Glottic insufficiency caused by vocal fold atrophy with or without sulcus: systematic review of outcome measurements.

PURPOSE: Identifying outcome measurements instruments (OMIs) to evaluate treatment efficacy in patients with vocal fold atrophy and/or sulcus. METHODS: Systematic review of records published before March 2021 by searching Pubmed and EMBASE. Included studies reported on adults (> 18 year) with dysphonia caused by glottic insufficiency due to vocal fold atrophy with or without sulcus, who were enrolled into a randomized controlled trial, a non-randomized controlled trial, a case-controlled study or a cohort study. All included studies described an intervention with at least one outcome measurement. RESULTS: A total of 5456 studies were identified. After removing duplicates, screening title and abstract and full text screening of selected records, 34 publications were included in final analysis. From these 50 separate OMIs were recorded and categorized according to the ELS protocol by DeJonckere et al. (Eur Arch Otorhinolaryngol 258: 77-82, 2001). With most OMIs being used in multiple studies the total number of OMIs reported was 265. Nineteen (19) individual OMIs accounted for 80% of reports. The most frequently used OMIs according to category were: VHI and VHI-10 (subjective evaluation); G of GRBAS (perceptual evaluation); F0, Jitter and Shimmer (acoustic evaluation); MPT and MFR (aerodynamic evaluation) and glottic closure and mucosal wave (endoscopic evaluation). Of these OMIs VHI had a high percentage of significance of 90%. CONCLUSION: This systematic review identifies the most used OMIs in patients with glottic incompetency due to vocal fold atrophy and/or sulcus as a step toward defining a Core Outcome Set (COS) for this population. PROSPERO REGISTRATION: 238274.

The Regenerative Effects of c-Met Agonistic Antibodies in Vocal Fold Atrophy.

BACKGROUND: Atrophy of the vocal folds and the accompanying glottic insufficiency affect the quality of life. Although growth factors have been used to treat muscle atrophy, their effectiveness is limited by their short half-life. METHODS: In total, 15 rabbits and 24 rats were used for the study. The right recurrent laryngeal nerves of all animals were transected. One month following nerve transection, PBS (PBS group), rHGF (HGF group), or a c-Met agonistic antibody (c-Met group) was injected into the paralyzed vocal folds. The larynges of the rabbits were harvested from each group for histologic examination and subjected to PCR analysis. RESULTS: Cross-sectional areas (CSAs) of thyroarytenoid muscles were evaluated. The c-Met group had increased CSAs compared to the PBS and HGF groups, but there were no significant differences compared to normal controls. The expression levels of myogenesis-related genes were evaluated three weeks after the injection. The expression levels of myosin heavy chain IIa were significantly increased in the PBS group, while the expression levels of MyoD were increased in the c-Met group. CONCLUSIONS: The c-Met agonistic antibody showed promise for promoting muscle regeneration in a vocal fold palsy model.

Laryngoscopic findings of age-related vocal fold atrophy are reliable but not specific.

OBJECTIVES: We aimed to evaluate the reliability of laryngoscopic features of vocal fold atrophy as assessed by novice otolaryngology trainees and expert laryngologists. DESIGN: Two expert fellowship-trained laryngologists and three non-expert otolaryngology resident trainees were recruited to view 50 anonymised laryngo-stroboscopic examinations of patients presenting with dysphonia and non-voice, laryngeal complaints. Reviewers were asked to stratify the patient's age, provide an opinion about the presence of age-related vocal fold atrophy and specify which laryngoscopy features were present to make the diagnosis. SETTING: Tertiary care laryngology practice. PARTICIPANTS: Two fellowship-trained laryngologists and three trainee otolaryngologists. MAIN OUTCOME MEASURES: Accuracy of age categorisation was determined and Kappa analysis was performed to assess inter-rater agreement. RESULTS: The mean age of patients was 54.9 years old with near equal male to female distribution. The overall accuracy of age category determination by raters was only 30.8%. Kappa analysis demonstrated fair agreement regarding the presence of vocal fold atrophy in non-expert reviewers, and moderate agreement amongst expert reviewers. Features of glottic gap, muscular atrophy of vocal folds and prominent vocal processes were all identified with high agreement (>80.0%). CONCLUSION: Our study illustrates that while raters can agree on the presence of age-related vocal fold atrophy, the findings may be non-specific and do not necessarily correlate with age.

Bilateral medialization thyroplasty in patients with vocal fold atrophy with or without sulcus.

PURPOSE: To evaluate voice outcome after bilateral medialization thyroplasty in patients with non-paralytic glottic insufficiency due to vocal fold atrophy with or without sulcus. METHODS: Retrospective cohort study on 29 patients undergoing bilateral medialization thyroplasty for vocal fold atrophy (14 procedures) or atrophy with sulcus (15 procedures) between October 2012 and November 2017. Voice data were collected and analyzed for the preoperative and the 3- and 12-month postoperative time point according to a standardized protocol, including Voice Handicap Index (VHI)-30 and perceptual, acoustic and aerodynamic parameters. Failure rate was based on number of revisions within 12 months and non-relevant improvement (< 10 points) in VHI-30 at 12 months. RESULTS: There was a clinically relevant (≥ 15 points) and statistically significant improvement (p < 0.0001) in the VHI-30 (preoperative: 55.8 points; postoperative at 12 months: 30.9 points). Fundamental frequency for male subjects decreased significantly from 175 to 159 Hz (p = 0.0001). The pre- and post-operative grade of dysphonia was significantly lower in patients with atrophy compared to atrophy and sulcus (mean difference 0.70, p = 0.017). CONCLUSION: Bilateral medialization thyroplasty is a valid treatment option for patients with atrophy with or without sulcus. Outcomes are comparable to other methods reported in literature. However, there is a great need for larger, prospective studies with long-term follow-up to gain more insight into the comparative voice outcomes for the different forms of surgery for patients with glottic incompetence due to atrophy with or without sulcus.

Bilateral vocal fold injection with autologous fat in patients with vocal fold atrophy with or without sulcus.

PURPOSE: To evaluate voice outcome after bilateral vocal fold injection with autologous fat in patients with non-paralytic glottic insufficiency due to vocal fold atrophy with or without sulcus. METHODS: This is a retrospective cohort study from September 2012 to December 2017 including 23 patients undergoing bilateral vocal fold injection with autologous fat (24 procedures) for vocal fold atrophy (15 procedures) or atrophy with sulcus (Ford type II or III) (9 procedures). Voice data were collected and analyzed for the preoperative and the 3- and 12-month postoperative time points according to a standardized protocol, including Voice Handicap Index (VHI)-30 and perceptive, acoustic and aerodynamic parameters. Failure rate was defined as non-relevant improvement (< 10 points) in VHI-30 at 12 months and number of revisions within 12 months. RESULTS: There was a clinically relevant (≥ 15 points) and statistically significant improvement in the VHI-30 (preoperative: 49.1 points; postoperative at 12 months: 29.7 points). Change in dynamic range was also statistically significant over time (p = 0.028). There were no differences in voice parameters between patients with atrophy only and atrophy with sulcus, although grade tended to be lower in patients with atrophy only over all time points. CONCLUSION: This study shows that bilateral vocal fold injection with autologous fat is a beneficial treatment not only for patients with atrophy but also for patients with sulcus. A comparison of the results with those reported from other forms of sulcus surgery confirmed this finding. However, there is a need for further prospective studies comparing the short- and long-term effects of different techniques.

Bilateral trial vocal fold injection with hyaluronic acid in patients with vocal fold atrophy with or without sulcus.

PURPOSE: To evaluate the outcome of bilateral trial vocal fold injection (VFI) with hyaluronic acid in patients with vocal fold atrophy ± sulcus and to assess the predictive value of trial VFI on the outcome of durable medialization procedure. METHODS: Voice data collected according to a standardized protocol before and one month after trial VFI of 68 patients with vocal fold atrophy (30) and atrophy with sulcus (38) were analyzed. Voice Handicap Index (VHI)-30 was compared to the outcome of a durable medialization at 3 and 12 months. RESULTS: The overall VHI-30 improvement was 16.8 points (from 49.9 to 33.1), which was statistically significant and clinically relevant. 57.8% of the patients experienced enough subjective benefit after trial VFI to undergo durable medialization. Of the patients that experienced subjective benefit 62% had a clinically relevant improvement in VHI-30. There was no relevant change in other parameters and no difference between ± sulcus. After durable medialization 90-94% of the patients had VHI-30 scores similar to or better than post-trial VFI. CONCLUSION: The majority of patients experience subjective improvement after bilateral trial VFI indicating that medialization is a valid treatment option for patients with vocal fold atrophy ± sulcus. The VHI-30 only partially overlaps with patients' subjective evaluation and does not predict which patients will experience subjective improvement. It is, however, predictive for VHI-30 outcome after durable medialization. The aerodynamic and acoustic parameters showed no relevant change. Further identification of voice assessment parameters accurately reflecting the subjective experience of these patients is warranted.

Comparison of long-term voice outcomes after vocal fold augmentation using autologous fat injection by direct microlaryngoscopy versus office-based calcium hydroxylapatite injection.

The objective is to compare the long-term voice outcomes of vocal fold augmentation (VFA) using autologous fat injection via direct microlaryngoscopy versus office-based calcium hydroxylapatite (CaHA) injection. Patients with glottal insufficiency and a gap no greater than 3 mm caused by unilateral vocal fold paralysis or vocal fold atrophy were prospectively recruited to the study from September 2012 to September 2015. From September 2012 to May 2014, VFA was only performed using autologous fat via direct microlaryngoscopy under general anesthesia (N = 14). From May 2014 to September 2015, VFA was performed as an office-based procedure using a transoral approach to inject CaHA (N = 17). Videolaryngostroboscopic evaluation, subjective satisfaction with voice, voice handicap index (VHI), and maximal phonation time (MPT) were analyzed pre-injection and 12 months after VFA. A total of 31 patients were analyzed. One year after VFA, 67.8% of the patients were satisfied with their voice, with no significant difference between groups (P = 0.247). The mean improvement in VHI in the autologous fat group was 31.6 ± 16.82 versus 35 ± 27.24 in the CaHA group (P = 0.664). MPT improvement was also similar in the two groups: 5.5 ± 2.52 for the autologous fat group versus 6.0 ± 3.98 for the CaHA group (P = 0.823). Both autologous fat injection via direct microlaryngoscopy and office-based CaHA injection have good long-term results. There were no differences in the treatment results of the two procedures 1 year after injection.

Symptom overlap between laryngopharyngeal reflux and glottic insufficiency in vocal fold atrophy patients.

OBJECTIVE: To determine in true vocal fold (TVF) atrophy patients if symptoms of throat clearing and mucus sensation, attributed to laryngopharyngeal reflux (LPR), are due to glottic insufficiency. Is the TVF atrophy population being prescribed proton pump inhibitors unnecessarily? METHODS: A retrospective review of patients with TVF atrophy but no other underlying laryngeal pathology seen at a tertiary voice center from July 2009 to May 2012 was conducted. Patient demographics, symptoms, LPR diagnosis, interventions, and pre-intervention and post-intervention Voice Handicap Index-10 (VHI) and Reflux Symptom Index (RSI) scores were recorded. RESULTS: Twenty-six patients met inclusion criteria, and 85% were treated for LPR. Throat clearing and mucus sensation (85%), dysphonia (54%), and globus sensation (46%) were recorded. Interventions included LPR medical management (65%), vocal fold augmentation (23%), and voice therapy (12%). Reflux Symptom Index scores improved in all groups. Voice Handicap Index-10 and RSI scores normalized in patients treated with augmentation. Globus was never present in patients who received augmentation. CONCLUSION: Throat clearing and mucus sensation may be due to underlying glottic insufficiency and changes of the aging larynx rather than LPR. High VHI and RSI scores normalized with TVF augmentation. Further work is needed to evaluate symptom presentation and risk versus benefit of treatment options, especially if it avoids unnecessary proton pump inhibitor trials.

Bilateral Functional Electrical Stimulation for the Treatment of Presbyphonia in a Sheep Model.

OBJECTIVES: The aim of the study was to increase muscle volume and improve phonation characteristics of the aged ovine larynx by functional electrical stimulation (FES) using a minimally invasive surgical procedure. METHODS: Stimulation electrodes were placed bilaterally near the terminal adduction branch of the recurrent laryngeal nerves (RLN). The electrodes were connected to battery powered pulse generators implanted subcutaneously at the neck region. Training patterns were programmed by an external programmer using a bidirectional radio frequency link. Training sessions were repeated automatically by the implant every other day for 1 week followed by every day for 8 weeks in the awake animal. Another group of animals were used as sham, with electrodes positioned but not connected to an implant. Outcome parameters included gene expression analysis, histological assessment of muscle fiber size, functional analysis, and volumetric measurements based on three-dimensional reconstructions of the entire thyroarytenoid muscle (TAM). RESULTS: Increase in minimal muscle fiber diameter and an improvement in vocal efficiency were observed following FES, compared with sham animals. CONCLUSION: This is the first study to demonstrate beneficial effects in the TAM of FES at molecular, histological, and functional levels. FES of the terminal branches of the RLN reversed the effects of age-related changes and improved vocal efficiency. LEVEL OF EVIDENCE: NA Laryngoscope, 134:848-854, 2024.

Changes in vocal fold gene expression and histology after injection augmentation in a recurrent laryngeal nerve injury model.

OBJECTIVE: To investigate changes in neuroregenerative pathways with vocal fold denervation in response to vocal fold augmentation. METHODS: Eighteen Yorkshire crossbreed swine underwent left recurrent laryngeal nerve transection, followed by observation or augmentation with carboxymethylcellulose or calcium hydroxyapatite at two weeks. Polymerase chain reaction expression of genes regulating muscle growth (MyoD1, MyoG and FoxO1) and atrophy (FBXO32) were analysed at 4 and 12 weeks post-injection. Thyroarytenoid neuromuscular junction density was quantified using immunohistochemistry. RESULTS: Denervated vocal folds demonstrated reduced expression of MyoD1, MyoG, FoxO1 and FBXO32, but overexpression after augmentation. Healthy vocal folds showed increased early and late MyoD1, MyoG, FoxO1 and FBXO32 expression in all animals. Neuromuscular junction density had a slower decline in augmented compared to untreated denervated vocal folds, and was significantly reduced in healthy vocal folds contralateral to augmentation. CONCLUSION: Injection augmentation may slow neuromuscular degeneration pathways in denervated vocal folds and reduce compensatory remodelling in contralateral healthy vocal folds.

Transcutaneous Laryngeal Ultrasound for Assessing Hyaluronic Acid Status in Patients Undergoing Injection Laryngoplasty.

OBJECTIVE: Injection laryngoplasty (IL) with hyaluronic acid (HA) is an effective treatment for patients with glottic insufficiency. The duration of HA maintenance in the vocal fold remains unknown. In this study, transcutaneous laryngeal ultrasound (TLUS) was used to evaluate the absorption and migration of HA after IL. Subsequent management might be provided based on the TLUS finding. METHODS: Patients diagnosed with unilateral vocal fold paralysis (UVFP) or vocal fold atrophy were recruited. All patients underwent IL with HA in an office-based setting along with TLUS to monitor the status of HA. The schedule of TLUS included assessments before and after IL until non-visualization. RESULTS: The study population comprised 38 women and 17 men. Of the patients, 54.1% underwent IL for UVFP, whereas 45.9% underwent IL for vocal fold atrophy. Multivariate Cox regression analysis for factors affecting HA absorption revealed that the cause of injection was the most important independent predictor (hazard ratio [HR], 2.15; 95% confidence interval [CI], 1.03-4.46; p = 0.040). The duration of HA maintenance was significantly longer in patients with UVFP than in those with vocal fold atrophy (8.77 vs. 4.70 months, HR, 2.33; 95% CI, 5.47-8.18; p = 0.002). CONCLUSION: TLUS is an objective assessment method for patients undergoing IL with HA. Subsequent tailor-made management could be offered based on the TLUS findings during follow-up. For patients at high risk of upper respiratory tract infection or who are intolerant to flexible nasopharyngoscopy, TLUS can be used as an alternative tool to evaluate the condition of the glottis after IL with HA. LEVEL OF EVIDENCE: Level 4 Laryngoscope, 2024.

A Systematic Review of Speech-Language Pathology Interventions for Presbyphonia Using the Rehabilitation Treatment Specification System.

BACKGROUND: The prevalence of voice disorders for people aged >65 years is four times higher than for the population at large. The most common cause of dysphonia in this group is presbyphonia, the preferred first-line treatment for which is voice therapy with a speech-language pathologist. This systematic review seeks to identify how voice therapy affects multidimensional voice outcomes in people with presbyphonia. METHODS: A systematic search of CINAHL, Embase, Emcare, MEDLINE, and Google Scholar was conducted in March 2023. Comparative and noncomparative studies of voice therapy in participants aged >50 years with presbyphonia were considered for inclusion. No limitations were placed on date or language of publication. Study quality and risk of bias were assessed with the Cochrane Risk of Bias 2 tool and the Methodological Index for Non-Randomized Studies. Subgroup analysis was used to compare studies based on participant sex, intervention duration, study design, and intervention content. Interventions were specified using the Rehabilitation Treatment Specification System (RTSS) employing a consensus methodology among reviewers. The results were synthesized utilizing meta-analysis when outcomes were adequately specified and narrative analysis when they were not. RESULTS: Twenty-three studies were included with 1050 subjects (mean age: 72.5 ±â€¯8.6 years; 51% female). The most reported intervention was vocal function exercises. Per the RTSS, 14 interventions employed a predominantly Organ Functions approach, and the 14 remaining interventions employed a Skills & Habits approach. Meta-analysis confirmed posttherapy improvement in patient-related outcome measures of 0.93 standard mean difference (P < 0.00001, 95% confidence interval [CI]: 0.70-1.17); studies with predominantly males and with longer treatment periods were associated with larger improvements, while randomized controlled trials reported more modest improvements. Meta-analysis also identified a mean posttherapy increase in maximum phonation time (MPT) of 5.37 seconds (P < 0.00001, 95% CI: 3.52-7.22). Treatments with an Organ Functions focus resulted in greater gains in MPT than those with a Skills & Habits focus (7.52 seconds versus 2.90 seconds). Finally, meta-analysis identified reductions in acoustic perturbation measures (jitter: 0.62%, P < 0.001, 95% CI: 0.26%-0.97%; shimmer 1.05%, P < 0.00001, 95% CI: 0.67%-1.44%). Narrative synthesis further identified improvement in auditory-perceptual voice quality in all active treatment groups as well as improved glottal function in most studies that reported this. CONCLUSIONS: Despite the uncertainty around internal validity introduced by the inclusion of a wide range of study designs, there is convincing evidence that voice therapy for presbyphonia results in significant improvement in patient-reported, aerodynamic, acoustic, and expert-rated voice outcomes. Treatments with an Organ Functions focus may better address the underlying physiological deficits of presbyphonia, although future comparative studies with multidimensional voice assessment are warranted.

Quantitative Evaluation of Vocal Bowing Following Bilateral Thyroplasty in Age-Related Vocal Atrophy.

OBJECTIVE: Age-related vocal atrophy (ARVA) is associated with vocal fold bowing, persistent glottal gap during phonation, and dysphonia. Bilateral medialization thyroplasty is sometimes performed in patients with ARVA to improve vocal fold closure and voice. We set out to quantify stroboscopic changes in vocal fold bowing, glottal closure, and abduction angle following bilateral thyroplasty and determine how these changes affect voice quality among patients with ARVA. METHODS: Fifteen individuals with ARVA who underwent bilateral medialization thyroplasty were included in this study. Two independent investigators calculated bowing index (BI), normalized glottal gap area (NGGA), and maximum abduction angle from laryngostroboscopic exams using ImageJ™. Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) and patient-reported measures were collected before and after thyroplasty. RESULTS: Thyroplasty resulted in a 10-point improvement in overall CAPE-V (Mean dif -10; 95% CI -17, -3.3, p < 0.01) and VHI-10 (mean dif -3.8; 95% CI -9.8, 2.3, p = 0.19, n = 8). NGGA and BI significantly decreased following surgery (mean dif -78; 95% CI -155, -1.5, p = 0.05; and mean dif -2.1; 95% CI -2.4, -0.84, p < 0.01, respectively). BI correlated with CAPE-V scores (r = 0.66, 95% CI 0.22, 0.87, p < 0.01). When considering the normalized combined contributions of both NGGA and BI, there was a stronger correlation in CAPE-V scores (r = 0.87, 95% CI 0.50, 0.97, p < 0.01) compared with either measure alone. CONCLUSIONS: Thyroplasty resulted in a decrease in vocal fold bowing, glottal gap area, and CAPE-V scores in patients with ARVA. Correction of vocal bowing and glottal gap, following bilateral thyroplasty, improved voice measures following surgery. Quantitative evaluation of vocal fold morphology may be valuable when assessing the severity and treatment-response in patients with ARVA following bilateral thyroplasty. Laryngoscope, 134:835-841, 2024.

Phonation Resistance Training Exercises (PhoRTE) With and Without Expiratory Muscle Strength Training (EMST) For Patients With Presbyphonia: A Noninferiority Randomized Clinical Trial.

OBJECTIVES: Presbyphonia negatively impacts quality of life in patients with age-related voice changes. A proof-of-concept study showed promise for high vocal intensity exercise to treat presbyphonia, which became the basis for a novel intervention for age-related voice changes known as Phonation Resistance Training Exercises (PhoRTE). Expiratory Muscle Strength Training (EMST) has also been proposed as an additional intervention to target and strengthen the aging respiratory system; however, EMST has undergone limited evaluation as an adjunct treatment for elderly patients undergoing voice therapy for presbyphonia. This study determined if the addition of EMST to PhoRTE voice therapy (PhoRTE + EMST) is at least as effective at voice improvement as PhoRTE alone. STUDY DESIGN: Prospective, randomized, controlled, single-blinded, non-inferiority. MATERIALS AND METHODS: Participants aged 55 years or older with a diagnosis of vocal fold atrophy were randomized to complete PhoRTE therapy or PhoRTE + EMST. The primary outcome was change in Voice Handicap Index-10 (VHI-10). Secondary outcomes included the Aging Voice Index, maximum expiratory pressure, and acoustic and aerodynamic measures of voice. Repeated measures linear mixed models were constructed to analyze outcomes at a significance level of α = 0.10. RESULTS: Twenty-six participants were recruited for the study, and 24 participants were randomized to either treatment arm. Sixteen participants completed the entire study. Both treatment arms showed statistically significant and clinically meaningful improvements in VHI-10 (PhoRTE mean [M] = -8.20, P < 0.001; PhoRTE + EMST M = -9.58, P < 0.001), and PhoRTE + EMST was noninferior to PhoRTE alone (P = 0.069). Both groups experienced a statistically significant pre-post treatment decrease (improvement) in AVI scores (PhoRTE M = -18.40, P = 0.004; PhoRTE + EMST M = -16.28, P = 0.005). PhoRTE+EMST had statistically significantly greater changes in maximum expiratory pressure compared to PhoRTE alone (PhoRTE M = 8.24 cm H2O, PhoRTE + EMST M = 32.63 cm H2O; P= 0.015). Some secondary acoustic and aerodynamic outcomes displayed trends toward improvement. CONCLUSION: This study demonstrates that voice therapy targeting high vocal intensity exercise (eg, PhoRTE) and EMST can play a role in improving voice outcomes for patients with presbyphonia.

Effects of Repeated Intracordal Glucocorticoid Injection on the Histology and Gene Expression of Rat Vocal Folds.

OBJECTIVES: Local injection of glucocorticoids (GCs) into the vocal folds has been used for treating the vocal fold lesions. While the positive effects on vocal fold nodules, polyps, or scarring have been clinically reported, some concern remains around the potential adverse effects such as vocal fold atrophy, and the mechanisms remain unclear. The present study examined the histology and gene expression of locally injected GC into the vocal folds in rats. METHODS: Thirteen-week-old male Sprague-Dawley rats were used in the experiments. Triamcinolone acetonide (TAA) or saline were administered repeatedly to the right vocal folds at a weekly interval, and rats were euthanized one week after the last administration for histological examination. Genetic examination was assessed hyaluronic acid (HA) metabolism at 1 or 3 days after a single TAA injection by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The group which underwent four TAA injections showed a significant decrease in HA in the lamina propria (LP), thickness of the LP and total cell numbers of the LP compared with the saline group. In contrast, there was no significant difference in the area of collagen accumulation and the thyroarytenoid muscle, although there was a tendency of atrophy of the muscle. After single injection of TAA, qRT-PCR showed a significant decrease in the expression of HA synthases, Has2 and Has3. CONCLUSIONS: The current animal study first demonstrates that repeated intracordal injection of GCs may lead to atrophy of vocal folds caused by decrease of deposition of HA in the LP and decrease of gene expression of Has.

Platelet-Rich Plasma for Vocal Fold Scar: A Preliminary Report of Concept.

INTRODUCTION: Vocal fold atrophy and scar can lead to loss of normal superficial lamina propria, negatively affecting the vibratory function of the vocal fold. These changes can lead to dysphonia, vocal fatigue, decreased volume, and altered pitch. Treatment options for these conditions are limited. Platelet-rich plasma (PRP) consists of platelets, growth factors, and cytokines derived from the patient's own blood and is believed to activate tissue regeneration. The purpose of this study was to review the technical aspects of collecting PRP and injecting it into the vocal fold injection - based on our initial experience with this procedure. CASE: A patient with vocal fold scar was identified and enrolled in an ongoing prospective clinical trial study of a series of 4 monthly subepithelial vocal fold PRP injections, which was temporarily halted due to the COVID-19 pandemic. Patient underwent a single injection of autologous PRP into the left vocal fold. There were no adverse events during the study period. Subjective improvement in voice was noted at 1 month after injection with subsequent return to baseline over the next 4 months. Videostroboscopy performed on postinjection day 1 and day 7 and demonstrated no concerning exam changes. Compared to the preinjection baseline, the patient-reported voice-handicap index-10 (VHI-10) and voice catastrophization index were similar at 4 months following injection (20 to 20 and 4 to 3, respectively). Independent perceptual analysis of voice showed improvement at 4 months postinjection, compared to baseline consensus auditory-perceptual evaluation of voice 60 to 44. CONCLUSIONS: This preliminary report was part of a prospective trial investigating the use of PRP to treat vocal fold atrophy and scar. This work highlights the technical considerations for injecting PRP into the vocal fold. Planned prospective enrollment in this study will help to validate the safety and efficacy of PRP injections.

Changes in serum basic fibroblast growth factor concentration following intracordal injection.

Objective: Although many studies have reported improvements in voice outcomes with intracordal trafermin injection, there is a lack of data documenting its changes in serum basic fibroblast growth factor (bFGF) blood concentration. This study examined whether serum bFGF concentrations change after intracordal trafermin injection. Methods: This retrospective study was conducted at Tokyo Voice Center. We investigated serum bFGF concentrations before and after injection in 40 patients who underwent intracordal trafermin injection. There were 26 males and 14 females, with an age ranging from 13 to 88 years (average 53.25 years). They were diagnosed with paralysis (15 patients), atrophy (15 patients), sulcus (8 patients), and others (2 patients: scar and functional), presenting with severe hoarseness that interfered with daily life. Results: The mean pre- and post-injective serum bFGF concentration of the 40 patients was 6.689 and 4.658 pg/mL, respectively. The difference in mean serum bFGF concentration between pre- and post-injective was -2.031 pg/mL. The Pearson correlation coefficient was calculated to evaluate the correlation between dosage of trafermin and post-injective serum bFGF concentration, and a moderate correlation was found at r = 0.52. Generalized linear model regression analysis was performed for the purpose of adjusting for confounding among variables. The only variable that showed a statistically predominant association with post-injective serum bFGF concentrations was the dosage of trafermin, with an estimated regression coefficient of 0.048. Conclusion: In this study, the dosage of trafermin we injected and post-injective serum bFGF concentrations were dose-dependent but the amount of changes in the serum bFGF concentration was negligible within the physiological range. Therefore, as with subcutaneous and wound administration, intracordal trafermin injections may be safe. Level of Evidence: Level IV.

Safety of Platelet-Rich Plasma Subepithelial Infusion for Vocal Fold Scar, Sulcus, and Atrophy.

OBJECTIVE: To demonstrate the safety profile of platelet-rich plasma (PRP) as an injectable therapeutic for the treatment of vocal fold scarring and atrophy. METHODS: Preliminary report on a prospective clinical trial of patients with vocal fold scar or atrophy undergoing unilateral vocal fold subepithelial infusion with autologous PRP. Enrolled patients underwent four subepithelial injections spaced 1 month apart. Adverse events were assessed peri and post-injection at each session. Patient-reported outcomes were collected at every visit using the Voice Handicap Index-10 (VHI-10) and Vocal Fatigue Index (VFI) questionnaires. RESULTS: Twelve patients underwent unilateral vocal fold injection with autologous PRP prepared according to Eclipse PRP® system protocol. Forty-three injections were performed using a peroral or percutaneous approach. An average of 1.57 ± 0.4 cc (range 0.6-2.0 cc) injectate was used. All patients tolerated the procedure without difficulty or peri-procedural complications. The average duration of follow-up was 3.6 ± 1.8 months. No significant inflammatory reactions or adverse events were seen to date. There was statistically significant improvement in patient-reported outcomes at the 3 month follow up (n = 9) follow-up (mean ΔVHI-10 = 10.8, p < 0.001, mean ΔVFI = 18.9, p = 0.01, t test, paired two sample for means, two-tail). All nine patients who completed the series of four injections subjectively (yes/no) reported they were satisfied with the results. CONCLUSION: This prospective study cohort demonstrated a favorable safety profile, with no adverse events or peri-procedural complications. Subjective improvements in vocal quality and reduction in vocal fatigue need to be clinically correlated with further study. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:647-653, 2023.

Long-term outcomes of bilateral medialisation thyroplasty in patients with vocal fold atrophy with or without sulcus.

OBJECTIVE: Evaluate long-term voice outcome after bilateral medialisation thyroplasty in glottic insufficiency due to vocal fold atrophy with or without sulcus. METHODS: Patients after medialisation thyroplasty for vocal fold atrophy with or without sulcus were identified. Long-term post-operative subjective voice outcomes (> 1 year) using Voice Handicap Index-30, subjective ratings on voice aspects and study-specific questionnaire were compared to pre-operative and shorter-term (1 year) values. RESULTS: Thirty-six patients were identified, of which 26 were included (16 atrophy, 10 sulcus) with median follow up of 6.7 years. Mean Voice Handicap Index score at > 1 year (40.0) showed clinically relevant (≥ 15 for groups) and statistically significant improvement compared to pre-operative score (58.1) and remained stable compared to post-operative score (35.7) at one year. Ten patients (56 per cent) reported clinically relevant improvement (≥ 10) after more than five years. CONCLUSION: Long-term improvement in subjective voice outcomes is attainable in a significant proportion of patients undergoing bilateral medialisation thyroplasty for atrophy with or without sulcus.

Platelet-rich plasma in treatment of scar, atrophy, and sulcus: Short- and long-term results.

Objective: Platelet-rich plasma (PRP) is rich in growth factors and is easily obtained from blood samples. Long-term data after PRP injection into the larynx should be improved. This study reports the short-term (3 months) and long-term (12 months) voice results after PRP injection. Materials and Methods: Sixty-three patients with scars (n = 34), sulcus vocalis (n = 17), recalcitrant nodules (n = 5), atrophy (n = 4), or a combination of these (n = 3) were included (158 injections; median follow-up = 12.3 months). Stroboscopy, voice handicap index (VHI-10), and cepstral spectral index of dysphonia (CSID) before and after treatment (3 months) and at 12 months were tabulated. Results: VHI-10 changed from 19.5 to 14 at 3 months and 21 to 15 in the long term. The CSID scores improved from 31 to 21 in the short term and 31 to 26 in the long term (p < 0.001, paired t-test). Patients reported improved vocal effort and stamina with slight VHI or CSID score changes. Stroboscopy revealed improved closure and mucosal waves. Patients with severe dysphonia were less likely to improve compared to those with mild to moderate dysphonia. Some patients showed short-term improvements and then deteriorated back to baseline CSID over time (p < .05, paired t-test). Conclusion: Both short- and long-term improvements in voice following PRP injection have been reported. Patients with mild-to-moderate dysphonia had better outcomes. PRP injection is an alternative treatment for patients with mild-to-moderate dysphonia due to vocal fold scarring, sulcus, and atrophy. Level of evidence: II Prospective case series treatment.