Can Tear Biomarkers Predict Which Dry Eye Treatments Will Work Best?

Dry eye treatment does not always follow a straightforward path. You may try lubricating eye drops, eyelid care, prescription treatments, or lifestyle changes and find that some options provide only limited relief.

This is because dry eye disease can develop from different underlying causes. Your symptoms may be linked to rapid tear evaporation, reduced tear production, inflammation, meibomian gland dysfunction, damage to the eye surface, changes in corneal nerve function, or a combination of these factors.

Tear biomarkers may help your specialist understand which biological processes are affecting your eyes. Although these tests cannot guarantee which treatment will work best, they may provide useful information to support a more personalised approach to managing dry eye.

Why the Same Dry Eye Treatment Does Not Work for Everyone

Dry eye symptoms can feel similar between people, but the reasons behind them may be very different. You may experience dryness, burning, grittiness, watering, or blurred vision because your eyes are not producing enough tears, or because your tears are evaporating too quickly due to problems with the eyelid oil glands.

Inflammation may be a key factor for some people but less significant for others. Other contributors can include eyelid conditions, allergies, contact lens irritation, certain medications, autoimmune conditions, previous eye surgery, or changes in the nerves that supply the eye.

This is why the same dry eye treatment does not always work for everyone. Your specialist will usually look at the specific causes and contributing factors affecting your eyes before recommending treatment, rather than using a single approach for every patient.

When Eye Symptoms Need Urgent Assessment

Dry eye usually causes symptoms such as irritation, grittiness, watering, or fluctuating vision rather than severe pain or sudden loss of sight. However, some other eye conditions can feel similar at first and may need urgent medical attention.

You should arrange an urgent appointment with an optometrist or GP, or contact NHS 111, if you develop a very painful red eye or a red eye while wearing contact lenses. These symptoms may need prompt assessment to identify the cause and start appropriate treatment.

Seek emergency eye care or go to A&E if you experience sudden vision loss, severe pain or light sensitivity, a red eye with a severe headache and nausea, a serious eye injury, chemical exposure, or an object stuck in your eye. If your eye becomes painful or unusually red, remove your contact lenses and do not wear them again until you have received professional advice.

What Are Tear Biomarkers?

Tear biomarkers are measurable biological characteristics detected in or derived from a tear sample. They may include proteins, enzymes, inflammatory molecules, electrolytes, lipids, antibodies, growth factors and measurements such as tear osmolarity.

Your tears contain a complex combination of substances that help lubricate the eye, protect against infection, control inflammation, support healing, and maintain clear vision. When the tear film or surface of your eyes becomes disrupted, the levels of certain components may change.

Testing selected changes may provide clues about inflammation, disturbed tear-film balance, reduced tear production or ocular-surface damage. However, biomarkers do not usually identify the exact dry-eye cause or subtype on their own. Your clinician will also need to assess tear stability, eyelid and meibomian-gland health, blinking, ocular-surface staining, symptoms and medical history.

What Does Predicting Treatment Response Mean?

Predicting treatment response does not mean that a test can tell you exactly which treatment will work. It means using information gathered before treatment to estimate whether one approach may be more suitable than another.

For a biomarker to become a reliable treatment-prediction tool, research would need to show consistently that patients with a particular result respond better to one treatment than patients without that result. Most tear biomarkers have not yet been validated to this level.

At present, biomarker results may add useful context to treatment planning. They should not replace clinical examination, discussion of your previous treatment response or careful review of the benefits, risks and suitability of each option.

How Close Are We to Truly Personalised Treatment?

Dry eye care is becoming more personalised, but no current tear biomarker can reliably determine which treatment will work best for an individual patient. Available tests provide additional information that may support your specialist’s decision rather than prescribing a particular treatment.

Some biomarkers have been studied more widely than others. Tests such as tear osmolarity and matrix metalloproteinase-9 (MMP-9) are available in some clinical settings, while more detailed analysis of cytokines, proteins, lipids, and genetic markers is still mainly used in research or specialist laboratories.

At present, the best approach is to combine biomarker results with your symptoms, eye examination findings, medical history, lifestyle factors, and previous treatment response. Looking at the full picture helps your clinician create a more accurate and personalised treatment plan.

How Clinical Findings May Influence Dry Eye Treatment

Finding	What It May Suggest	Possible Treatment Focus	Important Limitation
Raised MMP-9	Ocular-surface inflammatory activity	Further assessment of inflammation and supervised anti-inflammatory treatment where appropriate	Does not identify the best medicine or exclude other causes
Raised tear osmolarity	Disturbed tear-film homeostasis	Improving tear-film stability, reducing evaporation and supporting tear quantity	Cannot distinguish aqueous deficiency from evaporation by itself
Reduced tear production	Aqueous-deficient dry eye	Lubrication, tear conservation, inflammation control and investigation of relevant causes	Requires clinical tear-volume and surface assessment
Meibomian-gland obstruction	Evaporative dry eye	Eyelid care, gland treatment and improved blinking	Tear biomarkers cannot replace gland examination or meibography
Significant ocular-surface staining	Surface-cell injury	Protection, lubrication, inflammation control and investigation of the cause	Staining is not specific to one dry-eye subtype
Severe symptoms with limited visible damage	Possible nerve sensitisation or another pain mechanism	Further specialist assessment rather than escalating surface treatment automatically	No routine tear biomarker confirms neuropathic ocular pain
Reduced protective tear proteins	Possible lacrimal-gland dysfunction or severe surface disturbance	Further specialist assessment	Detailed protein testing remains mainly specialist or research-based

These findings guide a wider clinical assessment rather than functioning as a treatment prescription. Your response, tolerability, medical history and changing examination findings remain important throughout care.

Evidence Note

Small studies have explored whether MMP-9 status is associated with response to selected anti-inflammatory treatments. Some differences have been reported between MMP-9-positive and negative groups, but the studies were limited by their size, short follow-up and selected patient populations. The findings do not establish MMP-9 as a reliable treatment-selection test.

These findings are promising but do not prove that MMP-9 can reliably select treatment for every patient. The studies involved specific patient groups, relatively short follow-up periods and treatment approaches that may not reflect all UK clinical settings.

The Role of Inflammation in Dry Eye Disease

Inflammation plays an important role in dry eye disease for many people. An unstable or concentrated tear film can stress the surface of your eyes, triggering inflammatory responses that may make the tear film even less stable.

This can create a cycle where tear instability causes irritation and inflammation, while inflammation further affects tear quality, surface cells, tear production, and sensitivity. Treatments that target inflammation may help some patients, but the type and severity of inflammation can vary between individuals.

Understanding whether inflammation is a key factor in your dry eye may help your specialist choose a more suitable treatment approach. However, biomarker results are considered alongside your symptoms, examination findings, and overall eye health.

Can MMP-9 Help Guide Anti-Inflammatory Treatment?

Matrix metalloproteinase-9, commonly known as MMP-9, is an enzyme associated with inflammation and tissue remodelling on the ocular surface. A positive point-of-care result indicates that MMP-9 in the tear sample is above the test threshold, but it does not provide a precise measurement of inflammation severity.

The result may support your specialist’s assessment when ocular-surface inflammation is suspected. Small studies suggest that MMP-9-positive patients may respond differently to treatments such as topical ciclosporin or a short supervised course of corticosteroid eye drops. However, the evidence is not strong enough for the test to select a medicine independently.

Corticosteroid eye drops can cause side effects, including raised eye pressure and an increased risk of infection. Longer courses may also increase the risk of cataracts, so these medicines should only be used for the prescribed duration with appropriate clinical monitoring.

A positive MMP-9 result still cannot show exactly which treatment will work best for you. The marker can also increase in other eye surface conditions, and a negative result does not completely rule out inflammation or dry eye disease.

What a Negative MMP-9 Result May Mean

A negative MMP-9 result does not always mean that your eyes are healthy or that inflammation is not involved. The level of the marker may be below the detection limit, inflammation may be mild or occasional, or a different inflammatory pathway may be contributing to your symptoms.

Your dry eye symptoms may also be linked to other factors, such as rapid tear evaporation, blocked meibomian glands, reduced tear production, incomplete blinking, allergies, medication effects, or increased corneal nerve sensitivity. These causes may require different assessments and treatment approaches.

For this reason, your specialist will not usually rely on a negative MMP-9 result alone when assessing dry eye. It is one part of the overall picture and needs to be considered alongside your symptoms, eye examination findings, and other test results.

Can Osmolarity Show Whether Treatment Is Working?

Tear osmolarity may change as the surface of your eyes becomes more stable during treatment. A reduction over time may provide additional evidence that your treatment is helping to improve the tear environment.

However, osmolarity levels can vary between appointments and may even differ between your two eyes. Factors such as recent eye drop use, reflex tearing, environmental conditions, sample collection, and natural daily changes can affect the results.

Monitoring osmolarity can be helpful when the results are assessed consistently alongside your symptoms and other eye tests. One improved reading alone does not always mean that your dry eye is fully controlled.

Cytokines and the Future of Treatment Prediction

Cytokines are small signalling proteins that help control immune activity within your body. Researchers have found that the levels of certain cytokines and chemokines in tears may change in people with different types of dry eye disease.

Researchers hope that combinations of inflammatory markers may eventually help identify biologically distinct groups of dry eye disease. These patterns could support future research into treatment response, but no tear-cytokine profile can currently determine which anti-inflammatory treatment an individual patient should receive.

At present, detailed cytokine testing is not part of most routine dry eye assessments. More research is needed to establish reliable results, understand differences between patients, and confirm whether cytokine-guided treatment can consistently improve outcomes.

Research Insight

Future treatment prediction is more likely to involve combinations of information rather than one biomarker. Researchers are studying inflammatory molecules, tear proteins, lipids, imaging results, symptoms and clinical signs together to identify distinct dry-eye patterns.

This approach may eventually allow clinicians to classify patients more precisely and compare likely treatment responses. However, larger prospective studies, common laboratory standards and evidence that biomarker-guided care improves patient outcomes are still needed before these systems can become part of routine practice.

Tear Proteins and Lacrimal Gland Function

Your tears contain protective proteins produced by the lacrimal glands and the surface of your eyes. These include lactoferrin, lysozyme, lipocalin-1, lacritin, immunoglobulins, and growth factors, which all help maintain a healthy tear film.

Changes in certain tear proteins may provide supporting information about lacrimal-gland secretion or ocular-surface health. For example, reduced lactoferrin has been associated with aqueous-deficient dry eye, although results can be affected by age, collection technique and other ocular-surface conditions.

Measurements such as lactoferrin may provide supporting information about lacrimal-gland function or aqueous tear deficiency. However, detailed protein testing is not routinely available in every dry-eye clinic and cannot independently determine whether you need tear-conservation procedures, prescription treatment or biological tear substitutes.

Lipid Biomarkers and Meibomian Gland Dysfunction

Your meibomian glands release oils that form the outer layer of your tear film. This oily layer helps slow tear evaporation and keeps the surface of your eyes smooth and comfortable between blinks.

When these glands become blocked or their oil quality changes, your tears may evaporate too quickly and contribute to evaporative dry eye. Researchers are studying tear lipids to identify patterns that may help explain meibomian gland dysfunction and different types of dry eye.

At present, lipid biomarker testing is not widely used to guide routine treatment decisions. Your specialist will usually rely on eyelid examination, gland expression, tear break-up testing, lipid layer assessment, and meibography to understand the main factors affecting your eyes.

Choosing Treatment for Aqueous-Deficient Dry Eye

If your tests and eye examination suggest that you are producing fewer watery tears, your treatment plan may focus on improving moisture levels and reducing tear loss. Options may include preservative-free lubricating drops, methods to conserve your natural tears, and treatments to control inflammation.

Aqueous-deficient dry eye can sometimes be linked with autoimmune conditions, certain medications, ageing, hormonal changes, or problems affecting the lacrimal glands. This is why your medical history is an important part of understanding your condition alongside tear test results.

Biomarkers such as lactoferrin, osmolarity, and inflammatory markers may provide additional information about your dry eye. However, they cannot decide on their own whether you need treatments such as punctal occlusion, prescription medicines, specialised tear substitutes, or further investigation.

Choosing Treatment for Evaporative Dry Eye

When rapid tear evaporation is the main cause of your dry eye, simply adding more watery eye drops may only provide short-term relief. Your treatment plan may need to focus on the eyelid oil glands, blinking habits, environmental factors, and improving tear film stability.

Depending on your eye examination, your specialist may recommend eyelid hygiene, warm compresses, suitable lubricants and treatment for eyelid inflammation. In selected patients, specialist procedures such as gland expression, controlled heating or light-based treatment may also be considered. The right approach will depend on the specific factors affecting your eyes.

Tear lipid and inflammatory profiles may eventually help identify which treatments are more likely to benefit certain patients. At present, assessing your meibomian glands through clinical examination remains an important part of choosing and monitoring treatment.

Biomarkers and Prescription Anti-Inflammatory Drops

Prescription anti-inflammatory treatment may be considered when inflammation contributes to dry eye disease. In UK practice, topical ciclosporin is one option for selected adults with severe keratitis that has not improved despite treatment with tear substitutes. Treatment choice depends on the diagnosis, severity, previous care, possible side effects and whether the medicine is licensed and available for your circumstances.

A positive inflammatory biomarker result may support your specialist’s decision to consider anti-inflammatory treatment, but it cannot confirm that a specific medicine will work for you. Factors such as symptom severity, previous treatment response, other eye conditions, tolerability, and availability also need to be considered.

Research suggests that topical ciclosporin can improve selected signs or symptoms in some people with dry eye disease, but response varies and improvement may take time. MMP-9 and other inflammatory markers are being investigated as possible response predictors, but they cannot yet confirm whether ciclosporin or another treatment will work for an individual patient.

UK Guidance Note

UK dry-eye treatment is based on symptoms, examination findings, disease severity and the factors contributing to tear-film disturbance. Biomarker tests may provide additional information in selected specialist clinics, but they are not required before every treatment and cannot independently determine the best option.

NICE technology appraisal TA369 recommends ciclosporin emulsion (Ikervis) as an option, within its marketing authorisation, for treating severe keratitis in adults with dry eye disease that has not improved despite treatment with tear substitutes. This does not mean that ciclosporin is appropriate for every person with dry eye, ocular-surface inflammation or a positive MMP-9 result.

Biomarkers and Meibomian Gland Treatments

Treatments for meibomian gland dysfunction aim to improve the quality and flow of the oils released by your eyelids. Depending on your condition, your specialist may recommend options such as heat-based therapies, gland expression, intense pulsed light, eyelid cleaning, or treatment for related inflammation.

Clinical measurements of tear stability and meibomian-gland function may provide some information about likely treatment response. A small prospective study identified a possible association between lower baseline non-invasive tear break-up time and improvement after intense regulated pulsed-light treatment.

In the future, biomarker testing may combine information about your tear lipids, inflammation levels, gland structure, and tear stability. This could help your specialist understand whether your condition is mainly due to reversible gland blockage or other factors such as gland damage or additional causes of dry eye.

Blood-Derived Serum Eye Drops and Biomarker Research

People with severe ocular-surface disease that has not improved with conventional eye drops may sometimes be considered for blood-derived serum eye drops. These preparations contain proteins, growth factors and other components that resemble some of the substances found in natural tears.

Autologous serum eye drops are prepared from your own blood. In some UK services, donor-derived serum may also be used. These are specialist treatments that require appropriate assessment, preparation, storage and clinical monitoring.

Researchers are investigating whether tear-protein or ocular-surface patterns could eventually help identify patients who are most likely to benefit. At present, there is no validated biomarker test that determines whether serum eye drops are appropriate, so the decision is based on disease severity, ocular-surface findings, previous treatment and specialist judgement.

Can Biomarkers Monitor Treatment Progress?

In selected specialist or research settings, repeating a biomarker test may provide additional information about changes occurring during treatment. For example, MMP-9 test status or tear osmolarity may change over time, but these results can vary and are not required for monitoring every patient.

Changes in a biomarker may provide supplementary objective information, but they do not establish whether treatment has been successful overall. The healing of your eye surface, tear stability, inflammation levels, and corneal nerve sensitivity may all recover at different speeds.

In some cases, you may feel better even when a biomarker result remains abnormal. This is why your specialist will consider both test results and your experience, including comfort, vision, daily activities, and how well you tolerate your treatment.

Clinical Tip

Record which eye drops, eyelid treatments and procedures you have tried, how often you used them, how long you continued them and whether they caused irritation or provided relief. Bring this information, along with your current medicines and contact-lens details, to your appointment.

A treatment that appears unsuccessful may sometimes have been used for too short a period, inconsistently or without addressing another contributing factor. Do not restart, stop or combine prescription eye drops without advice from the clinician responsible for your care.

Why Biomarkers Must Be Combined with a Full Examination

No single tear biomarker can show every factor involved in your dry eye disease. Your specialist will also assess tear stability, tear volume, ocular surface staining, eyelid position, blink quality, meibomian gland function, corneal sensitivity, contact lens use, and environmental triggers to understand your condition fully.

Your symptoms and examination findings may not always match. You may experience significant discomfort with limited visible damage due to increased nerve sensitivity, while reduced corneal sensation may sometimes mean you have noticeable surface changes with fewer symptoms.

A specialist assessment may include biomarkers when they are clinically appropriate and available. These results should add biological information to your symptoms and examination findings rather than act as a stand-alone test that guarantees one treatment will work.

Myth vs Fact

Myth	Fact
A tear test can identify the treatment that will work best	No current tear biomarker can guarantee treatment response
A positive MMP-9 result means you need ciclosporin	It may support evidence of inflammation, but treatment depends on the full assessment
A negative MMP-9 result rules out inflammation	Other inflammatory pathways may be active and the marker may be below the test threshold
High osmolarity identifies the exact dry-eye subtype	It indicates disturbed tear-film balance but cannot distinguish every cause
Cytokine testing is routinely available	Detailed cytokine testing remains mainly research-based
Biomarkers can replace meibomian-gland examination	Eyelid and gland assessment remains essential in evaporative dry eye
An improved biomarker proves treatment has worked	Symptoms, surface healing, nerve sensitivity and biomarkers may change at different rates
Serum eye drops are selected through biomarker testing	Suitability is currently based on severity, examination and previous treatment response
More biomarker tests always produce a better plan	Testing is useful only when the result is clinically interpretable and may affect management
Personalised treatment means guaranteed success	Personalisation may improve treatment relevance, but individual response remains variable

Key Takeaways

• Dry eye disease has several possible causes, and more than one may be present.
• Tear biomarkers can provide additional biological information but cannot guarantee treatment response.
• MMP-9 may indicate ocular-surface inflammatory activity but does not select a specific medicine.
• Small studies suggest that MMP-9 positivity may be associated with a different response to selected anti-inflammatory treatments, but larger validation studies are needed.
• Tear osmolarity can identify disturbed tear-film homeostasis but not its precise cause.
• Detailed cytokine, protein and lipid tests remain largely research-based.
• Meibomian-gland examination remains central when evaporative dry eye is suspected.
• Biomarkers are not currently validated for choosing serum eye drops.
• Repeated biomarker testing is not necessary for every patient.
• UK treatment decisions must consider licensing, NICE guidance, disease severity and specialist assessment.
• Your symptoms, examination findings and previous treatment response remain essential.
• A painful red eye, sudden sight change or red eye in a contact-lens wearer requires urgent assessment.

Frequently Asked Questions

1. Can tear biomarkers tell which dry eye treatment will work for me?
   Tear biomarkers may provide information about the biological processes contributing to your dry eye, such as inflammation or tear instability. However, they cannot currently guarantee which treatment will work best and should be combined with a full eye assessment.
2. Are tear biomarkers used routinely for dry eye treatment decisions?
   Some tests, such as tear osmolarity and MMP-9 testing, are available in certain clinical settings. Other advanced biomarker tests, including detailed protein and cytokine analysis, are mainly used in research or specialist environments.
3. Can tear biomarkers show if inflammation is causing my dry eye?
   Certain biomarkers may provide evidence of increased inflammatory activity on the ocular surface. This can support the wider assessment, but no biomarker detects every inflammatory pathway or confirms that inflammation is the only cause of your symptoms.
4. Does a high MMP-9 result mean I need anti-inflammatory eye drops?
   A raised MMP-9 result may indicate ocular-surface inflammatory activity, but it does not mean that you automatically need anti-inflammatory eye drops. Your specialist will consider the result alongside your symptoms, ocular-surface findings, previous treatment, possible side effects and whether a particular medicine is appropriate and available.
5. Can tear osmolarity predict whether my dry eye will improve?
   Tear osmolarity can provide evidence that your tear-film balance is disturbed, but it cannot predict treatment success on its own. Changes in osmolarity may be useful when monitored alongside other signs of improvement.
6. Could biomarkers help identify my type of dry eye?
   Tear biomarkers may provide clues about inflammation, tear-film homeostasis or lacrimal-gland function. However, they cannot independently determine your dry-eye subtype. Tests assessing tear production, tear stability, the eyelids, meibomian glands and ocular surface are also needed.
7. Will personalised dry eye treatment become more common in the future?
   Research is moving towards more personalised approaches using combinations of biomarkers, imaging, symptoms, and clinical findings. Future testing may help specialists match treatments more accurately to individual patients. Current biomarkers are not yet sufficiently validated to guarantee that one treatment will be more effective than another.
8. Can tear biomarkers monitor whether treatment is working?
   Some biomarker results may change during treatment, but this does not always reflect meaningful overall improvement. Test results, symptom relief and ocular-surface healing may change at different rates. Repeat testing is not necessary for every patient, and its usefulness depends on the biomarker and clinical situation.
9. Why are tear biomarkers not enough to diagnose or treat dry eye alone?
   Dry eye disease involves many different factors, including tear production, evaporation, inflammation, eyelid health, and nerve sensitivity. A biomarker provides useful information but cannot replace a complete eye examination.
10. Who may benefit from tear biomarker testing?
    Tear biomarker testing may be considered during selected specialist assessments, particularly when symptoms are persistent, examination findings are complex or the response to previous treatment is difficult to interpret. However, not every patient needs biomarker testing, and standard clinical assessment may provide enough information to guide care.

Final Thoughts: The Future of Personalised Dry Eye Treatment

Tear biomarkers are a developing area of dry-eye research. Selected tests may provide additional information about inflammation, tear-film homeostasis and other biological processes, helping your specialist build a more complete picture of your condition. However, no current biomarker can guarantee treatment response, and results must be interpreted alongside your symptoms, examination findings and previous treatment response.

If you’d like to find out whether specialist testing using tear biomarkers in London is suitable for you, feel free to contact us at Eye Clinic London to arrange a consultation.

References:

1. Jones, L. et al. (2025) ‘TFOS DEWS III: Management and therapy’, American Journal of Ophthalmology, 279, pp. 289–386. Available at: https://pubmed.ncbi.nlm.nih.gov/40467022/
2. Wolffsohn, J.S. et al. (2025) ‘TFOS DEWS III: Diagnostic methodology’, American Journal of Ophthalmology, 279, pp. 387–450. Available at: https://pubmed.ncbi.nlm.nih.gov/40451408/
3. Kumar, N.R. et al. (2023) ‘Tear biomarkers in dry eye disease: progress in the last decade’, Indian Journal of Ophthalmology, 71(4), pp. 1190–1202. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC10276712/
4. Vigo, L. et al. (2019) ‘Ocular surface workup in patients with meibomian gland dysfunction treated with intense regulated pulsed light’, Diagnostics, 9(4), article 147. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC6963914/
5. Suárez-Cortés, T., Merino-Inda, N. and Benitez-del-Castillo, J.M. (2022) ‘Tear and ocular surface disease biomarkers: a diagnostic and clinical perspective for ocular allergies and dry eye disease’, Experimental Eye Research, 221, article 109121. Available at: https://www.sciencedirect.com/science/article/pii/S0014483522002019