The New Pharmacotherapy of Dry Eye and Meibomian Gland Dysfunction

Dry eye disease is multifactorial.

That sentence has become almost reflexive in optometric practice, but it carries real clinical weight: because the condition arises from decreased tear production, increased tear evaporation, or both, any single-mechanism treatment usually leaves something unaddressed. Over the past decade, the pharmacotherapy of dry eye has evolved considerably. We now have options that target aqueous deficiency through distinct mechanisms, at least one drug that directly addresses evaporation, and a pipeline that will soon offer still more tools.

Understanding where these options fit, and just as critically, how to actually get them into patients’ hands, is what differentiates providers who manage dry eye from those who effectively treat it.

The Foundation: Cyclosporine and Lifitegrast

Restasis (cyclosporine ophthalmic emulsion 0.05%, Allergan/AbbVie) arrived more than 2 decades ago as the first FDA-approved treatment for dry eye disease. Its mechanism is well understood: it inhibits T-cell activation and reduces ocular surface inflammation, thereby increasing tear production over time.

Clinical trials showed meaningful improvements in Schirmer scores at 3 months, and for a decade-plus, it was the only FDA-approved option.¹ For many practices, especially those serving large Medicaid and Medicare populations, it remains the most accessible entry point.

XIIDRA (lifitegrast ophthalmic solution 5%, Bausch + Lomb) expanded the toolkit by targeting a related but distinct inflammatory pathway, blocking LFA-1/ICAM-1 interaction to reduce T-cell migration to the ocular surface. Onset was faster than cyclosporine, and it demonstrated improvement in both signs and symptoms.^2,3 The challenge (at least in locations such as my home market of Miami-Dade County, Florida) has been formulary access. Insurance barriers have been real and ongoing. In practice, many providers prescribe cyclosporine not because it is their preferred drug, but because it is the drug they can reliably get to their patients. This is a meaningful clinical reality: a drug is only as effective as the patient’s ability to obtain it.

The utility of having two inflammation-targeting agents is not redundancy. Patients may respond to one but not the other. With both cyclosporine and lifitegrast available, practitioners have a second line to reach for when the first does not produce results. That said, neither addresses the component of dry eye that drives most cases: evaporation.

MIEBO: A Drug That Thinks Differently

MIEBO (perfluorohexyloctane ophthalmic solution, Novaliq/Bausch + Lomb) is a perfluorohexyloctane molecule with a distinct mechanism of action: it forms a protective shield over the tear film to directly reduce evaporation. For patients with meibomian gland dysfunction (MGD), this matters enormously. Because it does not contain water, it has no pH.

I like to explain to patients that the tear film’s lipid layer is like the stopper on a bottle. When meibomian glands are blocked, dropping out, or otherwise dysfunctional, that layer thins, and evaporation accelerates. Inflammation-targeting drops do not resolve this issue, whereas MIEBO does. By mimicking the function of healthy meibum, it stabilizes the tear film on the surface, regardless of what is happening at the gland level.

MIEBO requires no lag time for T-cell suppression, allowing it to work quickly. In my experience, patients notice an effect within days to weeks. The standard dosing is 4 times daily, although some patients may do fine with fewer than 4 daily doses. It is comfortable, which matters for a patient population that has often cycled through multiple drops and is skeptical of anything new.

Access to the drug remains a barrier. MIEBO is the only commercially available FDA-approved drug that targets the evaporative component of dry eye, which gives it a clear niche, but its cost and prior authorization burden have made the path to a patient’s medicine cabinet frustratingly narrow.

One notable footnote: the active molecule, perfluorohexyloctane, is sold for approximately $20 in an over-the-counter formulation in Europe as EvoTears (URSAPHARM Arzneimittel GmbH). The cost disparity exists because FDA regulatory pathways require US developers to conduct clinical trials for approval in the United States, which drives up costs.

For those with both evaporative and aqueous-deficient disease, MIEBO is an adjunct to, not a replacement for, cyclosporine or lifitegrast. Treating one mechanism does not necessarily resolve the other. Some patients need both an anti-inflammatory and an anti-evaporative agent.

VEVYE and TRYPTYR: New Molecules for Aqueous Deficiency

VEVYE (cyclosporine ophthalmic solution 0.1%, Novaliq/Harrow Health) is a distinct cyclosporine formulation, not an iteration of Restasis. The molecule is the same cyclosporine, but the vehicle is not water-based, which affects tolerability and bioavailability. Like MIEBO, it has no pH.

It has found a direct-to-patient commercial model through PhilRx. Users of PhilRx have out-of-pocket costs as low as $59, bypassing the insurance approval process that has slowed adoption of other agents. The strategy of removing insurance from the equation entirely, at least for commercially insured patients under 65, has been effective. Adoption grows as more practitioners realize this access pathway exists.

TRYPTYR (acoltremon ophthalmic solution 0.003%, Alcon) offers a different mechanism of action on the aqueous-deficiency side of the market. It is a TRPM8 ion channel agonist that stimulates corneal sensory nerve endings, triggering the lacrimal reflex and increasing natural tear production. Clinical data show onset of effect within the first week, possibly within the first day.⁴ In a category where some drugs take months to show measurable impact, that speed is clinically meaningful.

The question facing TRYPTYR is whether it will differentiate enough from existing options to earn consistent prescribing, and whether its commercial access pathway will support that. There are now three or four agents that increase tear production through distinct mechanisms. Not every patient is well served by the same drug. Some cannot tolerate eye drops at all, which is part of what made TYRVAYA (varenicline solution nasal spray, Viatris), a nasal spray that stimulates the trigeminal parasympathetic pathway, attractive as a concept. Uptake has been limited, partly because of formulary barriers and partly because some patients find a nasal spray for dry eye counterintuitive. But the premise was sound: if a patient cannot reliably instill a drop, the delivery mechanism is a meaningful variable.

From a prescribing-strategy standpoint, practitioners in Medicare- and Medicaid-heavy markets often still default to cyclosporine as a first-line agent, not because it is the best drug available, but because it is the most likely to be covered. The pragmatic approach is to use cyclosporine or lifitegrast to establish a track record, then leverage documented failure to build the case for a newer, more expensive agent.

Amniotic Membranes

Sometimes, patients with an insufficient response to pharmaceutical routes have turned to cryopreserved amniotic membrane (CAM) for relief. The DREAM study found that patients with moderate to severe dry eye who underwent treatment with a CAM after not finding relief with other treatments experienced significantly lower DEWS scores at 1 week, 1 month, and 3 months.⁵ No adverse events were reported in the study.

Patients may have trouble finding a provider who uses CAM for dry eye. However, patients may be a good fit for this technology, which is manufactured by companies such as BioTissue and Cellution Biologics.

Devices: IPL, TearCare, and the Business of In-Office Therapy

Pharmaceutical options address the biochemical environment of the tear film. In-office procedures like intense pulsed light (IPL) and thermal pulsation systems like TearCare (Sight Sciences) and LipiFlow (Johnson & Johnson Vision) target meibomian gland function more directly, applying heat and mechanical expression to restore meibum flow.

IPL remains a legitimate treatment for patients with significant MGD, particularly in tertiary care centers where the equipment is available and the patient population can absorb the cost. LipiFlow, a thermal pulsation device, has been on the market long enough that pricing has come down substantially, improving its feasibility in more practices.

TearCare has had a more complicated trajectory. An accessible, cash-pay model made it practical for a wider range of patients, including those willing to pay $300 to $500 out of pocket after trying multiple drops without adequate relief. When the pricing model shifted upward to pursue Medicare reimbursement, patient volume dropped. The logic is sound: charge more, negotiate with CMS, and eventually land reimbursement. But the timing matters. If pharmaceutical options like MIEBO (and other pipeline candidates) can deliver comparable therapeutic effects without any hardware, the business case for expensive in-office thermal therapy becomes harder to make.

What Is Coming: Azura Keratolytic

AZR-MD-001 (Azura Ophthalmics) generates the clinical excitement. MGD often involves not just gland dropout but physical blockage: a film or cap forms over the gland orifices, preventing even functional glands from secreting properly. AZR-MD-001, an ointment used twice weekly, relies on keratolytic chemistry to dissolve that surface blockage and restore meibum flow. Think of it as physically opening what was closed, rather than supplementing what is missing.

This positions it differently from MIEBO, which creates an evaporation shield when the lipid layer is thin, regardless of cause. AZR-MD-001 is intended to restore the gland’s own production capacity. For patients who have meibomian glands that are functional but blocked, that distinction is meaningful. Both could have a role in the same patient. The use pattern, twice-weekly application rather than daily drops, also lends itself to long-term maintenance rather than a finite treatment course.

MGD has been a condition where practitioners have had to piece together solutions from non-pharmaceutical interventions for years. The pharmacotherapy pipeline is finally catching up.