Dry eye disease (DED) is a multifactorial condition characterized by insufficient tear production, poor tear quality, or excessive tear evaporation.1 It leads to discomfort, irritation, and inflammation of the ocular surface. While numerous factors contribute to DED, emerging research highlights the crucial role of nutrition in both the prevention and management of this condition.
By recognizing the intricate relationship between nutrition and ocular surface health, eyecare professionals (ECPs) can better serve their patients through personalized and comprehensive treatment approaches. This knowledge is invaluable as the prevalence of DED continues to rise globally, affecting an increasingly diverse patient population.
This article will delve into the latest research on the impact of nutrition on DED, providing valuable insights for all ECPs with the goal of offering more complete and effective treatment options for their patients.
Current DED statistics
DED can affect anyone, but it is particularly prevalent in older adults, especially women over 50.2 While an estimated 16 million Americans have received a DED diagnosis,2 the true impact is likely far greater. Undiagnosed cases may push that number closer to 30 million,2 and the Eyes On Eyecare 2024 Dry Eye Report suggests that over half of all eyecare patients may be affected.3
This indicates that millions more may be experiencing DED symptoms without realizing the underlying cause.3 A global meta-analysis of epidemiological studies revealed that the global prevalence of DED ranged from 5 to 50%, increasing with age and disproportionately affecting women.4
Clinical studies on nutrition and DED
Numerous clinical studies have demonstrated strong correlations between dietary factors and the development, progression, and management of dry eye disease. These studies provide compelling evidence for the efficacy of nutritional interventions in mitigating DED symptoms and improving ocular surface health.
Beyond a DREAM: Benefits of omegas for DED
The landmark DREAM (Dry Eye Assessment and Management) study, published in the New England Journal of Medicine, initially cast doubt on omega-3 supplementation for DED.5 This 12-month randomized controlled trial compared daily doses of omega-3s (3000mg; 2000mg EPA and 1000mg DHA) against olive oil (5g) as a placebo.
While both groups showed improvement in their symptoms, the difference between the groups was not statistically significant. However, rather than proving omega-3s ineffective, the study's methodology raises significant concerns. The use of olive oil as a placebo was fundamentally flawed since it contains oleic acid, which reduces inflammation by suppressing pro-inflammatory cytokines and oxidative stress pathways—both key mechanisms in dry eye disease.6
In effect, the study compared two potentially therapeutic substances rather than testing omega-3s against a true placebo. While the study was well-designed in many aspects, it had notable limitations, including its focus on mild to moderate cases and the allowance of concurrent dry eye treatments, which made it difficult to isolate the specific effects of omega-3 supplementation.
However, subsequent research has demonstrated compelling evidence for the benefits of omega-3 fatty acids in DED management. A comprehensive 2019 meta-analysis that reviewed 19 clinical trials involving over 4,000 patients (including the DREAM study), concluded that omega-3 fatty acid supplementation effectively improves dry eye signs and symptoms and can be considered an effective treatment.7
Comparing ethyl ester and re-esterified triglyceride formulations of omega-3 supplements
The formulation of omega-3 supplements plays a critical role in their therapeutic effectiveness. Studies have shown that our bodies have difficulty processing and absorbing ethyl ester-based formulations, which are commonly found in many over-the-counter (OTC) fish oil supplements. In contrast, re-esterified triglyceride formulations demonstrate superior bioavailability and efficacy for DED.
Clinical evidence supports that patients receiving re-esterified omega-3 supplements showed significant improvements in tear osmolarity and OSDI symptom scores compared to those receiving ethyl ester formulations, highlighting the importance of supplement form in achieving therapeutic outcomes.8
More specific clinical evidence has shown significant improvements in computer vision syndrome-related dry eye with just 600mg daily of combined EPA and DHA over a 90-day period.9 The benefits included decreased tear evaporation rates and increased conjunctival goblet cell density.
More recently, one study found that higher doses of omega-3s (2,400mg daily) led to significant improvements in tear film stability, eye moisture, and goblet cell density, particularly in patients with low baseline omega-3 levels.10
Research on combining gamma-linolenic acid (GLA) with omega-3 supplements
Particularly noteworthy is the neuroprotective potential of omega-3 supplementation, as demonstrated in a pilot study. Using a daily dose of 1500mg combined EPA and DHA, researchers observed improvements in both symptoms and corneal nerve density over a 90-day period.11 These findings were further supported by a comprehensive meta-analysis, which reviewed 19 clinical trials involving over 4,000 patients.12
Their meta-analysis concluded that omega-3 supplementation effectively reduces DED symptoms, especially with higher doses (up to 3000mg daily), longer duration of use (up to 12 months), and increased EPA levels (up to 80%).
Understanding the role of omega fatty acids in ocular health requires a nuanced perspective. While excessive omega-6s, particularly arachidonic acid, can contribute to inflammation, a specific omega-6, gamma-linolenic acid (GLA), offers potent anti-inflammatory benefits.13 GLA serves as a precursor to prostaglandin E1 (PGE1), a crucial molecule for tear production and ocular surface health.14
Multiple controlled trials have demonstrated the positive effects of GLA, specifically in the context of dry eye.14-15 Combining GLA with eicosapentaenoic acid (EPA), an omega-3 fatty acid, can optimize this effect. EPA inhibits the conversion of other omega-6s into pro-inflammatory compounds, redirecting metabolic pathways toward the production of anti-inflammatory molecules.16
Despite the DREAM study's controversial results, the broader body of research suggests that omega-3 and 6 supplementation remains a valuable tool in the management of dry eye disease, particularly when appropriately dosed and targeted to specific patient populations.
Multi-nutrient studies for DED management
Clinical research has highlighted the therapeutic potential of multi-nutrient supplementation in treating DED. These investigations, examining combinations of vitamins, antioxidants, and bioactive compounds, demonstrate how comprehensive nutritional approaches may offer enhanced benefits for managing this challenging condition.
A randomized, placebo-controlled clinical trial examined the efficacy of a novel oral supplement for dry DED.17 This supplement (LCD), composed of lutein (20mg), zeaxanthin isomers (4mg), curcumin (200mg), and vitamin D3 (600 IU) was administered daily to participants for 8 weeks. Tear film homeostasis improved markedly, with significant increases in Schirmer's test scores, tear break-up time, and tear osmolarity compared to placebo at day 56.
The supplement also demonstrated notable anti-inflammatory effects, with a substantial decrease of matrix metalloproteinase-9 (MMP-9) levels by 64% in both eyes. Notably, participants experienced significant improvement in DED symptoms, as measured by the OSDI and SPEED questionnaires, within just 2 weeks.
These findings support the growing body of evidence suggesting that targeted nutritional interventions can effectively address the multifaceted pathophysiology of DED. Furthermore, a randomized controlled trial evaluated the therapeutic potential of a comprehensive oral multivitamin supplement (MVG) for patients with treatment-resistant dry eye symptoms.18
The study found significant improvements after using a vitamin complex containing tocopherol, ascorbic acid, thiamine, riboflavin, pyridoxine, β-carotene, zinc oxide, selenium, and ubidecarenone in patients with recalcitrant DED. After 3 months of twice-daily supplementation, patients showed a 38.2% increase in tear breakup time and improved Schirmer's test scores.
The treatment also reduced symptoms as measured by the OSDI by 30.5% and decreased visual analog pain scores by 20.1%. The researchers concluded that oral multivitamin supplementation may be an effective treatment option for patients with intractable dry eye, likely due to the antioxidant properties of the vitamins helping to reduce oxidative stress and inflammation of the ocular surface.
Key ingredients: Nutrients beneficial to the ocular surface
Vitamin A
A strong link exists between vitamin A deficiency and dry eye. Vitamin A is necessary for normal differentiation of non-squamous epithelium, as keratinization is a direct consequence of its deficiency.19 Vitamin A deficiency negatively impacts both the composition and secretion rate of the tear film.
This disruption can lead to xerophthalmia, a condition characterized by abnormal dryness of the conjunctiva and cornea. If left untreated, xerophthalmia can progress to corneal ulceration and even blindness.20 Adequate dietary intake of beta-carotene, a precursor to vitamin A, is essential to mitigate this risk. Orange vegetables and leafy greens are excellent sources of beta-carotene.
Vitamin C
Vitamin C, a potent antioxidant, protects against ocular damage induced by reactive oxygen species (ROS). Unmitigated ROS triggers inflammation, compromising the tear lipid layer and disrupting goblet cell function, resulting in a cyclical inflammatory process that contributes to DED.21 Vitamin C plays a protective role in ocular health by reducing oxidative stress and promoting corneal health.
Its antioxidant properties improve tear film stability and goblet cell density, contributing to a healthier ocular surface.21 Excellent dietary sources of vitamin C include citrus fruits, berries, tomatoes, and leafy green vegetables.
Vitamin D
Vitamin D deficiency appears to be significantly associated with dry eye, with research indicating a potential protective role for vitamin D in ocular health. A study involving premenopausal women found that those with vitamin D deficiency (serum levels < 20ng/mL) exhibited lower Schirmer's test and tear break-up time (TBUT) scores, as well as higher Ocular Surface Disease Index (OSDI) scores compared to controls.22
Furthermore, vitamin D levels were negatively correlated with OSDI scores and positively correlated with Schirmer's test and TBUT scores, suggesting that vitamin D may enhance tear film parameters and reduce ocular surface inflammation.
With approximately 50% of the world's population experiencing vitamin D deficiency,23 investigating its potential role in the development and severity of dry eye is crucial. Adequate vitamin D levels can be maintained through exposure to sunlight, dietary intake (e.g., fatty fish, fortified foods), and supplementation.
Vitamin E
Vitamin E, a fat-soluble antioxidant, plays a crucial role in protecting the ocular surface from oxidative damage. Similar to vitamin C, it helps neutralize free radicals that can disrupt tear film stability and contribute to dry eye. By reducing oxidative damage to corneal epithelial cells, vitamin E helps maintain the integrity of the tear film and promote a healthier ocular surface.24-25
This protection is essential in mitigating the inflammatory cycle associated with dry eye disease, where oxidative stress compromises the tear lipid layer and goblet cell function. Including vitamin E-rich foods like nuts, seeds, and leafy greens in a balanced diet can support overall eye health and contribute to managing dry eye symptoms.
Zinc
Zinc is essential for maintaining good ocular health. This mineral plays a crucial role in several ways: it aids in vitamin A metabolism, which is essential for tear production and a healthy ocular surface; it acts as an antioxidant, protecting eye tissues from damaging free radicals that can lead to inflammation and cellular damage; and it contributes to corneal health by promoting wound healing and tissue maintenance.26
Research suggests that zinc may improve tear film stability and reduce dry eye symptoms. A study found that using eye drops containing zinc-hyaluronate improved tear film stability and reduced dry eye symptoms, with participants experiencing a significant decrease in their OSDI score (from 35.66 to 15.03) and a significant improvement in tear film breakup time (from 3.83 to 8.67 seconds).27
To support optimal eye function, include zinc-rich foods like seafood, meat, legumes, and nuts in a balanced diet.
Lutein and zeaxanthin
As touched upon earlier, Lutein and zeaxanthin, two carotenoids found in high concentrations in the macula of the eye, are also gaining attention for their potential role in mitigating dry eye symptoms.17 Acting as powerful antioxidants, these compounds combat the oxidative stress and inflammation that contribute significantly to dry eye.
Studies suggest that lutein and zeaxanthin may improve tear film stability, reduce inflammation of the ocular surface, and enhance visual function in individuals with dry eye.17 Although more research is needed to fully understand their therapeutic potential, incorporating lutein and zeaxanthin-rich foods (e.g., leafy greens and eggs) into the diet is proving to be a beneficial strategy for managing DED.
The role of hydration in dry eye disease
While the link between dehydration and dry eye may seem intuitive, research findings on the direct impact of hydration are somewhat mixed. Adequate hydration is undoubtedly essential for overall health, including the production of tears.
Clinical evidence supports that dehydration increases tear film osmolarity in individuals with higher risk factors for dry eye disease. This increase in osmolarity results in reduced TBUT and increased ocular surface inflammation, further exacerbating dry eye symptoms.28
However, other research indicates that increasing fluid intake may not directly improve dry eye parameters. A recent study published in Acta Ophthalmologica challenges the common belief that drinking more water helps prevent DED.29 Researchers analyzed data from over 50,000 participants, tracking their water intake and DED symptoms.
Surprisingly, they found that higher water intake was actually associated with a slightly increased risk of DED, even after accounting for various factors like age, health conditions, and medications. While this large, population-based study provides compelling evidence, it's important to remember that it doesn't prove cause and effect.
More research is needed to understand the complex relationship between hydration and DED, but this study certainly raises questions about the conventional wisdom surrounding water intake and eye health.
Aggravators: Common irritants and triggers for DED
While certain nutrients and dietary substances support eye health, others can exacerbate DED symptoms:
Alcohol
Regular alcohol consumption can lead to dehydration and inflammation, potentially worsening dry eye symptoms. Studies have shown that alcohol intake can decrease tear production and alter tear film composition, leading to reduced TBUT and increased ocular surface inflammation.30
Caffeine
The relationship between caffeine and dry eye is complex. While caffeine can have a mild diuretic effect, research suggests it may actually increase tear production and reduce tear film osmolarity.31-35 Recent studies have challenged the view of caffeine as a risk factor, with both topical and oral caffeine showing potential benefits for tear production.31-35
Genetic factors, particularly variations in adenosine receptor and caffeine metabolism genes, appear to influence these effects.34 Current evidence indicates moderate caffeine consumption is unlikely to worsen dry eye symptoms and may even be beneficial.36,37
Sodium
High dietary sodium intake can disrupt tear film osmolarity, contributing to dry eye disease and inflammation of the ocular surface. Excess salt consumption leads to dehydration, reducing tear production and increasing the concentration of salts in tears.38
This heightened osmolarity draws water out of ocular surface cells, damaging the corneal epithelium and increasing ocular surface inflammation.39
Processed foods
Diets high in processed foods, particularly those rich in trans fats and refined sugars, may promote systemic inflammation that can affect ocular health. These foods often lack the essential nutrients needed for optimal tear production and ocular surface maintenance.40
Conclusion
The relationship between nutrition and dry eye disease is multifaceted and increasingly well-documented. The evidence supports a comprehensive approach to DED management that incorporates dietary considerations alongside traditional treatments.
Key findings on the impact of nutrition on DED include:
- Essential fatty acids, particularly omega-3s and specific omega-6s like GLA, demonstrate significant therapeutic potential in DED management, with research supporting various dosage levels for different patient populations.
- Micronutrients including vitamins A, C, D, and E, along with zinc and carotenoids (lutein and zeaxanthin), contribute to tear film stability, inflammation reduction, and ocular surface protection through multiple mechanisms.
- Multi-nutrient approaches show particular promise in addressing treatment-resistant cases, with clinical trials demonstrating significant improvements in tear film parameters and patient symptoms.
- The relationship between hydration and DED is more complex than previously understood, with recent large-scale studies challenging conventional wisdom about water intake's direct benefits.
- Dietary aggravators show varying levels of impact: while alcohol and high sodium intake generally worsen symptoms, caffeine's effects appear more nuanced and potentially beneficial in some cases.
For ECPs, these findings underscore the importance of incorporating nutritional counseling into DED management strategies. A holistic approach that considers both beneficial nutrients and potential dietary aggravators can enhance treatment outcomes. Future research should focus on optimizing nutrient combinations and dosages for specific patient populations, as well as investigating emerging nutritional compounds that may benefit ocular surface health.
As the prevalence of DED continues to rise globally, understanding and utilizing nutritional interventions becomes increasingly crucial for effective patient care. By integrating evidence-based nutritional strategies into comprehensive treatment plans, eyecare providers can better address the multifactorial nature of dry eye disease and improve outcomes for their patients.
