Treating Ocular Surface Disease: What Role Does the Nose Play?
Dry eye disease (DED) affects more than 16 million people in America.1 It is not surprising that the symptoms of the disease are now one of the leading causes for patient visits in the US.2 Whilst DED treatment is well-established with new formulations of effective topical drugs constantly evolving the vast majority of clinicians are not completely satisfied with the available therapies.2 The mode of delivery for drug therapies to the ocular surface is creating some interest. Is it now possible to administer a drug nasally that treats ocular surface disease?
The trigeminal nerve of the parasympathetic nervous system stabilises the tear film through innervation of the lacrimal functional unit which is made up of the cornea, conjunctiva, lacrimal gland, meibomian glands and goblet cells.2-5 The nasolacrimal reflex (NLR) is a proven contributor to normal tear film homeostasis and is triggered by the activation of the trigeminal nerve fibres in the nose.2 A randomized controlled trial has found the NLR to account for 35% of basal tear production.2 With this neurostimulation patients have shown significant improvements in chronic signs and symptoms of DED.
Oyster Point Pharma has formulated a drug that is administered via the nasal pathway to promote natural tear film production.6,7 The preservative-free nasal spray (OC-01) contains a nicotinic acetylcholine receptor (nAChR) agonist that stimulates the nasal trigeminal pathway.7
The ONSET study was a randomized Phase IIb study using OC-01 with 182 DED subjects from the United States.6 It tested the safety and efficacy of the nasal spray in the treatment of DED. There were four equal sized treatment groups, a placebo and three different concentrations of OC-01 (0.02%, 0.1% and 0.2%).6 Results produced a statistically significant improvement in the Schirmer score when comparing the placebo with all three drug concentrations.6 This treatment study demonstrated immediate onset of action with mild and transient adverse effects in the nose and no unfavourable ocular surface issues.7
Enrolment has now begun on a Phase III clinical trial of OC-01 nasal spray. The ONSET-2 trial will test 750 subjects across 20 US sites.8 Along with the Schirmer test score evaluation a secondary endpoint will look at any reduction in corneal surface staining.8 The first subject was enrolled last year and the trial is expected to be completed by July of this year.8
The prospect of an alternative mode of delivery to improve ocular surface disease is exciting. Often when there is active inflammation in DED topical drops exacerbate ocular irritation upon insertion. A novel nasal approach may be better tolerated by patients, and as the emerging trials reveal, equally effective in the fight against dry eye disease!
References
1. Farrand KF, Fridman M, Stillman IO, Schaumberg DA. Prevalence of diagnosed dry eye disease in the United States among adults aged 18 years and older. Am J Ophthalmol. 2017;182:90–98.
2. Friedman NJ, Butron K, Robledo N, et al. A nonrandomized, open-label study to evaluate the effect of nasal stimulation on tear production in subjects with dry eye disease. Clin Ophthalmol. 2016;10:795-804.
3. LeDoux MS, Zhou Q, Murphy RB, et al. Parasympathetic innervation of the meibomian glands in rats. Invest Ophthalmol Vis Sci. 2001;42(11):2434-41.
4. van der Werf F, Baljet B, Prins M, Otto JA. Innervation of the lacrimal gland in the cynomolgous monkey: a retrograde tracing study. J Anat. 1996;188(Pt 3):591-601.
5. Dartt DA, McCarthy DM, Mercer HJ, et al. Localization of nerves adjacent to goblet cells in rat conjunctiva. Curr Eye Res. 1995;14(11):993-1000.
6. Oyster Point Pharma. Oyster Point announces positive results from two separate Phase 2b clinical trials of the company’s investigational treatments for dry eye disease. https://oysterpointrx.com/oyster-point-announces-positive-results-from-two-separate-phase-2b-clinical-trials-of-the-companys-investigational-treatments-for-dry-eye-disease. Accessed February 13 2020.
7. Karpecki PM. Dry eye therapy: Getting nosy. Review of Optometry. 2019. https://www.reviewofoptometry.com/article/dry-eye-therapy-getting-nosy. Accessed February 15, 2020.
8. Oyster Point Pharma, Inc. Clinical Trial to Evaluate the Efficacy of OC-01 (Varenicline) Nasal Spray on Signs and Symptoms of Dry Eye Disease (The ONSET-2 Study). Clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/NCT04036292. Accessed February 15, 2020.
–Louise Wood
Louise Wood is a medical writer with experience in the clinical sector working alongside doctors and scientists. She holds a Bachelor’s degree (hons) in optometry with extensive experience in communication and patient care.
No financial disclosures.
