When does inflammation become a treatment target?
If you spend enough time reading about dry eye, eventually you will hear:
“Dry eye is an inflammatory disease.”
Then you may be prescribed:
And this can create a confusing impression:
Did inflammation cause my MGD? Did my MGD cause inflammation?
And if inflammation disappears, should the dry eye disappear too?
The answer is more complicated. Because in dry eye, inflammation can be a driver, a consequence, and sometimes part of a self-perpetuating cycle.
Understanding that distinction makes anti-inflammatory treatment much easier to understand.
Inflammation & Oxidative Stress: how inflammation fits into dry eye
Imagine that the tear film becomes unstable. Perhaps there is:
The ocular surface is now exposed to an abnormal environment. Tear osmolarity can increase. Epithelial cells become stressed. Inflammatory signaling can be activated. Immune cells become involved. The surface becomes increasingly irritated and damaged, and this can further disrupt tear-film homeostasis.
In simplified form:
tear-film dysfunctionocular-surface stressinflammationepithelial and lacrimal functional-unit dysfunctioneven poorer tear-film homeostasismore inflammation
This is often described as a vicious cycle.
That depends on the patient. And this is where the statement “dry eye is inflammation” becomes too simplistic.
Suppose someone develops severe obstructive MGD. Poor lipid secretion increases evaporation. The tear film becomes unstable. The ocular surface becomes stressed. Inflammation develops. Inflammation may now become an important part of the disease. But that does not mean inflammation necessarily caused the original gland obstruction.
In another patient with autoimmune disease, immune-mediated inflammation may be much closer to the original driver of lacrimal dysfunction. In another, several mechanisms may develop together.
So the fact that inflammation is present does not automatically tell us why the dry eye began.
Because a secondary process can become clinically important in its own right.
Imagine you cut your skin. The original problem was mechanical injury. Inflammation develops afterward. That inflammation may still influence pain, swelling and healing. Treating a downstream process does not require pretending it was the original cause.
The same logic applies to dry eye. Even if inflammation began as a consequence of MGD, aqueous deficiency, exposure or another problem, once established, it may contribute to maintaining ocular-surface disease.
So the treatment target becomes: break the inflammatory part of the cycle.
Different medications act on different inflammatory pathways. But broadly, the goal is to reduce immune and inflammatory activity that is contributing to ocular-surface dysfunction.
That can potentially improve:
TFOS DEWS III includes corticosteroids, T-cell immunomodulatory therapies and other pharmacological anti-inflammatory agents among treatments for dry eye where inflammatory mechanisms are relevant.
Cyclosporine is an immunomodulatory drug. Topically, it suppresses activation of T cells and inflammatory signaling involved in ocular-surface disease.
You may know formulations containing 0.05%, 0.09%, 0.1% or other concentrations, depending on the country and product.
But the central idea is not that cyclosporine adds moisture to the eye. It is that cyclosporine modifies an inflammatory immune pathway. That makes it fundamentally different from an artificial tear.
Yes, although response varies.
A systematic review and meta-analysis of 12 randomized controlled trials involving 1,367 patients found that topical 0.05% cyclosporine improved several outcomes compared with controls, including:
More recently, a 2025 meta-analysis of six randomized trials involving 2,170 patients found that 0.1% cyclosporine improved corneal and conjunctival staining and OSDI compared with vehicle.
So cyclosporine has a substantial clinical evidence base. But that does not mean every patient with dry eye will respond.
This is an interesting point. Cyclosporine is not a secretagogue like the treatments we discussed in the previous article. It does not simply press a biochemical button saying “make more tears.”
But if inflammation is interfering with the lacrimal functional unit, reducing that inflammation may allow the system to function better. So an improvement in Schirmer score after cyclosporine does not necessarily mean the drug directly stimulates secretion. It may reflect improvement in the environment in which tear production occurs.
This is an important distinction between stimulating a function and removing something that is interfering with that function.
Stimulating Natural Tear Production: the secretagogue approach
This is one of the biggest practical differences between cyclosporine and treatments such as artificial tears. An artificial tear can change the ocular surface within seconds. Cyclosporine is trying to modify an inflammatory biological process. That takes time.
Clinical trials generally evaluate outcomes over weeks to months, rather than minutes or days. For example, randomized studies included in the recent 0.1% cyclosporine meta-analysis followed patients for periods ranging from four weeks to six months.
So “I used cyclosporine for five days and nothing happened” does not tell us much about whether the treatment could eventually work.
This is one of the most common practical problems. People can experience:
This can be particularly frustrating because the medication is being placed onto an ocular surface that is already sensitive and inflamed. Clinical studies consistently report instillation-site discomfort among common adverse effects of topical dry-eye medications.
Importantly, formulation matters too. Different cyclosporine products use different drug-delivery systems and vehicles, so two cyclosporine preparations are not necessarily experienced identically by the patient.
Not automatically. Concentration is only one part of drug delivery. Formulation influences:
So comparing 0.05% with 0.1% purely by looking at the number on the box can be misleading. The clinically relevant question is whether that particular formulation delivers an effective amount of drug to the target tissue with acceptable tolerability.
Lifitegrast is another topical anti-inflammatory medication for dry eye, but it does not work the same way as cyclosporine. It inhibits the interaction between LFA-1 and ICAM-1, which is involved in T-cell adhesion, migration and inflammatory signaling.
So again, the target is immune activity. But the molecular mechanism is different. This is why cyclosporine and lifitegrast should not simply be thought of as two brands of the same medication.
Randomized clinical trials support its efficacy for dry-eye disease. A systematic review and meta-analysis incorporating five randomized trials plus additional clinical studies — more than 3,000 participants overall — found improvements across several signs and symptoms compared with placebo, although outcomes varied between studies.
And this variability is not unusual in dry-eye trials. A 2025 systematic review of topical pharmacological therapies found that significant improvements versus control were demonstrated more consistently for signs such as staining or Schirmer testing than for subjective symptom outcomes.
That discrepancy between what the eye looks like and how the eye feels is something we have encountered repeatedly throughout this Guide.
Common problems include instillation-site irritation or discomfort and an unusual taste sensation called dysgeusia.
The latter can seem bizarre for an eye drop. But medication placed on the eye can enter the lacrimal drainage system and reach the nasal/oropharyngeal region. So some patients notice an unpleasant or unusual taste after instillation.
Meta-analysis has found these effects to be generally mild or moderate, although they can certainly be bothersome enough for some people to stop treatment.
We do not have strong evidence supporting a simple universal answer. They act through different mechanisms. Formulations differ. Individual tolerance differs. And dry-eye populations differ.
A recurring problem in dry-eye pharmacology is that trials use different:
A systematic review of topical dry-eye drugs highlighted exactly this problem: even large trials frequently demonstrated benefit in either a sign or symptom endpoint without consistently demonstrating both simultaneously.
So “Which anti-inflammatory is best?” is often less useful than “Which inflammatory pathway and formulation make sense for this patient, and can they tolerate it long enough to benefit?”
Corticosteroids are powerful anti-inflammatory medications. They can suppress inflammation relatively quickly. That makes them very different from slower immunomodulatory treatments such as cyclosporine.
In dry eye, topical corticosteroids may be used for limited periods when significant ocular-surface inflammation needs to be brought under control. They may also sometimes be used as a short-term bridge while a slower-acting treatment begins to work.
TFOS DEWS III includes topical and oral corticosteroids among anti-inflammatory approaches for selected etiological drivers of dry eye.
Because corticosteroids come with important risks, particularly with prolonged or inappropriate use. Depending on the drug, dose and duration, ocular corticosteroids can increase the risk of:
That is why steroid eye drops are not simply another lubricant that can be used indefinitely without monitoring. They are medications requiring appropriate medical supervision.
It suggests that inflammation may be contributing to symptoms or signs. But it does not necessarily reveal the original cause.
Imagine someone has:
MGDrapid evaporationsurface stressinflammation
A steroid reduces inflammation. The patient feels dramatically better. That tells us the inflammatory component mattered. It does not prove that the MGD disappeared. If the original evaporative problem remains, inflammation may eventually return.
So treatment response can identify an important mechanism without necessarily identifying the root cause.
The pharmacological landscape of dry eye is expanding quickly. New formulations of existing immunomodulators and drugs targeting different inflammatory pathways continue to appear. A 2025 systematic review identified 107 publications examining topical prescription medications and newer therapies for dry eye, illustrating how rapidly this area has grown.
But newer does not automatically mean better. Every new drug needs to be evaluated for:
No. This is becoming increasingly important because prescription dry-eye treatment now includes several completely different mechanisms. For example:
A recent systematic review explicitly separates these pharmacological strategies according to their different treatment targets. So “prescription dry-eye medication” does not automatically mean “anti-inflammatory medication.”
This requires nuance. Cyclosporine or lifitegrast does not mechanically evacuate obstructed meibomian glands. It does not directly turn thick meibum into normal meibum. It does not recreate glands that have been lost.
But MGD and ocular-surface inflammation can interact. So reducing inflammation may improve the overall ocular-surface environment while another treatment addresses gland obstruction or secretion. This is another example of why one patient may need more than one treatment target.
Yes, inflammatory processes can involve the eyelids and meibomian gland environment. Conditions such as blepharitis and ocular rosacea can combine inflammatory and glandular abnormalities.
But again, we should avoid turning that into “all MGD is caused by inflammation.” MGD is heterogeneous. Obstruction, altered keratinization, changes in meibum, blinking, age, hormonal factors and inflammatory conditions can all play roles in different patients.
This is another common source of confusion. An eye does not need to look dramatically red for inflammatory signaling to be present. Some inflammatory activity occurs at a molecular level.
Tests such as tear MMP-9 can provide information about certain inflammatory pathways. But no single biomarker tells us everything about ocular-surface inflammation. A positive inflammatory marker does not automatically identify the cause. And a negative result does not necessarily prove that every inflammatory pathway is inactive.
No. This is exactly the kind of universal treatment logic that modern dry-eye management is trying to move away from. TFOS DEWS III emphasizes etiology-based targeted management of the relevant dry-eye subtype or subtypes.
The question should be:
Not:
There is no single perfect test. The clinician may consider:
Response to treatment can also provide additional information. But the decision should not rely on one number or one photograph.
Not necessarily. This may be the most important point in the article.
Suppose inflammation was primarily downstream of severe evaporation. Anti-inflammatory therapy breaks part of the cycle. The surface heals. Symptoms improve dramatically. Excellent. But if the tear film is still evaporating too quickly because the lipid layer remains severely deficient, the original stressor has not disappeared. The inflammatory cycle may restart.
That does not mean the anti-inflammatory treatment “stopped working.” It may mean that another treatment target remains untreated.
Yes. Sometimes controlling the upstream problem may allow inflammation to settle without requiring indefinite anti-inflammatory therapy. For example, if severe ocular-surface stress is being maintained by an identifiable mechanical or tear-film problem, correcting that driver may reduce the inflammatory stimulus.
Again, dry eye is not one linear chain. It is a system.
Because pain and discomfort are not generated solely by inflammation. Symptoms can also involve:
This is particularly important when symptoms become disproportionately severe compared with observable ocular-surface findings. So if staining improves and inflammation appears controlled but severe pain remains, simply escalating anti-inflammatory therapy indefinitely may miss another important mechanism.
We will return to this when we discuss the nervous system and dry-eye symptoms.
Not simply by asking “Did the eye stop hurting?” Look at the target. Depending on the treatment and disease phenotype, useful outcomes might include:
Then ask a second question: did the underlying driver also improve? Those are two different measurements.
Jones L, et al. TFOS DEWS III: Management and Therapy.
Current evidence-based management framework emphasizing treatment according to etiological drivers and including corticosteroids, T-cell immunomodulatory therapies and other anti-inflammatory treatments.
Wan KH, et al. Efficacy and Safety of Topical 0.05% Cyclosporine Eye Drops in the Treatment of Dry Eye Syndrome: A Systematic Review and Meta-analysis.
Twelve randomized trials involving 1,367 participants; improvements were reported in symptoms, TBUT, Schirmer testing, staining and goblet-cell density.
Aleksander-Ivanov Y, et al. Safety and Efficacy of 0.1% Cyclosporine Solutions in Dry Eye Syndrome.
Six RCTs involving 2,170 patients; found improvements in ocular-surface staining and OSDI compared with vehicle.
Lifitegrast Ophthalmic Solution 5% Is a Safe and Efficient Eyedrop for Dry Eye Disease: A Systematic Review and Meta-analysis.
Meta-analysis covering more than 3,000 participants overall and examining both clinical efficacy and adverse effects including instillation discomfort and dysgeusia.
Topical Pharmacologic Treatments for Dry Eye Disease: A Systematic Review.
Review of 107 publications demonstrating the range of current pharmacological targets and the frequent discrepancy between improvements in dry-eye signs and symptoms.