Eyeworld

APRIL 2022 | EYEWORLD | 87 C Contact de Luise: vdeluisemd@gmail.com Galor: AGalor@med.miami.edu Sheppard: jsheppard@cvphealth.com by Liz Hillman Editorial Co-Director About the physicians Vincent de Luise, MD Assistant Clinical Professor of Ophthalmology Yale University School of Medicine New Haven, Connecticut Anat Galor, MD, MPSH Assistant Professor of Clinical Ophthalmology Bascom Palmer Eye Institute Miami, Florida John Sheppard, MD, MMSc, FACS President Virginia Eye Consultants Norfolk, Virginia Relevant disclosures de Luise: None Galor: Oyster Point Pharma Sheppard: Oyster Point Pharma Nothing to sniff at: Intranasal spray for dry eye I t's not the first time the trigeminal nerve pathway or even intranasal delivery re- ceived approval as a treatment for dry eye, but clinicians are excited nonetheless about the October 2021 FDA approval of vareni- cline (TYRVAYA, Oyster Point Pharma), a nasal spray for the signs and symptoms of dry eye disease. According to Oyster Point Pharma, the varenicline nasal spray is "believed to bind to cholinergic receptors to activate the trigeminal parasympathetic pathway, resulting in increased production of basal tear film as a treatment for dry eye disease." The company shared that the mean change in Schirmer's scores among patients treated with TYRVAYA vs. vehicle in the two clinical trials was 11.7 mm and 11.3 mm and 3.2 mm and 6.3 mm, respectively. It might be the first and only nasal spray approved for this indication, but preceding it was a similar concept with a different mode of action. TrueTear, which was pulled from the market by Allergan in 2020 just 2 years after its launch, also operated based on stimulation of the trigeminal nerve pathway to increase production of a complete tear film. TrueTear, however, was an intranasal neurostimulator, which used randomly generated micro-electrical impulses to drive the reaction. Vincent de Luise, MD, also mentioned the iTEAR device (Olympic Ophthalmics), still on the market, which stimu- lates the nasal nerve externally to increase tear production. Anat Galor, MD, said she thinks there is a place for TYRVAYA in the dry eye space. "It's such a big market, I do think there is space for everyone," she said, noting that there is a subset of patients who might find intranasal delivery of therapy beneficial, such as those who have difficulty with drops (administering them or the topical effects). "There are people who are sensitive to eye drops; … they find it attractive to have tearing without the local site reaction," she said. "We know there is a trigeminal pathway that can ac- tivate a tearing response from stimulation of the anterior ethmoidal nerve in the nose. We saw a rapidly increasing tear lake." John Sheppard, MD, MMSc, FACS, said the trigeminal nerve stimulation pathway is familiar to him, having worked on development of TrueTear with Allergan. "It worked beautifully," he said, providing full stimulation of the lacrimal functional unit, which produced real tears with natural propor- tions of oil, mucin, aqueous, proteins, and other beneficial components. Targeting this pathway with TrueTear had its challenges though, such as patient acceptance, lack of insurance coverage, and a significant cohort of patients who didn't like the tingling sensation the device caused, Dr. Sheppard said. Thus, despite what Dr. Sheppard called "tremendous intellectual investment, large amounts of investigational time, and magnificent short- and long-term results," this neurostimulation approach was not a commer- cial success. It, however, established the viability of af- ferent trigeminal stimulation for varenicline. Dr. Sheppard called the results from the Phase 3 clinical trial exciting, noting that it produced excellent sign and symptom improve- ments and is thought to produce a classic physi- ologic tripartite tear film. Dr. Sheppard also said a significant subset of patients who don't like drops or who have issues with drop delivery, tremors, arthritis, poor depth perception, those who are already on other drops, or who don't want to use drops for aesthetic purposes will accept intranasal delivery. He said patients are familiar with nasal sprays, such as those for al- lergies, which may increase acceptance as well. Dr. Sheppard described TYRVAYA as not only a novel pathway but a novel delivery system. "It's dually innovative in this regard," he said.

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