Dee Stephenson, MD, and Cynthia Matossian, MD, recently completed a study to evaluate the effect of varenicline solution nasal spray 0.03 mg on the signs and symptoms of dry eye disease and tear film stability.
Varenicline (VNS) is a preservative-free, water-soluble small molecule and a highly selective nicotinic acetylcholine receptor (nAChR) agonist, believed to stimulate basal tear production upon binding receptors located in the anterior nasal cavity. The efficacy and safety of VNS for treating dry eye disease (DED) was established in the ONSET-1 (phase 2) and ONSET-2 (phase 3) clinical trials.
In this prospective study (TSUNAMI, NCT05514041), 50 DED subjects were randomized to receive VNS or vehicle-control (VC) nasal spray twice daily for 28 days. Study endpoints included surface regularity index (SRI) and surface asymmetry index (SAI) at 15 minutes post-first dose as measured by The Cassini Corneal Topographer (Cassini); as well as SRI, SAI, corneal fluorescein staining (CFS), tear breakup time (TBUT), eye dryness score (EDS), and dry eye questionnaire score (DEQS) at Day 28. The Cassini analyzes the appearance of reflected point-source color light-emitting diodes (LEDs) to assess the quality of the tear film.
The mean SRI and SAI in the VNS group at primary endpoint were 0.17±0.08 (p=0.668, comparison with baseline) and 0.71±0.34 (p=0.443), respectively. On Day 28, SRI and SAI improved to 0.14±0.11 (p=0.145) and 0.56±0.41 (p=0.03), respectively. The VNS group showed higher improvement than the VC group in mean CFS (55% vs.18%; p<0.001), EDS (44% vs. 27.2%; p=0.012), DEQS (13% vs. 1.5%; p=0.008), and TBUT (69% vs 29%; p=0.68). There were no serious adverse events. The outcomes of dry eye signs and symptoms and the improvement in SAI at Day 28 indicated that VNS is efficacious in achieving ocular homeostasis and fosters tear film stability.
DED treatment with intranasal spray may help reduce medication burden in patients who are already on topical eyedrops for other ocular conditions (e.g., glaucoma). It can also address compliance issues in older patients who might have difficulty with eyedrops due to tremors or dexterity issues. In contrast to topical eyedrops, twice-daily intranasal delivery spares the ocular surface, so there is no risk of preservative-induced ocular toxicity.
While the present study demonstrated good safety and efficacy of VNS in treating signs and symptoms of DED, it had some limitations, including a single-center study, small sample size, shorter follow-up, and varied patient population. Clinical tests such as Schirmer’s test score were not included. Future long-term studies to determine optimal strategies for use of VNS alone or with existing treatments for restoring tear film homeostasis and improving dry eye symptoms are warranted.
