The interest in gut health in recent decades stems from the realization that the gut plays a pivotal role in overall health. Beyond its traditional function in digestion, the gut microbiome not only aids in digestive aspects but also has a profound impact on immune responses, systemic inflammation, and various health conditions.

The growing prominence of recent studies has brought attention to the correlation between the gut microbiome and ocular conditions, termed the gut-eye axis. This gut-eye axis emphasizes the significance of gut health and its impact on eye conditions, such as retinal disease, inflammatory orbital disorders, and dry eye disease.

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What is Dry Eye Disease?

Approximately 6.8% of the U.S. adult population, equivalent to 16.4 million people, is estimated to have dry eye disease. However, the exact number remains uncertain as prevalence statistics vary among studies, with estimates ranging from 5% to 50%. Notably, research suggests that Asian populations exhibit a higher prevalence compared to Caucasian populations. Moreover, the incidence of dry eye shows a linear increase with age, with a higher prevalence in women than men, particularly with advancing age.

The Ocular Surface

The structures of the eye, including the cornea, conjunctiva, eyelids, eyelashes, tear film, lacrimal glands, and meibomian glands, comprise the entire unit known as the ocular surface. Dry eye disease is a multifactorial disorder of the ocular surface characterized by an imbalance of the tear film.

Causes of Dry Eye Disease

The primary causes of dry eye disease can be classified into two basic categories: aqueous deficiency and evaporative. Aqueous deficiency occurs when there is insufficient production of the watery component of the tear film, leading to inadequate lubrication and moisture. Evaporative dry eye results from any factors that cause increased tear evaporation, leading to reduced stability and protection of the tear film.

Aqueous deficiency and evaporative dry eye disease are further sub-classified based on pathophysiology. Intrinsic, or internal factors include autoimmunity, hormonal imbalance, systemic and hereditary diseases, nerve damage, and gut dysbiosis. External factors causing dry eye disease include environmental factors related to pollutants or extreme weather conditions, behavioral factors associated with smoking or prolonged use of electronic devices, contact lens wear, and damage resulting from ocular surgeries.

Symptoms of Dry Eye Disease

Symptoms of dry eye disease include ocular discomfort and impaired visual function. Ocular discomfort encompasses a wide range of symptoms but usually includes dryness, redness, foreign body sensation, a heavy sensation, pain, light sensitivity, discharge, itching, and eye fatigue.

Conventional Dry Eye Disease Treatment

Conventional approaches for managing dry eye disease range from tear replacement to surgical interventions. Given the multifactorial complexity of dry eye disease, contemporary management protocols emphasize tailoring treatments to the specific etiology of the condition.

The Gut-Health Connection

Trillions of microorganisms, consisting of bacteria, viruses, and fungi, reside in the human body, with the digestive tract harboring the most species compared to other parts of the body. This microbial community, known as the gut microbiota, exists in the gut microbiome, the habitat that contains all the genetic material where essential metabolic functions take place.

The gut microbiome is thought of as an organ because it plays a significant role in protective and metabolic functions. Notably, the gut microbiome assists the immune system by driving anti-inflammatory responses, directing the production of antibodies, managing the production of metabolites, and maintaining gut barrier integrity.

Disruption of the gut microbiome, referred to as gut dysbiosis, can have numerous consequences such as immune compromise and systemic inflammation, leading to conditions like obesity, autoimmune disorders, and cancer.

Understanding the Gut-Eye Axis

Growing research not only validates the local and systemic influence of the gut microbiota, but evidence also supports the ability of the gut microbiota to affect remote sites such as the eye. This relationship and communication between the gut and the eye is identified as the gut-eye axis.

Imbalance in the gut microbiota, disruption of the gut barrier, and inflammatory responses have been demonstrated to affect ocular health, resulting in retinal disorders and inflammatory conditions, such as dry eye disease. The gut-eye axis underscores the significance of gut health in systemic inflammation and its impact on ocular health.

Evidence Linking Gut Health to Dry Eye Disease

Current research on gut health has identified differences in the gut microbiome in patients with dry eye disease compared to normal patients. These variations involve changes in specific bacterial genera, particularly those related to bacterial competition and gut barrier function related to leaky gut syndrome.

Noteworthy findings from various studies include:

• Patients with dry eye disease were observed to have reductions in the Faecalibacterium and Bifidobacterium genus.
• Parabacteroides and Faecalibacterium genera were identified as less prevalent in patients with dry eye symptoms.
• An overabundance of Lactobacillus and Bifidobacterium genera, with a depletion of certain species, notably Fusobacterium varium and Prevotella stercorea was noted in patients with Sjögren's-related dry eye.
• Reduced levels of Anaerobutyricum hallii found in patients with Sjögren's-related dry eye suggest a connection to butyrate-related immunological dysregulation and disruption of the gut barrier.

Patients with dry eye disease exhibited deviations in the Firmicutes/Bacteroidetes ratio. This ratio is recognized as a marker of gut health in a variety of disorders, implying a link between gut dysbiosis and dry eye disease.

Dietary Considerations for Gut and Eye Health

Promoting good gut health involves a variety of dietary strategies, such as consuming foods with anti-inflammatory properties, incorporating essential fatty acids, and supplementing with probiotics. Interestingly, similar nutritional practices have been studied and are advised for maintaining ocular health; guidelines for maintaining a healthy gut microbiome parallel recommendations for managing dry eye symptoms. 

An early study in 2014 concluded that adherence to the Mediterranean diet did not significantly improve dry eye symptoms. However, the diet raised vitamin D levels which had a small but favorable effect on dry eye symptoms. Another study found that patients with metabolic syndrome experiencing dry eye symptoms benefitted from applying the Mediterranean diet for 6 months. In 2023, obese elderly patients with dry eye disease who ate a Mediterranean diet and exercised for 6 months showed improvements in symptoms and ocular surface parameters.

Anti-Inflammatory Foods for Dry Eye

Omega-3 fatty acids are the most studied dietary supplements in ocular surface disease as they transform into anti-inflammatory compounds, support the lacrimal gland, and promote lipid and tear production, resulting in a stable tear film. 

Long-chain omega-3 supplementation, specifically with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has been found to improve tear production in patients with dry eye disease. When paired with conventional dry eye therapy, the beneficial effects may be more pronounced.

The optimal dry eye management strategy with omega-3 fatty acids calls for an increased dosage of 3000 mg, a longer supplementation period of 12 months, and an 80% EPA content. 

EPA-rich fish consist of American shad, Chinook and Atlantic salmon, and Atlantic herring. Fish oils derived from menhaden, salmon, sardine, cod liver, and herring have high concentrations of EPA. Lastly, black and red granular caviar are other EPA dietary options.

Integrative Treatment Approaches for Dry Eye Disease

Combining conventional and complementary treatment approaches for dry eye involves incorporating strategies that not only address ocular symptoms but also support overall health, including gut health.

Hydration for Dry Eye Disease

Proper hydration is fundamental for overall health and maintaining moisture in ocular structures. Dry eye disease patients are inclined to have lower whole-body hydration levels, suggesting that elevating hydration levels could be a practical strategy for managing dry eye disease.

Vitamins A, C, and E for Dry Eye Disease

Adding vitamins A, C, and E might be useful in maintaining the ocular tear film and minimizing dry eye symptoms. Patients with dry eye disease reported a subjective improvement in dry eye symptoms when given an oral supplementation with vitamins A, C, and E over an 8-week period. A separate study observed that short-term oral vitamin A supplementation improved the quality, rather than quantity, of tears in patients with dry eye disease.

Vitamin D for Dry Eye Disease

Oral vitamin D supplementation has been found to augment dry eye symptoms by promoting tear secretion, decreasing tear instability, and reducing inflammation of the eyelid margin. Further, the addition of vitamin D seems to boost the efficacy of artificial tears compared to using artificial tears alone. 

Vitamin B12

A unique study found that parenteral vitamin B12 supplementation improved neuropathic dry eye pain in patients with pre-existing vitamin B12 deficiency, indicating it is an effective treatment for managing neuropathic dry eye pain.

Lifestyle Modifications for Eye Health

Recommendations minimizing the environmental impact of dry eye disease involve the avoidance of outdoor pollutants like particulate matter and ozone, the use of wrap-around glasses or goggles on windy days, and the reduction of indoor aeroallergens like dust mites and mold spores.

Optimal indoor temperatures and humidity levels play a significant role in managing the evaporation of the ocular tear film. Patients with evaporative dry eye find temperatures within the range of 68° to 77° Fahrenheit and humidity levels between 30% and 50% most comfortable.

Implementation of behavior modification strategies can effectively minimize potential factors contributing to dry eye disease. Notably, smoking cessation and the avoidance of cigarette smoke are imperative in reducing factors that advance dry eye disease.

Diminished blink rate during activities like watching TV or reading provokes tear film instability and evaporation, contributing to dry eye disease. In instances where prolonged periods of reading, using digital devices, watching TV, or driving are unavoidable, it is advisable to augment these activities by incorporating frequent breaks and increased dosing of artificial tears.

Potential Probiotic Interventions

Given recent research findings on the correlation between the gut microbiome and ocular health, specifically in addressing dry eye disease, it is logical to consider probiotics for therapeutic purposes. Probiotics, known for promoting healthy gut microbiota by reducing inflammation and supporting immune function, could have a significant impact on dry eye disease treatment.

An initial investigation of patients with dry eye disease found that a combined dietary supplement containing fish oil, lactoferrin, zinc, vitamin C, lutein, vitamin E, γ-aminobutyric acid, and Enterococcus faecium WB2000 improved tear production and subjective dry eye symptoms after 8 weeks.

In a different clinical trial, researchers investigated the effects of Bifidobacterium lactis and Bifidobacterium bifidum on the tear film of patients with dry eye disease. The trial concluded that the supplementation resulted in a measurable increase in tear production and decreased tear evaporation, resulting in improved subjective dry eye symptoms.

Recently, researchers examined the effects of MULTIBIOTIC™ Probiotics (Medlab Pty Ltd., Botany, NSW, Australia), which contain 21.075 billion CFU of bacteria per capsule, including Streptococcus, Lactobacillus, and Bifidobacterium species, on the ocular tear film. The results indicated that probiotic enrichment improved tear production and stability.

Despite these encouraging outcomes, further research is necessary to understand the role of probiotics in the gut microbiome and ocular health. Previous mouse models have explored five promising probiotic species in the treatment of dry eye disease: Lactobacillus casei, Lactobacillus acidophilus, Lactobacillus reuteri, Bifidobacterium bifidum, and Streptococcus thermophilus. Future human clinical trials may focus on investigating these specific strains.

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Gut Health and Dry Eye Disease: Final Thoughts

The treatment and management of dry eye disease are complex, with numerous therapeutic options and combinations tailored for individual patients. An integrative approach recognizes gut health as an important facet of the dry eye disease process. Protocol strategies, incorporating dietary changes and supplementation, along with lifestyle modifications, address the multifactorial nature of dry eye disease and mirror approaches to balancing gut health.