Treating Aqueous-Deficient Dry Eye

Aqueous-deficient dry eye, often abbreviated ADDE, occurs when the lacrimal system does not produce enough of the aqueous component of the tear film. The main lacrimal glands sit above and toward the outer side of each eye.

But tears are not simply water. The aqueous portion contains many substances important for ocular-surface health, including:

• •electrolytes
• •proteins
• •enzymes
• •growth factors
• •antimicrobial molecules
• •and other biologically active components

So when lacrimal secretion decreases, the problem is not simply less water. The entire ocular-surface environment can change.

Where Tears Come From

Because aqueous deficiency is a description of what is happening, not necessarily an explanation of why. Reduced aqueous production can occur in association with:

• •Sjögren disease
• •other autoimmune disease
• •lacrimal gland dysfunction or damage
• •age-related changes
• •certain medications
• •nerve dysfunction
• •previous surgery or radiation
• •and other conditions

Sometimes no single cause can be identified.

A review specifically addressing aqueous-deficient dry eye emphasizes that identifying the underlying cause is important because ADDE can sometimes be associated with systemic disease, not just an isolated eye problem.

So before asking “Which drops should I use?” there is sometimes a more important question: “Why am I not producing enough tears?”

Medications and Dry Eye

This is the most intuitive approach. If the natural tear film is insufficient, we can supplement it with artificial tears, gels or ointments. TFOS DEWS III describes ocular lubricants and tear supplements as a cornerstone of dry-eye management.

But artificial tears do not actually make the lacrimal gland work better. They primarily supplement the tear film from the outside. That distinction matters.

Artificial Tears & Lubricating Eye Drops

Not really. Natural tears are extraordinarily complex biological fluids. An artificial tear may contain combinations of:

• •water
• •electrolytes
• •lubricating polymers
• •osmoprotectants
• •lipids
• •preservatives or preservative-free systems
• •and other ingredients

Different formulations are designed to do different things. Some primarily lubricate. Some remain on the eye longer. Some are designed to supplement the lipid component. Some target tear-film osmolarity.

So “artificial tears” is a category containing many quite different products.

Because the eye continuously clears fluid from its surface. Tears evaporate, drain through the lacrimal drainage system, and are redistributed with every blink.

An ordinary low-viscosity eye drop may therefore provide only temporary supplementation. This is one reason someone with significant aqueous deficiency may say: “The drops help, but only for a short time.”

That does not necessarily mean the drops are useless. It may simply reflect the fact that they are replacing something the eye is continuously failing to produce.

Not automatically. Increasing viscosity can increase the amount of time a lubricant remains on the ocular surface. That is why gels and ointments can be useful, particularly at night or in more severe dryness. But increased viscosity can also cause:

• •blurred vision
• •stickiness
• •or discomfort

So the goal is not to use the thickest product possible. It is to find enough retention without creating unacceptable visual or sensory problems.

This becomes particularly important when drops are used frequently. Some preservatives can irritate or damage the ocular surface with repeated exposure, especially in already compromised eyes. For people requiring frequent lubrication, preservative-free formulations are often preferred.

This does not mean every preserved eye drop is inherently harmful. Frequency of use, preservative type and ocular-surface condition all matter. But if someone needs drops many times throughout the day, preservative exposure becomes a relevant consideration.

Now we move to a completely different strategy. Suppose the eye produces only a small amount of aqueous tears. Instead of continually adding more fluid from outside, perhaps we can make the existing tears stay on the eye longer.

This is the logic behind punctal occlusion. Normally, tears drain through tiny openings near the inner corners of the eyelids called the puncta, and from there enter the lacrimal drainage system. If we partially or completely block that drainage route, tears may remain on the ocular surface longer.

So artificial tears add fluid, while punctal occlusion reduces drainage. These are fundamentally different strategies.

Punctal Plugs & Tear Conservation

Punctal plugs are small devices inserted into the tear-drainage openings. Some are designed to remain temporarily. Others are intended for longer-term use. In more severe cases, the puncta can also be permanently closed using procedures such as cautery.

Punctal occlusion is commonly used for aqueous-deficient dry eye, and international clinical-practice data show it is much more commonly selected for aqueous-deficient than evaporative disease. But there is an important question.

Because retaining tears is not always automatically beneficial. Imagine the ocular surface is significantly inflamed. The tear film may contain inflammatory mediators and other products of ocular-surface disease. Reducing drainage changes tear clearance as well as tear volume. This is one reason clinicians may choose to control significant ocular-surface inflammation before or alongside punctal occlusion.

And punctal plugs themselves can have complications, including:

• •irritation
• •foreign-body sensation
• •plug loss
• •excess tearing
• •and occasionally infection or inflammation involving the drainage system

So punctal occlusion is a treatment with a specific target: insufficient tear retention. It is not simply a stronger version of artificial tears.

No. This distinction is important. Punctal plugs primarily change drainage. They do not directly repair a poorly functioning lacrimal gland.

A patient may therefore feel much better with punctal occlusion while the underlying tear-production problem remains. That is still a successful treatment if tear retention was the intended target. But improved tear volume is not the same as restored lacrimal gland function.

Now we come to perhaps the most interesting strategy. Instead of adding tears, or preventing tears from leaving, can we make the patient’s own lacrimal system produce more? Sometimes, yes.

These treatments are often called secretagogues or tear-stimulating therapies. TFOS DEWS III includes stimulation of natural tear production among the major approaches to tear-film management.

Stimulating Natural Tear Production

Secretagogues are treatments designed to stimulate secretion. But not all secretagogues act on exactly the same part of the tear system.

For example, diquafosol has been used in several Asian countries to promote aqueous and mucin secretion. Rebamipide is primarily associated with increased mucin production and ocular-surface effects. These treatments have been used extensively in Japan and parts of Asia, but availability varies substantially by country.

This is another reminder that dry-eye treatment options are not identical everywhere in the world.

This is a fascinating development because the tear system is controlled partly through neural reflexes. Think about what happens when you cut an onion, or when something irritates the inside of your nose. Your eyes can suddenly produce tears.

That happens because the lacrimal functional unit contains neural pathways connecting sensory stimulation with tear secretion. Modern treatments can take advantage of this pathway.

Yes. Intranasal treatments can activate neural pathways that stimulate natural tear production. One pharmacological example is varenicline nasal spray, which stimulates nicotinic acetylcholine receptors within the nasal cavity and activates the trigeminal parasympathetic pathway involved in tear production. Clinical trials of topical dry-eye therapies include evidence of increased tear production with this approach.

This is fundamentally different from artificial tears. Artificial tears put fluid onto the eye. Neurostimulation attempts to make the patient’s own lacrimal system produce more tear fluid.

Biologically, natural tears have an obvious advantage: they contain the complex mixture of proteins, lipids, electrolytes and signaling molecules produced by the lacrimal functional unit.

But that does not mean stimulation will work equally well for everyone. The system still needs enough functional neural and glandular capacity to respond. If the lacrimal gland is severely damaged, stimulating the pathway may have limited effect. Again, the treatment needs a functioning target.

Potentially, yes, but indirectly. This is where aqueous-deficient dry eye becomes more interesting than “my gland doesn’t make enough water.”

Chronic ocular-surface inflammation can become part of a self-perpetuating cycle. Reduced tear production can contribute to:

hyperosmolarity→inflammation→ocular-surface damage→further disruption of tear-film homeostasis

In some forms of aqueous-deficient disease, inflammation also involves the lacrimal functional unit itself. So anti-inflammatory treatment may help improve the environment in which normal tear secretion occurs.

That is one reason medications such as cyclosporine and lifitegrast are used in dry-eye disease. They are not artificial tears, and they are not simply lubricants. They target inflammatory pathways involved in the disease process. Reviews of ADDE management include topical anti-inflammatory agents among treatments used when inflammation contributes to lacrimal dysfunction and ocular-surface disease.

We will discuss anti-inflammatory treatment separately because it deserves its own section.

Anti-Inflammatory Treatment for Dry Eye

Sjögren disease deserves special attention because aqueous deficiency can be much more profound. In Sjögren disease, autoimmune processes can affect the lacrimal glands and substantially reduce tear secretion. Treatment may therefore require several strategies simultaneously:

• •replace tears
• •conserve tears
• •control inflammation
• •stimulate remaining secretion where possible
• •and sometimes protect the ocular surface using more advanced therapies

So simply telling someone with severe Sjögren-associated ADDE to “use artificial tears” may address only a small part of the problem.

Sjögren's Disease and Dry Eye

Treatment can move beyond standard lubricants. Options for more severe disease may include:

• •biological tear substitutes such as autologous serum or platelet-derived products
• •therapeutic contact lenses, including scleral lenses
• •punctal occlusion
• •anti-inflammatory or immunomodulatory treatment
• •and, in selected severe cases, more advanced interventions

TFOS DEWS III specifically discusses biologic tear substitutes, therapeutic approaches targeting inflammation, and advanced therapies for severe or refractory dry eye.

These treatments have different targets. A scleral lens, for example, does not make the lacrimal gland produce more tears. Instead, it can maintain a fluid reservoir over the cornea and physically protect the ocular surface. Again: same disease, completely different treatment mechanism.

Autologous Serum & Other Blood-Derived Eye Drops

Scleral Lenses for Dry Eye

This is an exciting research area. Researchers are investigating approaches involving:

• •stem cells
• •tissue engineering
• •regenerative medicine
• •and potential restoration of lacrimal gland function

But these remain investigational rather than established routine treatment. A review of lacrimal gland insufficiency describes regenerative medicine as a promising area of translational research, but not as current standard therapy.

So claims that an ordinary dry-eye treatment has “regenerated the lacrimal gland” deserve the same caution we used when discussing meibomian gland regeneration. Improved tear production does not automatically prove anatomical gland regeneration.

A low Schirmer result can support the presence of reduced aqueous tear production. But it should not be interpreted in isolation. Tear production varies. Testing conditions matter. Reflex tearing can influence the result. And aqueous deficiency can coexist with evaporative dry eye.

Low Schirmer → use punctal plugs

That is not a complete treatment algorithm. The clinician still needs to understand the broader ocular-surface picture.

The Schirmer Test

Absolutely, and this is extremely important. Dry eye does not always fit neatly into aqueous-deficient or evaporative. Mixed disease is common. Someone may simultaneously have reduced lacrimal secretion and poor meibomian gland function. In that situation, improving only one component may leave the tear film unstable.

This is one reason TFOS DEWS III emphasizes treatment according to the relevant etiological drivers and subtype(s) rather than assuming every patient belongs to one simple category.

Dry Eye Is Often Mixed

Again, return to the target. If the target is aqueous deficiency, useful questions might include:

• •Has tear volume increased?
• •Has tear meniscus height improved?
• •Has ocular-surface staining decreased?
• •Has tear-film stability improved?
• •Do I need artificial tears less often?
• •Are my symptoms improving?
• •Can I tolerate normal activities for longer?

Different treatments should also produce different expected changes. After artificial tears, we expect temporary supplementation. After punctal occlusion, we expect better tear retention. After a tear-stimulating treatment, we hope to see increased natural secretion. Those are not interchangeable outcomes.

How to Choose a Dry Eye Treatment