A Single Administration of OC-01 (Varenicline Solution) Nasal Spray Induces Short-Term Alterations in Conjunctival Goblet Cells in Patients with Dry Eye Disease.

INTRODUCTION: Dry eye disease is characterized by a persistently unstable or deficient tear film causing discomfort or visual impairment. Varenicline is a small-molecule nicotinic acetylcholine receptor agonist recently approved for use as a preservative-free nasal spray (OC-01 [varenicline solution] nasal spray [OC-01 VNS]) to treat signs and symptoms of dry eye disease, but its effect on conjunctival goblet cells has not been studied. METHODS: In this phase 2, single-center, vehicle-controlled study, patients aged 18 years or more with a diagnosis of dry eye disease and Ocular Surface Disease Index© score of at least 23 were randomized 2:1 to receive a 50-µL single dose of OC-01 0.06 mg VNS or vehicle nasal spray in each nostril. Image assessments for area and perimeter were performed pre and 10 min post treatment for goblet cells by in vivo confocal microscopy and for meibomian glands by infrared meibography. Non-parametric Wilcoxon signed-rank test compared pre- and post-treatment measurements for each treatment group. Treatment-emergent adverse events (TEAEs) were assessed. RESULTS: The study randomized 18 patients (mean age 61 years); 6 received vehicle (3/6 [50%] female) and 12 patients received OC-01 VNS (11/12 [92%] female). OC-01 VNS treatment decreased mean goblet cell area (pre-treatment, 106.4 µm2; post-treatment, 67.6 µm2; p = 0.02) and perimeter (pre-treatment, 38.9 µm; post-treatment, 31.2 µm; p = 0.03) but not vehicle did not (p = 0.25). There were no significant changes in mean meibomian gland area with either treatment (p ≥ 0.05). All TEAEs were non-ocular, non-serious, and mild. CONCLUSIONS: This study demonstrated that a single administration of OC-01 0.06 mg VNS in patients with dry eye disease reduced conjunctival goblet cell area and perimeter, suggesting goblet cell degranulation and associated release of lubricating mucin. By activating the natural tear film, OC-01 VNS may provide benefits over topical medications. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03688802.

The utility of anterior segment optical coherence tomography angiography for the assessment of limbal stem cell deficiency.

PURPOSE: To determine the utility of anterior segment optical coherence tomography angiography (AS-OCTA) in assessing limbal stem cell deficiency (LSCD). METHODS: Twenty-six eyes of 24 LSCD patients, classified clinically into stage I, II and III, and 12 eyes of 12 healthy subjects were included. AS-OCTA images were analyzed by two masked observers, measuring the maximum corneal vascular extension (CoVE) from the limbus to the furthest vessel over the cornea, and corneal vascular thickness (CoVT) from the most superficial to the deepest corneal vessel. RESULTS: CoVE was 0.27 ± 0.10, 0.79 ± 0.21, 1.68 ± 0.89 and 2.53 ± 0.82 mm in controls, stage I, II and III LSCD, respectively (p < 0.001). The CoVT was 51.0 ± 19.4, 113.7 ± 36.6, 129.7 ± 39.3 and 336.0 ± 85.0 µm, respectively (p < 0.001). There was a significant difference in CoVE and CoVT between all stages compared to controls, and between stage I and III LSCD (p < 0.001). Further, CoVE showed a significant difference between stage I and II, whereas CoVT showed a significant difference between stage II and III LSCD (p < 0.001). BCVA showed strong correlation with CoVT (r = 0.765, p < 0.001) and moderate correlation with CoVE (r = 0.547, p = 0.001). AS-OCTA parameters showed excellent intra- and inter-class correlation coefficients (>0.900). CONCLUSION: LSCD demonstrates significant changes in CoVE and CoVT as early as stage I LSCD in comparison to controls. CoVE and CoVT strongly correlate to both disease severity and BCVA. AS-OCTA may provide novel quantitative and non-invasive parameters to assess LSCD.

Infrared meibography allows detection of dimensional changes in meibomian glands following intranasal neurostimulation.

PURPOSE: Patients with dry eye disease (DED) may suffer from decreased tear break-up time due to meibomian gland (MG) dysfunction. Infrared meibography (IR Meibography) uses infrared wavelength light to visualize meibomian glands in vivo. We aimed to explore the feasibility of using serial IR Meibography imaging to assess morphological changes in MGs as an indirect measure of functionality, following intranasal neurostimulation (ITN). METHODS: Fifteen DED subjects were prospectively enrolled in a single-center, single-arm study. Changes in MGs were captured using IR meibography (RTVUE-XR, Optovue, Inc. Fremont, CA, USA) on the lower eyelids before and after 3 min of ITN (TrueTear®, Allergan, Dublin, Ireland) use that delivers a microcurrent to sensory neurons of the nasal cavity. The same MGs were selected pre- and post-stimulation, and MG area and perimeter were analyzed by two masked observers. RESULTS: Mean (±SD) pre- and post-stimulation MG areas were 2,187.60 ± 635.88 µm2 and 1,933.20 ± 538.55 µm2, respectively. The mean change in area, 254.49 µm2, representing an 11.6% reduction following ITN use, was statistically significant (p = 0.001). Mean (±SD) pre- and post-stimulation MG perimeters were 235.9 ± 51.38 µm and 222.2 ± 47.72 µm, respectively. The mean change in perimeter, 13.7 µm, representing a 5.81% reduction following ITN use, was statistically significant (p = 0.012). CONCLUSIONS: Our study shows that IR meibography can be used to detect immediate changes in gland area and perimeter, an indirect measure of MG activity following intervention by ITN.