The Dry Eye Toolbox: What’s New and What’s on the Horizon
Dry eye disease is highly prevalent in the United States. It’s estimated that dry eye affects more than 22 million Americans and the number of new patients are expected to increase as the population ages. Hello, this is Mark Dlugoss, senior contributing editor of Ophthalmology 360. In recognition of July being National Dry Eye Awareness Month, Ophthalmology 360 outlined some clinical points associated with this growing medical problem with the help of Darryl White, MD, founder of Sky Vision Center, located in Westlake, Ohio, in suburban Cleveland.
Ophthalmology 360: The year 2023 could have been an exciting year for dry eye clinicians as new medications have already have received FDA approval, and there are some newer therapies on the horizon. But let’s start our discussion with a review of the current landscape and dry eye medications and let’s begin with the early medications.
Darrell White, MD: The official start of pharmaceutical interventions for dry eye would have to be the approval of Restasis in 2003. Restasis is Cyclosporine 0.05% in a lipid moiety. It’s actually the Endura artificial tear made by Allergan, but you can actually go back a little bit further. In the late 1990s, both Bausch & Lomb and Alcon had steroids that had enormously helpful labeling from the FDA, and those medications really could have launched the pharmaceutical revolution, Flarex from Alcon and Lotemax from Bausch & Lomb. And for lots of complex reasons, neither company really added those medications officially to our armamentarium. And so the earliest kind of the Mac daddy, if you will, of dry eye medications would be Restasis. It’s been around for an awfully long time. It took a while for us to figure out how best to use it. It took us a while to realize that it wasn’t just for severe dry eye, which was where it was studied in the FDA trials.
And then it wasn’t just to increase a patient Schirmer test and it wasn’t the kind of medicine that was like a Tylenol. You have a headache, you take a Tylenol, you feel better, and whoever told you to take the Tylenol is a genius. Restasis was a medicine that took some patients, but if you applied your patients both on the patient’s side and the doctor’s side, gosh, it made an enormous difference and was revolutionary. It was a slow cooking revolution. We had to figure out how best to use it, but everything really started with Allergan making the big push to get Restasis into our hands.
Ophthalmology 360: Over the last few years, several new medications have been added to the dry eye toolbox, so to speak. Can you outline some of these recent medications and what have they brought to the table compared to past medications?
Darrell White, MD: I think the two biggest medications that have come onto the market in terms of access to dryness medications is one more cyclosporine, Cequa from Sun Pharmaceuticals, which is Cyclosporine 0.09% in a totally different vehicle. It’s a vehicle where the cyclosporine is encapsulated in micelles that allow the hydrophobic cyclosporine to penetrate the hydrophilic ocular surface. And Xiidra lifitegrast, that’s another immunomodulator and works on a similar, has a similar effect on white blood cells. And those were the big ones because those are ones that we can use on an ongoing basis. And those are medications that, again, if you have patients really, really are super effective in the hands of doctors who were taking care of dry eye. There’ve also been some new steroids which have come on the market, so whereas back in the ’90s, both Alcon and Bausch & Lomb really didn’t go for it when it came to dry eye.
We do have some steroids which are on the market now, which are really geared toward dryness. Eysuvis is the one that is really specifically designed to be used in dry eye, originally brought to the market by Kala and was recently purchased by Alcon. Eysuvis is a formulation of Loteprednol that was shown to be highly effective in treating flareups of dry eye and also incredibly safe. There was minimal elevation and intraocular pressure over the course of the FDA trials with vis, and it was dramatically successful at reducing the flares.
Dry eye can be characterized as a chronic disease, which can be controlled and you can largely have asymptomatic patients with long periods of time, but those periods of no symptoms are interspersed with flareups where for whatever reason, people will have everything that goes along with their dry eye. One of the things that Kala did beautifully and that Alcon has really picked up the ball and run with very nicely is to raise our awareness as ophthalmologists that these flareups are not super uncommon and they don’t mean that your base treatment is no longer effective. You can treat them in a pulse fashion with medications like Eysuvis. So I think Eysuvis was also a really, really nice addition to our armamentarium.
Ophthalmology 360: In the last couple months Bausch & Lomb received approval from Miebo and also Novaliq received for Vevye. They’re both received FDA approval. How do these two medications add to the options now available and how different are they?
Darrell White, MD: Well, the Novaliq cyclosporine Vevye I think it’s a super interesting version of cyclosporine. The data was very impressive. We now have a pretty crowded landscape when it comes to cyclosporine medications. This medication is 0.1%, so it is the strongest cyclosporine that’s on the marketplace with an FDA approval to treat the signs and symptoms of dry eye. It’s another option for us. No one really has very much experience with it, and so we don’t know if it stands apart from the other cyclosporine medications. It’s great to have more options. We also have to remember that in the marketplace now as I’m speaking to you, there are four generic versions of Cyclosporine. There are all generic versions of Cyclosporine, 0.05%. By and large, they’ve been pretty well accepted and pretty well utilized in the marketplace. It’ll be super interesting to see what happens when Vevye is out there and we have an opportunity to have it go head to head against the other cyclosporins.
Miebo the other hand is potentially a transformative medication, a revolution in the dry eye space. This is the first medication that we have to treat evaporative dry eye. It’s the first medication that we have to treat the dry eye that comes from meibomian gland disease, posterior blepharitis. Miebo directly treats the signs and symptoms of evaporative dry eye. This is killer. We’ve been, all of us have been waiting for something like this for two decades. I think that Miebo is certainly the most exciting thing that’s come on the market in at least 8, 9, 10 years, and I think it’s going to take the dry eye space by storm.
Ophthalmology 360: In the coming months, several medications are expected to receive FDA approval. What new medications do you see on the horizons and what outcomes can clinicians expect from these therapies?
Darrell White, MD: There are a couple of medications which I think are really interesting that are coming up. I think TP-03 from Tarsus is going to be super helpful. One of the big underlying causes of meibomian gland disease is demodex infestation and TP-03, if it’s approved, I think the PDUFA date is July something. So if it’s approved, we will again have something that we haven’t had before. We’re going to have a direct effective treatment from one of the underlying causes of meibomian gland disease. And then Reproxalap from Aldeyra is a medication which kind of sits atop all of the inflammatory cascades as a dry eye medication and potentially as an anti-allergy medication. It has lots of promise. It’s really hard to know how Reproxalap will fit in to all of our basic protocols. Will it be used as a rescue drug?
Will it be used before we use some of the anti-inflammatory drugs? Nobody really knows. I can’t really see the brand new medications in the areas that we know have inflammation as the basic pathophysiology are going to change the environment. I think that we’re still going to see battles in the cyclosporine arena where the lipid emulsion based medications are going to be competing against the micelline capsulation strategy to get the medication to the ocular surface. There’s some really impressive data for Cequa in that part of our world that shows that that micelline encapsulation increases the penetration of the cyclosporine into the Oculus surface tissues two and a half or three times greater than the lipid emulsions. I think that that’s very impressive, and I think that Cequa with the micelle encapsulation, but also the other cyclosporines are going to continue to be the backbone of what we’re doing and everything else is really going to evolve over time. It’s super exciting though. We’ve gone so long without something which was different and it’s a super exciting time to be a dry eye doctor