Treatment Durability of Injection Augmentation of Vocal Fold Atrophy

ABSTRACT

Objective

Injection augmentation (or injection laryngoplasty) is a common treatment for presbyphonia. As current injection materials are temporary, it is anticipated that patients injected for presbyphonia will either need a repeat injection or framework surgery to maintain glottal competence (or sufficient glottal closure). Despite the expected temporary nature of these injections, patients report variable durability of effect, and some do not require a repeat injection. The primary aim of this investigation was to identify factors that affect treatment durability of injection augmentation among patients with presbyphonia.

Methods

Patients who underwent one or multiple injection augmentations for presbyphonia between May 2008 and September 2017 were extracted from the UW Madison Voice and Swallow Outcomes Database. Variables collected included demographics (age, sex), injection material, volume, duration between injections, date of first and last follow‐up, voice therapy (yes/no, number of sessions), and pre‐ and post‐injection voice measures (Maximum Phonation Time, Dysphonia Severity Index, Glottal Function Index score, Vocal Handicap Index Score) in an observational cohort design. For patients receiving one injection (TF group), duration between injection and last follow‐up was taken as a durability measure termed “time to follow up.” For patients receiving multiple injections (TR group), duration between injection treatments were termed “time to reinjection.” Patients receiving one or more injections were compared separately and together (where treatment durability_TF+TR refers to the combined TF + TR group) in different statistical analyses.

Results

Thirty‐five patients with presbyphonia met inclusion criteria (mean age 74.3 years [SD 7.6], 78% male). Twenty patients received only one injection. Repeat injection augmentation was performed in 40% of patients (n = 15, ranging from 1 to 6 additional injection augmentations). Maximum phonation time increased after injection augmentation (or injection laryngoplasty) and was similar across injection materials (HA (mean change (SD)): +6 s (3) [95% CI 0.1–0.8], CaHa: +4 s (2.8) [95% CI 0.2–0.7], p < 0.001). Treatment durability_TF+TR was longer for hyaluronic acid injectables when compared to calcium hydroxyapatite injectables (1232 days [CI: 552–1911] vs. 257 days [168–345], χ ²(2) = 7.505, p = 0.023). Voice therapy extended treatment durability TF_+TR for injection augmentation compared to no voice therapy (1388 [95% CI: 772–2003] vs. 277 days [206–349 days], χ ²(1) = 9.173, p = 0.002). Age did not affect treatment durability TF_+TR (χ ² (1) = 1.01, p = 0.67).

Conclusion

Factors that affected treatment durability TF_+TR for injection augmentation treatments were the type of injectable and whether patients underwent adjuvant voice therapy.

Level of Evidence

III, Retrospective cohort study.

The primary aim of this investigation was to identify factors that affect the time to re‐injection among patients with presbyphonia. We found that completion of adjuvant voice therapy and injection material significantly affected the time to re‐injection.

1. Introduction

Presbyphonia, defined as age‐induced glottal insufficiency characterized by a breathy, hoarse, and soft voice quality, affects up to 10%–20% of the elderly population [1, 2, 3, 4]. Glottal insufficiency is the result of vocal lamina propria and thyroarytenoid muscle atrophy [3, 4]. Intensive voice therapy, bilateral injection augmentation [5, 6, 7, 8, 9, 10, 11], and bilateral thyroplasty are common treatment options for glottal insufficiency [1, 9, 10]. Overall, research on the efficacy of injection augmentation in presbyphonia is limited.

Injection augmentation for presbyphonia involves injecting a filler material (e.g., hyaluronic acid [HA]) into the adductor muscle compartment that augments the vocal folds in order to facilitate glottic closure [11]. Injectables resorb over time and therefore patients often require repeat injection or framework surgery when symptoms recur [12]. Factors impacting the durability of injection augmentation for presbyphonia have not been defined. However, data from unilateral vocal fold paralysis suggest that adjuvant voice therapy may be beneficial at extending the time to re‐injection for patients receiving multiple injection augmentation procedures [3].

The rationale for voice therapy extending the effects of injection augmentation relates to age‐related physiological changes associated with respiratory and laryngeal systems [13]. Glottal insufficiency and voice complaints are more common with advanced age [3]. Another factor known to affect treatment durability for vocal fold paralysis is injection material. Different injectables have different reabsorption timelines; therefore, the injectable used to treat presbyphonia is expected to result in predictable durations of voice improvement. Sex‐related differences may influence the progression or severity of presbyphonia. The primary aim of the study is to investigate the association of voice therapy, age, biological sex, and injection material on treatment durability in injection augmentation treatments for patients with presbyphonia. A secondary aim was to quantify improvements in voice measures following injection augmentation.

2. Methods

This retrospective cohort study accessed data from a prospective Voice and Swallow Clinics Outcomes Database that was approved by the University of Wisconsin Madison Institutional Review Board (IRB #2015–0948).

2.1. Inclusion and Exclusion Criteria

The study included adult patients (≥ 50 years of age), diagnosed with presbyphonia (age‐related glottal insufficiency) by a laryngologist based on videostroboscopy, with a Vocal Handicap Index (VHI) score > 11, who underwent injection augmentation in an outpatient clinic setting (Figure 1) between 2011 and 2020. Voice Handicap Index scores of 11 and above are considered abnormal [14, 15], thus, this was used as a cutoff in our study. Following screening of consecutive patients, those patients were excluded if they had co‐morbid neurological conditions causing glottal insufficiency (e.g., vocal fold paralysis, Parkinson's disease), or were lost to follow up post‐injection augmentation (i.e., did not have a follow‐up appointment following injection augmentation treatment).

FIGURE 1.

Flow diagram of study design.

2.2. Factors Affecting Injection Augmentation

Time (in days) to re‐injection was calculated as the duration between first and subsequent injection augmentations for patients receiving multiple injections. For patients who received only one injection, time to follow up was calculated as the duration from the initial injection augmentation to the last visit with an SLP and/or surgeon. Data extracted from the database included: demographics (age and sex), number of injection laryngoplasties, date of each injection, injection material used and volume (mL), date of patients' first and last office visits following every injection augmentation treatment, and number of voice therapy sessions following each injection (if voice therapy services were sought).

2.3. Voice Outcome Measures

Data for voice measures were obtained at office visits before and following an injection augmentation treatment. Patient‐reported outcome measures included the Glottal Function Index (GFI) (4‐item assessment delineating a patient's vocal effort, fatigue, quality, and pain) [16] and VHI (30‐item assessment that measures the effect of a voice problem on an individual's quality of life) [17, 18]. Acoustic voice measures were collected, includingmaximum phonation time (MPT), jitter, shimmer, and Dysphonia Severity Index. Change in acoustic voice measures was obtained by subtracting pre‐injection from post‐injection outcomes (Post‐injection value ‐ Pre‐injection value). Change in acoustic measures was compared for different injectables and between those patients who completed at least 2 sessions of voice therapy or who did not (0–1 session).

2.4. Statistical Analysis

For patients receiving one injection (TF group), duration between injection and last follow‐up was taken as a durability measure termed “time to follow up.” For patients receiving multiple injections (TR group), duration between injection treatments were termed “time to reinjection.” When patients receiving one or more injections were combined for analyses, they are referred to as treatment durability_TF+TR. Kaplan Meier survival analysis was employed to determine if age, injection material, sex and concurrent voice therapy affected treatment durability_TF+TR in presbyphonia. To compare factors of age, injection material and voice therapy, we used a two‐way ANOVA. Then, we performed survival analysis to determine if these factors affected treatment durability_TF+TR. Similar survival analysis for multiple injections has been employed to injection augmentation treatments in vocal fold paralysis [15]. We used Kaplan Meier survival analysis, where we employed log rank (Mantel‐Cox) comparisons to determine if survival functions were equal. The survival event was defined as re‐injection occurrence as the combined TF and TR group (i.e., treatment durability_TF+TR) was considered. These log rank tests are depicted with a Chi Squared test statistic and corresponding p value within the text. Kruskal Wallis comparisons or Mann–Whitney tests were used to compare baseline demographic variables (age, GFI, VHI score) across groups to confirm that there were no confounding variables in our Kaplan Meier survival analysis. Paired t‐tests (parametric data) or Mann–Whitney tests (non‐parametric data) were used to compare pre‐and post‐injection augmentation voice improvements comparing calcium hydroxyapatite (CaHa) and HA injection materials and voice therapy/no‐voice therapy conditions, depending on whether assumptions of normality and variance were met (Shapiro Wilk, Levene's test). Alpha level for Kaplan Meier log‐rank, Paired t‐test and Mann–Whitney tests were set at p ≤ 0.05. SPSS version 17, was used to complete all statistical analysis.

3. Results

3.1. Patient Characteristics

Of the 46 patients with a diagnosis of presbyphonia, 35 met inclusion criteria (mean age 74.3 years [SD 7.6]; 78% male; baseline GFI 10.6 [4.2], baseline VHI 42.8 [23.9];11F, 24 M Table 1, Figure 1). Injection laryngoplasties were completed using HA (n = 28, all received Juvederm Ultra Plus XC), CaHa (n = 19) or other materials (Renu Gel [7] and Cymetra [6]; total n = 13) and patients were followed for an average of 12 months (SD: 18 months). Twenty patients received only one injection, and repeat injection augmentation was performed in 40% of patients (n = 15). Of these, 11 required a third injection, and one patient each required 4, 6, and 7 total injection laryngoplasties. Repeat injections were completed with the same materials as previous in all but one patient. No patient received pre‐operative voice therapy. Ten out of the 20 patients in the TF group had adjuvant voice therapy post‐injection (50%). Eight out of 15 patients in the TR group received adjuvant voice therapy. Mean number of voice therapy sessions was 4 [SD: 2.8, range: 1–10]. There were no significant differences in number of voice therapy sessions among patients receiving different injectables (HA: 1.61 [0.49], CaHa: 1.68 [0.49], and other: 1.53 [0.48], p = 0.177). A single surgeon performed all injections across patients—transoral, regardless of material—in an outpatient setting. Injection material was chosen by a single surgeon based on availability in the office. We confirmed that volume administered (HA: 0.24 mL [0.15], CaHa: 0.24 mL [0.12], and other: 0.32 mL [0.22], p = 0.267), and the number of patients receiving bilateral versus unilateral injections were not significantly different across injectable types (HA: 43% unilateral, 57% bilateral, CaHa: 47% unilateral, 53% bilateral, other: 50% unilateral, 50% bilateral, p = 0.92). Due to the low sample size of Cymetra and Renu Gel injectables, these were not included in further analysis.

TABLE 1.

Demographic information for patients receiving different numbers of injections (Mean ± SD).

	Combined TF + TR group (n = 35, 24 M, 11F)	TF group only (n = 21, 12 M, 9F)	TR group only (n = 14, 12 M, 2F)	Test statistic, p value
Age	74.33 (7.6) years	75.95 (8.10) years	73.57 (7.30) years	U = 103, W = 169, p = 49
Baseline GFI score	10.6 (4.16)	9.52 (4.10)	11.2 (4.23)	U = 156.5, W = 223, P = 0.18
Baseline VHI score	52.83 (21.43)	42.81 (23.91)	58.29 (18.2)	U = 118, W = 184, p = 0.93
Mean (SD)	Treatment durability = 352.96 (244) days	Time to follow up = 342.4 (214) days	Time to reinjection = 358.25 (212) days	U = 410.5, W = 761.5, p = 0.52
Median	Treatment durability = 179 days	Time to follow up = 165 days	Time to reinjection = 204 days

Note: Results of Kruskal Wallis comparisons for demographic variables in patients receiving 1 and more than 1 injection. Left‐most column represents demographic variable information from the entire cohort of patients as a comparison.

Abbreviations: GFI, Glottal Function Index; VHI, Vocal Handicap Index.

3.2. Comparing Patients Who Received Single Versus Multiple Injections

We confirmed that there were no significant differences in average time to follow up (TF group only) (mean [SD]: 352.96 [144] days) compared to time to reinjection (TR group only) (mean [SD]: 342.4 [114] days [p = 0.52, Table 1]). We also compared baseline characteristics between TF and TR groups and determined no significant differences in baseline GFI (TF group [mean (SD): 10.6 (4.16)], TR group [mean (SD): 9.52 (4.10)] [p = 0.18, Table 1]), and VHI score (TF group [mean (SD): 52.83 (21.43)], TR group [mean (SD): 42.81 (23.91)] [p = 0.93, Table 1]), or age (TF group [SD]: 74.33 [7.6] years, TR group: 75.95 [8.10] years [p = 0.49, Table 1]), using Mann Whitney tests. We determined if factors of age, adjuvant voice therapy, and injection material affected patients differently by comparing TF and TR groups using two‐way ANOVAs. There were no significant main or interaction effects of age (p = 0.578). Adjuvant voice therapy significantly increased time to follow up (TF group only) (p = 0.038) and time to reinjection (TR group only) (p = 0.042). We also found that CaHA had a significantly reduced time to follow up (TF group only) (HA: 1204 [164] days vs. CaHa: 267 [64] days, p = 0.008) and time to reinjection (TR group only) (HA: 1289 [176] days vs. CaHa: 214 [85] days, p = 0.003) when compared to HA injectables.

Remaining analyses reported below are conducted with all patients (i.e., treatment durability_TF+TR) where multiple injection treatments were treated as independent data points (total N = 60).

3.3. Factors Associated With Time to Re‐Injection or Follow up for Injection Augmentation

Overall, mean treatment durability_TF+TR was 352 days [SD: 131 days], but differed based on the injectable used and whether patients underwent adjuvant voice therapy (Figure 2). Treatment durability_TF+TR was not associated with age.

FIGURE 2.

Kaplan Meier Curves for (a) Age, (b) injection material, and (c) concurrent voice therapy affecting treatment durability_TF+TR.

3.3.1. Injectable

Patients injected with HA had significantly increased treatment durability_TF+TR as compared to CaHa (HA: 1232 [134] days [CI: 552–1911]) vs. CaHa: 257 [70] days [168–345], χ ²[2] = 7.505, p = 0.02 (Table 2). There were no baseline differences in age (HA: 74 [8.16] years, CaHa: 75 [6.81] years [p = 0.76, Table 2]), baseline GFI (HA: 10.85 [4.85], CaHa: 7.88 [4.09] p = 0.24, Table 2), and baseline VHI score (HA: 50.14[6.18], CaHa: 50.52 [5.63], p = 0.84, Table 2).

TABLE 2.

Demographics by injection material (Mean ± SD).

Combined TF + TR				TF group only				TR group only
Injection material	HA‐based	CaHa‐based	p	Injection material	HA‐based	CaHa‐based	p	Injection material	HA‐based	CaHa‐based	p
# of Patients	29 (18 M, 11F)	18 (14 M, 4F)		# of patients	14 (7 M, 7F)	7 (5 M, 2F)		# of patients	8 (8 M)	6 (4 M, 2F)
Age	74 (8.16) years	75 (6.81) years	p > 0.05	Age	75 (8.91) years	74 (7.64) years	p > 0.05	Age	73 (8.34) years	76 (6.72) years	p > 0.05
Baseline GFI score	10.85 (4.85)	7.88 (4.09)	p > 0.05	Baseline GFI score	11.27 (3.29)	10.56 (4.71)	p > 0.05	Baseline GFI score	8.83 (4.15)	10.24 (5.2)	p > 0.05
Baseline VHI score	50.14 (6.18)	50.52 (5.63)	p > 0.05	Baseline VHI score	54.35 (24.28)	51.23 (23.25)	p > 0.05	Baseline VHI score	44.24 (22.13)	39.68 (23.76)	p > 0.05
Treatment durability	1232 (134) days	506 (31) days	p = 0.023	Time to Follow up	1204 (164) days	267 (64) days	p = 0.008	Time to re‐injection	1289 (176) days	214 (85) days	p = 0.003

Note: Results of Kruskal Wallis comparisons for demographic variables in different injection materials.

Abbreviations: GFI, Glottal Function Index; VHI, Vocal Handicap Index.

Kaplan Meier test results comparing treatment durability_TF+TR for different injection materials.

3.3.2. Voice Therapy

Patients who underwent post‐procedure voice therapy had 6‐times longer treatment durability_TF+TR for injection augmentation compared to those who did not have therapy (Voice Therapy: 1388 [147] days [95% CI: 772–2003] vs. No Therapy: 277 (27) days [206–349 days], χ ²(1) = 9.173, p = 0.01, Table 3). There were no baseline differences in age (Voice therapy: 73.307 (8.14)years, No Voice Therapy: 75.47 (7.033) years) (p = 0.12), baseline GFI (Voice Therapy: 10.44 (4.53), No Voice Therapy: 10.80 (4.06) [p = 0.70, Table 3]), and baseline VHI score (Voice Therapy: 51.44 (4.4), No Voice Therapy: 51.77 (4.22) [p = 0.27, Table 3]).

TABLE 3.

Demographic information by voice therapy (Mean ± SD).

	Post‐injection voice therapy (n = 18, 9 M, 9F)	No voice therapy (n = 17 15 M, 2F)
Age	73.307 (8.14)	75.47 (7.033)	U = 545, p > 0.05
Baseline GFI score	10.44 (4.53)	10.80 (4.06)	U = 411, p > 0.05
Baseline VHI score	51.44 (4.4)	51.77 (4.22)	U = 455, p > 0.05
Treatment durabilityTF+TR	1388 (147) days	277 (27)days	* χ2(1) = 9.173, p = 0.002

Note: Results of Mann Whitney comparisons for demographic variables in different injection materials.

Abbreviations: GFI, Glottal Function Index; VHI, Vocal Handicap Index.

^*Kaplan Meier test results comparing treatment durability_TF+TR for those who did and did not receive voice therapy.

3.3.3. Age

There were no differences in treatment durability_TF+TR in individuals < 75 years of age (< 75 years: 373 [481] days vs. > 75 years: 298 [408] days, χ ² (1) = 1.01, p = 0.67, Table 4). There were no baseline differences in baseline GFI (< 75 years (mean (SD)): 11 (4.91), > 75 years: 9.4 (4.19) [p = 0.75, Table 4]), and baseline VHI score (< 75 years (mean (SD)): 49.21 (22.86), > 75 years: 53.81 (23.76) [p = 0.69, Table 4]). It should be noted that there were no significant differences in the age of both groups (< 75 years (Mean (SD)): 65 (13) years, > 75 years: 78 (15) years, p > 0.05 Table 4).

TABLE 4.

Demographic information by age (Mean ± SD).

	Age (> 75 years) (n = 16 11 M, 5F)	Age (< 75 years) (n = 19, 13 M, 6F)
Mean + SD (age)	65.41 + 4.53	78.13 + 15.49	U = 549, p = 0.543
Baseline GFI score	11 (4.91)	9.4 (4.19)	U = 321, p > 0.05
Baseline VHI score	49.21 (22.86)	53.81 (23.76)	U = 477, p > 0.05
Treatment durabilityTF+TR	373 (481) days	298 (408) days	* χ2(1) = 1.01, p > 0.05

Abbreviations: GFI, Glottal Function Index; VHI, Vocal Handicap Index.

^*Results of Mann Whitney comparisons for demographic variables in different injection materials. Kaplan Meier test results comparing treatment durability_TF+TR for different age groups.

3.3.4. Sex

There were no differences in treatment durability_TF+TR between the biological sexes (Females: 721 [203] days vs. Males: 831 [528] days, χ ² [1] = 3.770, p = 0.52, Table 5). There were no baseline differences in baseline GFI (Males (mean (SD)): 10.4 [4.4], Females: 11.6 [2.80] [p = 0.17, Table 5]), and baseline VHI score Males (mean + SD): 51 (19), Females: 59 (26) (p = 0.24, Table 5). It should be noted that there were no significant differences in the age of both groups (Males [Mean (SD)]: 74 (9) years, Females: 72 (13) years, p = 0.25, Table 5).

TABLE 5.

Demographic information by sex (Mean ± SD).

	Female (n = 11)	Male (n = 35)
Mean + SD (Age)	72 + 13 years	74 + 9 years	U = 549, p = 0.543
Baseline GFI score	11.6 (2.80)	10.4 (4.4)	U = 321, p = 0.17
Baseline VHI score	59 (26)	51 (19)	U = 477, p = 0.24
Treatment durabilityTF+TR	721 (203) days	831 (528) days	* χ2(1) = 3.770, p = 0.52

Abbreviations: GFI, Glottal Function Index; VHI, Vocal Handicap Index.

^*Results of Mann Whitney comparisons for demographic variables in different injection materials. Kaplan Meier test results comparing treatment durabiliity_TF+TR for different sex groups.

3.4. Voice Outcomes After Initial Injection Augmentation

When comparing voice improvements across injection materials, only CaHa and HA‐based injection materials were included (excluding the third group of “other materials”, due to lack of sufficient sample size (n < 10). At their first post‐procedure follow‐up (which on average, for this cohort of patients, was collected 172 days post‐procedure, SD: 42 days), MPT significantly improved, and was not different based on injectable used (HA (mean change (SD)): +6 s (3) [95% CI 0.1–0.8], CaHa: +4 s (2.8) [95% CI 0.2–0.7]). There were no measured changes in other voice measures following injection (p > 0.5, Table 6) such as; jitter (HA (mean change, (SD)): −0.55% (1.56), CaHa: +0.56% (2.25)), Dysphonia Severity Index (mean change, (SD)): −0.73 (3.25), CaHa: 0.39 (3.54)), GFI score (mean change, (SD)): −1.23 (5.25), CaHa: −0.62 (4.89), VHI score (mean change, (SD)): 2 (6.52), CaHa: −1.62 (6.89).

TABLE 6.

Acoustic and self‐perceptual voice outcomes pre and post‐injection laryngoplasty for injection materials (CaHa and hyaluronic acid injections).

Acoustic and self‐perceptual voice outcomes
	Hyaluronic acid‐based material			CaHa based material
	Pre	Post		Pre	Post
Jitter (%)	2.57 (1.8)	2.02 (1.49)	p > 0.05	2.29 (2.1)	2.85 (2.51)	p > 0.05
Maximum phonation time (s)	9.9 (2.8)	16.25 (3.1)	p < 0.01	11.9 (3.2)	15.8 (2.6)	p < 0.01
Dysphonia severity index	−3.52 (3.54)	−2.79 (2.71)	p > 0.05	−4.61 (3.68)	−4.22 (3.91)	p > 0.05
GFI score	10.85 (4.85)	9.62 (5.43)	p > 0.05	7.88 (4.09)	8.5 (6.2)	p > 0.05
VHI score	50.14 (6.18)	48.14 (7.62)	p > 0.05	50.52 (5.63)	52.14 (6.45)	p > 0.05

Note: Results of Paired‐t‐test comparisons for voice measure improvement following injection laryngoplasty in different injection materials.

Abbreviations: GFI, Glottal Function Index; VHI, Vocal Handicap Index.

Similarly, post‐procedure voice therapy was not associated with a change in voice measures (p > 0.5, Table 7); jitter (HA (mean change, (SD)): −0.35% (1.48), CaHa: +0.08% (1.76)), MPT(mean change, (SD)): 2 s (3.58), CaHa: 2.2 s (3.24), Dysphonia Severity Index (mean change, (SD)): 0.56 (4), CaHa: −0.08 (3.25), GFI score (mean change, (SD)): 0.99 (5.18), CaHa: −0.82 (5.88), VHI (mean change, (SD)): −1.12 (5.96), CaHa: +0.82 (6.33).

TABLE 7.

Acoustic and self‐perceptual voice outcomes pre and post‐injection laryngoplasty for voice therapy (Voice therapy completion [> 2 sessions], and No Voice Therapy [0,1 session]).

Acoustic and self‐perceptual voice outcomes
	Voice therapy			No voice therapy
	Pre	Post	Sig	Pre	Post	Sig
Jitter (%)	2.38 (1.9)	2.03 (1.38)	p > 0.05	2.66 (1.6)	2.74 (2.29)	p > 0.05
Maximum phonation time (s)	12 (2.2)	14 (4.2)	p > 0.05	13.8 (2.2)	16 (3.6)	p > 0.05
Dysphonia severity index	−3.75 (4.25)	−3.19 (3.08)	p > 0.05	4.03 (3.08)	−3.94 (3.38)	p > 0.05
GFI score	10.44 (4.53)	11.43 (6.3)	p > 0.05	10.80 (4.06)	9.81 (5.2)	p > 0.05
Vocal handicap index score	51.44 (4.4)	50.32 (6.83)	p > 0.05	50.52 (5.63)	49.7 (6.35)	p > 0.05

Note: Results of Paired‐t‐test comparisons for voice measure improvements following injection laryngoplasty in those who did and did not receive voice therapy.

Abbreviations: GFI, Glottal Function Index; VHI, Vocal Handicap Index.

4. Discussion

Variability in treatment durability for patients with presbyphonia was associated with the type of injectable used and post‐injection voice therapy. Specifically, the use of HA injectable and receipt of voice therapy increased treatment durability in our cohort of patients. Findings were similar when considering TF and TR groups together and separately.

Completion of post‐procedure voice therapy extended the treatment durability in our cohort of patients with presbyphonia‐induced glottal insufficiency, when considering TF and TR groups together and separately. Prior research has shown that voice therapy independently improves acoustic and self‐perceptual voice outcomes in patients with presbyphonia [19, 20]. No study has conducted a direct comparison of voice outcomes in patients receiving injection augmentation with and without voice therapy. Previous work has shown that patients with a greater degree of age‐related vocal atrophy may have less improvement from voice therapy in patients with presbyphonia [21]. Given that injection augmentation augments the vocal fold, this may lead to a greater chance for improvements from concurrent voice therapy. As such, voice therapy may be beneficial for treatment of glottal insufficiency post‐injection.

Different materials differed in treatment durability when considering TF and TR groups together and separately. Whereas the nature of the material may provide a possible explanation for differing results across injectables, this contradicts prior literature wherein CaHa injections last longer than HA‐based materials [22, 23, 24]. Conversely, in the present study, we found that the HA‐based injection material was effective for a longer duration when compared to CaHa. A recent review reported a high variability in treatment outcomes for both CaHa and HA‐based materials [25]. This could be due to the differing techniques reported across studies. However, in our study, the same technique was used across all injections by the same surgeon. As our cohort had a relatively small sample size (N = 35 patients), we would like to be careful interpreting this result. Statistically, injection material affected treatment durability (when considering TF and TR groups together or separately), but other factors may be more important in influencing inter‐injection intervals (such as voice therapy). In other words, treatment durability may not be an ideal metric of treatment success. Future studies can include additional voice outcomes to measure injection augmentation success.

Age and sex did not affect treatment durability in our cohort of patients, whether TF and TR groups were considered together or separately. This finding is consistent with prior research showing that age and sex had no effect on treatment durability in patients with unilateral vocal fold paralysis [15]. To date, there are no studies investigating the effects of age or sex on treatment durability in presbyphonia. The age range of these patients (=67–81 years) represents a relatively homogenous group which may provide an explanation for age not affecting treatment durability (when considering TF and TR groups together and separately) in our cohort of patients. The proportion of males (n = 35) in this cohort was 3 times the proportion of females (n = 11), which may have provided some bias to the results.

The secondary aim of this study investigated self‐perceptual and acoustic improvements following injection augmentation. We found that MPT, but no other voice measures (jitter, shimmer, and Dysphonia Severity Index, GFI or VHI score), significantly changed after injection augmentation; however, clinical relevance was poor due to the small magnitude of change. Our results are supported by improved MPT in another study reporting outcomes in presbyphonia patients following injection augmentation (using both CaHa and HA‐based injections) [26]. Although voice therapy increased the durability of injection, there were no statistically significant improvements in other voice outcomes (excluding MPT) in our study. Voice therapy also increased the durability of injection augmentation in patients with vocal fold paralysis, and therein MPT was the only acoustic measure to show significant improvement in post‐procedure follow‐up (which occurred 2–3 months post‐procedure) [24]. A lack of improvement in other acoustic voice measures may be due to the variability in timing of outcome measurement (i.e., duration between injection augmentation and first follow‐up differed across all patients). With respect to self‐perceptual improvements following injection augmentation, there were no improvements in GFI or VHI. Studies reporting VHI improvements following injection augmentation in patients with presbyphonia remain mixed [7, 26].

The investigation has limitations that warrant discussion. Certain patients may have decided against receiving a second injection or delayed receiving a treatment for other factors that were not recorded in the database (scheduling, patient motivation, financial factors etc.), not primarily due to a lasting improvement in vocal function. These patients may have decided to pursue voice therapy due to their perceived benefit (or lack thereof); however, the retrospective nature of this study prevented us from collecting this information. Future prospective studies should record other factors that may influence patient decision‐making for pursuing additional injection augmentation procedures. It should be noted that no patient received bilateral thyroplasty in the present study. Another limitation is that voice improvements were not measured at the same time point for all patients following injection (i.e., data was collected at the first follow up). Future studies should measure voice improvements at the same interval across patients.

Voice therapy and injection material affected treatment durability in our cohort of patients receiving injection augmentation for presbyphonia (considering TF and TR groups together and separately); thus, adjuvant voice therapy may be beneficial following injection augmentation. MPT was the only voice outcome to show statistically significant improvements post‐injection augmentation treatment for patients in our study.

5. Conclusion

Factors that affected treatment durability in injection augmentation treatments were adjuvant voice therapy and type of injectable. In our cohort of patients, we found that adjuvant voice therapy and HA‐based materials were associated with greater treatment durability. MPT was the only voice measure that showed statistically significant improvement following injection augmentation; however, the clinical relevance may be poor due to the small magnitude of change. Future studies should be completed to better understand factors impacting success in injection augmentation for presbyphonia.

Conflicts of Interest

The authors declare no conflicts of interest.

Venkatraman A., Davis R. J., and Thibeault S., “Treatment Durability of Injection Augmentation of Vocal Fold Atrophy,” Laryngoscope Investigative Otolaryngology 10, no. 4 (2025): e70223, 10.1002/lio2.70223.