{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:18:31Z","timestamp":1791976711362,"version":"4.4.0"},"reference-count":51,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T00:00:00Z","timestamp":1604534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Unilateral vocal fold paralysis (UVFP) is a common disorder that may cause glottal closure insufficiency and then hoarseness of voice and aspiration during swallowing. We conducted a systematic review and meta-analysis to evaluate whether hyaluronic acid (HA) injection laryngoplasty (IL) is an effective treatment for patients with UVFP. Comprehensive systematic searches were undertaken using PubMed, EBSCO Medline, and Cochrane Library databases. We appraised the quality of studies according to preset inclusion and exclusion criteria. The lengths of follow-up were divided into \u201cshort-term\u201d (3 months or shorter), \u201cmedium-term\u201d (6 months), and \u201clong-term\u201d (12 months or longer). We performed random-effect meta-analysis to estimate the changes in voice-related quality of life, perceptual evaluation by grading systems, voice lab analysis of maximal phonation time, and normalized glottal gap area, before and after HA IL. Fourteen studies were eligible for the final analysis. The results showed that patients\u2019 glottal closure insufficiency could be improved; maximal phonation time could be prolonged; perceptual evaluations of the voice and quality of life were better after HA IL, but the duration of treatment effect varied among different studies. In conclusion, HA IL is an effective treatment for UVFP, which may achieve a long-term effect and therefore reduce the likelihood of requiring permanent medialization thyroplasty.<\/jats:p>","DOI":"10.3390\/cells9112417","type":"journal-article","created":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T00:00:37Z","timestamp":1604534437000},"page":"2417","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Hyaluronic Acid Injection Laryngoplasty for Unilateral Vocal Fold Paralysis\u2014A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5934-724X","authenticated-orcid":false,"given":"Chen-Chi","family":"Wang","sequence":"first","affiliation":[{"name":"School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan"},{"name":"Department of Speech Language Pathology &amp; Audiology, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Department of Audiology and Speech-Language Pathology, Asia University, Taichung 41354, Taiwan"},{"name":"Department of Otolaryngology-Head &amp; Neck Surgery, Taichung Veterans General Hospital, Taichung 40705, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shang-Heng","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head &amp; Neck Surgery, Taichung Veterans General Hospital, Taichung 40705, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2461-474X","authenticated-orcid":false,"given":"Yu-Kang","family":"Tu","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Jiun","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head &amp; Neck Surgery, Taichung Veterans General Hospital, Taichung 40705, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1213-9080","authenticated-orcid":false,"given":"Shih-An","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head &amp; Neck Surgery, Taichung Veterans General Hospital, Taichung 40705, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1002\/lary.28324","article-title":"Nonselective Reinnervation as a Primary or Salvage Treatment of Unilateral Vocal Fold Palsy","volume":"130","author":"Marie","year":"2020","journal-title":"Laryngoscope"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1002\/lary.26894","article-title":"Early-injection laryngoplasty may lower risk of thyroplasty: A systematic review and meta-analysis","volume":"128","author":"Vila","year":"2018","journal-title":"Laryngoscope"},{"key":"ref_3","first-page":"93","article-title":"Uber eine neue behandlungsmethode der rekurrenslahmung","volume":"18","author":"Brunings","year":"1911","journal-title":"Verh. Ver Laryngol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1002\/lary.20737","article-title":"Current practice in injection augmentation of the vocal folds: Indications, treatment principles, techniques, and complications","volume":"120","author":"Sulica","year":"2010","journal-title":"Laryngoscope"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1097\/01.moo.0000144393.40874.98","article-title":"Injection laryngoplasty for management of unilateral vocal fold paralysis","volume":"12","author":"Kwon","year":"2004","journal-title":"Curr. Opin. Otolaryngol. Head Neck Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1097\/00005537-200212000-00016","article-title":"Cross-linked hyaluronan used as augmentation substance for treatment of glottal insufficiency: Safety aspects and vocal fold function","volume":"112","author":"Laurent","year":"2002","journal-title":"Laryngoscope"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1097\/MOO.0b013e32833f85d1","article-title":"Hyaluronic acid for the treatment of vocal fold scars","volume":"18","author":"Chhetri","year":"2010","journal-title":"Curr. Opin. Otolaryngol. Head Neck Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/s10856-005-0531-2","article-title":"Evaluation of Injection Augmentation Treatment of Hyaluronic Acid Based Materials on Rabbit Vocal Folds Viscoelasticity","volume":"16","author":"Borzacchiello","year":"2005","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/j.1468-3083.1999.tb00881.x","article-title":"Comparative chemical evaluation of two commercially available derivatives of hyaluronic acid (hylaform from rooster combs and restylane from streptococcus) used for soft tissue augmentation","volume":"13","author":"Manna","year":"1999","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_10","first-page":"29","article-title":"Study on Hyaluronic Acid and Variations of Its Molecular Size","volume":"8","author":"Lacapere","year":"1960","journal-title":"Pathol. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/2046-4053-1-2","article-title":"The nuts and bolts of PROSPERO: An international prospective register of systematic reviews","volume":"1","author":"Booth","year":"2012","journal-title":"Syst. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Moher, D., Liberati, A., Tetzla, J., Altman, D.G., and PRISMA Group (2009). Preferred reporting items for systematicreviews and meta-analyses: The PRISMA statement. PLoS Med., 6.","DOI":"10.1371\/journal.pmed.1000097"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1111\/j.2044-8317.1988.tb00901.x","article-title":"Synthesizing standardized mean-change measures","volume":"41","author":"Becker","year":"1988","journal-title":"Br. J. Math. Stat. Psychol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.cct.2015.09.002","article-title":"Meta-analysis in clinical trials revisited","volume":"45","author":"DerSimonian","year":"2015","journal-title":"Contemp. Clin. Trials"},{"key":"ref_15","first-page":"42","article-title":"Voice performance in tonal language speakers with glottal insufficiency due to unilateral vocal fold paralysis after injection laryngoplasty: A multidimensional study of Cantonese patients","volume":"24","author":"Ng","year":"2018","journal-title":"Hong Kong Med. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.jvoice.2017.07.019","article-title":"Voice Range Change After Injection Laryngoplasty for Unilateral Vocal Fold Paralysis","volume":"32","author":"Pei","year":"2018","journal-title":"J. Voice"},{"key":"ref_17","first-page":"388","article-title":"Minimally invasive injection laryngoplasty in the management of unilateral vocal cord paralysis after video-assisted mediastinal lymph adenectomy","volume":"13","author":"Kara","year":"2018","journal-title":"Wideochirurgia Inne Tech. Maloinwazyjne"},{"key":"ref_18","first-page":"274","article-title":"Electromyography-guided Hyaluronic Acid Injection Laryngoplasty in Early Stage of Unilateral Vocal Fold Paralysis","volume":"68","author":"Puga","year":"2017","journal-title":"Acta Otorrinolaringol. Esp."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e1787","DOI":"10.1097\/MD.0000000000001787","article-title":"Office-Based Intracordal Hyaluronate Injections Improve Quality of Life in Thoracic-Surgery-Related Unilateral Vocal Fold Paralysis","volume":"94","author":"Fang","year":"2015","journal-title":"Medicine"},{"key":"ref_20","first-page":"121","article-title":"Early hyaluronate injection improves quality of life but not neural recovery in unilateral vocal fold paralysis: An open-label randomized controlled study","volume":"33","author":"Pei","year":"2015","journal-title":"Restor. Neurol. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1001\/jamaoto.2014.3466","article-title":"Laryngeal electromyography-guided hyaluronic acid vocal fold injection for unilateral vocal fold paralysis- a prospective long term follow up outcome report","volume":"141","author":"Wang","year":"2015","journal-title":"JAMA Otolaryngol. Head Neck Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1002\/lary.24689","article-title":"Glottal Gap as an Early Predictor for Permanent Laryngoplasty in Unilateral Vocal Fold Paralysis","volume":"124","author":"Fang","year":"2014","journal-title":"Laryngoscope"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1177\/0194599813508082","article-title":"Treatment Outcomes of Injection Laryngoplasty Using Cross-Linked Porcine Collagen and Hyaluronic Acid","volume":"149","author":"Wen","year":"2013","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"513","DOI":"10.3109\/00016489.2012.750034","article-title":"Long-term voice results of injection with hyaluronic acid-dextranomere in unilateral vocal fold paralysis","volume":"133","author":"Oguz","year":"2013","journal-title":"Acta Oto-Laryngol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.jvoice.2011.11.007","article-title":"Laryngoplasty with Hyaluronic Acid in Patients with Unilateral Vocal Fold Paralysis","volume":"26","author":"Rudolf","year":"2012","journal-title":"J. Voice"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.jvoice.2011.04.003","article-title":"Laryngeal Electromyography-Guided Hyaluronic Acid Vocal Fold Injection for Unilateral Vocal Fold Paralysis-Preliminary Results","volume":"26","author":"Wang","year":"2012","journal-title":"J. Voice"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.jvoice.2008.05.007","article-title":"Injection Laryngoplasty With Hyaluronic Acid for Unilateral Vocal Cord Paralysis. Randomized Controlled Trial Comparing Two Different Particle Sizes","volume":"24","author":"Lau","year":"2010","journal-title":"J. Voice"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1002\/lary.21097","article-title":"Early Versus Late Injection Medialization for Unilateral Vocal Cord Paralysis","volume":"120","author":"Friedman","year":"2010","journal-title":"Laryngoscope"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1044\/1058-0360.0603.66","article-title":"The Voice Handicap Index (VHI): Development and validation","volume":"6","author":"Jacobson","year":"1997","journal-title":"Am. Speech Lang. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1097\/00005537-200409000-00009","article-title":"Development and Validation of the Voice Handicap index-10","volume":"114","author":"Rosen","year":"2004","journal-title":"Laryngoscope"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0194-5998(99)70399-2","article-title":"Validation of a voice outcome survey for unilateral vocal cord paralysis","volume":"120","author":"Gliklich","year":"1999","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_32","unstructured":"Hirano, M. (1981). Clinical Examination of Voice, Springer."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1007\/s00106-005-1310-6","article-title":"Zur auditiven Bewertung der Stimmqualitat [On the auditory evaluation of voice quality]","volume":"54","author":"Ptok","year":"2006","journal-title":"HNO"},{"key":"ref_34","first-page":"179","article-title":"Voice Acoustic Analysis of Normal Taiwanese Adults","volume":"67","author":"Wang","year":"2004","journal-title":"Chin. Med. J."},{"key":"ref_35","first-page":"868","article-title":"Voice Aerodynamic Analysis of Normal Taiwanese Adults","volume":"104","author":"Wang","year":"2005","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"951","DOI":"10.2466\/pms.2000.91.3.951","article-title":"Effects of Race and Sex on Acoustic Features of Voice Analysis","volume":"91","author":"Xue","year":"2000","journal-title":"Percept. Mot. Skills"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.jvoice.2008.10.004","article-title":"Maximum Phonation Time: Variability and Reliability","volume":"24","author":"Speyer","year":"2010","journal-title":"J. Voice"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1177\/000348949610500407","article-title":"Quantitative videostroboscopic measurement of glottal gap and vocal function: An analysis of thyroplasty type I","volume":"105","author":"Omori","year":"1996","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1002\/lary.25739","article-title":"Comparison of Outcomes in Interventions for Unilateral Vocal FoldParalysis: A Systematic Review","volume":"126","author":"Siu","year":"2016","journal-title":"Laryngoscope"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1097\/00005537-199803000-00015","article-title":"(DiHA): A promising substance in treating vocal cord insufficiency","volume":"108","author":"Dahlqvist","year":"1998","journal-title":"Laryngoscope"},{"key":"ref_41","first-page":"CD009239","article-title":"Alternative Injectable Materials for Vocal Fold Medialisation in Unilateral Vocal Fold Paralysis","volume":"17","author":"Lakhani","year":"2012","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1016\/j.juro.2006.04.088","article-title":"The evolution of vesicoureteral reflux management in the era of dextranomer\/hyaluronic acid copolymer: A pediatric health information system database study","volume":"176","author":"Lendvay","year":"2006","journal-title":"J. Urol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1177\/0145561319835773","article-title":"Adverse Reaction to Restylane: A Review of 63 Cases of Injection Laryngoplasty","volume":"98","author":"Hamdan","year":"2019","journal-title":"Ear Nose Throat J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1002\/lary.26156","article-title":"Inflammatory reaction to hyaluronic acid: A newly described complication in vocal fold augmentation","volume":"127","author":"Dominguez","year":"2017","journal-title":"Laryngoscope"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2227","DOI":"10.1007\/s00405-012-2036-1","article-title":"Laryngeal electromyography: A proposal for guidelines of the European Laryngological Society","volume":"269","author":"Volk","year":"2012","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1007\/s00405-012-2211-4","article-title":"A proposal to extend application of laryngeal electromyography (LEMG)-guided vocal fold injection to treatment of unilateral vocal fold paralysis to enhance clinical popularity of LEMG: Response to the paper by G.F. Volk et al","volume":"270","author":"Wang","year":"2013","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1002\/lary.24980","article-title":"Laryngeal electromyography and prognosis of unilateral vocal fold paralysis\u2014A long-term prospective study","volume":"125","author":"Wang","year":"2015","journal-title":"Laryngoscope"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1097\/MLG.0b013e31802e9291","article-title":"Viscoelasticity of hyaluronan and nonhyaluronan based vocal fold injectables: Implications for mucosal versus muscle use","volume":"117","author":"Caton","year":"2007","journal-title":"Laryngoscope"},{"key":"ref_49","first-page":"491","article-title":"Safety data of injectable nonanimal stabilized hyaluronic acid gel for soft tissue augmentation","volume":"28","author":"Friedman","year":"2002","journal-title":"Dermatol. Surg."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1177\/000348940711600110","article-title":"Spontaneous laryngeal reinnervation after recurrent laryngeal or vagus nerve injury","volume":"116","author":"Woodson","year":"2007","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1002\/lary.21965","article-title":"Effect of temporary vocal fold injection medialization on the rate of permanent medialization laryngoplasty in unilateral vocal fold paralysis patients","volume":"121","author":"Yung","year":"2011","journal-title":"Laryngoscope"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/11\/2417\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:29:27Z","timestamp":1760178567000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/11\/2417"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,5]]},"references-count":51,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["cells9112417"],"URL":"https:\/\/doi.org\/10.3390\/cells9112417","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,5]]}}}