{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:20:43Z","timestamp":1787772043126,"version":"build-2784847793"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"Suppl 3","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:p>This study aimed to investigate the efficacy and safety of trigeminal parasympathetic pathway (TPP) stimulation in the treatment of dry eye. A comprehensive search for randomized clinical trials was performed in seven databases (MEDLINE, Embase, CENTRAL, etc.) up to 28 February 2023. After screening the suitable studies, the data were extracted and transformed as necessary. Data synthesis and analysis were performed using Review Manager 5.4, and the risk of bias and quality of evidence were evaluated with the recommended tools. Fourteen studies enrolling 1714 patients with two methods (electrical and chemical) of TPP stimulation were included. Overall findings indicate that TPP stimulation was effective in reducing subjective symptom score (standardized mean difference [SMD], -0.45; 95% confidence interval [CI], -0.63 to -0.28), corneal fluorescence staining (mean difference [MD], -0.78; 95% CI, -1.39 to -0.18), goblet cell area (MD, -32.10; 95% CI, -54.58 to -9.62) and perimeter (MD, -5.90; 95% CI, -10.27 to -1.53), and increasing Schirmer's test score (SMD, 0.98; 95% CI, 0.65 to 1.31) and tear film break-up time (SMD, 0.57; 95% CI, 0.19 to 0.95). Compared to inactive or low-activity stimulation controls, it has a higher incidence of adverse events. Therefore, TPP stimulation may be an effective treatment for dry eye, whether electrical or chemical. Adverse events are relatively mild and tolerable. Due to the high heterogeneity and low level of evidence, the current conclusions require to be further verified.<\/jats:p>","DOI":"10.4103\/ijo.ijo_2147_23","type":"journal-article","created":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T04:02:16Z","timestamp":1709870536000},"page":"S381-S392","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":7,"title":["Efficacy and safety of trigeminal parasympathetic pathway stimulation for dry eye: A systematic review and meta-analysis"],"prefix":"10.4103","volume":"72","author":[{"given":"Jindong","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China"},{"name":"Department of Integrative Medicine, Baoshan Campus of Huashan Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohan","family":"Ju","sequence":"additional","affiliation":[{"name":"Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjun","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Yichun Hospital of Traditional Chinese Medicine, Yichun, Jiangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinquan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongbao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Oncology, Shanghai Baoshan Luodian Hospital, Shanghai University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2024,3,8]]},"reference":[{"key":"R1-20260504","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.jtos.2017.05.008","article-title":"TFOS DEWS II definition and classification report","volume":"15","author":"Craig","year":"2017","journal-title":"Ocul Surf"},{"key":"R2-20260504","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.jtos.2017.05.003","article-title":"TFOS DEWS II epidemiology report","volume":"15","author":"Stapleton","year":"2017","journal-title":"Ocul Surf"},{"key":"R3-20260504","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.jtos.2017.04.001","article-title":"TFOS DEWS II sex, gender, and hormones report","volume":"15","author":"Sullivan","year":"2017","journal-title":"Ocul Surf"},{"key":"R4-20260504","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.jtos.2017.05.011","article-title":"TFOS DEWS II pathophysiology report","volume":"15","author":"Bron","year":"2017","journal-title":"Ocul Surf"},{"key":"R5-20260504","doi-asserted-by":"crossref","first-page":"3802","DOI":"10.1167\/iovs.08-2417","article-title":"Characterization of effector T cells in dry eye disease","volume":"50","author":"El Annan","year":"2009","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"R6-20260504","article-title":"Modern therapeutic approaches for noninfectious ocular diseases involving inflammation","volume":"6","author":"Ratay","year":"2017","journal-title":"Adv Healthc Mater"},{"key":"R7-20260504","first-page":"795","article-title":"A nonrandomized, open-label study to evaluate the effect of nasal stimulation on tear production in subjects with dry eye disease","volume":"10","author":"Friedman","year":"2016","journal-title":"Clin Ophthalmol"},{"key":"R8-20260504","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.exer.2003.09.003","article-title":"The role of the lacrimal functional unit in the pathophysiology of dry eye","volume":"78","author":"Stern","year":"2004","journal-title":"Exp Eye Res"},{"key":"R9-20260504","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.preteyeres.2012.02.003","article-title":"Ocular surface immunity: Homeostatic mechanisms and their disruption in dry eye disease","volume":"31","author":"Barabino","year":"2012","journal-title":"Prog Retin Eye Res"},{"key":"R10-20260504","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.jtos.2018.11.002","article-title":"Neurostimulation in dry eye disease-past, present, and future","volume":"17","author":"Dieckmann","year":"2019","journal-title":"Ocul Surf"},{"key":"R11-20260504","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1097\/ICU.0000000000000590","article-title":"Neurostimulation for tear production","volume":"30","author":"Park","year":"2019","journal-title":"Curr Opin Ophthalmol"},{"key":"R12-20260504","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1097\/ICO.0000000000002941","article-title":"ONSET-1 Phase 2b randomized trial to evaluate the safety and efficacy of OC-01 (Varenicline Solution) nasal spray on signs and symptoms of dry eye disease","volume":"41","author":"Wirta","year":"2022","journal-title":"Cornea"},{"key":"R13-20260504","doi-asserted-by":"crossref","first-page":"4219","DOI":"10.2147\/OPTH.S284622","article-title":"Stimulating tear production: Spotlight on neurostimulation","volume":"15","author":"Yu","year":"2021","journal-title":"Clin Ophthalmol (Auckland, NZ)"},{"key":"R14-20260504","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1097\/00003226-199711000-00008","article-title":"Nasolacrimal stimulation of aqueous tear production","volume":"16","author":"Gupta","year":"1997","journal-title":"Cornea"},{"key":"R15-20260504","doi-asserted-by":"crossref","first-page":"b2700","DOI":"10.1136\/bmj.b2700","article-title":"The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: Explanation and elaboration","volume":"339","author":"Liberati","year":"2009","journal-title":"BMJ"},{"key":"R20-20260504","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1136\/bmj.39489.470347.AD","article-title":"GRADE: An emerging consensus on rating quality of evidence and strength of recommendations","volume":"336","author":"Guyatt","year":"2008","journal-title":"BMJ"},{"key":"R21-20260504","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3892\/etm.2020.9305","article-title":"Effectiveness of transcutaneous electrical stimulation combined with artificial tears for the treatment of dry eye: A randomized controlled trial","volume":"20","author":"Cai","year":"2020","journal-title":"Exp Ther Med"},{"key":"R22-20260504","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1167\/iovs.18-23984","article-title":"Randomized, controlled, double-masked, multicenter, pilot study evaluating safety and efficacy of intranasal neurostimulation for dry eye disease","volume":"60","author":"Cohn","year":"2019","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"R23-20260504","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1007\/s40123-022-00530-x","article-title":"A Single Administration of OC-01 (Varenicline Solution) nasal spray induces short-term alterations in conjunctival goblet cells in patients with dry eye disease","volume":"11","author":"Dieckmann","year":"2022","journal-title":"Ophthalmol Ther"},{"key":"R24-20260504","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.ajo.2017.03.002","article-title":"Randomized controlled crossover trial comparing the impact of sham or intranasal tear neurostimulation on conjunctival goblet cell degranulation","volume":"177","author":"Gumus","year":"2017","journal-title":"Am J Ophthalmol"},{"key":"R25-20260504","doi-asserted-by":"crossref","first-page":"4291","DOI":"10.2147\/OPTH.S312108","article-title":"Efficacy of an intranasal tear neurostimulator in sj\u00f6gren syndrome patients","volume":"15","author":"Lilley","year":"2021","journal-title":"Clin Ophthalmol (Auckland, NZ)"},{"key":"R26-20260504","article-title":"Clinical Study to Evaluate Tear Characteristics Following Acute TrueTear\u2122 Use","year":"2017"},{"key":"R27-20260504","article-title":"Clinical Trial to Evaluate the Efficacy of OC-02 Nasal Spray on Signs and Symptoms of Dry Eye Disease (The RAINIER Study)","year":"2018"},{"key":"R28-20260504","article-title":"Goblet cell degranulation produced by intranasal tear neurostimulator (ITN) in dry eye disease","year":"2019"},{"key":"R29-20260504","article-title":"Clinical trial to evaluate the long term follow up of the efficacy of OC-01 nasal spray on signs and symptoms of dry eye disease (The ONSET Study)","year":"2019"},{"key":"R30-20260504","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.jtos.2019.09.006","article-title":"Symptom improvement in dry eye subjects following intranasal tear neurostimulation: Results of two studies utilizing a controlled adverse environment","volume":"18","author":"Pattar","year":"2020","journal-title":"Ocul Surf"},{"key":"R31-20260504","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jtos.2021.12.007","article-title":"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","volume":"24","author":"Quiroz-Mercado","year":"2022","journal-title":"Ocul Surf"},{"key":"R32-20260504","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.jtos.2018.11.009","article-title":"Characterization of tear production in subjects with dry eye disease during intranasal tear neurostimulation: Results from two pivotal clinical trials","volume":"17","author":"Sheppard","year":"2019","journal-title":"Ocul Surf"},{"key":"R33-20260504","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1016\/j.clinthera.2022.07.006","article-title":"Efficacy and safety of single-dose OC-02 (Simpinicline Solution) nasal spray on signs and symptoms of dry eye disease: The PEARL phase II randomized trial","volume":"44","author":"Torkildsen","year":"2022","journal-title":"Clin Ther"},{"key":"R34-20260504","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.ophtha.2021.11.004","article-title":"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","volume":"129","author":"Wirta","year":"2022","journal-title":"Ophthalmology"},{"key":"R35-20260504","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.jtos.2017.05.006","article-title":"TFOS DEWS II management and therapy report","volume":"15","author":"Jones","year":"2017","journal-title":"Ocul Surf"},{"key":"R36-20260504","doi-asserted-by":"crossref","first-page":"108115","DOI":"10.1016\/j.exer.2020.108115","article-title":"Biological functions of tear film","volume":"197","author":"Pflugfelder","year":"2020","journal-title":"Exp Eye Res"},{"key":"R37-20260504","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.jtos.2017.03.006","article-title":"TFOS DEWS II tear film report","volume":"15","author":"Willcox","year":"2017","journal-title":"Ocul Surf"},{"key":"R38-20260504","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1109\/TBME.2013.2244890","article-title":"Neuromodulation for brain disorders: Challenges and opportunities","volume":"60","author":"Johnson","year":"2013","journal-title":"IEEE Trans Biomed Eng"},{"key":"R39-20260504","first-page":"4244","article-title":"Lacrimal nerve stimulation by a neurostimulator for tear production","volume":"50","author":"Lora","year":"2009","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"R40-20260504","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/eye.1988.30","article-title":"Eyelid secretions and the prevention and production of disease","volume":"2","author":"Bron","year":"1988","journal-title":"Eye (London, England)"},{"key":"R41-20260504","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1097\/00003226-199603000-00005","article-title":"Aqueous tear production in patients with neurotrophic keratitis","volume":"15","author":"Heigle","year":"1996","journal-title":"Cornea"},{"key":"R42-20260504","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s40123-022-00616-6","article-title":"Effectiveness of intranasal tear neurostimulation for treatment of dry eye disease: A meta-analysis","volume":"12","author":"Li","year":"2023","journal-title":"Ophthalmol Ther"},{"key":"R43-20260504","first-page":"69","article-title":"Matching-adjusted indirect comparison of phase 3 clinical trial outcomes of OC-01 (varenicline solution) nasal spray and lifitegrast 5% ophthalmic solution for the treatment of dry eye disease","volume":"29","author":"White","year":"2023","journal-title":"J Manag Care Spec Pharm"},{"key":"R44-20260504","first-page":"892","article-title":"Matching-adjusted indirect comparison of phase 3 clinical trial outcomes: OC\u201301 (varenicline solution) nasal spray and cyclosporine a 0.05% ophthalmic emulsion for the treatment of dry eye disease","volume":"28","author":"Visco","year":"2022","journal-title":"J Manag Care Spec Pharm"},{"key":"R45-20260504","doi-asserted-by":"crossref","first-page":"3405","DOI":"10.2147\/OPTH.S383091","article-title":"OC-01 (Varenicline Solution) nasal spray demonstrates consistency of effect regardless of age, race, ethnicity, and artificial tear use","volume":"16","author":"Epitropoulos","year":"2022","journal-title":"Clin Ophthalmol"},{"key":"R46-20260504","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1097\/OPX.0000000000001986","article-title":"Does dry eye disease severity impact efficacy of varenicline solution nasal spray on sign and symptom treatment outcomes?","volume":"100","author":"Sheppard","year":"2023","journal-title":"Optom Vis Sci"},{"key":"R47-20260504","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1016\/j.clinthera.2022.09.013","article-title":"Bilateral Effect of OC-01 (Varenicline Solution) nasal spray for treatment of signs and symptoms in individuals with mild, moderate, and severe dry eye disease","volume":"44","author":"Katz","year":"2022","journal-title":"Clin Ther"},{"key":"R48-20260504","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s40123-022-00607-7","article-title":"Does menopausal status affect dry eye disease treatment outcomes with OC-01 (Varenicline Solution) nasal spray? A post hoc analysis of ONSET-1 and ONSET-2 clinical trials","volume":"12","author":"Nijm","year":"2023","journal-title":"Ophthalmol Ther"},{"issue":"10 A-Supplement","key":"R49-20260504","first-page":"S80","article-title":"Analyses of population subgroups with OC-01 (varenicline solution) nasal spray for dry eye disease: Menopause, systemic anticholinergic medication, and systemic antidepressant\/anxiolytic medication use","volume":"28","author":"Kabat","year":"2022","journal-title":"J Manag Care Spec Pharm"},{"key":"R50-20260504","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1016\/j.clinthera.2021.07.020","article-title":"A Phase I, open-label, randomized, 2-way crossover study to evaluate the relative bioavailability of intranasal and oral varenicline","volume":"43","author":"Nau","year":"2021","journal-title":"Clin Ther"},{"key":"R51-20260504","doi-asserted-by":"crossref","first-page":"910629","DOI":"10.3389\/fphar.2022.910629","article-title":"Semi-PBPK modeling and simulation to evaluate the local and systemic pharmacokinetics of OC-01(Varenicline) nasal spray","volume":"13","author":"Wu","year":"2022","journal-title":"Front Pharmacol"},{"key":"R52-20260504","doi-asserted-by":"crossref","first-page":"460","DOI":"10.3390\/pharmaceutics11090460","article-title":"Advanced formulation approaches for ocular drug delivery: State-of-the-art and recent patents","volume":"11","author":"Souto","year":"2019","journal-title":"Pharmaceutics"},{"key":"R53-20260504","doi-asserted-by":"crossref","first-page":"TFOS123","DOI":"10.1167\/iovs.13-13235","article-title":"The TFOS International workshop on contact lens discomfort: Report of the contact lens interactions with the tear film subcommittee","volume":"54","author":"Craig","year":"2013","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"R54-20260504","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1167\/tvst.9.12.23","article-title":"Novel extranasal tear stimulation: Pivotal study results","volume":"9","author":"Ji","year":"2020","journal-title":"Transl Vis Sci Technol"},{"key":"R55-20260504","doi-asserted-by":"crossref","first-page":"e328","DOI":"10.1111\/j.1755-3768.2010.02027.x","article-title":"Acupuncture for treating dry eye: A randomized placebo-controlled trial","volume":"88","author":"Shin","year":"2010","journal-title":"Acta Ophthalmol"}],"container-title":["Indian Journal of Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/IJO.IJO_2147_23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T18:25:49Z","timestamp":1787768749000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/IJO.IJO_2147_23"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,8]]},"references-count":51,"journal-issue":{"issue":"Suppl 3","published-print":{"date-parts":[[2024]]}},"URL":"https:\/\/doi.org\/10.4103\/ijo.ijo_2147_23","relation":{},"ISSN":["0301-4738","1998-3689"],"issn-type":[{"value":"0301-4738","type":"print"},{"value":"1998-3689","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,8]]},"assertion":[{"value":"2023-08-10","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-28","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}