Systemic Conditions and Dry Eye

A systemic condition is one that affects the body more broadly rather than being limited to one local structure. For example, Sjögren’s disease is an autoimmune disease that can affect the glands responsible for producing tears and saliva. Diabetes is a metabolic disease that can affect many tissues, including nerves and structures involved in maintaining the ocular surface. Thyroid disease can be associated with ocular-surface problems through several mechanisms, and thyroid eye disease can alter eyelid position and increase exposure.

So there is no single pathway called “systemic dry eye.” Different diseases can affect the ocular surface in very different ways. TFOS DEWS III describes systemic diseases as potential contributors to dry eye disease through mechanisms including inflammation, autoimmunity, metabolic dysregulation and ocular-surface exposure.

The list is long, and an association does not necessarily mean that the disease directly caused someone’s dry eye. Some of the better-recognized examples include:

• •Sjögren’s disease
• •rheumatoid arthritis
• •systemic lupus erythematosus
• •diabetes
• •certain thyroid-related conditions

Other systemic inflammatory, autoimmune, dermatological and neurological disorders can also be associated with ocular-surface disease. We are not going to turn this guide into a catalogue of every disease ever reported alongside dry eye. Instead, the following articles will concentrate on the systemic conditions that are particularly useful for a dry-eye patient to understand.

Normally, the immune system protects the body. In autoimmune disease, immune activity becomes directed against the body’s own tissues.

Depending on the disease, this can affect structures involved in maintaining the ocular surface. One particularly important example is the lacrimal gland, which produces much of the aqueous component of our tears. In systemic autoimmune and inflammatory diseases, immune-cell infiltration and inflammatory processes can impair lacrimal-gland function and alter the ocular-surface environment. TFOS DEWS III specifically discusses this mechanism in conditions including Sjögren’s disease, rheumatoid arthritis and systemic lupus erythematosus.

But autoimmune disease does not produce exactly the same dry-eye pattern in every patient. The ocular surface is a connected system, and several mechanisms may coexist.

Where Tears Come From: the lacrimal gland and the aqueous layer

Sjögren’s deserves particular attention because dry eye and dry mouth are central manifestations of the disease. In Sjögren’s, autoimmune processes can damage or disrupt the function of the lacrimal and salivary glands. This can result in significant aqueous tear deficiency.

But there is an important distinction: aqueous-deficient dry eye is not the same as Sjögren’s disease. There are other reasons why aqueous tear production may be reduced. And having dry eyes, even very dry eyes, does not by itself diagnose Sjögren’s. We will look at Sjögren’s separately because understanding when it should be considered, and how it is actually investigated, deserves much more detail.

Sjögren's Disease and Dry Eye: when dry eye is part of an autoimmune disease

Aqueous Deficiency

Yes. Both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have documented associations with dry eye disease. Systemic inflammation and immune dysregulation may affect the lacrimal functional unit and ocular surface. Some people may also have secondary Sjögren’s disease alongside another autoimmune disorder.

But again, having RA or lupus does not mean that every ocular symptom is caused by the systemic disease. Someone with rheumatoid arthritis can still have MGD, incomplete blinking, medication-related effects, exposure or another dry-eye driver. The purpose of knowing about the systemic association is not to replace an ocular-surface evaluation. It is to make the evaluation more complete.

Diabetes illustrates why systemic disease and dry eye cannot be reduced to “inflammation causes dryness.” Long-term metabolic changes associated with diabetes can affect multiple tissues relevant to the ocular surface. Neuropathy can alter corneal sensation and the normal communication between the ocular surface, nerves and tear-producing system.

Changes may also occur in tear secretion, epithelial health and other parts of ocular-surface homeostasis. So diabetes may influence dry eye through a different combination of mechanisms than Sjögren’s disease. We will explore these separately in the diabetes article.

Diabetes and Dry Eye

This relationship also needs careful wording. It is tempting to say:

“Thyroid problems cause dry eye.”

But that is much too broad. Different thyroid disorders and their associated conditions may affect the ocular surface differently. One particularly clear mechanism occurs in thyroid eye disease, where changes such as eye prominence and eyelid retraction can increase ocular-surface exposure. But thyroid-related ocular-surface disease is more complicated than exposure alone.

We will therefore look separately at what is actually known, and what should not be assumed, about thyroid disease and dry eye.

Thyroid Disease and Dry Eye

Not automatically. Severity alone cannot tell you the cause. A person can have severe dry eye for reasons that are entirely ocular or environmental. Conversely, systemic disease can sometimes be present when ocular findings initially appear relatively nonspecific.

The more useful question is: are there other clues that make a systemic condition worth investigating?

TFOS DEWS III specifically recommends considering general health as part of dry-eye assessment and includes questions about symptoms such as mouth dryness and enlarged salivary glands when evaluating possible differential diagnoses and associated conditions.

The relevant clues depend on the suspected disease. For example, alongside dry eye, a doctor may want to know about:

• •persistent dry mouth
• •swelling of the salivary glands
• •joint symptoms
• •skin or facial changes
• •systemic inflammatory symptoms
• •known autoimmune disease
• •diabetes
• •thyroid disease
• •or other significant medical history

None of these symptoms alone establishes why your eyes are dry. Their importance lies in the pattern. Dry eye plus persistent dry mouth, for example, creates a different clinical question from dry eye that appears only after many hours of contact-lens wear.

Contact Lenses and Dry Eye

Usually, it is not that simple.

There is no general “systemic dry-eye blood test.” Blood tests may be appropriate when a particular systemic condition is suspected, but the tests depend on what the doctor is looking for. TFOS DEWS III discusses inflammatory and autoimmune serum markers, but also notes an important limitation: common systemic inflammatory markers such as ESR and CRP do not reliably correlate with dry-eye symptoms or tear parameters. So a normal inflammatory marker does not simply prove that your dry eye has no systemic component. And an abnormal blood result does not automatically establish that it caused your ocular symptoms.

The results have to be interpreted in the context of the entire clinical picture.

How Dry Eye Is Diagnosed

Sometimes the first clue appears during an eye examination. Sometimes it comes from a primary-care doctor, rheumatologist, endocrinologist, dermatologist or another specialist. When an underlying systemic condition is suspected, collaboration can be important. TFOS DEWS III specifically emphasizes interdisciplinary care for dry-eye patients with systemic disease, for example coordination with rheumatology or endocrinology when appropriate.

That makes sense because an ophthalmologist can assess what is happening on the ocular surface, while another specialist may be needed to determine what is happening elsewhere in the body.

No. This may be the most important point in this article. Suppose someone has rheumatoid arthritis and dry eye. It is tempting to draw a straight line:

Rheumatoid arthritis→dry eye

But that person may also have:

• •MGD
• •reduced blinking
• •contact-lens history
• •medication effects
• •exposure
• •or several other contributors

The systemic disease may be a major driver, a smaller contributor, or simply one piece of a multifactorial picture. TFOS DEWS III emphasizes exactly this broader principle: dry eye is a multifactorial disease, and more than one etiological driver may be present in the same person.

Dry Eye Is Often Mixed

Medications and Dry Eye

That does not mean your dry eye is unexplained or less real. Many people with dry eye will never discover a systemic disease behind it.

Dry eye can arise from abnormalities within the ocular system itself (the tear film, meibomian glands, eyelids, blinking, ocular surface or nerves) as well as from environmental, lifestyle and iatrogenic factors.

Finding the relevant drivers is more useful than assuming that every patient must eventually discover one hidden “root cause.” Sometimes there is one dominant cause. Often there isn’t.