The Use of Hyaluronic Acid in the Treatment of Unilateral Vocal Fold Paralysis: A Systematic Review and Meta-Analysis

Unilateral vocal fold paralysis (UVFP) is a neurological condition characterized by glottal insufficiency, commonly resulting from iatrogenic damage sustained during head and neck surgery. Hyaluronic acid (HA), a naturally occurring glycosaminoglycan, has been shown to influence vocal cord function positively. This study aimed to evaluate the effectiveness of HA in treating UVFP. A systematic review and meta-analysis were conducted following the PRISMA guidelines (PROSPERO ID: CRD42024560084). Literature searches were performed in PubMed, Cochrane Library, Web of Science, and Google Scholar up to August 2024 using a comprehensive combination of terms related to HA and UVFP. Two independent reviewers conducted study selection, data extraction, and quality appraisal using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk of Bias tool for randomized controlled trials. Thirty-two studies involving 1,917 adult patients were included. Outcomes assessed included quality of life (QOL), maximal phonation time (MPT), and normalized glottal gap area (NGGA). Meta-analysis demonstrated significant short- and medium-term improvements in patient-reported QOL following HA injection (standardized mean difference [SMD]=0.87, 95% CI [0.65-1.09]; p < 0.0001; I²=0%). Medium-term MPT also improved significantly (SMD=0.45, 95% CI [0.16-0.74]; p=0.003; I²=2%). Similarly, NGGA improved in the medium term (SMD=0.51, 95% CI [0.19-0.83]; p=0.002; I²=0%). Adverse events were rare and mostly minor, including transient dysphonia and inflammation. The overall risk of bias was low in most included studies. HA injection laryngoplasty appears effective in improving vocal function and quality of life in patients with UVFP in the short to medium term. However, the current evidence is limited by variable follow-up durations, technique heterogeneity, and insufficient long-term data. Future studies should explore patient-specific outcomes, standardized intervention protocols, long-term efficacy, and safety across diverse populations.