The SARS-CoV-2 Virus and the Cholinergic System: Spike Protein Interaction with Human Nicotinic Acetylcholine Receptors and the Nicotinic Agonist Varenicline.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the worldwide coronavirus disease 2019 (COVID-19) pandemic. Although the pathophysiology of SARS-CoV-2 infection is still being elucidated, the nicotinic cholinergic system may play a role. To evaluate the interaction of the SARS-CoV-2 virus with human nicotinic acetylcholine receptors (nAChRs), we assessed the in vitro interaction of the spike protein of the SARS-CoV-2 virus with various subunits of nAChRs.

OC-01 (Varenicline Solution) Nasal Spray for the Treatment of Dry Eye Disease Signs and Symptoms in Subjects with Autoimmune Disease: Integrated Data from ONSET-1 and ONSET-2.

Purpose: We evaluate the treatment effect of OC-01 (varenicline solution) nasal spray (VNS) in dry eye disease (DED) subjects from two randomized trials who self-reported autoimmune disease (AID).

Patients And Methods: Post hoc subgroup analysis of subjects reporting a history of AID from the integrated OC-01 VNS 0.03 or 0.

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.

A phase II randomized trial to evaluate the long-term (12-week) efficacy and safety of OC-01 (varenicline solution) nasal spray for dry eye disease: The MYSTIC study.

Purpose: Dry eye disease is characterized by loss of tear film stability. OC-01 (varenicline solution) is a small-molecule nicotinic acetylcholine receptor agonist administered as a nasal spray that stimulates tear production.

Methods: In MYSTIC (NCT03873246) patients aged ≥22 years with dry eye disease were randomized 1:1:1 to OC-01 0.

Efficacy and Safety of OC-01 (Varenicline Solution) Nasal Spray on Signs and Symptoms of Dry Eye Disease: The ONSET-2 Phase 3 Randomized Trial.

Purpose: To evaluate the efficacy and safety of OC-01 (varenicline solution) nasal spray for treatment of patients with dry eye disease.

Design: Randomized, multicenter, double-masked, vehicle-controlled, phase 3 study.

Participants: Adults 22 years of age or older with a diagnosis of dry eye disease, artificial tear use, Ocular Surface Disease Index score of 23 or more, and Schirmer test score (STS) of 10 mm or less.

A Phase I, Open-label, Randomized, 2-Way Crossover Study to Evaluate the Relative Bioavailability of Intranasal and Oral Varenicline.

Purpose: To estimate the systemic bioavailability of OC-01 (varenicline) nasal spray, an investigational treatment for dry eye disease, relative to oral varenicline approved for smoking cessation.

Methods: The Study to Evaluate the Relative Bioavailability of Varenicline Administered as OC-01 (Varenicline) Nasal Spray as Compared to Varenicline Administered Orally as Chantix (ZEN study) was a Phase I, open-label, randomized, single-center, 2-way crossover study. On day 1, 22 healthy participants were randomized 1:1 to a single intranasal dose of varenicline 0.

Macular epiretinal brachytherapy in treated age-related macular degeneration (MERITAGE): month 24 safety and efficacy results.

Purpose: To evaluate the safety and efficacy of epimacular brachytherapy for the treatment of chronic, active neovascular age-related macular degeneration.

Methods: A prospective, multicenter, interventional noncontrolled clinical trial recruited 53 participants with previously treated neovascular age-related macular degeneration. Participants underwent pars plana vitrectomy with a single 24 Gray dose of epimacular brachytherapy, delivered using an intraocular cannula containing a Strontium 90/Yttrium 90 source that was positioned over the active lesion.

Safety testing of epimacular brachytherapy with microperimetry and indocyanine green angiography: 12-month results.

Purpose: To determine if epimacular brachytherapy is associated with reduced retinal sensitivity or choroidal nonperfusion.

Methods: A prospective intervention case series of 12 participants with neovascular age-related macular degeneration requiring frequent ranibizumab underwent vitrectomy and epimacular brachytherapy. The Strontium 90/Yttrium 90 source delivered a single 24-Gy dose at the center of the treatment zone.

Epimacular brachytherapy for neovascular age-related macular degeneration (CABERNET): fluorescein angiography and optical coherence tomography.

Purpose: To report the fluorescein angiography (FA) and optical coherence tomography (OCT) results of a clinical trial of epimacular brachytherapy (EMBT) used for the treatment of neovascular age-related macular degeneration (AMD).

Design: Pivotal multicenter, active-controlled, randomized clinical trial.

Participants: A total of 494 participants with treatment-naïve, neovascular AMD.

Macular epiretinal brachytherapy in treated age-related macular degeneration (MERITAGE): month 12 optical coherence tomography and fluorescein angiography.

Purpose: To report the optical coherence tomography (OCT) and fundus fluorescein angiography (FFA) results of the Macular Epiretinal Brachytherapy in Treated Age-Related Macular Degeneration study.

Design: Prospective, multicenter, interventional, noncontrolled clinical trial.

Participants: Fifty-three eyes of 53 participants with chronic, active neovascular age-related macular degeneration (AMD) requiring frequent anti-vascular endothelial growth factor retreatment.

Epimacular brachytherapy for neovascular age-related macular degeneration: a randomized, controlled trial (CABERNET).

Purpose: To evaluate the safety and efficacy of epimacular brachytherapy (EMBT) for the treatment of neovascular age-related macular degeneration (AMD).

Design: Multicenter, randomized, active-controlled, phase III clinical trial.

Participants: Four hundred ninety-four participants with treatment-naïve neovascular AMD.

Epimacular brachytherapy for the treatment of retinal angiomatous proliferation.

Purpose: The purpose of this study was to present a case of a retinal angiomatous proliferation (RAP) treated with epimacular brachytherapy that was refractory to continued ranibizumab therapy.

Patients: An interventional case report of an 89-year-old woman with angiographically confirmed RAP had shown a poor response to 8 anti-vascular endothelial growth factor (anti-vascular endothelial growth factor) retreatment injections over a 10-month period.

Methods: The patient underwent pars plana vitrectomy combined with beta irradiation of the RAP lesion using a Strontium-90 applicator (NeoVista).

Macular epiretinal brachytherapy in treated age-related macular degeneration: MERITAGE study: twelve-month safety and efficacy results.

Purpose: To evaluate the safety and efficacy of epimacular brachytherapy (EMB) for the treatment of chronic, active, neovascular age-related macular degeneration (AMD).

Design: Prospective, multicenter, interventional, noncontrolled clinical trial.

Participants: Fifty-three eyes of 53 participants with neovascular AMD requiring frequent anti-vascular endothelial growth factor (VEGF) retreatment.

Radiation maculopathy after epimacular brachytherapy for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration.

Purpose: To describe a case of radiation maculopathy after a 24-Gy single-fraction epimacular brachytherapy delivered concomitantly with ranibizumab for the treatment of age-related macular degeneration.

Methods: Case report.

Results: An 82-year-old man with neovascular age-related macular degeneration was treated with epiretinal brachytherapy and 2 intraocular injections of ranibizumab with initial good response.

Three-year safety and visual acuity results of epimacular 90 strontium/90 yttrium brachytherapy with bevacizumab for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration.

Purpose: To evaluate the long-term safety and visual acuity outcomes associated with epimacular strontium 90 brachytherapy combined with intravitreal bevacizumab for the treatment of subfoveal choroidal neovascularization because of age-related macular degeneration.

Methods: Thirty-four treatment-naive patients with predominantly classic, minimally classic, and occult subfoveal choroidal neovascularization lesions participated in this prospective, 2-year, nonrandomized multicenter study. Subjects from 1 center (n = 19) were reconsented and followed-up for 3 years.

Twelve-month safety and visual acuity results from a feasibility study of intraocular, epiretinal radiation therapy for the treatment of subfoveal CNV secondary to AMD.

Purpose: The purpose of this study was to evaluate the short-term safety and feasibility of intraocular, epiretinal delivery of beta radiation for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration for 12 months. A 3-year follow-up period is planned to assess the long-term safety of the procedure.

Methods: In this nonrandomized, multicenter feasibility study, 34 treatment-naïve patients with predominantly classic, minimally classic, or occult lesions due to subfoveal choroidal neovascularization secondary to age-related macular degeneration received a single treatment with either 15 Gray (Gy) (8 patients) or 24 Gy (26 patients) beta radiation (strontium-90) using a novel intraocular delivery device.