasing blue light protection and having a mechanism which increases the density of macular pigments, Unibar’s research suggests that capsanthin could protect against white light damage, improve recoveries from eye strain and fatigue, and reduce intraocular pressure. “Though AMD and blue light are important, so are serious emerging issues such as eye fatigue and IOP. There needs to be a shift in focus to include eye fatigue and IOP as vital parts of proper eye care,” Mehta said.

Saffron, too, contains certain antioxidants that have piqued the interest of eye health formulators, including Pharmactive/Gencor, which launched AffronEye, a saffron-sourced eye health ingredient standardized to 3% crocins. In addition to evidence supporting its role in mitigating symptoms of AMD, including retinal flicker sensitivity, the ingredient also appears to preserve the retina’s photoreceptor function, and can reach maximum blood concentration after only 1.5 hours, a mere fraction of the time it takes for traditional carotenoids, according to the companies. In addition to possessing antioxidant and anti-inflammatory properties in the eye, the crocin content in the ingredient was also antiapoptotic. “AffronEye increased oxygen available to the photoreceptors, which have high metabolic demands, and thus protect them from death,” Diaz said, pointing to a study published in the International Journal of Molecular Sciences (August 2019).

Vitamin E has long been regarded as a vital nutrient to supporting eye health, since it was prominently featured in the formula used in the AREDS trials. However, some research placing special emphasis on the tocotrienols faction of the broader vitamin E family suggest that this branch of the vitamin E category is more vital to the eyes than the alpha-tocopherol used in AREDS. One in vitro trial, for example, showed that a tocotrienol complex was significant in reducing the severity of diabetic retinopathy, now the leading cause of blindness in individuals between the ages of 20 and 64, in diabetes-induced rats. The trial also found that tocotrienol supplementation significantly reduced vascular endothelial growth factor, one of the most important pathological features of diabetic retinopathy.

Some nutritional ingredients can play a just-as-important role in ensuring the bioavailability of other eye health ingredients, as evidenced by research on a number of compounds believed to have a synergistic or complementary relationship with more mainstay ingredients featured in trials such as AREDS. Lycored’s eye health formula, Lyc-O-InVision, for example, blends lutein with lycopene, a phytochemical present in tomatoes and other red fruits. Clinical evidence suggests that lutein is transported more effectively to the eye without oxidizing in the presence of lycopene. Carnosic acid in the formula is also believed to allow the ingredient to penetrate the blood-brain barrier more effectively, and increase antioxidant defense mechanisms in the eye. Combined, these mechanisms increase retinal capillary bloodflow, another biomarker of healthy vision.

Botanicals with strong antioxidant capacity are now being studied for potential benefits in the area of eye fatigue, according to Bush.

“Bilberry has long been considered for its vision support benefits, largely passed down from anecdotal usage,” she said. “Another berry ingredient that has been generating some buzz in this area is blackcurrant, with its unique anthocyanin profile tied to its antioxidant capacity and other health benefits. Current clinical studies are underway to further explore this specific tie to vision fatigue and carve out blackcurrant as the vision ingredient to seek out for anyone suffering from screen-weary eyes.”

Bush cited a preliminary study (Alternative Medicine Review, 2000) which opened the working hypothesis that anthocyanins in particular are especially helpful in a dose-dependent manner with many of the visual stressors related to the ongoing lifestyle changes, including dark adaptation, video display terminal, work-induced transient refractive alteration, and subjective visual fatigue symptoms including eye and back strain. Additionally, participants saw fewer reductions in their performance on a refraction test typically used in eye exams when supplementing with blackcurrant, in a dose-dependent manner, while the placebo group experienced significant reductions in refraction test scores, to a level of borderline significance. “A current human clinical trial is underway to corroborate these findings and to demonstrate this unique angle of vision support from berry nutraceutical ingredients,” Bush said.

Looking Ahead
While the eye health market will continue to prosper by leaning into the top-level issues of age-related macular degeneration and blue light, clear indications from those currently developing products suggest that a shift in focus toward younger demographics will likely broaden the widespread usage of dietary supplements for a range of ocular conditions, with a stronger mix of age groups. Just as important will be leveraging technology to make the most well-established ocular support ingredients more effective and available to the eyes through new innovations.

“Now it’s time to look deeper into the issues faced by younger generations,” Mehta said. “Older populations are no longer the only ones at risk for eye health challenges and complications. Younger generations are also suffering from eye health issues and it will be a disaster when the age-related complications collide with what they currently face.”  

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Mike Montemarano has been the Associate Editor of Nutraceuticals World since February 2020. He can be reached at MMontemarano@RodmanMedia.com.