Meibomian Gland Dysfunction: A Systemic Condition

For years, meibomian gland dysfunction (MGD) was mostly thought of as a localized problem of the eyelid margin, associated with clogged glands and meibum changes. Most therapeutic options focus on treating the ocular surface and eyelid margin. However, recent research now suggests systemic inflammation may be contributing to the inflammation of the eyelid margin, specifically through the gut-eye axis.

As eye care providers, we know that many systemic conditions affect the eyes. So, it should come as no surprise that there is more to the story of where the inflammation is coming from in MGD. This gives us a unique opportunity to connect the dots for our patients between chronic inflammation, gut health, and ocular surface disease and begin to think not only about symptoms, but also their root causes.

BEYOND THE EYELID

MGD is a disorder in which increased tear evaporation, tear hyperosmolarity, and a chain of inflammatory events create a self-perpetuating inflammatory loop.¹ The tear hyperosmolarity state stimulates a cascade of events involving proinflammatory mediators such as interleukin-1 beta and tumor necrosis factor alpha and proteases such as matrix metalloproteinase-9, which recruit inflammatory cells to the ocular surface.¹ This process also plays a role in goblet cell loss.

This inflammatory cascade exists beyond the meibomian glands and ocular surface. Many systemic conditions, such as metabolic syndrome, hormonal imbalances, autoimmune conditions, and gastrointestinal conditions, are associated with both inflammation and ocular surface manifestations.^1,2 These conditions are influenced by systemic signals, including circulating cytokines, gut permeability, microbial metabolites, nutritional health, and hormonal changes.¹

Additionally, conjunctival-associated lymphoid tissue has been proven to behave like other mucosal-associated lymphoid tissue in the body.^1,3 This plays a role in the innate and adaptive immune response of the ocular surface. However, conjunctival-associated lymphoid tissue does not act in isolation. These tissues are interconnected, meaning inflammatory signals originating elsewhere in the body can also play a role in increasing inflammation of the ocular surface.^1,3

Looking at the bigger picture, the eye has its own immune response and is a target of systemic inflammation.

THE GUT–EYE AXIS

The gut is typically thought of as the site of digestion, but it is much more than that. Approximately 70% to 80% of the human immune system is found in the gut.⁴ A healthy gut microbiome helps support immune balance, nutrient absorption, and barrier integrity. If this balance is disrupted through mechanisms like dysbiosis, leaky gut, poor diet, or chronic stress, inflammatory changes can spread throughout the body.

Gut dysbiosis, defined as an imbalance in the microbiome, is associated with a variety of immune conditions due to increased intestinal permeability. This causes lipopolysaccharides to trigger local inflammation, which then allows immune cells to travel through lymphatic vessels to distant tissues such as the ocular surface and meibomian glands.⁴ Additionally, commensal microorganisms in the gut microbiome help protect the host by fighting against pathogen growth and producing short-chain fatty acids, which have strong immunomodulatory effects and antiinflammatory properties.^4,5

Recent studies have shown an association between patients with dry eye disease (DED) and a lower gut microbial diversity compared with healthy controls.^6,7 A study comparing the gut of patients with Sjögren syndrome demonstrated that gut dysbiosis is not only prevalent in this population, but is also associated with ocular disease severity.⁷ Let’s not forget the well-documented association between rosacea (and the subset ocular rosacea) and various gastrointestinal diseases such as inflammatory bowel disease, celiac disease, Helicobacter pylori infection, and small-intestine bacterial overgrowth (Figure).⁸

Demodex mite overgrowth is a well-known contributor to ocular surface inflammation that is often seen in patients with rosacea. This further demonstrates the complex microbiome relationship between the ocular surface, skin, and gut.

In recent years, the gut-eye axis has become a popular topic in research on the management of MGD and DED. Current studies are also looking at the link between the gut microbiome and the ocular surface microbiome. Although more research is needed, these findings support the theory that gut dysbiosis may be a systemic contributor to the ocular surface inflammatory cascade in MGD.

NUTRITION AND SYSTEMIC INFLAMMATION

Nutrition is one of the most underused tools that we can use to influence systemic and ocular inflammation. It plays a crucial role in the composition of the gut microbiota and the immune system and has a large effect on the development of health and disease.4 Yet for some reason, it is not often discussed in the management of DED or MGD.

High intake of processed foods and refined carbohydrates drive a proinflammatory state in the body.⁹ These foods tend to be low in nutrients, yet high in sugars and additives, which can spike blood glucose and insulin levels. Repeated blood sugar spikes lead to an increase in oxidative stress and inflammatory cytokines such as interleukin-1, interleukin-1 beta, and tumor necrosis factor alpha.⁹ The ultra-processed dietary pattern can also contribute to gut dysbiosis, as previously mentioned. Conversely, foods rich in antioxidants, protein, fiber, omega-3 fatty acids, and phytonutrients help support an antiinflammatory diet, along with immune system regulation and microbial diversity in the gut microbiome.^9-11 These diets help feed the beneficial bacteria that create the short-chain fatty acids that suppress excess inflammatory signaling.⁴

In addition to diet, other lifestyle factors such as optimal hydration, stable blood sugar, restorative sleep, stress regulation, and regular movement are also critical factors in calming the inflammatory cascade. Poor sleep, chronic stress, and a sedentary lifestyle can elevate cortisol and inflammatory cytokines, making systemic inflammation worse and perpetuating MGD and DED.^12,13

NEW CONSIDERATIONS FOR CHRONIC LID DISEASE

When we think of MGD as simply a mechanical disorder, we miss the bigger picture and may cause a delay in optimal treatment. We need to consider systemic inflammation and gut dysbiosis in overall disease development and management.

The gut-eye axis helps us understand how systemic inflammation can lead to inflammation at the ocular tissue level. By helping address and reduce the root causes of systemic inflammation, we can help improve MGD symptoms, slow disease progression, and offer our patients a deeper understanding of their overall health. In addition to in-office dry eye procedures, future MGD management should include nutrition, gut health, and lifestyle guidance for deeper-level healing.