Armed with an arsenal of newer, easier-to-use injection materials, many otolaryngologists-head and neck surgeons are treating patients with vocal fold insufficiencies in their own offices, avoiding the hassle and expense of going to the operating room.
Since 1980, at least eight materials-all of which can be injected in the outpatient setting-have been introduced for vocal fold augmentation, said Dale P. DeVore, PhD, Vice President of Research and Development at BioForm Medical, Inc., of San Mateo, CA, which develops and markets injectable products.
The office-based outpatient setting is particularly appropriate for temporary treatment of vocal fold insufficiency, typically performed when the prognosis is unknown, when a return of laryngeal nerve function is expected, or as a bridge to surgery, specialists say. But permanent vocal fold injections are being performed more frequently in the outpatient setting as well.
Among the conditions that can be treated with in-office injectables are unilateral vocal fold paralysis, vocal fold paresis, vocal fold atrophy, vocal fold scarring, vocal fold weakness or bowing, and spasmodic dysphonia.
C. Gaelyn Garrett, MD, Medical Director of the Vanderbilt Voice Center and Associate Professor in the Department of Otolaryngology at Vanderbilt University School of Medicine in Nashville, Tenn., said the most common reason she turns to injectables is for temporary treatment of patients with unilateral vocal fold paralysis.
My preference is for temporary augmentation, as none of the available injectables gives me the long-term results I would like to see. Then I use a different procedure-that is, surgery-for more permanent results, she said.
In patients with bowing, Dr. Garrett said she uses bilateral injections as a test to determine if adding bulk will improve voice. If it works, she then proceeds to a bilateral thyroplasty; if it does not, she said she then knows not to do anything aggressive.
Gary Y. Shaw, MD, Medical Director of the Voice and Swallowing Care Center at Research Medical Center in Kansas City and Associate Professor of Surgery at the Kansas City University of Biomedical and Health Sciences, said he primarily performs in-office procedures for patients with vocal cord atrophy or paresis.
If someone has paralysis, injectables are good for fine-tuning, but you really need an implant, usually with silicone, which requires a surgical procedure, he said. The implants are hard, not soft like the fillers.
The in-office procedure is relatively simple: After the airway is topically anesthetized, the affected vocal fold is injected with a resorbable material under endoscopic guidance. The injected material reduces the gap between the vocal cords so that they can make closer contact with one another, thereby improving vocal function.
In patients with vocal fold insufficiencies, the vocal folds do not close completely, which allows air to escape, resulting in a more breathy, weaker voice with less projection, Dr. Garrett explained. Basically the materials are just filler that add bulk to the vocal fold so they can better close.
Advantages of Office-Based Injections
In addition to convenience and cost and time savings, advantages of office-based injections include real-time monitoring of voice quality, avoidance of general anesthesia, and a reduced risk of complications compared with open surgical procedures, the specialists say.
The newest injection material on the block is calcium hydroxylapatite (CaHA) particles in a gel carrier composed of water, glycerine, and sodium carbomethylcellulose (Radiesse, BioForm). Dr. Shaw said that advantages of the CaHA voice gel, which has been approved by the FDA for vocal fold augmentation, are that it lasts a long time and could even be permanent.
Additionally, it does not require extra time to harvest, prepare, or reconstitute, which is common with other injectable materials, said Dr. Shaw, who participated in a prospective study of the gel.
Preliminary results on more than 50 patients, presented by Clark A. Rosen, MD, of the Eye and Ear Institute in Pittsburgh, at the annual Combined Otolaryngology Spring Meetings in May 2006, showed that 73% reported their voice was greatly or significantly improved after 12 months of treatment. The patients suffered from either unilateral vocal fold paralysis or glottal insufficiency due to vocal fold atrophy and/or vocal fold paresis.
Autologous fat, which is typically harvested from the patient’s abdomen or hip and purified, has the advantages of coming from the own patient and being relatively inexpensive, Dr. Shaw said.
Dr. Garrett said that she finds it difficult to inject in the clinic, as you usually have to go through the mouth due to the size of the needle. But theoretically you could inject it percutaneously like the others.
Additionally, variability in resorption leads to unpredictable long-term outcomes and repeat injections may be necessary, she said.
Many people had hoped it would be a permanent fix, but I would rather do a procedure where I can better predict the outcomes, she said.
Human and Bovine Collagen
Dr. Garrett said that she prefers to use human collagen (Cymetra), a freeze-dried micronized dermis purified from cadaver dermis. In my experience, it has the longest and most predictable duration of effect in that it can be used to augment the paralyzed vocal fold for two to five months, Dr. Garrett said.
Dr. Shaw said that in his experience, human collagen, like the CaHA gel, can last even longer and may even offer a permanent fix. It’s a little difficult to work with because it is so viscous, but definitely it is a step up in that there is not nearly as much resorption as with fat or bovine collagen, he said.
Another disadvantage, Dr. Garrett said, is that human collagen requires extra time for reconstituting and preparation-you have to mix it with lidocaine in the clinic setting or saline in the operating room. There is a definite learning curve.
Cross-linked bovine collagen (Zyplast/Zyderm) is another effective material that comes ready to inject, Dr. Garrett said. The big drawback is the need for allergy skin testing [about two weeks before] injection to ensure there will not be any hypersensitivity reaction.
Dr. Shaw added that up to 70% of the material is resorbed so you really need to reinject about six months to two years later.
Hyaluronic Acid, Bovine Gelatin, Teflon
Yet another filler introduced since 1980 is hyaluronic acid, a crosslinked nonimmunogenic polysaccharide, said Dr. DeVore. Widely used as a filler in facial plastic surgery, hyaluronic acid can also be used as a temporary injection material to medialize the paralyzed vocal fold, he said.
Dr. Garrett said she doesn’t know of anyone who still uses it, mainly due to an unpredictable duration of effect. One potential advantage, however, is that it is technically easier to inject, she said.
Introduced in 1978, bovine gelatin (Gelfoam) is still available as a temporary injectable. But most otolaryngologists have switched to newer materials due to the need to use a large, 18 gauge needle and a short duration of effect-about four to six weeks.
First introduced in the 1960s, Teflon is also rarely used anymore, in this case because of a high risk of side effects, chiefly foreign body reaction or vocal fold granuloma formation in more than 50% of patients, Dr. Garrett said.
It is probably the only one of the injectable that has shown permanent results, but the complication rate keeps most people from using it, she said.
Botulinum toxin type A, the muscle weakening agent better known as Botox, has been used off-label for years to help people with spasmodic dysphonia, a neurological disorder in which the laryngeal muscles are hyperactive on certain sounds, making the voice sound strained, broken, or breathy. The shots relax the muscles in the vocal cords, improving voice.
A prospective study of 36 patients with the adductory form of spasmodic dysphonia who were treated with Botox up to six times showed good results, according to senior author Norman D. Hogikyan, MD, Director of the University of Michigan Health System Vocal Health Center in Ann Arbor.
As rated on a 100-point Voice-Related Quality of Life measure developed by the researchers, the patients improved from an average score of 32.7 points before the first injection to an average score of around 80.6 points by the end of treatment.
The average time between injections for study participants was 25 weeks. During the study period, 23 patients required at least two injections, five of whom required six injections.
The Future of Vocal Fold Injections
So what is on the horizon?
For starters, there may a rise in voice fold injections for age-associated vocal fold bowing, specialists say.
As we age, presbylaryngitis sets in and we lose muscles in our voice folds like everywhere else. This can result in lower pitch, fatigue when speaking, and an inability to maintain a high volume, Dr. Shaw said. Vocal fold injections can restore some of that bulk that you have lost.
The procedure is sometimes referred to as voice lift surgery, as a rise in procedures in Europe appears to accompany an increase in the popularity of cosmetic surgery. Baby boomers who have face lifts and other procedures see a disparity between their appearance and their vocal age, resulting in a demand for a younger voice.
It’s already picking up in Europe and I wouldn’t be surprised if we see an increase in requests over the next few years here, Dr. Shaw said.
Dr. Garrett said she objected to the term voice lifts. Some people in their fifties might not otherwise be able to do their jobs because their voices are too weak, for example. It is not the equivalent of a face lift for cosmetic reasons, she said.
As for injectable materials, new products in the pipeline include stem cells in matrix, cells in atelopeptide collagen for tissue regeneration, cultured autologous fibroblasts, autologous fibroblasts to improve vocal cord scarring, and bioreactors for stimulating vocal fold biomechanics, according to Dr. DeVore.
Animal results of some of these approaches have already been reported. In one study, researchers successfully repaired the damaged vocal cords of eight adult beagle dogs using selective cultured autologous mesenchymal stem cells (Ann Otol Rhinol Laryngol 2003;112:915-20).
In another study of beagle dogs, autologous cultured fibroblasts improved mucosal pliability and returned normal or near normal mucosal waves in experimentally scarred vocal folds (Otolaryngol Head Neck Surg 2004;131:864-70).
These novel therapeutic modalities, all of which use tissue engineering approaches, may hold new promise for treating vocal fold insufficiency and scarring, Dr. DeVore said.
©2006 The Triological Society