Time to talk about evaporative dry eye disease
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We should talk a bit about evaporative dry eye disease.
Why now? A couple of reasons. It is a scourge in our practices, a disease that is wreaking havoc across almost all age groups and nearly every occupation in the developed world, including professional sports. Eye doctors’ offices are literally overflowing with people suffering from this disease. Three of our esteemed colleagues at Bascom Palmer are skeptical about the “evaporative” part. We should come to some agreement on what it is, what causes it and how we should treat it as a new option from Bausch + Lomb is about to arrive.
For years, we have understood that inflammation is the underlying pathophysiology responsible for the signs and symptoms of dry eye disease (DED). This is still true, but the location of the inciting inflammation may need to be refined. Aqueous-deficient DED is characterized by inflammation on the ocular surface. This inflammation is responsible for both the decrease in tear volume as well as many (most?) of the associated symptoms. There is a clear association with elevated tear osmolarity, itself a likely cause of inflammation. Even if the “original sin” of the DED is evaporation, reduced tear volume from any source is a cause of inflammation.
The root cause of evaporative dry eye disease (EDED) lies in the meibomian glands. Whatever the source, meibomian gland dysfunction (MGD) is the culprit. Inflammation is the bad actor here as well, causing the glands to begin producing oil that is ineffective in the role of maintaining the integrity of the tear film between blinks. This inflammation likely has multiple origins. Once initiated, the lipid produced in the meibomian glands undergoes changes at a molecular level like an increased melting point, leading to thickened, ineffectual secretions. Even worse, the ineffective lipid secreted dumps all kinds of proinflammatory cytokines and chemokines on the ocular surface, increasing the inflammatory milieu.
Why do people get MGD? We can lay most of the blame on the unintended consequences of living in the developed world. Studies have shown that decreased dietary intake of omega-3 fatty acids can lead to MGD. In our world of industrial farming, nearly all our high-density protein sources are raised on feed that is primarily corn. Corn is high in omega-6 fatty acid, which is proinflammatory and essentially bereft of omega-3 fatty acid.
The thickened meibomian gland secretions then run afoul of another unintended consequence of the modern world: A supermajority of people in the developed world spend almost all their work time looking at screens. Most people who spend their days in front of a computer blink neither frequently nor completely enough to release the oil sequestered in the glands, producing chronic obstruction at the mouth of the gland. This then leads to “meibomian gland constipation” (hat tip to Preeya Gupta) and eventual gland destruction.
What can we do to treat EDED? Over the last several years, a fairly uniform outline of treatment has emerged, with some variations around the edges. First shot across the bow? Daily heating of the lids to melt the oil plugging the glands. Clean the lid margins with premedicated pads afterward. Many options exist on the market. The leader to date is OcuSoft, but Bruder has recently entered the fray with two options.
Treat any inflammation on the ocular surface, of course. Start with a topical steroid in “pulse” mode, attempting to quell both the visible inflammation and symptoms quickly without ongoing prescription therapy. If this fails, I favor putting patients on long-term topical treatment with AzaSite (azithromycin ophthalmic solution, Thea Pharma) at bedtime. After a loading phase, they can often be treated either every other night or twice a week. There are other pharmaceutical solutions, of course. Intermittent pulse therapy with oral azithromycin is effective, as is chronic treatment with doxycycline or minocycline. I admit to a bias for localized topical treatment if possible. For those practices that have made the commitment to providing advanced MGD care, the continued presence of significant symptoms will prompt a selection of in-office treatments that would include thermal application, gland evacuation, biofilm removal and light-based treatments such as intense pulsed light, intense regulated pulsed light and low-level light therapy.
What is missing is a medication that is specifically geared toward treating the ocular surface in EDED.
Beginning with the approval of Restasis (cyclosporine ophthalmic emulsion 0.05%, Allergan) in the early 2000s, we have been treated to a parade of medications for which approval was based on the venerable Schirmer’s test. Well, maybe not a parade, exactly. More like a few random flautists and the odd trumpeter sauntering across a sidewalk. It could have been a full-blown Macy’s extravaganza based on treating inflammation. Bausch + Lomb and Alcon both marched away. They declined to promote Lotemax (loteprednol etabonate ophthalmic gel 0.38%) and Flarex (fluorometholone acetate ophthalmic suspension 0.1%, now Santen), respectively, to treat the surface inflammation of dry eye despite the broad indications on both medications’ labels.
Enter Miebo to fill the void. Originally developed by Novaliq, Miebo is pure perfluorohexyloctane. There is no vehicle; the drop is the drug, and the drug is the drop. That means no water. No water means that there is no way for bacteria to grow inside the bottle, which means no preservative. Your patient gets a bottle of perfluorohexyloctane and nothing else.
Here is the science: It is not entirely clear how, but Miebo seems to work by reducing evaporation off the ocular surface. Strictly on label, the drop will be used four times daily. In two FDA phase 3 pivotal studies, Miebo met both of its primary sign and symptom endpoints. The two primary endpoints were change from baseline at week 8 (day 57 ± 2) in total corneal fluorescein staining (tCFS) and eye dryness visual analog scale (VAS) score. Patients experienced relief of symptoms as early as day 15 and through day 57, with statistically significant reduction in VAS eye dryness score favoring Miebo observed in both studies. Additionally, at day 15 and day 57, a significant reduction in tCFS was observed in both studies.
The obvious place to use Miebo is in patients who have symptomatic EDED. The signature findings will be a rapid tear breakup time, tear levels that are only moderately decreased if at all, and a low tear osmolarity (with or without asymmetry). They may or may not have a positive InflammaDry (Quidel), but fluorescein staining is quite likely to be present. Miebo will be appropriate as a first-line therapy, but I also foresee using it for those patients who continue to have symptoms despite treatment that has eradicated most or all of their original signs.
Bausch + Lomb seems to be planning a conservative rollout. It has not yet published an official market release date, but I think we will see it before Halloween. We should all anticipate using a specialty pharmacy, coupon program or both while we await action by Medicare and other third-party payers. I anticipate being hugely frustrated by this process. From where I am sitting, at the slit lamp like all of you, Miebo looks like a potentially transformative therapy. Although I envision using it initially in classic EDED, I literally cannot think of any category of DED where it will not apply.
Fingers crossed on behalf of patients and doctors that access to Miebo is quickly and easily available once Bausch + Lomb releases it into the wild.
- For more information:
- Darrell E. White, MD, of SkyVision Centers in Westlake, Ohio, can be reached at dwhite@healio.com.
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