During Saturday’s Cornea Subspecialty Day, Gerami Seitzman, MD, shared an update on novel dry eye treatments under investigation. In addition to introducing the treatments, she shared summaries of preliminary data and new drugs headed your way.
Lotinaler eyedrops. Excited that Demodex blepharitis is getting attention, Dr. Seitzman shared that lotinaler is an acaricide (mite killer) that blocks GABA receptors in fleas and ticks but not in humans. “Interestingly, it’s an eyedrop and not an eyelid scrub,” she added.
In a month-long efficacy trial, 60 patients were randomized to two daily drops of treatment or placebo. At 28 days, the primary outcome (collarette cure) showed that the treatment arm had a lower collarette score than the placebo arm. Epilation of four lashes per patient showed that 26% of the placebo group and 67% of the treated group had complete mite eradication.
Sleeve versus collarette. Although the audience already knew about diagnosing Demodex circumferential damage, Dr. Seitzman took a moment to point out that everyone has been taught different definitions of sleeve and collarette (and scurf). She follows the BCSC’s definition that a sleeve is a cylindrical dandruff buildup and indicative of Demodex. A collarette is circumferential and indicative of staphylococcal blepharitis. Although they are not interchangeable, many people use them as such—including in the lotinaler study.
“I just think all the external disease nerds of this world need to unite and make sure we say the same noun so that treatment efficacy can be accurately compared,” said Dr. Seitzman, a self-proclaimed external disease nerd, who received applause from the audience.
Varenicline nasal spray. “If you take varenicline orally, it can help you stop smoking, but it turns out that if you spray it in your nose, it may help your dry eye,” Dr. Seitzman said. This treatment stimulates the nicotinic acetylcholine receptors in the nose to trigger lacrimal function.
Primary data were collected in the ONSET 1, 2, and 3 randomized controlled trials. Study patients had symptomatic dry eye with corneal staining and were mildly aqueous deficient but capable of producing aqueous. Researchers randomized 758 patients to receive two sprays of treatment (0.03 mg or 0.06 mg) or vehicle twice daily.
The primary outcome at four weeks: 27% of the placebo and approximately 47% of treatment group had an increased Schirmer of 10 mm or more over their baseline. About adverse outcomes, she noted, “just remember to tell patients that there is a 96% chance of sneeze when they take the medication.”
KPI-121 ophthalmic suspension 0.25%. This is a formulation of the corticosteroid loteprednol. “What is novel is the vehicle to which the loteprednol is attached, and its [mucous-membrane penetrating (MPP)] technology,” Dr. Seitzman explained. Because these nanoparticles evade mucous entrapment, the MPP vehicle may be able to deliver a higher concentration of treatment at the ocular surface.
Primary data were collected in the STRIDE 1, 2, and 3 randomized controlled trials. Researchers recruited several thousand patients with clinically diagnosed dry eye disease in both eyes and randomized them to receive KPI-121 four times a day for two weeks or placebo.
“Anyone who has ever used a steroid for any indication will not be surprised at all that people who took the steroid feel better and their eyes look a bit less red,” she concluded.
New treatments on the horizon that Dr. Seitzman thinks are interesting include the following:
- NOV03. The drug is an inert and anhydrous semifluorinated alkane perfluorohexyloctane (F6H8). It is already available in Europe and Australia as NovaTears, and she thinks it is on its way to the United States. The mechanism has not been described, but it is a liquid that is free of water, preservatives, or surfactants that cools the ocular surface. Not only can it act as an artificial tear but also some people are attaching drugs to it to explore its use as a vehicle. As F6H8 enters the market further, Dr. Seitzman is curious to see how other drops will utilize this mechanism.
- AZR-MD-001. Finally, Dr. Seitzman is also interested in AZR-MD-001, which is a selenium sulfide ointment being developed by Azura Ophthalmics. It is a keratolytic that might be useful for chronic meibomian gland disease, particularly for patients with hyperkeratinization of their lid margin.
“Here’s the secret that I want to remind everyone of when you’re assessing efficacy for novel dry eye treatment,” Dr. Seitzman teased. “We just need to remember to also look at the placebo group.”
Individuals in the placebo groups of dry eye trials seem to do very well, based on objective criteria assessed by trained masked clinicians. She calls for everyone to be discerning consumers and patient advocates. Carefully consider the statistical significance.
“We put billions of dollars into these drugs, and we need to make sure that we’re putting money into treatments that are genuinely effective for our patients,” Dr. Seitzman concluded.
Financial disclosures: Dr. Seitzman: Dompe: C.
Disclosure key: C = Consultant/Advisor; E = Employee; EE = Employee, executive role; EO = Owner of company; I = Independent contractor; L = Lecture fees/Speakers bureau; P = Patents/Royalty; PS = Equity/Stock holder, private corporation; S = Grant support; SO = Stock options, public or private corporation; US = Equity/Stock holder, public corporation For definitions of each category, see aao.org/eyenet/disclosures.
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