The magic of Miebo
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There is simply no other way to put this: Miebo is magic.
Dry eye disease (DED) and the space around it has been the “hot dot” in topical medical therapy in eye care for many years. Not since 2016 and Xiidra (lifitegrast ophthalmic solution 5%, Bausch + Lomb) have we had an FDA approval for a new compound or chemical to treat the signs, symptoms or both attributed to DED. This 7-year fallow period was preceded by an even longer 13-year drought that began with the approval and launch of Restasis (cyclosporine ophthalmic emulsion 0.05%, Allergan).
Of course, there have been other topical medications that have been approved that had a label indication covering signs, symptoms or both — Flarex (fluorometholone acetate ophthalmic suspension 0.1%, Harrow) and Lotemax (loteprednol etabonate ophthalmic gel 0.5%, Bausch + Lomb) — but none specifically tied in writing to DED. Kala made the near-heroic effort to make and market a loteprednol approved to treat DED, but using loteprednol in this manner was hardly a breakthrough. All of these treat inflammation, the presumed pathophysiology underlying DED.
Even my beloved AzaSite (azithromycin ophthalmic solution 1%, Thea), which is not approved to treat anything involved in DED, works by reducing inflammation in the meibomian glands.
Over the years following the approval of Restasis, there have certainly been other treatment options entering our space. Both TrueTear (Allergan) (electrical) and Tyrvaya (varenicline solution 0.03 mg, Viatris) (chemical) stimulate the trigeminal nerve in the nose. This leads to the production of a complete “real” tear by all three elements of the lacrimal functional unit (lacrimal glands, goblet cells, meibomian glands). TrueTear never found a viable business model; Tyrvaya must overcome the unconventional approach of using medicine in your nose to treat your eye disease. It continues to be my strong contention that Tyrvaya is the logical choice as the first “real” treatment for mild DED.
As more and more research has been done on DED, it is evident that a majority of DED in the modern world is either partly or completely due to poor tear function. Evaporative DED (eDED) is strongly associated with meibomian gland dysfunction (MGD)/posterior blepharitis resulting in meibum of insufficient quality, quantity or both. Desiccation stress caused by evaporation in excess of production leads to elevated osmolarity among other insults, with eventual damage to corneal and conjunctival epithelium. Exposed and damaged sensory nerves cause pain, and a combination of high osmolarity-driven light scatter (which can equal the effect of grade 2 nuclear sclerosis) and locally variable lubrication results in fluctuating or outright poor vision.
What we have been missing is something that directly treats the evaporation causing the discomfort and visual problems of eDED. Enter Miebo (perfluorohexyloctane ophthalmic solution). Originally developed by Novaliq and licensed to Bausch + Lomb in 2019, Miebo is uniquely designed to treat the immediate cause of signs and symptoms of eDED: evaporation of tears from the ocular surface. It is the first topical medication to be FDA approved to treat the signs and symptoms of patients who have dry eye and concurrent MGD, and boy, does it ever do that.
Miebo is pure perfluorohexyloctane. The active ingredient is the drop; the drop is the ingredient. There is nothing else in the bottle but perfluorohexyloctane. It is not dissolved or suspended in anything else. In your little bottle of Miebo you have just the active ingredient. Miebo is water free, preservative free and steroid free. On-label treatment is four times a day. The drops are super tiny, only 11 µL to 14 µL as opposed to the typical 50 µL to 60 µL in a typical drop. You barely know it is in.
What underlies the magic happening on the ocular surface when a patient puts a drop of Miebo in? There are three Ms involved (hat tip to Dr. Selina McGee for this excellent vocabulary and description): molecule, monolayer and mechanism of action. The hexyloctane/carbon “base” of the molecule is both hydrophilic and heavier than water. It “sinks” through the tear layer only to be suspended just above the ocular surface by the extremely strong aerophilic nature of the perfluoro “flag” flying above the base and suspending the molecule upright in the tears. Miebo has a low surface tension, which makes for rapid spreading of a single-molecule thick monolayer of Miebo across the ocular surface that lasts for up to 6 hours.
While the precise mechanism of action is not fully worked out, this Miebo monolayer is thought to work by mimicking the anti-evaporative properties of healthy meibum. In vitro studies have shown that a combination of Miebo and meibum reduces evaporation of a saline solution four times as effectively as meibum alone. A sorta, kinda oil, it may reduce friction between the lid and ocular surface, further contributing to increased comfort.
Want some data? Of course you do. Miebo was studied in two large phase 3 studies that included approximately 1,200 subjects equally divided between drug and placebo. Total corneal (fluorescein) staining and change from baseline in the visual analog scale (VAS) dryness symptom score were evaluated at 15 and 57 days. Typically, one would pit the complete drug against a placebo consisting of the drug vehicle minus the active ingredient, a tough task because the only thing in this drug is the drug itself. Miebo was therefore compared against hypotonic saline, a somewhat more formidable foe because we know that it has proven beneficial effects on both signs and symptoms in DED.
Did not matter one bit. Miebo rocked it in both studies.
Total corneal staining was improved in both the saline and Miebo groups as early as 15 days. At both day 15 and day 57, Miebo was statistically significantly superior to the saline. There was a two times improvement in total corneal staining at the 57-day mark in the Miebo group. Likewise, with symptoms on the VAS scale, there was a marked improvement in symptoms at 15 days, and this increased through the 57-day mark, at which there was a 28.5-point decrease (from an average entry score of 60). That is an almost 50% decrease in symptoms. More than anything else, this Miebo attribute, a dramatic reduction in symptoms, is going to have a profound impact on our patients’ lives.
Which leaves us with positioning. Where will Miebo fit into our established protocols? Note that you should continue to treat the underlying causes of DED, especially MGD. I foresee two primary places where we will be prescribing Miebo. The obvious is patients who have pure eDED characterized by a normal or near-normal tear volume and a rapid tear breakup time. These patients will typically have a low tear osmolarity (perhaps asymmetric) and mild to moderate corneal and conjunctival staining. Miebo will be the first-line and perhaps sole treatment in this cohort.
The second group will be those patients with inflammatory DED that has been well treated with traditional medications (ie, immunomodulators) who are best described as incomplete treatment successes (hat tip to Dr. Mark Milner). Having a mix of both aqueous-deficient and evaporative DED, these patients are substantially improved compared with the onset of treatment; they continue to have symptoms that we can ascribe to evaporation. Miebo would be added to their treatment regimen. Note that Miebo should be the last drop instilled when multiple medications are administered at the same time, and artificial tears should not be used along with Miebo.
My wife and I, along with several SkyVision staff members, have been on Miebo for several weeks, and it is just incredible. Dr. Sheri Rowen describes it as “liquid silk” on your eye, and she is spot-on. Miebo is the next big thing. It could transform how we treat DED and should be in the quiver of every DED doctor.
I have consulted with Bausch + Lomb on every aspect of the Miebo project since 2018.
- References:
- Sheppard JD, et al. Am J Ophthalmol. 2023;doi:10.1016/j.ajo.2023.03.008.
- Tauber J, et al. Ophthalmology. 2023;doi:10.1016/j.ophtha.2022.12.021.
- For more information:
- Darrell E. White, MD, of SkyVision Centers in Westlake, Ohio, can be reached at dwhite@healio.com.
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