Deep Vocal Fold Injection

Deep vocal fold injection (VFI) functions to correct glottal incompetence from various causes. Materials injected into the lateral aspect of the thyroarytenoid/lateral cricoarytenoid muscle complex (medial aspect of the paraglottic space) result in an augmented and/or medially displaced vocal fold. Cadaveric studies suggest that increased free-edge height and medial rotation and displacement of the arytenoid may be added benefits, although these subtle effects have not been substantiated in live subjects with residual motion or synkinetic tone. Deep VFI is most commonly used to address dysphonia and dysphagia associated with vocal fold immobility or paralysis. Advances in the safety profile of injection materials have broadened the indications to include glottal insufficiency arising from vocal fold hypomobility or paresis, vocal fold atrophy, and vocal fold scar or sulcus vocalis.

Current nomenclature classifies deep VFI into temporary, trial, or permanent/durable, based on duration of material biointegration and indication.

Temporary VFI is most commonly used to restore glottal competence in patients with an acute vocal fold paralysis or paresis with expectant or unknown recovery.

In certain clinical scenarios it is unclear whether vocal fold augmentation will result in improved voice, as is common with vocal fold atrophy, scar, and sulcus vocalis. In these instances, patients may undergo a trial injection to determine if, and to what extent, augmentation will provide symptomatic improvement.

Permanent/durable VFI is used to treat glottal incompetence that is long-standing or paralysis/paresis that has a poor prognosis for recovery. In addition, permanent VFI may be used after a positive result with trial VFI.

Materials for deep VFI are typically classified based on the duration of biointegration or, more practically, duration of efficacy.

The durable material most commonly used for office-based VFI is calcium hydroxylapatite (Radiesse Voice). Office-based autologous fat injection is not routinely performed secondary to the need for subcutaneous harvest and requirement of a large-bore needle for injection.

Temporary injection materials used in-office include collagen-based products (Cymetra), hyaluronic acid (Restylane, Hyalaform), and carboxymethylcellulose (Radiesse Voice Gel).

Clinically, the material’s expected duration of efficacy guides selection, and pragmatically, ease of preparation and delivery may also factor into surgeon preference. Several available materials are provided ready-to-use in a self-contained delivery system, increasing convenience and decreasing preparation time. Materials also vary in biocompatibility and viscoelastic properties, and although this may guide surgeon selection, systematic comparison of voice outcomes with modern materials has not been reported to date.

Superficial Vocal Fold Injection

Superficial VFI is a distinct office-based injection that targets the subepithelial space of the vocal fold. With this technique, the subepithelial space is injected with biomaterials to replace the lamina propria or inflammatory modulators to promote scar remodeling. It is indicated for vocal fold scar and lamina propria deficits, with the goal of improving vibratory abnormalities and medial edge height, rather than providing global augmentation or medialization. The limited materials applicable for superficial VFI have been used sparingly and have not been studied extensively. Superficial saline infusion has been described as a diagnostic means of assessing the extent of tethered scar. Temporary lamina propria replacements include collagen. In clinical practice, corticosteroid injection is the most commonly used scar modulator. Though still experimental, promising small-scale trials have examined superficial VFI with autologous fibroblasts to promote lamina propria regeneration.

VFI as Viable Alternative to Microsuspension or Direct Laryngoscopy

Several factors have established office-based VFI as a viable alternative to microsuspension or direct laryngoscopy VFI. Pointing to the popularity of this technique, a recent multi-institutional review revealed that VFI was performed equally often in the office as in the operating room. Office-based VFI has the distinct advantage of allowing real-time assessment of injection results and voice outcome during the procedure. Inherent risks of general anesthesia can be avoided, especially in patients with medical comorbidities. In addition, office-based VFI does not carry the risks associated with oral and pharyngeal trauma from rigid endoscopy. Voice outcomes are comparable between the two settings, and complications are typically minor and self-resolving. Patient preference may play a role as well. Patients avoid preoperative workup, have the procedure completed in 1-2 hours, and are able to resume daily activities immediately. Finally, with a national drive toward reducing health care spending, the dramatic cost reduction of VFI in the office in comparison with an operating-room procedure should not be ignored.

Office-based VFI may be performed through several approaches:

• •
  

  Peroral

  
  
• •
  

  Percutaneous

  
  
• •
  

  Transcricothyroid and transthyroid cartilage

  
  
• •
  

  Transnasal endoscopic

The peroral approach uses a curved needle directed through the oral cavity and oropharynx toward the vocal folds.

Percutaneous VFI techniques are performed by passing the injection needle into the vocal fold via a transcricothyroid membrane, transthyroid cartilage, or transthyrohyoid membrane route.

With the transcricothyroid and transthyroid cartilage approaches, the needle is passed through the skin and takes an entirely submucosal or “blind” path to the vocal fold. The transthyrohyoid approach is distinct from the other percutaneous approaches in that the needle tip takes a visualized, intraluminal path to the vocal fold after insertion through the thyrohyoid membrane.

The transnasal endoscopic approach uses a 23- or 25-gauge flexible needle delivered through the working channel of a flexible laryngoscope, and may require a high-pressure injection device, depending on the material of choice. In most cases of the above approaches, an assistant provides visualization with a distal-chip flexible laryngoscope for confirmation of needle placement and observation of injection results.

Some have also described peroral VFI using a 70° rigid telescope for visualization. Each approach has advantages and disadvantages, and selection is often based on surgeon familiarity and experience. Certain patient factors, such as oropharyngeal or supraglottic anatomy, strong gag reflex, and external neck anatomy may preclude one or more approaches. Thus the laryngologist is well served by being facile with at least several of the above-described approaches.

Patient’s Mental Faculties

Initial screening for office-based injection should begin with assessment of the candidate’s mental faculties. A patient should be cooperative, able to follow commands appropriately, and be able to sit upright without assistance. To this end, a proper candidate for office-based injection should have relatively intact cognition; this excludes, with exception, very young children and patients with deficits of mental status.

Anxiety may play a large factor in patient selection, as even the patient with the best intentions may become uncooperative if extremely anxious. Anxiety should be assessed during the preprocedural visit, and if needed the surgeon may prescribe an oral benzodiazepine, such as diazepam 1 mg or alprazolam 0.25 mg or 0.5 mg, to be taken by the patient several hours before the procedure. If an oral benzodiazepine is prescribed, the patient should provide written consent for the VFI before taking this, and should not drive on the day of the procedure. Anxiety levels toward in-office procedures have been shown not to change procedure completion rates. However, these results likely have a selection bias, as patients who are able to overcome anxiety are more likely to be selected for office-based procedures.

Patient’s Physical and Anatomic Aspects

The second consideration in screening for office-based VFI should be the physical and anatomic aspects of the candidate. Adequate nasal patency and presence of septal deflections should be assessed, as most office-based VFIs are performed with a larger-caliber working-channel flexible laryngoscope. Although this is rarely a limiting factor, the occasional patient will have a nasal passage that cannot accommodate the larger laryngoscope. For planned peroral VFI, the oropharynx and supraglottis should be assessed to ensure that large base of tongue, elongated soft palate, redundant tonsil pillars, retroflexed epiglottis, and occasionally anterior cervical spine osteophytes will not physically impede the needle from reaching the larynx. Especially important is a candidate’s gag reflex; a strong gag reflex may not be overcome even after adequate anesthesia, which can prevent successful peroral VFI. Poor visualization, attributed to overhanging arytenoid cartilage or false vocal fold abnormalities, accounts for a small percentage of procedure failures. For planned percutaneous VFI, the surgeon must ensure that the laryngeal cartilages can be readily palpated and used as surface landmarks; patients with large necks or previous neck surgery may potentially be excluded from these approaches. Radiation to the larynx is not a contraindication in itself, and percutaneous VFI in such patients has been proved to be safe, although it may be more challenging.

Anticoagulation status should be noted, although office-based VFI has been shown to be safe in patients taking anticoagulation medication. Evidence points away from airway obstruction or permanent sequelae secondary to hemorrhage during office-based VFI. Paraglottic hematoma and vocal fold hemorrhage have been reported, although the relation to anticoagulation is not consistent. In patients taking warfarin, it is prudent to check preprocedural international normalized ratio to ensure the level is not supratherapeutic. In most instances patients taking warfarin, aspirin, clopidogrel, or other anticoagulants/antiplatelets can be continued on these medications safely, as the risks of stopping them may be greater than the risks attributed to office-based VFI.

High Completion Rates are Typical

Overall, tolerance for office-based VFI is very good, highlighted by a high completion rate of VFI in the literature. In a recent multi-institutional prospective study, 93% of patients were able to complete a first-choice approach for office-based VFI. Of the 7% requiring a second or third approach, 87.5% successfully completed the injection. Because of such an eventuality, it is helpful if the surgeon is familiar with more than one technique for office-based VFI. Patient tolerance factors attributed to failure include excess secretions, inability to suppress gag reflex, and vasovagal syncope, although these were found in a minority of patients overall.

Deep Vocal Fold Injection

Deep vocal fold injection (VFI) functions to correct glottal incompetence from various causes. Materials injected into the lateral aspect of the thyroarytenoid/lateral cricoarytenoid muscle complex (medial aspect of the paraglottic space) result in an augmented and/or medially displaced vocal fold. Cadaveric studies suggest that increased free-edge height and medial rotation and displacement of the arytenoid may be added benefits, although these subtle effects have not been substantiated in live subjects with residual motion or synkinetic tone. Deep VFI is most commonly used to address dysphonia and dysphagia associated with vocal fold immobility or paralysis. Advances in the safety profile of injection materials have broadened the indications to include glottal insufficiency arising from vocal fold hypomobility or paresis, vocal fold atrophy, and vocal fold scar or sulcus vocalis.

Current nomenclature classifies deep VFI into temporary, trial, or permanent/durable, based on duration of material biointegration and indication.

Temporary VFI is most commonly used to restore glottal competence in patients with an acute vocal fold paralysis or paresis with expectant or unknown recovery.

In certain clinical scenarios it is unclear whether vocal fold augmentation will result in improved voice, as is common with vocal fold atrophy, scar, and sulcus vocalis. In these instances, patients may undergo a trial injection to determine if, and to what extent, augmentation will provide symptomatic improvement.

Permanent/durable VFI is used to treat glottal incompetence that is long-standing or paralysis/paresis that has a poor prognosis for recovery. In addition, permanent VFI may be used after a positive result with trial VFI.

Materials for deep VFI are typically classified based on the duration of biointegration or, more practically, duration of efficacy.

The durable material most commonly used for office-based VFI is calcium hydroxylapatite (Radiesse Voice). Office-based autologous fat injection is not routinely performed secondary to the need for subcutaneous harvest and requirement of a large-bore needle for injection.

Temporary injection materials used in-office include collagen-based products (Cymetra), hyaluronic acid (Restylane, Hyalaform), and carboxymethylcellulose (Radiesse Voice Gel).

Clinically, the material’s expected duration of efficacy guides selection, and pragmatically, ease of preparation and delivery may also factor into surgeon preference. Several available materials are provided ready-to-use in a self-contained delivery system, increasing convenience and decreasing preparation time. Materials also vary in biocompatibility and viscoelastic properties, and although this may guide surgeon selection, systematic comparison of voice outcomes with modern materials has not been reported to date.

Superficial Vocal Fold Injection

Superficial VFI is a distinct office-based injection that targets the subepithelial space of the vocal fold. With this technique, the subepithelial space is injected with biomaterials to replace the lamina propria or inflammatory modulators to promote scar remodeling. It is indicated for vocal fold scar and lamina propria deficits, with the goal of improving vibratory abnormalities and medial edge height, rather than providing global augmentation or medialization. The limited materials applicable for superficial VFI have been used sparingly and have not been studied extensively. Superficial saline infusion has been described as a diagnostic means of assessing the extent of tethered scar. Temporary lamina propria replacements include collagen. In clinical practice, corticosteroid injection is the most commonly used scar modulator. Though still experimental, promising small-scale trials have examined superficial VFI with autologous fibroblasts to promote lamina propria regeneration.

VFI as Viable Alternative to Microsuspension or Direct Laryngoscopy

Several factors have established office-based VFI as a viable alternative to microsuspension or direct laryngoscopy VFI. Pointing to the popularity of this technique, a recent multi-institutional review revealed that VFI was performed equally often in the office as in the operating room. Office-based VFI has the distinct advantage of allowing real-time assessment of injection results and voice outcome during the procedure. Inherent risks of general anesthesia can be avoided, especially in patients with medical comorbidities. In addition, office-based VFI does not carry the risks associated with oral and pharyngeal trauma from rigid endoscopy. Voice outcomes are comparable between the two settings, and complications are typically minor and self-resolving. Patient preference may play a role as well. Patients avoid preoperative workup, have the procedure completed in 1-2 hours, and are able to resume daily activities immediately. Finally, with a national drive toward reducing health care spending, the dramatic cost reduction of VFI in the office in comparison with an operating-room procedure should not be ignored.

Office-based VFI may be performed through several approaches:

• •
  

  Peroral

  
  
• •
  

  Percutaneous

  
  
• •
  

  Transcricothyroid and transthyroid cartilage

  
  
• •
  

  Transnasal endoscopic

The peroral approach uses a curved needle directed through the oral cavity and oropharynx toward the vocal folds.

Percutaneous VFI techniques are performed by passing the injection needle into the vocal fold via a transcricothyroid membrane, transthyroid cartilage, or transthyrohyoid membrane route.

With the transcricothyroid and transthyroid cartilage approaches, the needle is passed through the skin and takes an entirely submucosal or “blind” path to the vocal fold. The transthyrohyoid approach is distinct from the other percutaneous approaches in that the needle tip takes a visualized, intraluminal path to the vocal fold after insertion through the thyrohyoid membrane.

The transnasal endoscopic approach uses a 23- or 25-gauge flexible needle delivered through the working channel of a flexible laryngoscope, and may require a high-pressure injection device, depending on the material of choice. In most cases of the above approaches, an assistant provides visualization with a distal-chip flexible laryngoscope for confirmation of needle placement and observation of injection results.

Some have also described peroral VFI using a 70° rigid telescope for visualization. Each approach has advantages and disadvantages, and selection is often based on surgeon familiarity and experience. Certain patient factors, such as oropharyngeal or supraglottic anatomy, strong gag reflex, and external neck anatomy may preclude one or more approaches. Thus the laryngologist is well served by being facile with at least several of the above-described approaches.

Patient’s Mental Faculties

Initial screening for office-based injection should begin with assessment of the candidate’s mental faculties. A patient should be cooperative, able to follow commands appropriately, and be able to sit upright without assistance. To this end, a proper candidate for office-based injection should have relatively intact cognition; this excludes, with exception, very young children and patients with deficits of mental status.

Anxiety may play a large factor in patient selection, as even the patient with the best intentions may become uncooperative if extremely anxious. Anxiety should be assessed during the preprocedural visit, and if needed the surgeon may prescribe an oral benzodiazepine, such as diazepam 1 mg or alprazolam 0.25 mg or 0.5 mg, to be taken by the patient several hours before the procedure. If an oral benzodiazepine is prescribed, the patient should provide written consent for the VFI before taking this, and should not drive on the day of the procedure. Anxiety levels toward in-office procedures have been shown not to change procedure completion rates. However, these results likely have a selection bias, as patients who are able to overcome anxiety are more likely to be selected for office-based procedures.

Patient’s Physical and Anatomic Aspects

The second consideration in screening for office-based VFI should be the physical and anatomic aspects of the candidate. Adequate nasal patency and presence of septal deflections should be assessed, as most office-based VFIs are performed with a larger-caliber working-channel flexible laryngoscope. Although this is rarely a limiting factor, the occasional patient will have a nasal passage that cannot accommodate the larger laryngoscope. For planned peroral VFI, the oropharynx and supraglottis should be assessed to ensure that large base of tongue, elongated soft palate, redundant tonsil pillars, retroflexed epiglottis, and occasionally anterior cervical spine osteophytes will not physically impede the needle from reaching the larynx. Especially important is a candidate’s gag reflex; a strong gag reflex may not be overcome even after adequate anesthesia, which can prevent successful peroral VFI. Poor visualization, attributed to overhanging arytenoid cartilage or false vocal fold abnormalities, accounts for a small percentage of procedure failures. For planned percutaneous VFI, the surgeon must ensure that the laryngeal cartilages can be readily palpated and used as surface landmarks; patients with large necks or previous neck surgery may potentially be excluded from these approaches. Radiation to the larynx is not a contraindication in itself, and percutaneous VFI in such patients has been proved to be safe, although it may be more challenging.

Anticoagulation status should be noted, although office-based VFI has been shown to be safe in patients taking anticoagulation medication. Evidence points away from airway obstruction or permanent sequelae secondary to hemorrhage during office-based VFI. Paraglottic hematoma and vocal fold hemorrhage have been reported, although the relation to anticoagulation is not consistent. In patients taking warfarin, it is prudent to check preprocedural international normalized ratio to ensure the level is not supratherapeutic. In most instances patients taking warfarin, aspirin, clopidogrel, or other anticoagulants/antiplatelets can be continued on these medications safely, as the risks of stopping them may be greater than the risks attributed to office-based VFI.

High Completion Rates are Typical

Overall, tolerance for office-based VFI is very good, highlighted by a high completion rate of VFI in the literature. In a recent multi-institutional prospective study, 93% of patients were able to complete a first-choice approach for office-based VFI. Of the 7% requiring a second or third approach, 87.5% successfully completed the injection. Because of such an eventuality, it is helpful if the surgeon is familiar with more than one technique for office-based VFI. Patient tolerance factors attributed to failure include excess secretions, inability to suppress gag reflex, and vasovagal syncope, although these were found in a minority of patients overall.