The anticipation has been brewing and it’s finally here after years of clinical trials—Miebo (perfluorohexyloctane ophthalmic solution, Novaliq, Bausch + Lomb). Formerly known as NOV03, the drop is indicated to treat the signs and symptoms of dry eye disease (DED). More notably, this therapeutic is the first on the market to directly target tear evaporation, which is a common culprit of DED.

Miebo is expected to be available in the second half of this year and should make a significant impact on the numerous patients with DED, especially those with evaporative eye disease. Let’s get to know this potentially game-changing therapeutic.

Miebo's Mechanisms

This drug is a water-free, single-component, preservative-free topical drop. Perfluorohexyloctane (PFHO) ophthalmic solution is a semi-fluorinated alkane. What exactly is that? Alkanes have been used in the eye previously in complex retinal detachment surgery primarily for inferior retinal detachments. The molecule has a lipophobic fluorinated component that quickly evaporates in the air, plus an alkane base that easily mixes with the lipid layer to ground the molecule. This combination creates a monolayer within the lipid-to-air interface.3 It also allows for extremely fast spreading of the drop across the ocular surface. The agent was found to remain in the tear film for six hours and the meibomian glands for over 24 hours.

The research in question is the first FDA study where all patients had MGD and the first approval of a drug requiring only two pivotal trials to reach statistical significance in signs and symptoms.

Unique Properties

The extremely low surface tension of this molecule allows Miebo to have a small drop size of about 11µL. Compared with typical eye drops at 30µL to 50 µL, it is barely noticeable on the eye.4,5 Unlike other preservative-free, multidose bottles, it comes in a normal, easy-to-squeeze 5mL bottle. Each bottle contains 3mL of PFHO or about 280 drops. It has a refractive index similar to that of water, helping minimize vision blur after instillation.6

In the Phase III FDA clinical trials, the most common adverse event experienced was blurred vision, but only at a rate of 2.1%. Burning and stinging—common side effects of many dry eye medications—were extremely low at 0.5% or three out of 614 patients, and most telling regarding this drop’s comfort was the discontinuation rate secondary to an adverse event, at only 0.2% or one patient out of 614, due to mild irritation. The safety/comfort profile of this product is unheard of in the dry eye space.

Regarding the PFHO mechanism of action, data suggests that PFHO penetrates the meibum, potentially acting as a surrogate of the lipid layer.7 In 48 dry eye patients, PFHO significantly increased tear film thickness and lipid layer thickness over four weeks compared to the control group.8

PFHO helps inhibit evaporation, based on a study comparing its use with hypotonic saline.9 Evaporation rates were measured where 100µL PFHO alone inhibited saline evaporation by 88%, and adding PFHO to meibum lipids significantly inhibited evaporation even greater.

Miebo may particularly benefit those with dry eye related to MGD, as it targets evaporative DED.

Miebo may particularly benefit those with dry eye related to MGD, as it targets evaporative DED. Click image to enlarge.

Corneal Staining and Symptoms

Although this medication has been shown to inhibit evaporation significantly, it also quickly improves signs of corneal staining. In fact, the primary endpoints for the Phase III clinical trials were changes in complete corneal staining as well as improvements in the Visual Analog Scale for eye dryness. 

Miebo was able to achieve a clinical statistical improvement in total corneal staining scores and symptoms of eye dryness as soon as day 15 and also the primary endpoint at day 57 vs. the control group. The repeatability of the data is most impressive, as these were similar results to the Phase II trials. The approved dosing is QID based on the testing in Phase III clinical trials.

Fitting in to the Therapeutic Landscape

Miebo targets the most critical component of dry eye—the lipid layer—by preventing evaporation. Target patients are those with MGD, given that the clinical trial involved 100% of patients with this condition, but even patients with aqueous-deficient dry eye would benefit from a decrease in evaporation and improvement in ocular surface staining. 

Miebo appears to work best when it can stabilize existing meibum as opposed to patients with severely thin lipid layers or significant meibomian gland atrophy such as those with severe ocular rosacea or previously taking Accutane (isotretinoin). It can also affect contact lenses, so it’s recommended that Miebo be placed in the eye 30 minutes prior to insertion and not used on a contact lens. It should be compatible with anti-inflammatory drops, if inflammation is present.

Having a new therapeutic that targets evaporation is a first in many aspects, including the speed to FDA approval, consistency of data, quick response and especially the low side effect profile. Miebo is a welcome addition to our dry eye treatment options.

Special thanks to Josh Davidson, OD, for his contributions to this column.

Dr. Karpecki is the director of Cornea and External Disease for Kentucky Eye Institute, associate professor at KYCO and medical director for Dry Eye Institutes of Kentucky and Indiana. He is the Chief Clinical Editor for Review of Optometry and chairman of the affiliated New Technologies & Treatments conferences. A fixture in optometric clinical education, he provides consulting services to a wide array of ophthalmic clients. Dr. Karpecki’s full disclosure list can be found here.

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