Health ConditionsThe 2007 Report of the International Dry Eye Workshop (DEWS) defines dry eye disease as "a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability, with potential damage to the ocular surface," and notes that it "is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface." This definition, also adopted in subsequent workshops, underscores that dry eye disease (DED) is not a single, uniform condition but a spectrum of overlapping disorders united by a common pathological endpoint: a failing tear film.
DED is also recognized under a variety of names, including keratoconjunctivitis sicca (KCS), sicca syndrome, keratitis sicca, xerophthalmia, dry eye syndrome (DES), dysfunctional tear syndrome (DTS), and ocular surface disease (OSD).
It is a common clinical problem, with surveys over the last 20 years estimating a prevalence of between 5% and more than 30% at various ages. The prevalence of DED is high, affecting up to 34% of certain populations, particularly female and elderly patients over 65 years of age, with a significant impact on patients' quality of life and a significant burden on society.
Dry eye disease is caused by tear deficiency or excessive evaporation, leading to damage to the interpalpebral ocular surface, and is associated with subjective symptoms including ocular discomfort, visual disturbance, dryness, and soreness. These subjective complaints are central to diagnosis and monitoring.
DED is a common chronic disorder that results in ocular discomfort, fatigue, visual disturbance, and pain, thereby affecting overall quality of life. Studies suggest that dry eye is associated with decreased ability to perform daily activities, social functioning, and physical and emotional well-being. It is also accompanied by lower workplace productivity and increased healthcare costs to society.
DED is one of the most frequently encountered ocular morbidities and is considered one of the top three most prevalent chronic eye diseases, together with glaucoma and age-related macular degeneration. Nearly 14% of Americans 50 years and older, of all races, and more commonly women, are affected by dry eye disease.
The human tear film coats the anterior surface of the eye and is composed of three distinct layers: an inner mucin coating, a middle aqueous component, and a lipid overlay. Each layer originates from a distinct anatomical source and serves a specific protective function.
The tear film lubricates the eyes for comfort; protects against forces on the ocular surface during blinking; shields the eyes from environmental challenges such as extremes of temperature and humidity, pollutants, allergens, and infection; and maintains a smooth refractory surface to facilitate clear vision.
The ocular surface (cornea, conjunctiva, accessory lacrimal glands), meibomian glands (specific sebaceous glands of the eyelid margin, which produce the outer lipid film of the tear film), the main lacrimal gland, and the innervation between them form a functional unit. This integrated structure is referred to as the lacrimal functional unit (LFU).
Dysfunction of any lacrimal functional unit component can lead to DED by causing alterations in the volume, composition, distribution, and/or clearance of the tear film. Two mutually reinforcing global mechanisms — tear hyperosmolarity and tear film instability — have been identified as central to DED pathophysiology.
Tear film instability can be triggered by insufficient tear production, or by poor tear film quality that results in increased tear evaporation. Dry eye is typically categorized into two groups: (1) aqueous tear-deficient dry eye disease and (2) evaporative dry eye disease.
Aqueous-deficient DED can be caused by lacrimal alterations — including autoimmune disorders, either primary or secondary to systemic autoimmune diseases such as rheumatoid arthritis — or by blockade of reflex secretion or medication causes. Evaporative DED also has various causes, including meibomian gland disease, eyelid aperture disorders or lid/globe incongruity, blink disorders, and ocular surface disorders.
Clinical and laboratory studies performed over the past few decades have established that dry eye is a chronic inflammatory disease that can be initiated by numerous extrinsic or intrinsic factors that promote an unstable and hyperosmolar tear film. These changes in tear composition, in some cases combined with systemic factors, lead to an inflammatory cycle that causes ocular surface epithelial disease and neural stimulation.
Acute desiccation activates stress signaling pathways in the ocular surface epithelium and resident immune cells. This triggers production of innate inflammatory mediators that stimulate matrix metalloprotease production, inflammatory cell recruitment, and dendritic cell maturation. These mediators, combined with exposure of autoantigens, can lead to an adaptive T cell-mediated response.
Corneal barrier disruption develops by protease-mediated lysis of epithelial tight junctions, leading to accelerated cell death; desquamation; and an irregular, poorly lubricated surface. Conjunctival goblet cell dysfunction and death are promoted by the T helper 1 cytokine interferon gamma. These epithelial changes further destabilize the tear film, amplify inflammation, and create a vicious cycle.
Individuals with specific non-modifiable demographic risk factors may be at increased risk of developing dry eye disease. Advanced age, female sex, and East Asian ethnicity have been identified as key non-modifiable demographic features predisposing individuals to dry eye disease.
A 2022 systematic review and meta-analysis published in PLOS ONE aggregating data from PubMed, Embase, and the Cochrane Library found substantial associations across a broad spectrum of conditions: older age (OR: 1.82), female sex (OR: 1.56), visual display terminal use (OR: 1.32), cataract surgery (OR: 1.80), contact lens wear (OR: 1.74), depression (OR: 1.83), post-traumatic stress disorder (OR: 1.65), sleep apnea (OR: 1.57), asthma (OR: 1.43), allergy (OR: 1.38), hypertension (OR: 1.12), diabetes mellitus (OR: 1.15), rosacea (OR: 1.99), thyroid disease (OR: 1.60), arthritis (OR: 1.76), and migraines (OR: 1.53) were all associated with an increased risk of dry eye syndrome.
Systemic conditions that have been associated with an increased risk of dry eye disease include migraine, Sjögren syndrome, connective tissue disorders, mental health disorders, diabetes mellitus, and androgen deficiency. Medications that may contribute to this risk include antidepressants, antihistamines, and hormone replacement therapy.
Ocular and iatrogenic risk factors of dry eye disease include blepharitis, Demodex infestation, ocular surgery, blink completeness, contact lens wear, and topical ophthalmic medications.
Risk factors for DES include vitamin D deficiency and diabetes mellitus. A 2026 retrospective cohort study published in PubMed found that vitamin D deficiency was significantly associated with an increased risk of developing DED, with a 28.6% higher hazard compared with matched controls.
The occupational risk factor of visual display terminal (VDT) use was related to the progression of DES, which could be explained by a decreased blink rate and increased proportion of incomplete blinks that could be caused by the increased exposure of the ocular surface to the environment.
Outdoor environments, sunlight, and air pollution in tropical countries are also associated with an elevated risk of DES.
Research reveals a decrease in tear film and an increase in meibomian gland dysfunction (MGD) among individuals with a 10-year history of smoking compared with non-smokers. Research shows that cigarette smoke extract can activate NF-κB and enhance the release of IL-1β and IL-6 in human corneal epithelial cells. Corneal and conjunctival epithelial damage occurs, the corneal structure becomes altered, and the density of goblet cells decreases with consistent exposure to cigarette smoke.
As one of the core drivers of dry eye disease is inflammation, it is believed that omega-3 supplementation may be a viable treatment option. However, there have been a number of randomised controlled trials examining this with mixed results.
The body of evidence from systematic reviews is substantial but heterogeneous. A 2019 Cochrane systematic review by Downie et al. examined omega-3 and omega-6 polyunsaturated fatty acids for dry eye disease. The authors of that Cochrane review concluded that omega-3 supplementation offered potential benefit in clinical signs of dry eye disease but very little in symptomatic profile.
A 2019 meta-analysis (Giannaccare et al., published in Cornea) found: this meta-analysis provides evidence that omega-3 FA supplementation significantly improves dry eye symptoms and signs in patients with dry eye disease, indicating that omega-3 FA supplementation may be an effective treatment for dry eye disease.
A more recent and larger 2023 meta-analysis (Wang & Ko, published in Journal of Clinical Medicine), incorporating 19 RCTs assessed by the Cochrane Risk of Bias tool and encompassing 4,246 DED patients, reported that patients given omega-3 treatment demonstrated more significant improvements in dry eye symptoms, tear break-up time (TBUT), Schirmer test scores, corneal fluorescein staining (CFS), and osmolarity compared to those on a placebo regimen. In meta-regression analysis, the daily dose of omega-3, duration of omega-3 intake, and percentage of eicosapentaenoic acid (EPA) exhibited a significant positive correlation with a reduction in dry eye symptom scores. The authors concluded that omega-3 FAs effectively reduce DED symptoms, especially in high doses, for a long duration, and with increased EPA levels; however, given the heterogeneity in study results and diverse patient characteristics, caution is needed in generalizing these findings.
A 2017 systematic review of 15 RCTs totaling 2,591 patients found that significant differences in favour of the experimental group were found in seven of the studies for subjective improvement, measured using mainly the Ocular Surface Disease Index (OSDI) test and Dry Eye Severity Score (DESS) test.
The DREAM Study — A Key Counterpoint: The most methodologically rigorous single trial to date is the Dry Eye Assessment and Management (DREAM) study. The DREAM Study was a multicenter (27 sites), randomized, double-masked clinical trial for people with moderate to severe dry eye disease. Between October 2014 and July 2016, 535 participants were assigned in a 2:1 ratio to either active omega-3 fatty acid daily supplements (2 g eicosapentaenoic acid and 1 g docosahexaenoic acid) or placebo (5 g refined olive oil). One-year results showed no difference between the omega-3 and placebo groups for the primary outcome of symptoms, as measured by the Ocular Surface Disease Index, or the traditional signs of DED including conjunctival and corneal staining, tear film break-up time, and Schirmer test results.
Prescribing omega-3s became somewhat controversial when the 2018 DREAM study results seemed to question the validity of fish oils, as the study found omega-3 fatty acids offered no benefit over the olive oil placebo. Importantly, the olive oil used as a placebo itself has anti-inflammatory properties, which may have attenuated the detectable between-group difference. Additionally, the omega-3s used in the treatment arm were 3,000 mg of fish-derived EPA and DHA but did not include the omega-6 gamma-linolenic acid (GLA). Many researchers argue that a combined omega-3/GLA approach may be needed for optimal effect.
Evidence strength: Overall, the evidence for omega-3s in DED is moderate and mixed. Multiple meta-analyses support benefit, particularly for objective measures such as tear break-up time, but the large NIH-funded DREAM trial found no benefit for symptoms over a high-quality olive-oil placebo at one year. Heterogeneity across trials in doses, formulations, populations, and outcomes limits firm conclusions.
Evening primrose oil (Oenothera biennis) has been used in traditional North American herbal practice for inflammatory conditions of the skin and mucous membranes, though its historical use specifically for ocular dryness is not well-documented in traditional systems of medicine in the manner that some botanicals are.
Evening primrose oil contains about 74% linoleic acid and 10% gamma-linolenic acid. The body can convert GLA to prostaglandins. Some studies suggest evening primrose oil may help with dry eyes, while other studies do not show a difference. A few smaller studies in patients with Sjögren's syndrome showed benefit using EPO. However, without more research, it is unclear if the oil helps lower burning, dryness, and light sensitivity.
A small study in women with dry eyes found that a daily dose of evening primrose oil containing 300 mg of GLA improved symptoms over six months, though this is a single, small trial. Combined supplementation with omega-3 EFAs (1,000 mg) derived from flaxseed oil and omega-6 EFAs (500 mg of GLA) derived from evening primrose oil has been investigated in clinical research, with both substances microencapsulated to improve absorption.
Evidence strength: Preliminary and inconsistent. The evidence base for GLA/evening primrose oil in isolation for dry eye is limited to small trials with largely positive but not robustly replicated results. Larger RCTs are lacking.
Flaxseed oil is the richest plant-based source of alpha-linolenic acid (ALA), a short-chain omega-3 fatty acid. Additional analysis of studies on flaxseed suggests the alpha-linolenic acid (ALA) — an omega-3 fatty acid — in flaxseed may be responsible for observed effects on dry eye. ALA must be converted to EPA and DHA in the body to exert the anti-inflammatory effects attributed to marine omega-3 fatty acids; this conversion is biochemically limited in humans, which constrains its potency relative to direct EPA/DHA supplementation.
Evidence strength: Preliminary. Flaxseed oil appears in several small dry eye trials, often as part of combination fatty acid products, but has not been independently evaluated in large, well-controlled trials. The indirect pathway of ALA conversion to active omega-3 metabolites is a relevant limitation.
Vitamin A has been recognized for its essential role in vision and eye surface health since antiquity, with traditional dietary wisdom emphasizing liver and other retinol-rich foods for maintaining healthy eyesight. The formal scientific understanding of vitamin A's role in the eye — particularly in night vision and epithelial integrity — was established through early 20th-century nutrition research.
Vitamin A deficiency can lead to DED by causing goblet cell loss, mucin deficiency, and corneal epitheliopathy. Long-term deficiency may result in metaplasia and the keratinization of the corneal and conjunctival epithelial cells.
Vitamin A is essential for the maintenance of goblet cells and mucin at the ocular surface. Disorders that precipitate goblet cell loss include vitamin A deficiency, as well as cicatrizing conjunctival disorders such as Stevens-Johnson syndrome, trachoma, pemphigoid, and chemical burns.
The base layer of the tear film, including goblet cells and mucin production, is vitamin A-dependent. Vitamin A deficiency can lead to DED by causing goblet cell loss, mucin deficiency, and corneal epitheliopathy. Supplementation has been shown to be helpful for improving ocular surface damage and DED.
Risk factors for DES include advanced age, female sex, cataract surgery, vitamin A deficiency, and contact lens wear. This explicitly places vitamin A deficiency in the category of established risk factors.
Evidence strength: Well-established for deficiency states. The relationship between vitamin A deficiency and dry eye/goblet cell loss is robustly supported across animal and human studies. The evidence for supplementation in vitamin A–replete individuals is less conclusive; benefit is primarily demonstrated in those with documented deficiency.
Vitamin D is a steroid hormone that has a widespread role in human physiology, not only in the maintenance of calcium homeostasis but also in immunomodulation, cellular differentiation, and proliferation. The immunomodulatory effects of vitamin D are well known and are applicable to the ocular surface immune cells and structural cells. The role of vitamin D in ocular surface conditions such as dry eye disease has received widespread and well-deserved attention.
Vitamin D supplementation is shown to improve DED clinically as well as in experimental models. The anti-inflammatory properties may be crucial in the treatment of ocular surface conditions such as DED.
A 2020 systematic review and meta-analysis of 14 observational studies found: serum 25(OH)D3 was lower in dry eye disease subjects compared to healthy ones (WMD −5.93; 95% CI, −7.47 to −4.40; P < 0.001), with evidence of significant heterogeneity. Vitamin D correlated significantly with ocular surface disease index (Fisher's Z: −0.26; 95% CI, −0.48 to −0.04; P = 0.018). Serum vitamin D had a significantly lower level in dry eye disease patients and correlated with ocular surface disease index but not with other dry eye parameters.
A 2024 systematic review and meta-analysis of 8 intervention studies with 439 cases found that vitamin D is a vitamin with anti-inflammatory and immunomodulatory effects, and several studies have shown that vitamin D deficiency is associated with the incidence and severity of dry eye disease in humans.
Vitamin D receptors found within the human eye suggest that vitamin D plays a significant role in eye cell functions and may reduce ocular surface inflammation associated with DED, thereby improving symptoms.
Evidence strength: Moderate for association; preliminary for supplementation benefit. Observational data consistently demonstrate lower serum vitamin D levels in DED patients. Intervention data from small studies suggest improvement following supplementation. Large, well-powered RCTs specifically examining vitamin D supplementation for DED are still needed.
Vitamins C and E are known for their antioxidant properties, which help combat oxidative stress. Vitamin C is present in every ocular tissue at 20 to 30 times serum concentration and has antioxidant, anti-inflammatory, and immunomodulatory functions, which can be helpful for the prevention of DED. It also has a therapeutic role in corneal wound repair. These roles are biologically plausible given that oxidative stress is recognized as a contributor to lacrimal gland and ocular surface dysfunction. However, large, controlled human trials examining vitamin C or E supplementation specifically for DED outcomes are limited, and this area remains understudied relative to omega-3 fatty acids.
Evidence strength: Preliminary and mechanistic. The antioxidant roles of vitamins C and E in the eye are established at the physiological level, but their direct efficacy in treating or preventing DED in clinical populations has not been rigorously demonstrated in large RCTs.
Curcumin has been used in Ayurvedic medicine and traditional Chinese medicine as a curative and preventive agent for many disorders for thousands of years. In these traditions, turmeric was most commonly applied to inflammatory conditions, wounds, and digestive disorders; its use specifically for eye complaints in historical literature is less prominent than its broader anti-inflammatory applications.
Oral curcumin is being increasingly investigated in the treatment of eye conditions, showing potential value in the treatment of several ocular disorders. Curcumin is a major phytochemical isolated from the plant Curcuma longa and is the principal curcuminoid of the popular spice turmeric, which has been extensively used as a coloring agent in South Asian countries.
DED is associated with increased tear osmolality and inflammation of the ocular surface. The presence of proinflammatory cytokines such as IL-6, IL-8, and IL-1β has been observed in corneal cells and in patients with DED in hyperosmotic conditions. Curcumin is mechanistically plausible as an anti-inflammatory agent in this context.
Curcumin reveals a wide range of pharmacological effects including anticancer, anti-inflammatory, antioxidant, antiarthritic, anti-diabetic, antimutagenic, and antimicrobial properties. Curcumin can suppress inflammation and oxidative stress and protect retinal cells.
A randomized, double-masked, placebo-controlled clinical study at a tertiary eye center assessed the role of oral bio-enhanced curcumin in DED. A key challenge identified by the research is that a limitation of oral curcumin is the inadequate bioavailability of oral curcumin to ocular tissues due to intestinal metabolism. Bioavailability-enhancing formulations are therefore being actively investigated.
Evidence strength: Preliminary (human evidence) and mixed (preclinical evidence is supportive). The mechanistic case for curcumin in DED is strong, and preclinical and early clinical data are promising, but the bioavailability challenge is real, and evidence from large, well-powered human RCTs remains limited.
Western diets typically consist of high ratios of omega-6 in comparison with omega-3. This is thought to be implicated in the pathogenesis of inflammation leading to cardiovascular disease, malignancy, and autoimmune conditions. In comparison, omega-3 fatty acids appear to suppress these inflammatory reactions. The relevance to DED is that dietary patterns favoring high omega-6 intake relative to omega-3 may promote the pro-inflammatory state that underlies ocular surface disease.
A cross-sectional study drawing on the Korea National Health and Nutrition Examination Survey found complex relationships between dietary nutrients and DED prevalence among Korean women aged 40 and above. Higher intake of carbohydrates (adjusted OR: 1.23), sugar (adjusted OR: 1.30), fat (adjusted OR: 1.25), cholesterol (adjusted OR: 1.32), sodium (adjusted OR: 1.18), iron (adjusted OR: 1.28), and zinc (adjusted OR: 1.26) correlated with an increased risk of dry eye syndrome. No significant associations were found between the prevalence of dry eye syndrome and the intake of omega-6 fatty acids and vitamin D in that specific cohort. The findings suggest that dietary choices could influence the likelihood of developing dry eye syndrome, indicating a potential role for dietary intervention in its management. These findings should be interpreted with caution given the cross-sectional design and the potential for dietary recall bias.
Research reveals a decrease in tear film and an increase in meibomian gland dysfunction (MGD) among individuals with a 10-year history of smoking compared with non-smokers. Research shows that cigarette smoke extract can activate NF-κB and enhance the release of IL-1β and IL-6 in human corneal epithelial cells. Corneal and conjunctival epithelial damage occurs, the corneal structure becomes altered, and the density of goblet cells decreases with consistent exposure to cigarette smoke.
Alcohol consumption was not significantly associated with prevalent dry eye symptoms in some analyses, but there was such an effect in incidence data. Evidence remains inconsistent and further research is warranted to characterize the relationship between alcohol intake and DED risk.
Factors such as smoking, excessive screen time, low humidity, and dehydration can worsen dry eye symptoms and increase the nutritional demands on the eyes. Adequate hydration is considered a basic supportive measure in maintaining tear volume, though the evidence specifically linking systemic hydration status to tear production in non-dehydrated populations is limited.
ALA is a plant-derived short-chain omega-3 fatty acid that reduces corneal epithelial damage and inflammation in DED animal models when applied topically. As the primary omega-3 in flaxseed oil, oral ALA has shown clinical benefit in observational studies. Short-chain precursor status requires enzymatic conversion to EPA/DHA, making it less potent than long-chain forms for oral use.
Omega-3s in algal oil, particularly DHA and EPA, may ease dry eye symptoms by slowing tear evaporation and reducing ocular surface inflammation. Clinical reviews support omega-3 supplementation for dry eye relief, with effects attributed to DHA's anti-inflammatory properties in the lacrimal gland and ocular surface. Benefits have been noted for contact lens wearers and screen users.
A prospective quasi-experimental clinical study (n=60 patients, 120 eyes, Beijing Tongren Hospital) found oral astaxanthin 6 mg twice daily for 30 days significantly improved OSDI, TBUT, corneal fluorescein staining, and meibomian gland function in mild-to-moderate DED. It crosses the blood-retinal barrier and inhibits HMGB1, TNF-α, and IL-1β in corneal epithelial cells.
Bilberry (Vaccinium myrtillus) anthocyanins have been studied in clinical RCTs for dry eye, with a 3-month pilot RCT (n=24, 600 mg bilberry + fish oil) showing improvements in OSDI, NITBUT, tear secretion, and meibomian gland openings. A separate RCT found 160 mg bilberry extract for 4 weeks improved tear volume by Schirmer test. Anti-inflammatory and vasoprotective anthocyanins reduce oxidative stress on the ocular surface.
EPA and DHA supplementation from marine sources reduces dry eye disease (DED) symptoms by dampening ocular surface inflammation. Multiple RCTs have shown improvements in tear breakup time, osmolarity, and Ocular Surface Disease Index (OSDI) scores. Calamari oil provides the same DHA/EPA active components studied in these trials.
Capsanthin from Capsicum annuum was tested in a rat benzalkonium chloride-induced dry eye model, demonstrating significant improvements in tear break-up time, Schirmer scores, intraocular pressure, and corneal inflammation. Antioxidant enzyme levels were also improved.
Chondroitin sulfate is used both as an active lubricant and as a vehicle in ophthalmic formulations for dry eye disease (DED). Multiple clinical trials have evaluated CS-containing eye drops, demonstrating improvements in goblet cell density, tear break-up time, OSDI scores, and corneal staining. A phase III multicenter RCT and a phase IV double-blind RCT have both assessed CS-based solutions against comparators, showing non-inferior or superior outcomes.
Chrysanthemum has both traditional TCM use and emerging scientific evidence for dry eye conditions. A 2025/2026 Inflammopharmacology study showed wild chrysanthemum essential oil improved tear production, corneal integrity, and goblet cell density in a dry eye mouse model via NF-κB pathway suppression. A clinical RCT using a chrysanthemum-containing botanical formula improved dry eye symptoms in 360 participants.
Omega-3 fatty acids from cod liver oil reduce ocular surface inflammation implicated in dry eye disease. Multiple RCTs and meta-analyses have examined oral omega-3 supplementation for dry eye, with evidence of improvements in tear break-up time and ocular surface staining. However, a large recent trial (DREAM study) found no significant benefit over placebo.
CoQ10 has been studied for dry eye disease through clinical trials showing topical CoQ10 with crosslinked hyaluronic acid improved DED outcomes, reduced all cytokine levels, and elevated total antioxidant status. Histopathological analyses confirmed CoQ10 protects lacrimal gland structure and function from oxidative damage. It is one of ten evidence-supported DED nutrients per a 2024 Frontiers in Pharmacology systematic review.
An 8-week prospective randomized double-blind placebo-controlled RCT (n=155 DED patients) using curcumin 200 mg + lutein + zeaxanthin + vitamin D3 met both primary DED endpoints (Schirmer and OSDI, p<0.001). Curcumin reduces pro-inflammatory cytokines in corneal epithelial cells, inhibits NF-κB, and reduces oxidative stress and MMP-9 in ocular surface models.
DHA is the other principal long-chain omega-3 fatty acid co-evaluated with EPA in dry eye RCTs. It is incorporated into lacrimal gland cell membrane phospholipids, modulating inflammatory signaling. Clinical meta-analyses confirm combined EPA+DHA supplements improve TBUT, Schirmer test, and OSDI scores in DED patients.
DHA and EPA modulate ocular surface inflammation through eicosanoid pathways, shifting the balance toward anti-inflammatory mediators. DHA plays an active role in organizing the lacrimal lipid film, reducing tear evaporation and improving Meibomian gland lipid secretion. Phase 3 clinical trials have been conducted for EPA+DHA supplementation in dry eye disease.
EPA-containing omega-3 supplementation has been evaluated in multiple RCTs for dry eye disease (DED). A meta-analysis of 19 RCTs (n=4,246 patients) found significant improvements in tear break-up time, Schirmer's test, corneal staining, and osmolarity, with EPA percentage a significant predictor of symptom improvement.
EPA is a primary long-chain omega-3 fatty acid studied in dry eye disease across multiple RCTs and meta-analyses. Higher EPA percentages within omega-3 formulations are associated with greater reductions in DED symptom scores. EPA suppresses pro-inflammatory cytokines and modulates the ocular surface inflammatory cascade as a precursor to anti-inflammatory prostaglandins.
Fish oil EPA and DHA modulate tear film quality through anti-inflammatory and specialized pro-resolving mediator (resolvin, protectin) pathways. Multiple RCTs and the large DREAM extension study have evaluated omega-3 for dry eye disease. A 2025 RCT in Sjögren's syndrome patients found significantly lower dry eye symptom scores with omega-3 versus placebo.
Flaxseed oil, rich in ALA omega-3, has been studied for dry eye through a prospective observational study (n=200) reporting 85% symptom relief at 2 months with oral flaxseed oil. Topical flaxseed oil artificial tears showed benefit in a randomized controlled trial. Preclinical studies confirmed topical ALA from flaxseed reduced corneal inflammation.
GLA is an omega-6 fatty acid and precursor to prostaglandin E1 (PGE1), a key molecule for tear production and lacrimal gland secretion. Multiple RCTs using GLA combined with EPA/DHA showed improved tear film lipid layer stability, reduced tear evaporation, and reduced DED inflammation. Sources include borage and evening primrose oil.
In an animal model of dry eye disease, goji berry extract (GBE) at multiple doses significantly improved Schirmer's test scores and tear break-up time within one week and reduced keratoconjunctival staining severity. The berry's antioxidant and anti-inflammatory constituents are proposed mechanisms. Human clinical data are not yet available, but preclinical evidence is robust.
Oral hyaluronic acid supplementation combined with topical HA more efficiently improves corneal epithelial wound healing and DED symptoms than topical HA alone, per a pilot study. Topical HA combined with CoQ10 and vitamin E shows clinical improvements in DED. Hyaluronic acid is a humectant that attracts water and promotes ocular surface hydration and repair.
A double-blind, placebo-controlled RCT (Deinema et al., Ophthalmology 2017; n=60) showed krill oil supplementation for 90 days significantly reduced tear osmolarity and OSDI symptom scores versus placebo, with the krill oil group uniquely achieving significant reductions in the proinflammatory cytokine IL-17A. These benefits were superior to or additive versus fish oil on symptom measures.
Lactoferrin is a natural glycoprotein in healthy tear fluid; low tear lactoferrin correlates with DED severity. Clinical RCTs show oral lactoferrin ameliorates DED symptoms and improves tear film stability by downregulating TNF-α, IL-1, IL-6, and IL-8. Animal studies confirm oral lactoferrin maintains tear secretion in DED models. It is one of ten evidence-supported DED nutrients per a 2024 Frontiers in Pharmacology review.
Multiple RCTs demonstrate that lutein supplementation (typically 20 mg/day) improves TBUT, tear meniscus height, Schirmer test, OSDI, and MMP-9 in DED patients within 3–8 weeks. Lutein inhibits IL-6 secretion in corneal epithelial cells via NF-κB signaling, reducing ocular surface inflammation. It is one of four active ingredients in a validated 8-week DED RCT meeting primary endpoints.
Maqui berry extract is among the best-supported applications, with a pilot trial and a full RCT both showing significantly increased tear fluid production. A randomized, double-blind, placebo-controlled trial in 74 adults found that 60 mg MaquiBright® daily for 4 weeks produced significantly higher tear fluid volume vs. placebo. A further 2022–2023 prospective interventional study confirmed improvement in DED signs and reduction in ocular surface inflammatory markers.
Mucin deficiency on the ocular surface is a recognized driver of dry eye disease (DED), and pharmacological agents that stimulate mucin secretion (mucin secretagogues) are clinically proven treatments. Randomized controlled trials demonstrate that mucin secretagogue eye drops (diquafosol, rebamipide) significantly improve corneal staining, tear breakup time, and symptom scores. Alterations in both cell surface-associated and gel-forming mucins occur in dry-eye-related ocular surface diseases.
Multiple meta-analyses of RCTs confirm that omega-3 supplementation significantly improves dry eye disease (DED) symptoms, tear break-up time (TBUT), Schirmer test scores, and tear osmolarity. A 2023 meta-analysis of 19 RCTs (4,246 patients) found significant benefits especially at higher doses and longer durations. The anti-inflammatory mechanism involves modulating prostaglandin metabolism and enhancing lacrimal gland secretion.
Sea buckthorn oil—rich in omega-7 palmitoleic acid—has been studied in RCTs for dry eye disease. Larmo et al. (J Nutr, 2010) conducted a double-blind, placebo-controlled trial in 100 participants and found oral sea buckthorn oil attenuated tear film osmolarity and reduced dry eye symptoms over 3 months. A further study in Sjögren's syndrome patients reported overall improvement in ocular mucosal symptoms with sea buckthorn supplementation.
Vitamin A palmitate eye gel has been tested clinically for dry eye syndrome and shown to improve tear film stability. Topical retinyl palmitate supports the goblet cells and mucin layer of the ocular surface.
Dexpanthenol has been investigated as an active ingredient in eye drops for dry eye disease (DED). A randomized double-blind placebo-controlled study in 50 dry eye patients showed significant improvement in corneal epithelial permeability and tear film parameters with dexpanthenol-containing artificial tears. A ClinicalTrials.gov-registered trial (NCT06210373) is assessing 5% dexpanthenol eye gel for moderate-to-severe DED.
Saffron's active constituents (crocin, crocetin, safranal) have antioxidant and anti-inflammatory properties studied in ocular diseases. A 2022 systematic review of antioxidants for eye aging noted that saffron extract is a relevant ocular antioxidant that can alleviate symptoms of dry eye disease. Evidence is primarily from mechanistic data and indirect clinical observations rather than dedicated DED-specific RCTs.
Selenium is an antioxidant trace mineral that protects the ocular surface and lacrimal gland from oxidative stress relevant to DED. It is included in validated DED multivitamin formulations showing significant clinical benefit. A 2024 Frontiers in Pharmacology systematic review confirmed selenium as one of ten evidence-supported nutrients for dry eye management.
Reduced SPM levels have been measured in human tear fluid in dry eye disease. An RvE1 stable analog (RX-10045) successfully completed a Phase II human clinical trial for dry eye inflammation, demonstrating reduced corneal staining and symptom scores. Dry eye disease represents the most clinically advanced SPM indication in ophthalmology.
Vitamin A deficiency directly causes xerophthalmia and DED via goblet cell loss and corneal keratinization. Topical and oral vitamin A supplementation reduces dry eye signs and symptoms and promotes goblet cell proliferation, as confirmed in clinical studies. It is recognized as an essential nutrient for ocular surface integrity by major ophthalmic bodies.
Vitamin C is an antioxidant present in tear fluid that neutralizes reactive oxygen species and prevents UV-induced ocular surface damage. It is included in validated DED multivitamin formulations showing significant symptom improvement. Deficiency contributes to oxidative ocular surface damage relevant to DED pathogenesis.
A meta-analysis of 14 studies found serum 25(OH)D3 significantly lower in DED patients versus controls (WMD −5.93; p<0.001). Clinical trials show vitamin D3 supplementation improves TBUT, Schirmer, and OSDI. When combined with lutein, zeaxanthin, and curcumin in an 8-week RCT (n=155), it met primary DED endpoints (p<0.001 both measures).
Vitamin E (tocopherol) is a fat-soluble antioxidant included in validated DED multivitamin formulations showing significant symptom improvement. It has analgesic antioxidant effects in neuropathic ocular pain relevant to DED. Topical vitamin E combined with crosslinked hyaluronic acid and CoQ10 also improves dry eye in clinical studies.
Zeaxanthin co-supplemented with lutein improves tear production, stability, and quality while reducing ocular surface inflammation in DED across multiple RCTs. An 8-week double-blind RCT (n=155) with zeaxanthin 4 mg + lutein + curcumin + vitamin D3 significantly improved Schirmer test and OSDI (p<0.001). A 20-day RCT (n=110) reduced OSDI by ~52%.
Zinc is critical for activating antioxidant enzymes, cellular repair of ocular surface cells, and modulating immune responses in DED. A clinical DED multivitamin study found oral zinc-containing supplements improved intractable dry eye. Topical zinc-hyaluronate improves DED symptoms by reducing corneal receptor excitability, confirmed in published clinical studies.
Eyebright (Euphrasia officinalis) has been used in European herbal medicine since the 14th century for eye ailments including irritation, conjunctivitis, and dry eyes, based on its astringent tannins and iridoid constituents. However, no rigorous clinical RCTs have confirmed efficacy specifically for dry eyes; PeaceHealth and WebMD note the absence of good scientific evidence for its traditional uses.
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