Dry eye disease (DED) is a multifactorial ocular surface disorder that affects millions of people worldwide, with prevalence estimates ranging from 5% to as high as 50%, depending on diagnostic criteria and demographics.1,2
In the United States alone, as many as 16 million Americans have been formally diagnosed, while undiagnosed cases could push that figure closer to 30 million.3 Additionally, recent survey data suggest that more than half of all eyecare patients may experience DED symptoms.4
Recent advances in pharmacologic treatments have expanded therapeutic options beyond traditional artificial tears and anti-inflammatory drops, offering greater precision in targeting underlying pathophysiologic mechanisms. This article provides an overview of the most up-to-date and emerging therapies, including a practical cheat sheet for quick reference.
A brief overview of DED
According to the TFOS DEWS II Definition and Classification Report, DED is “a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms.”¹ It involves imbalances in tear production, tear composition, and/or excessive tear evaporation.1,2
Key drivers of DED include chronic inflammation, tear hyperosmolarity, and tear film instability, among other factors, all of which can lead to epithelial damage of the cornea and conjunctiva.1,2 Ongoing research and drug development aim to address these specific processes—reducing inflammation, stabilizing the tear film, and restoring tear film homeostasis—to mitigate disease progression and enhance patient quality of life.
Current pharmacological options for dry eye
Miebo
Miebo (perfluorohexyloctane ophthalmic solution, Bausch + Lomb) is a newer prescription option that prioritizes tear film stability rather than simply replenishing moisture.5 Its single-ingredient formulation, perfluorohexyloctane (PFHO), creates a temporary barrier on the ocular surface to reduce tear film evaporation and improve lubrication.5-8
Clinical research indicates that PFHO spreads quickly to form a protective monolayer, decreasing friction during blinking, and potentially supporting ocular surface healing.6-8 This mechanism is particularly beneficial for evaporative DED, often linked to meibomian gland dysfunction (MGD), as it addresses the fundamental issue of excessive tear evaporation.
Mechanism of action
Miebo’s active ingredient, PFHO, a semifluorinated alkane, forms a monomolecular layer over the tear film, thereby reducing tear evaporation by acting as a physical barrier. This water-free, preservative-free formulation consists of 100% active ingredient, eliminating the need for a vehicle while ensuring optimal biocompatibility.
By creating a protective coating, PFHO also helps minimize friction during blinking, which may protect corneal epithelial cells and support overall ocular surface healing.6-8 Unlike most traditional artificial tears that attempt to replace the aqueous component of the tear film, Miebo’s unique focus on decreasing tear film evaporation is particularly beneficial for those with evaporative DED.
Clinical evidence shows that PFHO effectively inhibits evaporation by forming a protective barrier over the tear film, as demonstrated in a recent in vitro study by Vittitow et al.9 Their findings showed that PFHO significantly decreased saline evaporation, supporting its role as an effective antievaporative agent.
This aligns with Miebo’s proposed mechanism of action, where PFHO mimics the natural lipid layer to enhance tear stability. By reducing tear evaporation, PFHO may not only alleviate symptoms associated with MGD but also provide long-term benefits by improving ocular surface health and lubrication.9
Clinical studies: Miebo
GOBI Trial:6
- Design: Phase 3, randomized, controlled trial evaluating the safety and efficacy of PFHO in DED patients with MGD.
- Key outcomes: At Week 8, PFHO significantly improved total corneal fluorescein staining (tCFS, -0.97 LS mean difference; P < 0.001) and eye dryness score (-7.6 LS mean difference; P < 0.001), demonstrating its effectiveness in reducing ocular surface damage and discomfort.
- Safety profile: Most adverse events (AEs) were mild or transient, with no serious treatment-related AEs.
- Ocular AEs occurred in 9.6% (PFHO) vs. 7.5% (saline), with blurred vision (3.0%) as the most common. Only one patient discontinued due to eye irritation.
MOJAVE Trial:7
- Design: Phase 3, multicenter, randomized, double-masked, saline-controlled trial evaluating the efficacy and safety of PFHO in adults with DED associated with MGD.
- Key outcomes: At Week 8, PFHO significantly improved both signs and symptoms of DED, with a least-squares (LS) mean reduction in tCFS of 2.3 (versus 1.1 in the saline group) and a LS mean reduction in eye dryness score (VAS) of 29.4 (versus 19.2 in the saline group).
- Notably, significant improvements in both tCFS and eye dryness were observed as early as Week 2.
- Safety profile: Most adverse events (AEs) were mild or transient, with no serious treatment-related AEs reported.
- Ocular AEs occurred in 12.9% of PFHO-treated patients versus 12.3% in the saline group.
KALAHARI Trial:8
- Design: A phase 3, multicenter, open-label extension of the GOBI trial, conducted over 52 weeks in 208 patients (97 previously on perfluorohexyloctane, 111 previously on hypotonic saline).
- Long-term efficacy:
- Subjects continuing perfluorohexyloctane from GOBI maintained significant reductions in tCFS and dryness scores (VAS) through Week 52.
- Those switched from hypotonic saline to perfluorohexyloctane experienced rapid improvement by Week 4, sustained for the remainder of the study.
- Safety:
- In total, 12% of participants reported ≥1 ocular AE, with mild severity in most cases.
- The most frequent AEs were allergic conjunctivitis (1.4%) and blurred vision (1.4%).
- No serious treatment-related AEs were recorded, reinforcing perfluorohexyloctane’s suitability for extended therapy.
Dosage
Prescribed as one drop in each affected eye four times daily.
Side effects
Across trials (GOBI, MOJAVE, KALAHARI), the most common side effects of PFHO include:6-8
- Mild stinging or burning on instillation (~2 to 4%)
- Temporary blurred vision (~1 to 4%)
- Mild conjunctival hyperemia (~1 to 2%)
Notably, overall discontinuation rates due to these effects remained low (<5%), reflecting a favorable safety profile.
Indications
Miebo is indicated for signs and symptoms of dry eye disease in adult patients. By reducing tear film evaporation, it can be especially beneficial for individuals with evaporative DED secondary to MGD.
Contraindications
- Hypersensitivity to perfluorohexyloctane or other formulation components.
- Active ocular infection: While not an absolute contraindication, additional treatments or precautions may be necessary if an infection is present.
- Remove contact lenses before using MIEBO and wait at least 30 minutes before reinserting them.
MIEBO takeaways
- Rapid symptom relief: The MOJAVE Study demonstrates improvements can manifest in as little as 2 weeks.
- Long-term data: Both the GOBI and KALAHARI trials confirm sustained efficacy over 52 weeks, with a low incidence of mild side effects.
- Evaporative DED emphasis: Miebo’s distinct mechanism targets tear film evaporation, a principal factor in MGD-related dry eye.
These findings position Miebo as a promising long-term management option for DED, delivering prompt relief and supporting ocular surface health with extended use. Its unique mechanism of action, favorable safety profile, and preservative-free formulation underscore its value in contemporary DED management.
Download the Dry Eye Disease Pharmacologic Therapy Cheat Sheet here!
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Dry Eye Disease Pharmacologic Therapy Cheat Sheet
Use this cheat sheet to compare key features, such as active ingredients, dosages, indications, and side effects, of FDA-approved and pipeline pharmacologic therapies for dry eye.
Xdemvy
Xdemvy (lotilaner ophthalmic solution 0.25%, Tarsus) represents a significant advancement in the targeted treatment of Demodex blepharitis, a common comorbid condition of DED.
Figure 1: The characteristic collarettes with lid telangiectasia associated with Demodex blepharitis.
Figure 1: Courtesy of Bradley Daniel, OD, FAAO, Dipl ABO.
This prescription medication addresses the underlying etiology of Demodex blepharitis—infestation of the eyelids with Demodex mites. These microscopic mites, while naturally present on human skin, can overpopulate in some individuals, and this overgrowth can result in inflammation and disruption of tear film stability, leading to the signs and symptoms of Demodex blepharitis.10,11
There are two species of Demodex mites found on humans, Demodex folliculorum, which inhabit the lash follicles, and Demodex brevis, which are found in the meibomian glands and disrupt the delicate balance of the meibum's composition.10
This disrupts its flow and ultimately leads to symptomatic DED secondary to MGD.10,15 Currently, Xdemvy is the only FDA-approved medication indicated for the treatment of Demodex blepharitis and it has also been shown to improve meibomian gland function in patients with both Demodex blepharitis and MGD.11
Mechanism of action
Unlike traditional therapies that focus on managing symptoms or inflammation, Xdemvy offers a targeted approach by directly eliminating the Demodex population. The active ingredient in Xdemvy, lotilaner, is a parasiticide with specific activity against Demodex mites.
Its mechanism of action involves disrupting the mite's nervous system, leading to paralysis and subsequent death.11 This action reduces the mite population on the eyelids, thereby decreasing inflammation and associated symptoms. Notably, lotilaner does not inhibit mammalian GABA-gated chloride channels at concentrations up to 30µM,12 indicating a favorable safety profile for human use.
Xdemvy's mechanism of action:
- Inhibits GABA-gated chloride channels in mites
- Causes paralysis in the target organism
- Leads to mite death
This targeted approach provides several advantages. By eradicating Demodex mites, Xdemvy addresses the root cause of Demodex blepharitis, potentially resulting in significant improvement in clinical signs like eyelid erythema, irritation, and lash debris.
Clinical Studies: Xdemvy
SATURN-1 Trial13
- Design: A phase 2b/3, randomized, double-masked, vehicle-controlled trial evaluating the efficacy and safety of lotilaner ophthalmic solution 0.25% in patients with Demodex blepharitis.
- Findings: At day 43, 44% of lotilaner-treated patients achieved ≤2 collarettes on the upper eyelid vs. 7.4% in the vehicle group (p < 0.0001).
- Mite eradication: 67.9% of lotilaner patients vs. 17.6% vehicle group.
- Erythema cure rate: 42.5% of lotilaner patients vs. 11.4% in the vehicle group (p < 0.0001).
- Post-hoc analysis: 64.9% of lotilaner-treated patients achieved a reduction to 10 or fewer collarettes, compared to 20.3% in the vehicle group (p < 0.0001).
- Safety profile: The most common treatment-related ocular adverse event was instillation site pain, reported in 7.9% of patients in the lotilaner group. No serious treatment-related adverse events were observed.
SATURN-2 Study14
- Design: A phase 3, randomized, double-masked, vehicle-controlled trial assessing the efficacy and safety of lotilaner ophthalmic solution 0.25% in Demodex blepharitis patients.
- Findings: By day 43, 56% of participants receiving lotilaner achieved a reduction to ≤2 collarettes on the upper eyelid, compared to 12.5% in the vehicle group (p < 0.0001).
- Mite eradication: 51.8% of lotilaner group versus 14.6% in the vehicle group.
- Erythema cure rate: 48.1% in the lotilaner group vs. 13.2% in the vehicle group (p < 0.0001).
- Post-hoc analysis: 72.4% of lotilaner-treated patients achieved a reduction to 10 or fewer collarettes vs. 22.7% in the vehicle group (p < 0.0001).
- Safety profile: Similar to SATURN-1, the most common treatment-related ocular adverse event was instillation site pain, occurring in 7.9% of patients in the lotilaner group. No serious treatment-related adverse events were reported.
Dosage
The recommended dosage of Xdemvy is one drop in each affected eye twice daily, approximately 12 hours apart, for a duration of 6 weeks. If a patient is using other topical ophthalmic drugs as well, they should be administered with a minimum of 5 minutes between each application.
It's important to understand how the Demodex life cycle relates to Xdemvy’s 6-week treatment regimen. Most patients will experience significant improvement in symptoms, potentially even complete resolution, within 3 weeks, as this corresponds to one life cycle of the mites.
However, completing the full 6-week course is crucial as this covers two life cycles, and the full treatment regimen ensures the eradication of both adult mites and developing eggs, preventing them from hatching and repopulating the eyelid.10 This approach helps prevent a quick recurrence of Demodex blepharitis and ensures long-lasting relief from symptoms.
Side effects
Across trials (SATURN-1 & SATURN-2), the most common side effects of lotilaner include:13,14
- Mild stinging or burning on instillation (10%)
- Other adverse reactions (< 2%)
- Chalazion/hordeolum
- Punctate keratitis
Indications
Xdemvy is indicated for the treatment of Demodex blepharitis. By targeting the underlying cause—Demodex mite infestation—it effectively reduces eyelid inflammation and associated symptoms.
Contraindications
- There are no listed contraindications for Xdemvy.
Xdemvy’s role in meibomian gland function and MGD
Two recent phase 2a clinical trials, ERSA and RHEA, have provided compelling evidence of Xdemvy’s ability to improve meibomian gland function, which is critical in reducing MGD-related symptoms in patients with DB and MGD.15,16 Studies indicate that 57% of MGD patients also present with Demodex blepharitis, with 90% reporting significant ocular symptoms such as burning, fluctuating vision, and irritation.
Further supporting this connection, a recent study by Lee et al. found that Demodex infestation was present in 52.7% of patients and was associated with worsened meibum quality (p=0.001) and increased gland expressibility dysfunction (p=0.021) in younger and middle-aged individuals.15
Notably, younger patients with Demodex blepharitis exhibited more symptomatic MGD, suggesting that early intervention targeting Demodex mites—such as with Xdemvy—may be particularly beneficial in mitigating gland dysfunction and patient discomfort in this population.
Understanding the Meibomian Gland Secretion Score (MGSS)
The MGSS scale (0 to 45) is used to assess meibomian gland function based on the number and quality of gland secretions from 15 central glands of the lower eyelid.16
The total score is derived by evaluating each gland's meibum quality on a 0 to 3 scale:
- Grade 0: No secretion (severe gland dysfunction)
- Grade 1: Granular/opaque meibum, inspissated (thick/toothpaste-like)
- Grade 2: Cloudy liquid secretion
- Grade 3: Clear liquid secretion (healthy function)
A higher MGSS indicates better gland function, with increased clear meibum secretion being the ideal outcome in MGD management.
ERSA and RHEA: Findings on meibomian gland function improvement
Key results from ERSA and RHEA for the efficacy of Xdemvy on meibomian gland function improvement include:15,16
- Reduction in collarettes:
- Day 43 collarette cure: 56.0% of patients in the study group achieved complete collarette cure (collarette grade 0) compared to 12.5% in the control group.
- Additionally, 89.1% of patients in the study group had a clinically meaningful collarette reduction to 10 collarettes or fewer (grade 0 or 1) compared to 33.0% in the control group.
- Sustained collarette clearance: Long-term follow-ups from the SATURN-1 trial suggest that many patients maintained collarette clearance (0 to 2 collarettes) at 6 months (day 180) and one year (day 365), indicating lasting efficacy beyond the initial 6-week treatment period.
- Day 43 collarette cure: 56.0% of patients in the study group achieved complete collarette cure (collarette grade 0) compared to 12.5% in the control group.
- MGSS improvement:
- Baseline MGSS: 21.9 in the lotilaner group vs 22.0 in the vehicle group (confirming no baseline difference).
- Day 43 MGSS: Improved to 33.2 in the lotilaner group, compared to 27.8 in the vehicle group
- Day 85 MGSS: Further increased to 34.3 in the lotilaner group, compared to 23.1 in the vehicle group.
- Increase in meibomian glands secreting any liquid (score 2 to 3):
- Day 43: Increased from 7.1 to 12.7 glands in the lotilaner group vs 7.3 to 10.7 glands in the vehicle group.
- Day 85: Further increased to 13.2 glands in the lotilaner group vs 7.6 glands in the vehicle group.
- Improvement in number of glands secreting clear liquid meibum (score 3):
- Day 43: Increased from 0.8 to 5.8 glands in the lotilaner group vs 0.7 to 2.9 glands in the vehicle group.
- Day 85: Further improved to 6.3 glands in the lotilaner group vs 1.3 glands in the vehicle group.
- Patient-reported symptom improvements (VAS score, 0 to 100 scale: 0 is best and 100 is worst):
- Fluctuating vision improved from 51.9 to 22.2 in the lotilaner group vs 46.5 to 30.8 in the vehicle group.
- Itching decreased from 52.8 to 16.9 in the lotilaner group vs 47.0 to 40.5 in the vehicle group.
- Burning reduced from 46.0 to 20.0 in the lotilaner group vs 35.4 to 31.6 in the vehicle group.
- Redness improved from 43.6 to 18.6 in the lotilaner group vs 42.5 to 32.6 in the vehicle group.
Figure 2: Slit lamp images of collarettes in the above photos with corresponding chalazion (top right). Lower photos are of the same eyes taken 2 weeks later. Note the significant reduction in collarettes and associated resolution of the secondary chalazion (bottom right).
Figure 2: Courtesy of Bradley Daniel, OD, FAAO, Dipl ABO.
The presence of Demodex brevis in the meibomian glands may contribute to gland obstruction and inflammatory mediator release, leading to thickened meibum, decreased gland expression, and obstructive MGD.15,16
Xdemy’s targeted mechanism directly eliminates Demodex mites, breaking the inflammatory cycle and restoring gland function, allowing for better meibum quality, improved tear film stability, and symptom relief.
Xdemvy takeaways
XDEMVY is the first and only FDA-approved treatment for Demodex blepharitis. Look at the lids! Instructing patients to look down during a slit-lamp exam reveals collarettes, which are pathognomonic for the condition—if you see them, the patient has Demodex blepharitis. This simple diagnostic approach enables swift identification and treatment.
Clinical trials have demonstrated significant efficacy, with BID dosing leading to a marked reduction in collarettes and successful mite eradication within 6 weeks. Additionally, Xdemvy boasts a favorable safety profile, with the most common adverse event being mild instillation site discomfort (10%).13,14 By inhibiting GABA-gated chloride channels, Xdemvy directly eliminates Demodex mites, addressing the root cause of blepharitis rather than just its symptoms.
Beyond Demodex blepharitis, ongoing research is exploring Xdemvy’s potential in managing MGD, particularly in cases where Demodex infestation contributes to gland obstruction and inflammation. For patients with both MGD and Demodex blepharitis, prioritizing mite eradication with Xdemvy is a crucial first step.
By reducing inflammation and swelling of the eyelid margin, it helps prevent further obstruction of the meibomian glands, enhances gland function, and improves meibum quality and tear film stability. This, in turn, optimizes the effectiveness of adjunctive MGD treatments, such as warm compresses, lid hygiene, and meibomian gland expression therapy.
With increasing evidence supporting its role in improving meibomian gland function and alleviating MGD symptoms in patients with Demodex blepharitis, Xdemvy is emerging as a game-changing therapeutic option. By eliminating the root cause of Demodex-related eyelid disease, it sets the stage for long-term relief and improved ocular surface health, redefining treatment strategies for patients with MGD and concurrent Demodex blepharitis.
Figure 3: Dense collarettes prior to treatment with Xdemvy (left) and 2-week follow-up after initiating Xdemvy treatment (right).
Figure 3: Courtesy of Bradley Daniel, OD, FAAO, Dipl ABO.
Vevye
Vevye (cyclosporine ophthalmic solution 0.1%, Harrow) is a water-free, preservative-free formulation of cyclosporine 0.1% indicated for dry eye disease. By combining perfluorobutylpentane (PFBP)—a semifluorinated alkane technology—with cyclosporine, Vevye is designed to penetrate the cornea more effectively while providing immunomodulatory benefits.17
Approved by the FDA in June 2023, Vevye is the first and only cyclosporine solution indicated to treat both the signs and symptoms of DED.17
Mechanism of action
Cyclosporine inhibits calcineurin and subsequently T-cell activation, reducing the production of pro-inflammatory cytokines on the ocular surface. By lowering chronic inflammation, Vevye can help increase tear production, stabilize the tear film, and improve corneal integrity.17-20
Central to Vevye’s efficacy is its semifluorinated alkane vehicle, which not only ensures enhanced drug penetration but also optimizes the overall performance of the formulation. PFBP, a colorless, amphiphilic, non-aqueous liquid, plays a crucial role in enhancing drug delivery by rapidly and evenly spreading across the ocular surface.18
Being a water-free vehicle, it has a low surface tension that improves lipid layer grading immediately after administration, while its ability to dissolve hydrophobic drugs like cyclosporine significantly enhances bioavailability.21
Studies indicate that PFBP delivers approximately 22 times more cyclosporine into the cornea compared to Restasis (cyclosporine ophthalmic emulsion 0.05%, AbbVie), with detectable levels remaining in tears for up to 8 hours.19,20
Clinical studies: Vevye
ESSENCE-1 Trial19
- Design: A phase 3, randomized, double-masked, vehicle-controlled trial to assess the efficacy and safety of water-free cyclosporine 0.1% in adults with DED. Measured improvements in corneal health (tCFS score) and dry eye symptoms (OSDI score)
- Key findings:
- By Day 29, 71% of patients treated with water-free cyclosporine 0.1% achieved a clinically meaningful reduction in tCFS of 3 grades or more, compared to 59.7% in the vehicle group.
- Patients using water-free cyclosporine 0.1% had 11% greater improvement in corneal health than those using the vehicle alone.
- Significant improvement in OSDI scores, indicating a reduction in patient-reported symptoms of dry eye disease.
- Symptom relief is often noted by Week 4, with continued gains in ocular comfort over the study period.
- Safety profile:
- Treatment-emergent adverse events (TEAEs): Reported by 16.8% of participants in the cyclosporine group and 17.8% in the vehicle group.
- Ocular TEAEs: Occurred in 13.5% of participants receiving cyclosporine and 15.1% of those on the vehicle.
- Instillation-site reactions: Reported by 10.2% of participants in the cyclosporine group and 8.8% in the vehicle group; these reactions were predominantly mild, with only one case in each group classified as more severe.
ESSENCE-2 Trial20
- Design: A phase 3, multicenter, randomized, double-masked, vehicle-controlled study assessed water-free cyclosporine 0.1%’s efficacy, safety, and tolerability over 4 weeks. Primary endpoints measured at 4 weeks were tCFS and dryness score.
- Key findings:
- At Day 29, patients treated with water-free cyclosporine 0.1% showed a mean reduction in tCFS of 4.0 grades, compared to 3.6 grades in the vehicle group.
- In total, 71.6% of patients in the water-free cyclosporine 0.1% group achieved a clinically meaningful reduction in tCFS of 3 grades or more, compared to 59.7% in the vehicle group.
- No statistically significant difference in dryness scores between the water-free cyclosporine 0.1% and vehicle groups.
- Safety profile:
- TEAEs: Reported by 16.8% of participants in the cyclosporine group and 17.8% in the vehicle group.
- Ocular TEAEs: Occurred in 13.5% of participants receiving cyclosporine and 15.1% of those on the vehicle.
- Instillation-site reactions: Reported by 10.2% of participants in the cyclosporine group and 8.8% in the vehicle group; these reactions were predominantly mild, with only one case in each group classified as more severe.
ESSENCE-2 open-label extension (OLE) Study21
- Study design:
- 1-year study
- Patients used water-free cyclosporine 0.1% twice daily for 52 weeks
- Assessed long-term safety and effectiveness
- Key findings:
- Corneal health improvements were maintained for the entire year.
- Symptom relief remained stable, showing no decline in effectiveness.
- Safety profile:
- Completion rate:
- At week 52, 175 patients (86.6%) completed the ESSENCE-2 OLE study.
- Ocular TEAEs:
- Reported by 55 patients (27.5%), totaling 74 ocular TEAEs.
- The most common ocular TEAE was mild instillation site pain, experienced by 13 patients (6.5%).
- Reduced visual acuity was reported by 6 patients (3.0%).
- Only one patient (0.5%) withdrew from the study due to an ocular adverse event (mild burning/stinging).
- Completion rate:
Table 1: Key differences between the ESSENCE-1 and ESSENCE-2 trials.
| Feature | ESSENCE-1 Study | ESSENCE-2 Study |
|---|---|---|
| Study design | 12-week, phase 3, randomized double-masked, vehicle-controlled trial | 4-week, phase 3, randomized, double-masked, vehicle-controlled trial |
| Number of patients | 328 patients | 834 patients (more than double ESSENCE-1) |
| Primary endpoints | tCFS and OSDI score at Week 4 | tCFS and dryness score at Week 4 |
| Statistical outcome | Met primary endpoint for tCFS (P=0.0002), but OSDI score improvement was not statistically significant (P=0.2634) | Met primary endpoint for tCFS (P < 0.001), but dryness score did not show a statistically significant difference |
| Symptom relief | Improvement in OSDI scores was observed, but did not reach statistical significance | Improvement in dryness score was observed, but did not reach statistical significance |
| When effects were noticed | Improvement in corneal staining was significant by Week 2 and continued through Week 12 | Improvement in corneal staining was significant by Day 15 and continued through Week 4 |
| Study size and scope | Smaller patient population, longer follow-up (12 weeks) | Larger patient population, shorter follow-up (4 weeks) |
| Long-term follow-up | Did not include a long-term extension | ESSENCE-2 had an OLE study, assessing safety for 1 year |
Table 1: Courtesy of Bradley Daniel, OD, FAAO, Dipl ABO.
Dosage
One drop of Vevye is instilled twice daily (morning and evening) into each affected eye.
Side effects
Clinical data indicate that Vevye is generally well tolerated, with side effects primarily mild in nature:17
- Mild redness or irritation (~8%)
- Blurred vision (3%)
Indications
Vevye is indicated for the treatment of signs and symptoms of dry eye disease in adult patients, especially those with chronic or moderate-to-severe forms of DED driven by ocular surface inflammation.
Contraindications
- Hypersensitivity to cyclosporine or any other formulation components.
- Active ocular infection: While not an absolute contraindication, clinicians should be cautious and treat any infections before initiating therapy.
Vevye takeaways
- Targeted immunomodulation: Vevye’s mechanism—reducing T-cell activation—addresses the inflammatory component of DED, supporting tear film homeostasis.
- Early symptom relief: Improvements may occur as soon as Week 4, with continuing benefits over extended use.
- Long-term benefits: Data from extended follow-up studies show sustained efficacy and low rates of adverse events, making Vevye a promising option for long-term DED management.
Figure 4: Baseline corneal fluorescein staining of a patient with chronic dry eye syndrome prior to initiating Vevye treatment. Notable findings include 2+ conjunctival staining, reduced tear film, and rapid tear break-up time.
Figure 4: Courtesy of Bradley Daniel, OD, FAAO, Dipl ABO.
Figure 5: 1-month follow-up of the same patient after initiating Vevye twice daily in both eyes. Significant improvements observed in conjunctival staining, increased tear film height, and prolonged tear break-up time, indicating enhanced ocular surface health.
Figure 5: Courtesy of Bradley Daniel, OD, FAAO, Dipl ABO.
Don't forget to check out the Dry Eye Disease Pharmacologic Therapy Cheat Sheet!
Emerging therapies for DED
Reproxalap
Reproxalap (reproxalap ophthalmic solution 0.25%, Aldeyra/AbbVie) is a novel ophthalmic drop designed to target the underlying inflammation associated with DED and allergic conjunctivitis. Unlike traditional artificial tears or immunomodulators, reproxalap is an investigational reactive aldehyde species (RASP) inhibitor that aims to reduce ocular inflammation at its source.
By neutralizing RASP, which contributes to oxidative stress and inflammation, reproxalap represents a promising new approach for patients with DED and allergic conjunctivitis.22
Mechanism of action
Reproxalap’s mechanism of action focuses on inhibiting RASP, which are elevated in patients with dry eye and other inflammatory ocular surface diseases.
By reducing RASP levels, reproxalap helps:22-26
- Decrease inflammation-driven ocular surface damage.
- Improve tear film stability and overall eye comfort.
- Mitigate patient-reported symptoms such as irritation, burning, and redness.
- Unlike corticosteroids or cyclosporine-based treatments, reproxalap works upstream in the inflammatory cascade, potentially leading to faster onset of action with fewer side effects.24,25
Clinical studies: Reproxalap
TRANQUILITY Study24
- Design: Randomized double-masked phase 2a trial to assess the safety and efficacy of reproxalap, a novel reactive aldehyde species (RASP) inhibitor, for treating dry eye disease.
- Key outcomes: Improvements in DED symptoms were evident within 1 week of therapy, and pooled data from the 28-day treatment period demonstrated significant improvement from baseline in:
- Symptom Assessment in Dry Eye Disease (SADED) score
- Ocular Discomfort Scale score
- Ocular Discomfort Score and 4-Symptom Questionnaire overall score
- Schirmer's test
- Tear osmolarity
- Lissamine green total staining score
- Safety profile: Reproxalap was well tolerated, with no serious treatment-related adverse events reported.
INVIGORATE Study25
- Design: Prospective, quadruple-masked, vehicle-controlled, crossover, sequence-randomized phase 3 trial assessing the efficacy and safety of reproxalap, a novel RASP modulator, in patients with seasonal allergic conjunctivitis (SAC) using an allergen chamber model.
- Key outcomes: Reproxalap demonstrated significant improvements compared to vehicle in treating allergic conjunctivitis symptoms over a controlled allergen exposure period: Reproxalap was statistically superior to the vehicle in reducing ocular itching and redness, with significant improvements observed across typical symptoms and signs of allergic conjunctivitis.
- Ocular itching reduction: Mean (SE) difference of −0.50
- Ocular redness reduction: Mean (SE) difference of −0.14
- Responder analyses: Confirmed clinical relevance of itching and redness improvements
- Prolonged time to symptom worsening:
- Itching: Mean difference of 14.7 minutes
- Redness: Mean difference of 22.1 minutes
- Tearing reduction: Significant improvement
- Safety profile: Reproxalap was well tolerated, with no serious or severe treatment-emergent adverse events reported.
- The most common adverse event was mild and transient instillation site irritation (69% vs 4% with vehicle).
ALLEVIATE Study26
- Design: Parallel-group, double-masked, randomized phase 3 trial evaluating the efficacy and safety of two concentrations of reproxalap (0.25% and 0.5%) versus vehicle in patients with seasonal allergic conjunctivitis following conjunctival allergen challenge.
- Key outcomes: Both 0.25% and 0.5% concentrations of reproxalap achieved the primary endpoint and demonstrated rapid resolution of ocular itching and redness. Interestingly, the weaker concentration of reproxalap (0.25%) outperformed the stronger concentration (0.5%).
- Primary endpoint: Reduction in area under the ocular itching score curve from 10 to 60 minutes post-challenge.
- Key secondary endpoint: Proportion of subjects with ≥2-point improvement from peak ocular itching score.
- Responder analysis: Clinically relevant improvements confirmed using a responder-based questionnaire.
- Safety profile: Reproxalap was well tolerated, with no serious or severe treatment-emergent adverse events reported. The most common adverse event was mild and transient instillation site irritation.
Dosage
Prescribed as one drop in each affected eye four times daily.
Side effects
Across trials (TRANQUILITY, INVIGORATE, ALLEVIATE), the most common side effects of reproxalap include:
- Mild stinging or burning upon instillation (~3 to 5%)
- Temporary blurred vision (~1 to 3%)
- Mild conjunctival hyperemia (~2%)
- Discontinuation due to side effects remains low (<5%), reinforcing a favorable safety profile.
Indications
Reproxalap is being evaluated for the treatment of signs and symptoms of dry eye disease and allergic conjunctivitis. Its RASP-inhibition mechanism makes it particularly relevant for patients with inflammation-driven DED who have not responded well to traditional therapies.
Contraindications
- Hypersensitivity to reproxalap or other formulation components.
- Active ocular infection: While not an absolute contraindication, clinicians may consider additional treatment or precautions before initiating therapy.
Reproxalap takeaways
- Rapid symptom relief: Clinical trials indicate improvements can occur within weeks, with some patients experiencing relief within days.
- Novel anti-inflammatory approach: Targets RASP to address inflammation at its root cause rather than simply managing symptoms.
- Favorable safety profile: Low rates of adverse events and discontinuation, making it a promising alternative to traditional immunomodulators and steroids.
With its unique mechanism of action and rapid onset of symptom relief, reproxalap is positioned as a potentially transformative therapy in DED management. Ongoing and future studies will further elucidate its efficacy and safety profiles, potentially offering a novel treatment avenue for patients with unmet needs in DED and allergic conjunctivitis.
To read more about the FDA's second rejection of reproxalap's NDA, read FDA rejects Aldeyra's reproxalap NDA for a second time.
Acoltremon
Acoltremon (acoltremon ophthalmic solution 0.003%, Alcon), also known as AR-15512, is an investigational ophthalmic solution developed by Alcon for the treatment of dry eye disease. It functions as a topical agonist of the transient receptor potential melastatin 8 (TRPM8) receptor, aiming to alleviate the signs and symptoms associated with dry eye.27
TRPM8 receptors and their role in tear production:28-32
- TRPM8 receptors are integral to activating trigeminal neural pathways and the lacrimal functional unit (LFU), facilitating the coordinated innervation of the lacrimal gland, goblet cells, and meibomian glands.
- This coordination is essential for regulating basal tear production and maintaining ocular surface health.
- TRPM8 receptors are expressed on cold thermosensory nerve endings innervating the cornea.
- They monitor for small reductions in temperature and increases in osmolarity caused by evaporative cooling between blinks.
- TRPM8 is considered a master regulator of basal tear production, ensuring consistent tear volume on the ocular surface.
- When activated—whether by small shifts in temperature/osmolarity or agonist binding—TRPM8 triggers trigeminal nerve signaling, increasing tear secretion.
Mechanism of action
Acoltremon (AR-15512) is a potent, selective TRPM8 agonist. It works by targeting the TRPM8 ion channel, a key regulator of ocular surface sensation and tear production.
TRPM8, part of the transient receptor potential (TRP) superfamily, is a nonselective cation channel primarily activated by cool temperatures and osmotic stress.27-32 Its activation triggers a cascade of physiological responses that enhance tear secretion and improve ocular comfort.
By activating TRPM8, acoltremon leads to:
- TRPM8 Activation:
- Stimulated by slight reductions in temperature, osmotic changes, and certain ligands.
- Opens TRPM8 channels, allowing calcium (Ca²⁺) and sodium (Na⁺) ion influx.
- Neural signaling and tear production:
- Membrane depolarization initiates afferent sensory signaling to the brainstem.
- Triggers parasympathetic efferent output, enhancing tear secretion.
- Therapeutic effects:
- Increases basal tear production, improving tear film stability.
- Provides a cooling sensation, alleviating discomfort from dry eye disease.
By modulating TRPM8 activity, acoltremon addresses both symptoms and tear homeostasis dysfunction, offering a distinct mechanism of action compared to anti-inflammatory or lubricating treatments.
Clinical studies: Acoltremon
COMET-1 Trial33
- Design:
- Phase 2b, randomized, vehicle-controlled trial evaluating two concentrations of acoltremon AR-15512 (0.0014% and 0.003%) in patients with dry eye disease (DED).
- Key assessments:
- Signs of DED: Schirmer score (with and without anesthetic), ocular surface staining, and hyperemia.
- Symptoms of DED: Ocular Discomfort Scale (ODS-VAS), Symptoms Assessment in Dry Eye (SANDE), Eye Dryness-VAS, and Ocular Pain-VAS.
- Quality of life (QoL): Evaluated using QoL-VAS.
- Primary endpoints: Change from baseline in ODS-VAS and anesthetized Schirmer score at Day 28.
- Key findings:
- 0.003% AR-15512 group (n=122) demonstrated early and sustained improvements:
- Unanesthetized Schirmer score: Significant increases as early as Day 1 and Day 14
- Ocular surface staining: Significant improvements at Days 14 and 84
- Hyperemia: Significant reduction observed at Day 84
- Symptom relief:
- SANDE scores improved at Days 14, 28, and 84
- ODS-VAS improvement at Day 84
- Eye Dryness-VAS reduction at Day 84
- Multiple QoL measures significantly improved at Days 14, 28, and 84
- However, the study did not meet its predefined co-primary endpoints (ODS-VAS and anesthetized Schirmer score at Day 28).
- Acoltremon's inability to achieve its endpoint in anesthetized Schirmer testing stems from its direct action on nerves; when these nerves are anesthetized, they cannot respond to the drug. Consequently, subsequent trials employed unanesthetized Schirmer testing to accurately assess acoltremon's efficacy.
- 0.003% AR-15512 group (n=122) demonstrated early and sustained improvements:
- Safety:
- Well-tolerated, with no serious ocular adverse events reported.
- Most common side effects were mild burning and stinging upon instillation (47.1%).
COMET-2 and COMET-3 Trials28,34
- Design:
- Based on the data from COMET-1, two identical phase 3 studies (COMET-2 and COMET-3) were designed to evaluate the safety and efficacy of topical acoltremon 0.003% compared with its vehicle administered BID for 90 days in subjects with DED
- Key findings:
- Primary endpoint met in both trials: ≥10-mm increase in unanesthetized Schirmer score at Day 14.
- Rapid and sustained increase in tear production: a 10mm increase in unanesthetized Schirmer’s score was noted at Day 14. Additionally, secondary endpoints demonstrated a rapid onset of increased tear production as early as Day 1, sustained through Day 90.
- DED symptom reduction: Improvements in global SANDE scores were statistically significantly greater than vehicle scores in COMET-2 and within the pooled analysis and directionally in favor of acoltremon 0.003% in COMET-3.
- Ocular surface staining: As exploratory endpoints, both individual studies and the pooled analysis showed reductions in total corneal and conjunctival staining.
- Safety:
- Well-tolerated, with no serious ocular adverse events.
- Similar side effect profile to COMET-1, with transient mild burning or stinging upon instillation (51%.
Dosage
Administered as one drop in each affected eye twice daily.
Side effects
Across clinical trials (COMET-1, COMET-2, COMET-3), the most commonly reported side effect of Acoltremon (AR-15512) was:
- Stinging or burning upon instillation (~51%)
- Temporary blurred vision (~1 to 3%)
- Mild conjunctival hyperemia (redness, ~2%)
While instillation site discomfort (burning/stinging) was reported in over half of patients, it was considered mild and transient, with 98% of subjects describing it as mild and <1% of subjects discontinuing the studies due to burning or stinging. Overall, acoltremon was well-tolerated, supporting its favorable safety profile.
Indications
Acoltremon is being developed for the treatment of DED by targeting TRPM8 receptors. Its tear-stimulating mechanism makes it particularly relevant for patients with either aqueous deficient or evaporative DED or those who have not responded well to traditional lubricants or anti-inflammatory treatments.
Contraindications
- Hypersensitivity to acoltremon or any component of the formulation.
- Active ocular infection: While not a strict contraindication, additional treatment or precautions may be required before initiating therapy.
Acoltremon takeaways
- Rapid tear production: Clinical trials show tear production increases as early as Day 1, with sustained effects through Day 90.
- Novel TRPM8 activation: Stimulates cold-sensitive receptors to enhance basal tear production and ocular comfort.
- Favorable safety profile: Well tolerated with a low discontinuation rate, making it a promising option for DED management.
With its unique mechanism of action and rapid symptom relief, acoltremon is positioned as a potential breakthrough in dry eye therapy. Ongoing research will further clarify its long-term efficacy and safety, offering an alternative for patients with unmet needs in DED treatment.
Download the Dry Eye Disease Pharmacologic Therapy Cheat Sheet to compare dry eye medications!
Pipeline therapies for dry eye disease
As research into DED evolves, numerous agents are under investigation. These pipeline therapies may offer novel mechanisms of action and improved efficacy for refractory cases.
AZR-MD-001
AZR-MD-001 (selenium sulfide ophthalmic ointment 0.5%, Azura Ophthalmics) is an investigational ophthalmic ointment developed by Azura Ophthalmics, formulated with selenium sulfide (SeS2) to address the underlying causes of MGD.35 In MGD, keratin proteins form aggregates that alter meibum quality and viscosity which can ultimately obstruct the flow of meibum out of the glands.
Its multi-modal mechanism of action includes reducing abnormal keratin production, breaking down existing keratin blockages, and enhancing the quality and quantity of meibum. Applied directly to the lower eyelid, AZR-MD-001 aims to restore normal meibomian gland function and alleviate associated ocular surface symptoms.35
AZR-MD-001 is currently being studied to evaluate the safety, efficacy, and tolerability of the study drug in patients with clinical signs of MGD and symptoms of DED, but has not been approved by the US FDA.
Overview of AZR-MD001:
- Indications: Targets MGD-related evaporative dry eye.
- Mechanism of action: Designed to reduce abnormal keratin production, break down blockages, and improve meibum quality to restore meibomian gland function and alleviate MGD symptoms.
- Clinical trials:36 Phase 2 studies have demonstrated significant improvements in meibomian gland function, leading to increased lipid layer thickness, enhanced tear film stability, and improved patient symptoms over 6 months.
- Ongoing phase 3 trials are assessing the long-term efficacy and safety of AZR-MD-001 in treating MGD. Primary endpoints include changes in gland function and symptom severity at the 3-month mark.
- Side effects: most common treatment-emergent adverse event was application-site pain, reported in approximately 15% of patients; overall well tolerated.
AXR-270
AXR-270 (glucocorticoid receptor agonist, developed by AxeroVision Inc, acquired by CS Pharmaceuticals) is an investigational topical cream designed as a selective glucocorticoid receptor (SeGR) agonist with a unique gene transactivation and transrepression profile.37,38
Formulated for once-daily application to the eyelids, AXR-270 aims to enhance periorbital drug delivery, providing a targeted approach to reduce inflammation and improve meibomian gland function. Preclinical studies show greater and more prolonged exposure with AXR-270 cream versus topical drop delivery, supporting a once-daily treatment regimen.37,38
Overview of AXR-270:37,38
- Indications: Aims to treat posterior blepharitis and dry eye disease associated with MGD.
- Mechanism of action: Selective glucocorticoid receptor agonist inhibits the production of pro-inflammatory cytokines and chemokines on the ocular surfaces without unwanted metabolic side effects associated with corticosteroids.
- Clinical trials: Phase 2 results showed AXR-270 provided rapid symptom relief in posterior blepharitis and dry eye disease, with improvements in eye discomfort after 1 week and statistically significant, clinically meaningful differences from placebo by 3 weeks.
- Significant improvements in eye dryness, corneal staining (1 week), and tear break-up time (2 weeks) continued to progress through 3 weeks of treatment.
- Following these positive results, phase 3 trials are planned to further evaluate the efficacy and safety of AXR-270 in this patient population.
- Side effects: Transient ocular discomfort; no systemic steroid-related adverse events observed.
CBT-006 and CBT-00839
CBT-006 and CBT-008 (ophthalmic solution, Cloudbreak Therapeutics) are investigational ophthalmic solutions developed by Cloudbreak Therapeutics, targeting MGD-associated DED.39 CBT-006 is an eye drop formulation containing hydroxypropyl beta-cyclodextrins (HP-ß-CD), designed to dissolve excess cholesterol at the meibomian gland orifice and within the meibum.
By improving meibum secretion, CBT-006 enhances tear film quality and alleviates MGD-related symptoms. CBT-008, a follow-on compound, is undergoing phase 2 evaluation.
Overview of CBT-006 and CBT-008
- Indications: Designed for the treatment of MGD-associated DED.
- Mechanism of action: CBT-006 and CBT-008, containing HP-ß-CD, function as cholesterol-sequestering agents.
- By dissolving cholesterol deposits at the orifices of the meibomian glands, these treatments aim to enhance the quality of meibum secretion, thereby stabilizing the tear film and alleviating dry eye symptoms.
- Clinical trials:40
- CBT-006: A phase 2 clinical trial evaluated the safety and efficacy of CBT-006 in patients with MGD-associated DED. Participants administered the ophthalmic solution TID over 3 months. The study reported significant improvements in both the signs and symptoms of dry eye, with a favorable safety profile.
- CBT-008: As a follow-on compound to CBT-006, CBT-008 has undergone phase 2 clinical evaluation. This multicenter, double-masked, randomized, vehicle-controlled study assessed the safety, efficacy, and pharmacokinetics of CBT-008 ophthalmic solution in patients with MGD-associated DED.
- Participants received one drop in each eye three times daily for 4 weeks. The trial aimed to determine the optimal concentration and dosing regimen, with results indicating potential benefits in improving meibomian gland function and tear film stability.
- Side effects: Both treatments were well-tolerated in clinical studies, with no significant adverse events reported. Some participants experienced mild ocular discomfort, which was transient in nature.
Meizuvo
Meizuvo ([pending brand name] HY-02, minocycline microparticle ophthalmic ointment 0.3%, Hovione) is the first minocycline repurposed for ophthalmic use, developed to treat blepharitis-driven ocular surface disease, particularly in patients with meibomian gland dysfunction.41,42
Hovione’s preservative-free formulation stabilizes minocycline as a microparticle, enhancing bioavailability while minimizing systemic effects. Minocycline’s lipophilicity improves meibomian gland affinity, supporting its anti-inflammatory and MMP-inhibitory actions. It may also inhibit lipase, reducing lipid degradation and fatty acid release—helping to break MGD’s chronic cycle.41,42
Overview of Meizuvo
- Indications: Designed for the treatment of inflamed MGD and associated dry eye symptoms.
- Mechanism of action: Minocycline inhibits pro-inflammatory cytokines and matrix metalloproteinases while also exerting antibacterial effects against pathogenic bacteria contributing to MGD.
- Additionally, it helps regulate lipid composition in the meibum, improving its fluidity and stability to enhance tear film quality and reduce evaporative dry eye.
- Clinical trials: A phase 2, vehicle-controlled study evaluated two concentrations of HY-02 ointment administered twice daily over 12 weeks in subjects diagnosed with MGD and signs of inflammation.
- The trial aimed to assess the efficacy and safety of HY-02 in reducing ocular surface inflammation and improving tear film stability.
- Results indicated a statistically significant improvement in both signs and symptoms of dry eye, particularly in patients with a positive inflammatory biomarker at baseline.
- Side effects: Mild ocular discomfort and transient blurring vision (3%); no significant systemic adverse events reported.
Topical vitamin D
Vitamin D (ophthalmic solution, investigational) plays a crucial role in maintaining ocular surface homeostasis by modulating immune responses and reducing inflammation, key factors in DED pathophysiology. It suppresses pro-inflammatory cytokines like IL-6 and TNF-α while promoting anti-inflammatory mediators, helping to stabilize the tear film and improve ocular surface health.43,44
Recent clinical studies suggest that topical vitamin D may provide significant benefits for patients with MGD-related DED.43,44 Research also indicates that vitamin D deficiency worsens dry eye symptoms, and supplementation improves tear stability and ocular health, making it a promising therapeutic option.
Overview of topical vitamin D:43,44
- Indications: Aimed at patients with DED linked to MGD.
- Mechanism of Action: Vitamin D modulates immune responses and reduces pro-inflammatory cytokine production, improving tear film stability and meibomian gland function. Its role in epithelial cell proliferation and differentiation may further contribute to ocular surface healing.
- Clinical Trials:44 A recent study found that patients receiving topical vitamin D had significantly greater improvements in subjective and objective dry eye metrics compared to placebo.
- These improvements were evident as early as 4 weeks and continued to 8 weeks, with a statistically significant reduction in inflammation and tear film instability.
- Side Effects: No significant adverse effects were reported; well tolerated by study participants
Key takeaways on current pharmacological therapies for dry eye
- Targeted therapies address specific disease mechanisms: Unlike traditional artificial tears, novel agents such as Miebo specifically reduce tear evaporation, while Xdemvy directly eradicates Demodex mites, and Vevye optimizes corneal penetration of cyclosporine to modulate inflammation. These treatments exemplify a shift toward addressing root causes rather than merely alleviating symptoms.
- Clinical trials confirm efficacy and safety: Rigorous phase 3 studies, such as GOBI and MOJAVE for Miebo, SATURN-1 and SATURN-2 for Xdemvy, and ESSENCE-1 and ESSENCE-2 for Vevye, have demonstrated significant improvements in both objective signs and subjective symptoms of DED, with favorable safety profiles that support long-term use.
- Demodex blepharitis and MGD are crucial considerations: The increasing recognition of Demodex blepharitis and its contribution to MGD highlights the importance of targeted interventions like Xdemvy. Addressing these underlying conditions can lead to better management of evaporative DED and improved meibomian gland function.
- Groundbreaking results from the ERSA and RHEA studies further support this connection, demonstrating significant improvements in MGSS, reduction in collarettes, and enhanced tear film stability following targeted Demodex blepharitis treatment.
- These findings reinforce the critical need to assess and treat Demodex infestation in patients with MGD to optimize long-term therapeutic outcomes. Additionally, it underscores the importance of evaluating the lids and lashes as part of routine DED and MGD assessment to identify signs of Demodex infestation early and implement timely intervention.
- Pipeline therapies offer future potential: Investigational treatments such as reproxalap, acoltremon, and selenium sulfide-based ointments are exploring novel mechanisms, including reactive aldehyde species inhibition, TRPM8 receptor activation, and keratolytic and keratostatic function, respectively, which may provide additional options for refractory DED patients.
- Personalized treatment approaches are key: With multiple FDA-approved and emerging therapies available, tailoring treatment plans based on individual patient profiles, disease severity, and underlying etiology will be essential for optimizing therapeutic outcomes.
- The integration of novel therapies into clinical practice should consider factors such as symptom onset, long-term efficacy, and potential for combination strategies.
As pharmacologic research continues to push the boundaries of DED treatment, the future holds promise for improved disease management through targeted, evidence-based approaches. By leveraging these advancements and utilizing the Dry Eye Disease Pharmacologic Therapy Cheat Sheet, clinicians can streamline treatment decisions, optimize patient outcomes, and provide lasting relief for those affected by this complex and often debilitating condition.
Conclusion
The evolving landscape of DED treatment has expanded significantly with the introduction of innovative pharmacologic therapies designed to target the underlying mechanisms of disease progression.
Traditional management strategies have focused on symptomatic relief with artificial tears and anti-inflammatory agents, but emerging therapeutics now offer precise and long-lasting benefits for patients with various subtypes of DED.
As our understanding of DED continues to grow, these advancements will provide clinicians with more effective options to improve patient outcomes.
