Targeted therapies shaping dry eye disease treatment
Click Here to Manage Email Alerts
In dry eye care, 2023 was a year of substantial changes, and ophthalmologists and their patients have welcomed more treatment options that bring relief.
Source: Preeya K. Gupta, MD
For a condition as multifactorial as dry eye disease, recent advances have delivered on the promise of more targeted and specific therapy. Healio/OSN Board Member Laura M. Periman, MD, said that management of dry eye continues to shift.
“It’s a mistake to think of it algorithmically,” she said. “You can’t algorithmize dry eye. It’s busy, noisy and messy, and there are too many contributing factors.”
With more targeted therapies, Periman said she can identify components of ocular surface disease and directly address them.
“I’ve got all these tools for directly addressing the components I identify on testing and examination,” she said. “That’s what’s finally shifting. Treat what is in front of you.”
After several years with not much new in dry eye, 2023 was transformative, according to Healio/OSN Board Member Darrell E. White, MD.
“Over the years, we’ve had lots of incremental improvements or additions to a particular basket,” he said. “With a few exceptions, there wasn’t really anything new under the sun. All the devices we were using had been developed anywhere from 2005 on, and there were no new entrances into the marketplace.”
That stasis ended last year with the approval of Miebo (perfluorohexyloctane ophthalmic solution, Bausch + Lomb) in May and Xdemvy (lotilaner ophthalmic solution 0.25%, Tarsus Pharmaceuticals) in July.
Miebo is designed to treat the signs and symptoms of dry eye disease by directly targeting tear evaporation, while Xdemvy was approved for the treatment of Demodex blepharitis. Experts agree that the approval of these two game-changing drugs in the same year made 2023 a revolutionary time in dry eye care.
Xdemvy
Before the approval of Xdemvy, the available treatments for Demodex blepharitis were not particularly effective. They generally had relatively poor patient adherence in addition to not having the desired effect of eliminating Demodex mites.
Healio | OSN Cornea/External Disease Section Editor Preeya K. Gupta, MD, said Demodex blepharitis has always been difficult to diagnose and tricky to treat. In fact, none of the usual treatments were FDA approved.
“We’d use tea tree oil cleansers, different kinds of wipes and things like that,” she said. “But lotilaner actually kills the mites so that the eyelid can then do its normal function. Patient dosing is only one drop twice a day, so it’s very patient friendly.”
White said Tarsus did a lot of heavy lifting not only in designing Xdemvy but also in the way ophthalmologists diagnose Demodex blepharitis.
“Diagnosing it had been a real nuisance,” he said. “You had to pluck eyelashes and look at them under the microscope. That actually got a few people in trouble because their state lab boards accused them of running an unauthorized lab simply because they had a microscope in their office.”
The solution was to have patients look down during a slit lamp examination and look for collarettes — cylindrical dandruff around the base of the eyelash.
“If you see collarettes, there’s a 95% chance there’s a Demodex mite in that eyelash,” White said. “If you have inflammation on the eyelid margins, then you have Demodex blepharitis.”
Gupta said Xdemvy was exciting on its own, but identifying the collarette as a sign of Demodex is just as significant for clinicians.
“We haven’t been great at diagnosing Demodex,” she said. “Not a lot of people spent time plucking eyelashes at the slit lamp, and now that we know that the collarette is a pathognomonic sign for Demodex and we have something to treat it, it is something that a lot more clinicians are looking for. When they see it, especially in a symptomatic patient, they can treat it to give patients improved eyelid health.”
The FDA approval for Xdemvy was based on the Saturn-1 and Saturn-2 studies, which comprised more than 800 patients. By day 43 of treatment, patients who received Xdemvy experienced eyelid improvement and reduction to no more than two collarettes per upper lid, as well as improvement in mite eradication and erythema endpoints.
As more research on Demodex blepharitis comes to light, Periman said it was surprising how common it was in her patients.
“We did a multicenter study of all-comers on any given day, and we found that close to 60% of patients had collarettes when they looked down during exam,” she said. “If you start looking at specialized populations like patients with contact lens intolerance, the number of cases that have collarettes goes up to 90%. So, it’s far more common than we realize.”
Having an easy and rapid way to diagnose and treat Demodex blepharitis makes it worth investigating in any patient who complains of dry eye disease-like symptoms.
“With a single course of twice-a-day therapy, it’s an easy thing to get out of the way. I think our colleagues will be reaching for it often when there’s evidence of Demodex blepharitis,” Periman said.
“As clinicians, when we have something targeted, specific and directed, it decreases our frustration factor, and it actually decreases chair time quite a bit. You don’t have to waste your breath on warm compresses, which nobody ever uses anyway. Xdemvy is a huge bonus offering for our colleagues across the country that deal with dry eye all day every day, whether they want to or not,” she said.
Nandini Venkateswaran, MD, said the introduction of Xdemvy changed the way she manages Demodex blepharitis and lid margin disease in her practice.
“Many of us, including myself, are finally starting to actually look for Demodex on the lid margin,” she said. “When you do your eye exam, you should spend a few extra seconds looking at the lids and lashes and the meibomian glands in addition to examining the tear film and patterns of corneal and conjunctival staining. This complete eyelid and ocular surface exam has become a mainstay of my practice. As a result, I am talking about Demodex blepharitis more often with patients. The fun and rewarding part is that I can say that there’s a treatment for this condition rather than offering therapies that only partially worked but weren’t really addressing the inciting organism itself.”
Miebo
Another new frontier in 2023 was finding a way to tackle evaporative dry eye disease. White said Demodex blepharitis and all types of meibomian gland diseases cause inflammation in the meibomian glands that leads to ineffective oil.
“Evaporative dry eye is caused when we have an imbalance between the amount of effective tears that we’re creating and the amount of evaporation we have off the surface of the eye, and anything can cause that evaporation,” he said. “You can have exposure by incomplete blinking. When you look at a computer screen of any type, not only do you blink less frequently, you blink less completely. You could also have a condition that causes the oil that the meibomian glands produce to be ineffective. Even if you have a normal blink rate and amplitude, you still have accelerated evaporation off the surface of the eye because the oil is not slowing down that evaporation.”
An imbalance between the effective tear on the surface and how much it evaporates can cause desiccation stress, which leads to inflammation, White said. Miebo offers a way to stall that evaporation by creating a barrier over the ocular surface.
“It’s a novel molecule because it’s not how we think of our typical pharmacological therapy,” Gupta said. “It’s not treating inflammation directly. What it does is restrict evaporation on the surface of the eye, which can have some positive downstream effects. It stabilizes the tear film and does the functions of what oil from the meibomian glands would do.”
Gupta said this is particularly exciting for clinicians because it is complementary to other common dry eye therapies. Patients who use Restasis (cyclosporine ophthalmic emulsion 0.05%, Allergan) or Xiidra (lifitegrast ophthalmic solution 5%, Bausch + Lomb) to treat inflammation can benefit from Miebo because they also experience lipid deficiencies.
“It can be a good primary therapy, but it can also help patients on other medications,” she said. “They might not be as well controlled, and it’s something that can help them because it’s leveraging a different pathway.”
Miebo was investigated in the phase 3 MOJAVE study, which was eventually used to support its approval by the FDA. In the study, 620 patients with a history of dry eye disease associated with meibomian gland dysfunction were randomly assigned to receive either Miebo or saline four times daily for 8 weeks.
At 8 weeks, Miebo demonstrated greater improvements in total corneal fluorescein staining and visual analog scale eye dryness. It also met key secondary endpoints, including burning and stinging, as well as central corneal fluorescein staining.
Venkateswaran said she notices that patients undergoing therapy with Miebo are having better quality of vision and fewer fluctuations in their tear film.
“There are many artificial tear drops that have been commercially available that might have a lipid or an omega-3 component that is supposed to help maintain the lipid layer to prevent tear evaporation,” she said. “However, there really hasn’t been a medication that truly addresses evaporative dry eye. Miebo has been a nice adjunct in my practice. We have so many of these patients who have tried the gamut of treatments, and having one more option in our tool kit has been great.”
In her practice, Periman said she uses Miebo with flexible dosing on top of a preservative-free artificial tear.
“I’ll use it for relief of friction from conjunctivochalasis, tear instability cases, low tear volume cases,” she said. “I’ll test dose it in the chair, and patients are amazed at how comfortable it is. For the first time, we have a drop that’s just beautifully comfortable. It’s refreshing to have something that doesn’t sting or burn.”
If Xdemvy and Miebo are examples of what more targeted and specialized therapies can do, Periman said it will only get better as more targeted therapies arrive.
“It has made it easier to be a hero to your patient,” she said. “I have all these wonderful modalities and suite of services I can offer, and I can get there so much faster than I could 10 years ago or even 5 years ago. I can get my patients lasting, meaningful relief.”
Unmet needs
A few areas of unmet need remain in dry eye care. Periman said two of the biggest are corneal pain and neuropathic pain.
“I think those are the two things that we need better tools for,” she said. “The National Eye Institute has earmarked a lot of grant money for basic science and clinical science to help us do a better job at dealing with ocular pain, so I’m excited for that.”
New additions to the dry eye armamentarium create a lot of excitement for clinicians looking for ways to help their patients. Now, they have more options than ever to treat their patients and better means to diagnose them, White said.
“There’s really no great unmet need right now in the dry eye world that affects a large number of patients,” he said. “There are needs that are adjacent to the big needs — evaporative dry eye, Demodex blepharitis, basic meibomian gland disease — but we have a majority of those things taken care of.”
However, some patients may struggle to get the medications they need due to affordability issues, White said.
“There’s nothing unique about this in dry eye or even in eye care,” he said. “This is a national problem that’s an issue for people with insulin-dependent diabetes, just as it’s a big deal for people with rheumatoid arthritis.”
Gupta said that the drug manufacturers do a fairly good job of offering coupons or discounts to help patients afford their medications. Patients with commercial insurance generally have good access, she said, but that does not account for all patients.
“Where some of the challenges still lie are in our Medicare-age population,” she said. “Medicare requires companies to petition over a year in advance to get into the formulary. When there’s a new therapy, Medicare patients often won’t have coverage for it because of the Medicare rules.”
This can cause problems for patients who have something that is now treatable but cannot get that treatment, Gupta said.
White said this split between commercial and Medicare insurance coverage will ultimately create a bifurcated population — one with access to these new dry eye medications and one without.
“We will have younger people who are going to have reasonable out-of-pocket costs for these transformative medications, and we’re going to have patients in more mature age groups who are not,” he said. “It’s one of the huge challenges for every type of medical practice and every type of surgical practice.”
Periman said access to medication is a major unmet need in dry eye care and called for action from a regulatory and political perspective.
“The arbitrary and capricious prior authorization obstacles from health insurance companies — while they sit on record profits quarter over quarter — is mind-boggling to me,” she said. “The process is wasteful, abusive, obstructionist, and patients suffer. Clinics suffer. Doctors can’t keep up with it, and finding staff that are willing to do that battle is hard. It needs to change so we can get these amazing tools into patients’ hands.”
The entire process is a massive drain on resources, White said, and has the potential to create a lot of burnout among physicians and their practices.
“It’s a barrier to the doctors, nurses, physician assistants, technicians and all of the staff who have to help the patient navigate that Byzantine economic system,” he said. “It’s really time consuming just to take care of the disease state. If you add in the other time requirements to get things covered, people just throw up their hands and say, ‘No. We’re just not going to do it.’”
Periman said there are a lot of exciting things to come in dry eye and hopes that more of her colleagues take interest and see how satisfying, efficient and fun treating dry eye can be.
“That’s something that we need to keep pushing for in medical education,” she said. “I think these efficient tools will help.” – by Alex Young
Click here to read the At Issue, “What was the biggest innovation in dry eye in the last year?”
- References:
- Bausch + Lomb and Novaliq announce FDA approval of Miebo (perfluorohexyloctane ophthalmic solution) for the treatment of the signs and symptoms of dry eye disease. https://ir.bausch.com/press-releases/bausch-lomb-and-novaliq-announce-fda-approval-miebotm-perfluorohexyloctane. Published May 18, 2023. Accessed Jan. 11, 2024.
- FDA approves Xdemvy (lotilaner ophthalmic solution) 0.25% for the treatment of Demodex blepharitis. https://ir.tarsusrx.com/news-releases/news-release-details/fda-approves-xdemvytm-lotilaner-ophthalmic-solution-025. Published July 25, 2023. Accessed Jan. 11, 2024.
- Sheppard JD, et al. Am J Ophthalmol. 2023;doi:10.1016/j.ajo.2023.03.008.
- For more information:
- Preeya K. Gupta, MD, of Triangle Eye Consultants in Raleigh, North Carolina, can be reached at preeyakgupta@gmail.com.
- Laura M. Periman, MD, of Periman Eye Institute in Seattle, can be reached at dryeyemaster@gmail.com.
- Nandini Venkateswaran, MD, of Massachusetts Eye and Ear, can be reached at nandini.venkat89@gmail.com.
- Darrell E. White, MD, of SkyVision Centers in Westlake, Ohio, can be reached at dwhite@healio.com.
Collapse
Read more about
Click Here to Manage Email Alerts