Vocal Fold Scarring Research Articles

Patient Experience With Absolute Voice Rest Following Phonomicrosurgery: A Qualitative Study.

Voice rest is commonly recommended following phonomicrosurgery to minimize vocal fold scarring, but associated quality of life (QoL) is low resulting in poor compliance. This study aimed to explore patients' experiences with voice rest following phonomicrosurgery to identify facilitators and barriers. This qualitative study used prospective, typical case technique for purposive sampling of consecutive patients who underwent voice rest following phonomicrosurgery for benign vocal fold lesions. Participants were enrolled at a single tertiary Laryngology center located at Unity Health Toronto - St. Michael's Hospital from 2020 to 2022. Semi-structured virtual interviews were conducted 4 weeks following patients' surgery. All interview transcripts were transcribed verbatim and underwent thematic analysis. Participant recruitment was stopped once thematic saturation was achieved. Twenty participants were recruited and 4 withdrew due to scheduling conflicts. Sixteen participants completed interviews, all of whom reported minimal impact of postoperative voice rest on QoL. The participants attributed their success to facilitators such as notifying close contacts of their situation beforehand and adopting nonverbal forms of communication. No participant endorsed a negative attitude toward voice rest. Understanding the rationale for voice rest and the consequences of noncompliance were reported to be effective in encouraging compliance. Overall, the participants tolerated voice rest well owing to facilitators such as early preparation, lifestyle modifications, and understanding the rationale for voice rest. Social disconnect and work demands were barriers of voice rest. Moving forward, facilitators and barriers should be addressed in efforts to optimize the voice rest experience for future patient populations. 4 Laryngoscope, 134:361-366, 2024.

Histological Assessment of The Regenerative Potential of Platelet-Rich Plasma for Severe Vocal Fold Scar in A Rat Model

Histological Assessment of The Regenerative Potential of Platelet-Rich Plasma for Severe Vocal Fold Scar in A Rat Model

5-Fluorouracil for Treatment of Vocal Fold Scar

Vocal fold (VF) scar can result from trauma, neoplasm, inflammatory processes, congenital causes, surgery and other etiologies. In general, once the vibratory margin of the VF has been scarred, it has not been possible to return VF function to normal; but often it can be improved. The drug 5-fluorouracil (5-FU) is a pyrimidine antimetabolic that has many clinical applications ranging from systemic chemotherapy to topical treatment of actinic keratosis and basal cell carcinoma of the skin. Local injection with 5-FU also has been used for hypertrophic scar and keloids. 5-FU was shown to have benefit in animal models of VF scar and subglottic stenosis. The present study aimed to evaluate the effect of 5-FU injection on VF vibratory function in patients with VF scar. Outcomes of 5-FU injection were compared to controls injected with dexamethasone. Adult voice center patients who had undergone VF injection with dexamethasone or a series of three 5-FU injections for treatment of VF scar were included in the study. Postoperative outcomes included percentage of subjects demonstrating improvement after injection, change in scar size, glottic closure, and VF stiffness, as well as digital image analysis measurements of mucosal wave. Outcomes were compared between subjects who received 5-FU and those who received dexamethasone. There were 58 VFs injected with 5-FU and 58 historical controls injected with dexamethasone. Baseline subject characteristics and etiology of scar did not differ significantly between the 5-FU and dexamethasone cohorts, except that scar size was greater in the 5-FU group and mucosal wave was worse at baseline. After a series of three 5-FU injections, 61.22% improved, 8.16% demonstrated no change, and 30.61% worsened. In the dexamethasone cohort, 51.06% improved, 0.00% demonstrated no change, and 48.94% worsened. The response differed significantly between the 5-FU and dexamethasone cohorts, with a greater proportion of subjects who underwent 5-FU injection demonstrating improvement postoperatively. In the 5-FU cohort, 32.76% of subjects previously had undergone and failed dexamethasone injection for VF scar: and within that group 84.21% improved, 5.26% demonstrated no change, and 10.53% worsened following 5-FU injection. On digital image analysis, the percent improvement in postoperative mucosal wave was significantly greater in the 5-FU cohort compared to the dexamethasone group, which demonstrated a worsening of mucosal wave. A series of three intralesional injections with 5-FU outperformed dexamethasone for improving mucosal wave in patients with VF scar. A prior failed trial of dexamethasone injection predicted a favorable response to 5-FU. Further research is encouraged to confirm or refute these findings.

The use of basic fibroblast growth factor to improve vocal function: A systematic review and meta-analysis.

This systematic review and meta-analysis examines if intralaryngeal injection of basic fibroblast growth factor 2 (FGF2) can improve voice outcomes in those with vocal disability. A Systematic review of original human studies reporting voice outcomes following intra-laryngeal injection of basic fibroblast growth factor 2 in those with vocal dysfunction. Databases searched were Medline (1946-July 2022), Embase (1947-July 2022), Cochrane database and Google Scholar. Secondary or tertiary care centres that undertook the management of voice pathology Hospital. Inclusion criteria were original human studies reporting voice outcome measurements following intralaryngeal injection of FGF2 to treat vocal fold atrophy, vocal fold scarring, vocal fold sulcus or vocal fold palsy. Articles not written in English, studies that did not include human subjects and studies where voice outcome measures were not recorded before and after FGF2 injection were excluded from the review. The primary outcome measure was maximum phonation time. Secondary outcome measures included acoustic analysis, glottic closure, mucosal wave formation, voice handicap index and GRBAS scale. Fourteen articles were included out of a search of 1023 and one article was included from scanning reference lists. All studies had a single arm design without control groups. Conditions treated were vocal fold atrophy (n = 186), vocal cord paralysis (n = 74), vocal fold fibrosis (n = 74) and vocal fold sulcus (n = 56). A meta-analysis of six articles reporting on the use of FGF2 in patients with vocal fold atrophy showed a significant increase of mean maximum phonation time of 5.2 s (95% CI: 3.4-7.0) at 3-6 months following injection. A significant improvement in maximum phonation time, voice handicap index and glottic closure was found following injection in most studies assessed. No major adverse events were reported following injection. To date, intralaryngeal injection of basic FGF2 appears to be safe and it may be able to improve voice outcomes in those with vocal dysfunction, especially vocal fold atrophy. Randomised controlled trials are needed to further evaluate efficacy and support the wider use of this therapy.

Voice Outcomes Following Serial Office-Based Steroid Injections and Voice Therapy for Vocal Fold Scar

Previous studies indicate that certain voice outcomes can improve following a single office-based steroid injection with voice therapy for vocal fold scar. We evaluated voice outcomes after a series of three timed office-based steroid injections with voice therapy. Retrospective case series with chart review. Academic medical center. We evaluated pre-and postprocedural patient-reported, perceptual, acoustic, aerodynamic, and videostroboscopic parameters. We evaluated 23 patients who underwent three office-based dexamethasone injections into the superficial lamina propria one month apart. All patients pursued voice therapy. Voice Handicap Index (n=19; P= .030) decreased after injection series. Total GRBAS score (grade, roughness, breathiness, asthenia, strain) decreased (n=23; P=0.001). Dysphonia severity index score improved (n=20; P=0.041). Phonation threshold pressure did not decrease significantly (n=22; P=0.536). Videostroboscopic parameters of vocal fold edge (P=0.023), right mucosal wave (P=0.023) improved or normalized after injection series. Glottic closure (P=0.134) did not improve. Series of three office-based steroid injections combined with voice therapy for vocal fold scar does not appear to provide further benefit than one injection. Despite lack of improvements of PTP and other parameters, injection series is likewise unlikely to worsen dysphonia. A partially negative study provides value in investigation of less invasive treatment alternatives for a disorder that is challenging to treat. Future studies exploring effects of voice therapy alone without other intervention and consideration of sham injection versus steroid injection are warranted.

Effects of compound betamethasone on vocal fold wound healing in rabbit model: A preliminary study.

The compound betamethasone is widely used to prevent scarring in dermatology. This study aims to explore the effects of compound betamethasone on vocal fold (VF) wound healing. Prospective animal study in rabbits. Eighteen rabbits underwent bilateral VF stripping and three rabbits served as controls. 0.1 mL of compound betamethasone (1mL: betamethasone sodium phosphate 5mg and betamethasone dipropionate 2mg) was injected into the right VF of each rabbit, and 0.1mL 0.9% saline was injected into the contralateral VF. Endoscopy was performed for morphologic observation. Six larynges were harvested for histological analysis at 3 days, 7 days, and 1month. The VFs were stained with hematoxylin and eosin (H&E), Alcian blue, and Masson' trichrome staining. In morphological analysis, there was no visible difference between betamethasone-treated and saline-treated VFs at 3 and 7 days. After 1month, more VF scars appeared on the saline-treated VFs than the VFs treated with betamethasone. Inflammatory cell number showed significant difference between both VFs at 3 days (p=.037) and 7 days (p=.045). No significant different was found in epithelial thickness at 1month between the betamethasone and saline groups. The collagen in the saline-treated VFs was significantly denser than that of the betamethasone-treated group (p=.037). There was also a significant increase in the level of hyaluronic acid(HA) in betamethasone-injected VFs in comparison to the saline-injected VFs (p=.006). Based on this study, compound betamethasone can improve VF healing. Our findings suggest that VF injection with compound betamethasone helps to minimize scarring by increasing HA level and decreasing collagen density.

Establishment and characterization of immortalized human vocal fold fibroblast cell lines.

Vocal fold scarring is abnormal scar tissue in the lamina propria layer of the vocal fold. To facilitate investigation of vocal fold scarring, we established and characterized immortalized human vocal fold fibroblast (iHVFF) cell lines. Human vocal fold fibroblasts were immortalized by introducing Simian virus 40 large T antigen (SV40TAg) by transfection. Successfully transfected fibroblasts were sorted using flow cytometry. Immunofluorescence cytochemistry and western blot were applied to analyze the expression of fibronectin, vimentin, alpha-smooth muscle actin (α-SMA) and fibroblast activation protein (FAP). Cell proliferation rate was measured by CCK-8 assay. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to analyze the mRNA expression level. The iHVFFs continued to proliferate for more than 30 generations and appeared spindle-shaped. The expression of Vimentin and α-SMA were detected in both iHVFFs and primary fibroblasts, and enhanced expression of FAP was observed in iHVFFs. Furthermore, iHVFFs exhibited an increased proliferative capability compared with the primary fibroblasts. RT-qPCR results suggested that collagen type III alpha 1 chain (COL3A1), interleukin-6, cyclooxygenase 2 (COX2), hyaluronan synthase 2 (HAS2), hepatocyte growth factor (HGF) in the iHVFFs significantly increased, whereas transforming growth factor-β1 (TGF-β1), elastin and matrix metallopeptidase-1 (MMP-1) expression significantly downregulated. No differences in mRNA expression of α-SMA, fibronectin and collagen type I alpha 2 chain (COL1A2) were noted between iHVFFs and primary fibroblasts. iHVFFs can be used as a novel tool cell for future researches on the mechanisms of pathogenesis and treatment of vocal fold scarring.

Duration of Clinical Response After In-Office Steroid Injection for Vocal Fold Scar.

To assess the duration of clinical response after in-office vocal fold steroid injection (VFSI) for vocal fold (VF) scar. Demographic and clinical data for in-office VFSI occurring from 2017 to 2020 were collected. Two Speech-Language Pathologists (SLPs) used perceptual evaluation of voice and functional scales to evaluate blinded voice and laryngovideostroboscopy (LVS) samples collected pre- and post-injection across multiple timepoints. Blinded SLP ratings were used for 30 individual VFs undergoing initial injection in 18 patients. Persistent improvement in voice past 6 months was seen in 57% of patients after VFSI. Multiple measures of voice and amplitude, percent vibrating tissue, and closed phase predominance significantly improved at various follow-up timepoints on average. Accounting for patient heterogeneity and disease progression, in-office VFSI for VF scar is associated with sustained improvement in a subset of patients. Approximately half of patients can expect to experience a lasting improvement in voice. Future studies of larger scale are required to identify patient factors associated with long-term benefit. 4 Laryngoscope, 133:2333-2339, 2023.

Using Diffusion Tensor Imaging to Explore the Changes in the Microstructure of Canine Vocal Fold Scar Tissue

To apply diffusion tensor imaging (DTI) in measurement of the diffusion characteristics of water molecules in vocal fold scar tissue, combined with the analysis of textural characteristics of collagen fibers in the cover layer of the vocal folds to explore the feasibility of DTI in the qualitative and quantitative diagnosis of vocal fold scars and the evaluation of microstructural changes of vocal fold scar tissue. A unilateral injury was created using micro-cup forceps in the left vocal fold of six beagles. The contralateral normal vocal fold was used as a self-control. Five months postinjury, the larynges were excised and placed into a magnetic resonance imaging (MRI) system (9.4T BioSpec MRI, Bruker, German) for scanning and extraction of the diffusion parameters, fractional anisotropy (FA) and tensor trace in the anterior, middle, and posterior portions of the vocal fold cover layer. These parameters were then analyzed for statistical significance between the scarred vocal fold and the normal vocal fold. After MRI scanning, the tissue of the vocal folds was divided into anterior, middle, and posterior parts for sectioning and staining with hematoxylin and eosin, and samples were subsequently digitally scanned for texture analysis. The irregularity parameters, energy, contrast, correlation, and homogeneity, of collagen fibers of the vocal folds and the mean gray value of collagen fibers were calculated by the gray-level co-occurrence matrix (GLCM) texture analysis method. The differences in the mean value of the two sides of the vocal fold were compared. In addition, Pearson correlation analysis was performed between DTI parameters and irregularity parameters. The FA of the left vocal fold cover layer was significantly lower compared to the self-control group (P=0.0366), and the tensor trace value on the left vocal fold cover layer was significantly higher compared to the self-control group (P=0.0353). The FA was significantly higher in the anterior part of the right vocal fold cover layer compared to the middle and posterior parts of the same side (P=0.0352), and the tensor trace was significantly lower in the anterior part of the right vocal fold cover layer compared to the middle and posterior parts of the same side (P=0.0298). There were no significant differences in FA and tensor trace between the middle and posterior parts of the vocal fold cover layer. The mean gray value of the left vocal folds cover layer was significantly smaller than the right vocal fold cover layer (P=0.0219), the energy of the left vocal fold cover layer was significantly smaller than that of the right vocal fold cover layer (P < 0.0001), the contrast of the left vocal folds cover layer was significantly larger than that of the right vocal fold cover layer (P=0.0002), the correlation of the left vocal folds cover layer was significantly smaller than the right vocal fold cover layer (P=0.0002), and the homogeneity of the left vocal folds cover layer was significantly smaller than the right vocal fold cover layer (P=0.0003). Pearson correlation analysis yielded values of r=0.926, P=0.000 between the FA and mean gray value; r=-0.918, P=0.000 between FA and energy; r=-0.924, P=0.000 between the FA and homogeneity, r=-0.949, P=0.000 between tensor trace and mean gray value; r=0.893, P=0.000 between the tensor trace and energy; and r=0.929, P=0.000 between the tensor trace and homogeneity. FA and tensor trace can be used as effective parameters to reflect microstructural changes in vocal fold scars. DTI is an objective and quantitative method of analyzing vocal fold scarring, and it noninvasively evaluates the microstructure of vocal fold collagen fibers.

Analysis of the Effect of Intralesional Steroid Injection on the Voice During Laryngeal Microsurgery

Background and Objectives Vocal fold (VF) scar is known to be the most common cause of dysphonia after laryngeal microsurgery (LMS). Steroids reduce postoperative scar formation by inhibiting inflammation and collagen deposition. However, the clinical evidence of whether steroids are helpful in reducing VF scar formation after LMS is still lacking. The purpose of this study is to determine whether intralesional VF steroid injection after LMS helps to reduce postoperative scar formation and voice quality.Materials and Method This study was conducted on 80 patients who underwent LMS for VF polyp, Reinke’s edema, and leukoplakia. Among them, 40 patients who underwent VF steroid injection after LMS were set as the injection group, and patients who had similar sex, age, and lesion size and who underwent LMS alone were set as the control group. In each group, stroboscopy, multi-dimensional voice program, Aerophone II, and voice handicap index (VHI) were performed before and 1 month after surgery, and the results were statistically analyzed.Results There were no statistically significant differences in the distribution of sex, age, symptom duration, occupation and smoking status between each group. Both groups consisted of VF polyp (n=21), Reinke’s edema (n=11), and leukoplakia (n=9). On stroboscopy, the lesion disappeared after surgery, and the amplitude and mucosal wave were symmetrical on both sides of the VFs in all patients. Acoustic parameters and VHI significantly improved after surgery in all patients. However, there was no significant difference between the injection and control group in most of the results.Conclusion There was no significant difference in the results of stroboscopy, acoustic, aerodynamic, and subjective evaluation before and after surgery in the injection group and the control group.

Regenerative Medicine and Amniotic Membrane Application for Vocal Fold Scars and Sulcus

Vocal fold scars and sulcus cause severe vocal problems, but no optimal treatment has been established. In severe cases, in which the entire lamina propria is occupied by severe fibrosis and the vibratory function is completely lost, more powerful regeneration materials should be used, or the mucosa should be totally replaced. Amniotic membrane is a scaffold material that is rich in stem cells and growth factors and has a high regenerative effect. It can be clinically applied in many fields. Several studies have already investigated the effects of amniotic membrane on the vocal fold in animal studies. These studies have shown that the amniotic membrane is effective for vocal fold regeneration. In particular, our study showed that the transplantation of an amniotic membrane to the rabbit vocal fold induced high hyaluronic acid retention and the suppression of collagen deposition after three months without rejection. We hope that the use of the amniotic membrane for vocal fold regeneration will be broadly applied in the future.

Official Report of Epidemiologic Survey of the Vocal Fold Scar and Sulcus in Japan

Official Report of Epidemiologic Survey of the Vocal Fold Scar and Sulcus in Japan

Ultrafast laser surgery probe for sub-surface ablation to enable biomaterial injection in vocal folds

Creation of sub-epithelial voids within scarred vocal folds via ultrafast laser ablation may help in localization of injectable therapeutic biomaterials towards an improved treatment for vocal fold scarring. Several ultrafast laser surgery probes have been developed for precise ablation of surface tissues; however, these probes lack the tight beam focusing required for sub-surface ablation in highly scattering tissues such as vocal folds. Here, we present a miniaturized ultrafast laser surgery probe designed to perform sub-epithelial ablation in vocal folds. The requirement of high numerical aperture for sub-surface ablation, in addition to the small form factor and side-firing architecture required for clinical use, made for a challenging optical design. An Inhibited Coupling guiding Kagome hollow core photonic crystal fiber delivered micro-Joule level ultrashort pulses from a high repetition rate fiber laser towards a custom-built miniaturized objective, producing a 1/e2 focal beam radius of 1.12 ± 0.10 μm and covering a 46 × 46 μm2 scan area. The probe could deliver up to 3.8 μJ pulses to the tissue surface at 40% transmission efficiency through the entire system, providing significantly higher fluences at the focal plane than were required for sub-epithelial ablation. To assess surgical performance, we performed ablation studies on freshly excised porcine hemi-larynges and found that large area sub-epithelial voids could be created within vocal folds by mechanically translating the probe tip across the tissue surface using external stages. Finally, injection of a model biomaterial into a 1 × 2 mm2 void created 114 ± 30 μm beneath the vocal fold epithelium surface indicated improved localization when compared to direct injection into the tissue without a void, suggesting that our probe may be useful for pre-clinical evaluation of injectable therapeutic biomaterials for vocal fold scarring therapy. With future developments, the surgical system presented here may enable treatment of vocal fold scarring in a clinical setting.

Matrix Adhesiveness Regulates Myofibroblast Differentiation from Vocal Fold Fibroblasts in a Bio-orthogonally Cross-linked Hydrogel.

Repeated mechanical and chemical insults cause an irreversible alteration of extracellular matrix (ECM) composition and properties, giving rise to vocal fold scarring that is refractory to treatment. Although it is well known that fibroblast activation to myofibroblast is the key to the development of the pathology, the lack of a physiologically relevant in vitro model of vocal folds impedes mechanistic investigations on how ECM cues promote myofibroblast differentiation. Herein, we describe a bio-orthogonally cross-linked hydrogel platform that recapitulates the alteration of matrix adhesiveness due to enhanced fibronectin deposition when vocal fold wound healing is initiated. The synthetic ECM (sECM) was established via the cycloaddition reaction of tetrazine (Tz) with slow (norbornene, Nb)- and fast (trans-cyclooctene, TCO)-reacting dienophiles. The relatively slow Tz-Nb ligation allowed the establishment of the covalent hydrogel network for 3D cell encapsulation, while the rapid and efficient Tz-TCO reaction enabled precise conjugation of the cell-adhesive RGDSP peptide in the hydrogel network. To mimic the dynamic changes of ECM composition during wound healing, RGDSP was conjugated to cell-laden hydrogel constructs via a diffusion-controlled bioorthognal ligation method 3 days post encapsulation. At a low RGDSP concentration (0.2 mM), fibroblasts residing in the hydrogel remained quiescent when maintained in transforming growth factor beta 1 (TGF-β1)-conditioned media. However, at a high concentration (2 mM), RGDSP potentiated TGF-β1-induced myofibroblast differentiation, as evidenced by the formation of an actin cytoskeleton network, including F-actin and alpha-smooth muscle actin. The RGDSP-driven fibroblast activation to myofibroblast was accompanied with an increase in the expression of wound healing-related genes, the secretion of profibrotic cytokines, and matrix contraction required for tissue remodeling. This work represents the first step toward the establishment of a 3D hydrogel-based cellular model for studying myofibroblast differentiation in a defined niche associated with vocal fold scarring.

5-Aminolevulinic Acid-Mediated Photodynamic Therapy Improves Vocal Fold Wound Healing in Rats.

Studies showed that photodynamic therapy (PDT) might be able to prevent vocal fold scar formation when treating laryngeal lesions. We aim to investigate if PDT improves vocal wound healing and reduces scar formation in both prophylactic and remodeling procedures performed in vivo. In vivo. Vocal fold stripping was performed in Sprague-Dawley rats. PDT was performed with intraperitoneal injection of 100 mg/kg 5-Aminolevulinic Acid (5-ALA) and 635 nm laser irradiation of 20, 40, and 60 J/cm2 . PDT was performed immediately after surgery to study the prophylactic effect and 4 weeks after surgery to study the remodeling effect. Gene expression was evaluated with real-time PCR at 1 week after PDT. Histologic evaluations were performed 12 weeks after PDT, including hematoxylin-eosin, Masson, Alcian blue staining, and immunohistochemical staining of collagen I and III. PDT induced similar effects on the vocal fold wound healing outcomes in both prophylactic and remodeling procedures. Expression of MMP8, MMP13, HAS2, and TGFβ1 was significantly elevated. Histologic evaluation revealed significantly increased thickness, decreased density of collagen, and increased deposition of hyaluronic acid in the lamina propria. Immunohistochemistry also revealed better distribution and reduced density of collagen I and III. The most obvious changes were seen in the 60 J/cm2 PDT group. PDT could significantly improve vocal wound healing by providing both prophylactic effects and remodeling effects. It may be a minimally invasive treatment for vocal fold lesions with slight vocal scarring, and may be used to treat acute or chronic vocal injury to reduce vocal scarring. N/A Laryngoscope, 133:1943-1951, 2023.

Phonation Threshold Pressure as a Unique Outcome Measure of Phonatory Physiology Changes Following Submucosal Saline Injection for Vocal Fold Scarring

Purpose: This study aimed to describe the utility of phonation threshold pressure (PTP) measurement as an additional outcome measure for changes in vocal fold vibration secondary to submucosal saline injection in the case of an individual with idiopathic vocal fold scarring. Method: An 8-week program of voice therapy, followed by submucosal saline infusion, was administered, using multiple outcome measures to assess voice quality, effort, and function in a 38-year-old woman with idiopathic bilateral vocal fold scarring. Transoral rigid video-endoscopy with stroboscopy in conjunction with the Stroboscopy Evaluation Rating Form provided measures of the vibratory characteristics of the vocal folds (amplitude, mucosal wave, nonvibratory portion, edge smoothness, and straightness). Auditory-perceptual measures were obtained using the Consensus Auditory-Perceptual Evaluation of Voice. Acoustic measures included jitter (%local), shimmer (%local), harmonics-to-noise ratio (dB), and Cepstral Spectral Index of Dysphonia. Additionally, PTP was measured 1 day prior to, and 1 month after, saline infusion. Results: Acoustic, auditory-perceptual, and stroboscopic variables suggested minimal change to the vibratory properties of the vocal folds in response to submucosal saline infusion for the treatment of vocal fold scarring. PTP measurements across the patient's frequency range, however, revealed a marked decrease post infusion. This was consistent with the patient's report of improved functioning and her request for repeat saline infusion. Conclusion: These results are consistent with the possibility of using PTP as an independent means of quantifying changes in phonatory physiology across the frequency range in patients with vocal fold scarring. Supplemental Material: https://doi.org/10.23641/asha.21313725

Intracordal injection therapy for vocal fold scarring: Steroid versus basic fibroblast growth factor.

ObjectivesVocal fold scarring is caused by replacement of vocal fold mucosa with fibrous tissue due to repeated inflammation or trauma. It can lead to severe dysphonia. It is currently treated conservatively and with phonosurgery and intracordal injections. Intracordal injection of steroid or basic fibroblast growth factor (bFGF) has been recently found to be useful for treating vocal fold scarring that does not respond to voice therapy.MethodsThis retrospective study involved the administration of steroid injection and bFGF injection bilaterally under local anesthesia in 16 patients each. Laboratory measurements of voice parameters were performed before and 3–6 months after injection.ResultsIn the steroid injection group, the Voice Handicap Index (VHI) score significantly improved from 57.1 to 40.5, total Grade, Roughness, Breathiness, Asthenia, Strain (tGRBAS) score significantly improved from 4.2 to 2.6, and mean speech fundamental frequency (SFF) increased from 192.5 to 211.4 dB, but there was no improvement in maximum phonation time (MPT) and mean airflow rate (MFR). In the bFGF injection group, significant improvements in the VHI score (from 53.3 to 35.7), MPT (from 16.9 to 21.8 s) and MFR (from 314.6 to 210.5 ml/s) were seen; however, the tGRBAS score did not improve. In addition, the SFF significantly decreased from 178.1 to 160.5 Hz.ConclusionThese results suggest that both steroid and bFGF injections are effective for treating vocal fold scarring, with steroids improving voice quality and bFGF improving glottic closure, thereby contributing to improvements in VHI scores.Level of Evidence4.

Scarless Healing of Injured Vocal Folds Using an Injectable Hyaluronic Acid-Waterborne Polyurethane Hybrid Hydrogel to Tune Inflammation and Collagen Deposition.

Vocal fold (VF) scarring results from injury to the unique layered structure and is one of the main reasons for long-lasting dysphonia. A minimally invasive procedure with injectable hydrogels is a promising method for therapy. However, current surgical techniques or standard injectable fillers do not yield satisfactory outcomes. In this work, an injectable hybrid hydrogel consisting of oxide hyaluronic acid and hydrazide-modified waterborne polyurethane emulsion was injected precisely into the injury site and cross-linked in situ by a dynamic hydrazone bond. The prepared hydrogel displays excellent injectability and self-healing ability, showing favorable biocompatibility and biodegradability to facilitate endogenous newborn cell migration and growth for tissue regeneration. With the aim of evaluating the antifibrosis and regeneration capacity of the hybrid hydrogel in the VF scarring model, the morphology and vibration characteristics of VFs, inflammatory response, and healing status were collected. The hybrid hydrogel can decrease the inflammation and increase the ratio of collagen III/collagen I to heal damaged scar-free tissue. Fascinatingly, the mucosal wave oscillations of healing VF by injecting the hybrid hydrogel were vibrated like the normal VF, achieving functional restoration. This work highlights the utility of hybrid hydrogels consisting of synthetic biodegradable waterborne polyurethane emulsions and natural hyaluronic acid as promising biomaterials for scarless healing of damaged VFs.

Injection laryngoplasty in pediatrics

Injection laryngoplasty is a procedure that provides support to a vocal fold that lacks either the bulk or the mobility it once had. Two indications are vocal fold immobility from vocal fold paralysis, scarring, or atrophy among other causes or glottic insufficiency resulting from vocal atrophy, sulcus vocalis, or vocal fold neoplasm. A comprehensive pre-operative work up includes evaluation of the vocal folds by indirect flexible laryngoscopy, stroboscopy, direct operative laryngoscopy, and/or ultrasound. Measuring impacts of vocal pathology that may be suited to injection laryngoplasty is done through pediatric reported outcome measures of voice and evaluation of swallow. During the operation the surgeon can choose from different injection materials depending on the need of the procedure. In children, the most typical method of delivery in children is under direct or telescopic and/or microscopic visualization during a procedure under anesthesia. The surgeon must take caution for proper placement of material in relation to the true vocal fold to reduce risks of voice dysfunction, airway obstruction, airway hemorrhage, or injury to the adjacent laryngeal structures. Injection laryngoplasty is the preferred method of surgical management of vocal fold immobility and has proven safe in children of all ages. Injection laryngoplasty is a procedure that provides support to a vocal fold that lacks either the bulk or the mobility it once had. Two indications are vocal fold immobility from vocal fold paralysis, scarring, or atrophy among other causes or glottic insufficiency resulting from vocal atrophy, sulcus vocalis, or vocal fold neoplasm. A comprehensive pre-operative work up includes evaluation of the vocal folds by indirect flexible laryngoscopy, stroboscopy, direct operative laryngoscopy, and/or ultrasound. Measuring impacts of vocal pathology that may be suited to injection laryngoplasty is done through pediatric reported outcome measures of voice and evaluation of swallow. During the operation the surgeon can choose from different injection materials depending on the need of the procedure. In children, the most typical method of delivery in children is under direct or telescopic and/or microscopic visualization during a procedure under anesthesia. The surgeon must take caution for proper placement of material in relation to the true vocal fold to reduce risks of voice dysfunction, airway obstruction, airway hemorrhage, or injury to the adjacent laryngeal structures. Injection laryngoplasty is the preferred method of surgical management of vocal fold immobility and has proven safe in children of all ages.

Cryotherapy Modifies Extracellular Matrix Expression of Vocal Fold in Rat Models

Vocal fold (VF) scarring is the major cause of voice disorders. Cryotherapy is an effective anti-scarring therapy for skin lesions. The aim of this study was to explore the anti-scarring potential of cryotherapy in vocal folds. The extracellular matrix (ECM) mRNA expression of cryotherapy on normal VF tissue and the histologic results of cryotherapy on vocal fold healing were studied. Fifteen rats were introduced cryotherapy on the normal VF bilaterally and were harvested for real-time polymerase chain reaction (RT-PCR) analysis for collagen I, collagen III, TGFβ1, decorin, fibronectin and HAS1 at 1 day, 3 days and 7 days. Ten rats were unilaterally injured by stripping lamina propria and immediately treated with or without cryotherapy and were harvested at 2 months for histological and immunohistochemical analysis. Regenerative effect of cryotherapy was validated of ECM gene expression. Histological and immunohistochemical analysis showed significantly increased hyaluronan, decreased collagen, and increased decorin deposition in injury-cryotherapy cohort compared with injury control cohort and normal control cohort. Cryotherapy may provide an optimal environment for vocal fold tissue regeneration. The results of the present investigation suggest that cryotherapy has therapeutic potential in prevention and treatment of vocal fold scarring.