Varenicline Solution Nasal Spray for the Treatment of Dry Eye Disease in Sjogren’s Disease: A Pilot Study

Angela S Gupta,1,&ast; Taylor J Linaburg,1,&ast; Emma Iacobucci,1 Patrick A Augello,2 Vivian L Qin,3 Gui-Shuang Ying,1,2 Vatinee Y Bunya,1 Mina Massaro1 1Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, USA; 2Department of Ophthalmology, Center for Preventive Ophthalmology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; 3Department of Ophthalmology, University of California Los Angeles, Los Angeles, CA, USA&ast;These authors contributed equally to this workCorrespondence: Taylor J Linaburg, Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, 51 N. 39th St, Philadelphia, PA, 19104, USA, Tel +1 412 576 – 7668, Email [email protected]: We evaluated the efficacy of varenicline solution nasal spray (VNS) in treating dry eye disease (DED) associated with moderate to severe Sjogren’s disease and analyzed tear film cytokine levels of patients with DED and Sjogren’s disease before and after VNS use.Methods: This was a pilot study involving a single-center, single-arm investigator-initiated trial. Patients with moderate to severe Sjogren’s disease were given VNS 0.03 mg twice daily for 28 days. Patients were assessed on day 0 before VNS use, day 14 and day 28. Clinical exam findings, symptomatology as measured by the eye dryness score, and tear cytokines were assessed at baseline and day 28.Results: Thirty-nine subjects were included. Between day 0 and day 28, there was a statistically significant improvement in the eye dryness score (p = 0.01), corneal staining (p < 0.001), and conjunctival staining (p = 0.04). There was a statistically significant increase in tear secretion by unanesthetized Schirmer’s in subjects with a baseline Schirmer’s ≤ 5 mm (n = 35 eyes, p = 0.02) and a non-statistically significant increase in tear secretion in subjects with a baseline Schirmer’s of 6– 10 mm (n = 16 eyes, p = 0.79). There was a statistically significant decrease in tear film cytokine concentration of IFNγ (p = 0.0003), IL-12p70 (p < 0.0001), IL-17a (p = 0.004), IL-1β (p = 0.007), IL-2 (p < 0.0001), IL-4 (p = 0.01), and TNF-α (p = 0.02), and no significant change in IL-6 (p = 0.56) and IL-10 (p = 0.18).Conclusion: Our findings add to existing evidence that VNS improves subjective dry eye symptoms, corneal and conjunctival staining, and tear secretion in a subset of tear-deficient patients, while providing new evidence that VNS reduces concentration of pro-inflammatory cytokines in the tear film.Clinical Trial Registration Number: NCT05700422.Keywords: dry eye disease, Sjogren’s disease, varenicline, tear film, cytokines