Initially compiled 9-10-2021 by Brady Anderson, BS and Henry Hoffman, MD with future adaptations per additional contributors

see: video of setup - Blue Light Laser (445 nm wavelength) Video of Setup and Equipment

and Transnasal Laryngoscopy with Blue Light Laser (445 nm wavelength) - Case Example with Dosimetry, Equipment and Modified Operative Note

History

• Einstein proposed in 1917 that molecules stimulated by linear energy entered an excited state, a return from which would lead to emission of linear energy (Einstein, 1917; Franck et al., 2016).
• In 1960, T. H. Maiman developed the first working laser by stimulating ruby with a high-power lamp (Maiman, 1960).
• Lasers entered the clinical arena in 1961 with Dr. Goldman's laser treatment of a melanoma (Song, 2017).
• Lasers have been used in otolaryngology for treatment of benign and malignant lesions of the larynx, sinonasal cavities, ear and other sites (Karkos, 2021).

Definitions:

• Gain medium: In a laser, the substance (solid, liquid, or gas) which absorbs photons, leading to electron excitation and emission of laser light (Franck et al., 2016)
  • Figure 1 Schematic of a LASER, using Nd:YAG (neodymium-doped yttrium aluminum garnet) as a gain medium.

 downloaded with permission from wikicommons 09092021( https://upload.wikimedia.org/wikipedia/commons/e/e8/Lasercons.png)  DrBob (talk) (Uploads), CC BY-SA 3.0 <http://creativecommons.org/licenses/by-sa/3.0/>, via Wikimedia Commons

• Chromophore: the light absorbing-component of a molecule responsible for its color. These include conjugated systems as well as porphyrins and flavins (Wilson, 2014).
• Fluence: The amount of energy absorbed over a target area, measured in joules/cm² (Franck et al., 2016).
• Selective Photothermolysis: Intrinsic chemical properties of different tissue components (e.g. chromophores) absorb different wavelengths of light to varying degrees
  • By applying short “pulses” of a given wavelength, selective tissues may be damaged while leaving surrounding structures intact (Anderson & Parrish, 1983; see Fig. 2).
• Semiconductor: A material with conductive properties between a metal and insulator, due to presence of charge carriers. May be produced by introducing ("doping") atoms of differing valence electron number into a crystal to create areas of positive or negative charge.
  • Semiconductors form the base of many electronic technologies due to the ability to selectively influence their conductive properties (Lowe, 2021).
• Diode: A semiconductor with areas of both positive (p-type) and negative (n-type) charge-carrying capacity.
  • Connection to a circuit allows one-way current and light emission from the diode.
  • Wavelength of emitted light depends on the semiconductor used (Müller et al., 2013; Wilson, 2014).
• Diode laser: A laser using a diode as the source of light.
  • A one-way current applied to the diode allows for continuous emission of light, which is then focused and targeted (Müller et al., 2013). See figure in gallery (above).
• Laser dye: One of dozens of organic molecules with chemical properties that can be "tuned" to absorb and emit various wavelengths of laser light (Duarte, 2013).
• Irradiation: Administration of electromagnetic radiation (including light emitted by lasers) (Hess et al., 2018).
• Photoangiolysis: Lasers with wavelengths highly absorbed by hemoglobin are used to selectively target blood vessels, leading to thrombosis and coagulation of vessels (Zeitels & Burns, 2006).

Laser Mechanisms

• Photons from an energy source (lamp, electrical current) cause electrons in a gain medium (solid, liquid, gas) to enter a higher-energy “excited” state.
• As electrons return to the non-excited state, they emit photons of electromagnetic radiation.
  • Continuous excitation of already-excited electrons leads to a chain reaction forming a beam of emitted photons.
• A series of mirrors (optical resonator) focuses and directs the laser beam toward a target tissue.
• Wavelength of emitted laser light is influenced by characteristics of the gain medium (Franck et al., 2016).

Predecessors to the Blue Light Laser

• CO2 laser - excitation of CO2 gas leads to emission of infrared light with wavelength near 10,600 nm (Dyer & Snelling, 2013).
  • Absorbed by water in soft tissue, causing an increase in tissue temperature:
    • Above 70-80^o C, nucleic acids are denatured and membranes become permeable, causing coagulation necrosis (Anderson & Parrish, 1983).
    • Above 100^o C, water in tissue vaporizes, allowing for hemostatic separation (cutting) or ablation of tissue (Ibid., 1983).
  • Limitations include bulky size, thermal damage and scarring to epithelium, and lack of flexible fiber delivery (Dyer & Snelling, 2013; Karkos, 2021).
    • CO2 laser is emitted in a straight line, limiting targeting of structures not visualized in a direct line-of-sight (Karkos, 2021).
    • Flexible fiber capabilities developed to allow laser delivery to structures not visible via the traditional straight line (Shurgalin & Anastassiou, 2008).
• Photoangiolytic lasers - brief pulses of 577 nm (Pulsed-Dye Laser) or 532 nm (KTP) are selectively absorbed by chromophores in hemoglobin (Hb), allowing for photoangiolysis without epithelial damage (Yan et al., 2010).
  • Leads to involution of highly vascularized structures (e.g. papillomas, tumors, hemangiomas) (Zeitels & Burns, 2006).
  • To avoid damage to surrounding structures, sufficient time should be given between pulses to allow for diffusion of thermal energy (Anderson & Parrish, 1983).
  • Classification System for results of KTP laser treatment (Mallur et al., 2011)
    • KTP V – noncontact, angiolysis (ablation of vessels without mucosal blanching or disruption)
    • KTP 1 – noncontact, epithelium intact (mucosal blanching without disruption)
    • KTP 2 – noncontact, epithelium disruption (shallow indentation in mucosa, with some dark discoloration)
    • KTP 3 – contact mode with epithelial ablation, without tissue removal (significant damage to epithelium, without deliberate tissue excision)
    • KTP 4 – contact mode, epithelial ablation with tissue removal (epithelium disrupted and frank tissue removal)
    • Eigsti et al. (2019) correlated clinical estimate of KTP laser effect (Mallur Classification System) with histopathologic assessment of resected specimens that has been treated
  • Delivery of laser via flexible fibers allows for targeting of areas not easily visualized by the CO2 laser (Karkos, 2021).
  • Limitations included impaired color visualization due to color-confusing effects of KTP protective eyewear (Johnson, Pate, & Postma, 2018).

Reported advantages of the 445 nm blue light diode laser (TruBlue®, A.R.C. Laser Company, Nuremberg, Germany)

• The wavelength maximally absorbed by chromophores (absorption peak) in hemoglobin (Hb) is near 430 nm (Braun et al., 2018; Reichelt et al., 2017; Figure 2).
  • 445-nm blue-light wavelength is absorbed to a greater degree in Hb and a lesser degree in water than larger-wavelength diode lasers (Frentzen et al., 2016; Figure 2).
  • Compact in size, with flexible fibers for use in operating room or clinic (Hess et al., 2018).
• 445-nm laser displays cutting ability of CO2 and photoangiolytic ability of KTP and PDL lasers at one laser frequency (Hess et al., 2018).
• Less scarring
  • In a rat model, the 445-nm blue light laser resulted in decreased protein deposition and fibrosis at 90 days when compared to KTP (Lin et al., 2021).
• Powerful cutting with minimal local damage
  • In a pork jaw model, blue laser had highest depth of incision and lowest area of local tissue denaturation relative to incision depth when compared to high-frequency electrosurgical devices and higher-wavelength lasers (Braun et al., 2018).
• Improved wound healing
  • MG63 cells irradiated with blue light showed faster wound healing in the central area of clearance vs. 970-nm IR light (Reichelt et al., 2017).

Figure 2. Relative absorption of lasers by wavelength. Based on information from Hess et al., 2018; BritaMed, Inc. 2018; Braun et al., 2015.

(Figure adapted from "File:Coefficients d'absorption.gif." Wikimedia Commons, the free media repository. 22 Oct 2020, 17:56 UTC. 7 Sep 2021, 20:27 <https://commons.wikimedia.org/w/index.php?title=File:Coefficients_d%27absorption.gif&oldid=497542142>.)

Proposed Settings for Use of the Blue Light Laser

A. Update (10-23-2021) Personal Communication from Marcus Hess MD (with permission)

"I [Marcus Hess] would now go for: 

- photoangiolysis in close-to-contact mode, 400 micron fiber, 1-2 Watts, on time 10-20ms for small to medium capillary ectasias, single pulse mode.

-for RRP, something like 4 Watts 30ms on 200ms off for carpet-like RRP,

-maybe something like 6-8 Watts 30ms on 200off for bulky RRP.

-only in massive bulky lesions I would go for maximum settings, if at all."

B. Lin et al. (Lin 2021)

A useful study was done by Lin et al. (Lin 2021) employing a rat vocal fold model in comparing KTP and BL (blue light) laser treatment to induce shallow epithelial disruption (“crème brûlée”).  This non-contact shallow epithelial disruption was considered a "KTP effect 2" as per  Mallur et al. (Mallur 2014). Initial treatment was done with 'usual settings' for the KTP (35 W) and BL (10W) but due to the laryngeal tissues being 'badly burned' at these settings, the experiments were done using lower settings of KTP (10W) and BL (2 W).

As a result of the tissue damage occurring at these higher laser settings, in this study by Lin et al. (2021) the blue light (BL) laser settings tested were therefore decreased to:

2W, 10 ms pw, and pulse-pause duration of 300 ms.  The tips of the lasers were kept approximately 3 mm form the true vocal folds.

Both lasers (KTP and BL) employed a 400-μm flexible laser fiber introduced via a size 5 Frazier tip suction directing "non-overlapping pulses of the vocal folds to prevent significant epithelial disruption"

C. Proposed settings by manufacturer from promotional demonstration (adapted from BritaMed Inc., 2018)

   Note: the fluence (amount of energy aborbed by the tissue) is dependent on many factors including the distance from the tip of the fiber to the target.

   Power and pulse on/off settings should be appropriately modified from those listed below to accommodate these multiple factors.

Higher settings for the laryngeal use of the blue light laser (presumably used for more aggressive ablation or with the laser tip at a greater distance) are reported from an online presentation from A.R.C LASER (WOLF TruBlue laser) as summarized in the table below (reference BritaMed, Inc. 2018):

Clinical Use (adapted from BritaMed Inc., 2018)	Power	Pulse On	Pulse Off	Accessory Informatino
Laryngeal Surgery Examples
Papilloma 1	10 W	20 ms	300 ms	400 µm fiber
Papilloma 2	6 W	80 ms	300 ms	400 µm fiber
Capillary Ectasia	10 W	30 ms	300 ms	400 µm fiber
Cyst	10 W	20 ms	300 ms	400 µm fiber
Synechia	10 W	50 ms	200 ms	400 µm fiber
Leukoplakia	10 W	30 ms	300 ms	400 µm fiber
Otologic Surgery
Stapes cutting	3 W	20 ms	SP	Otology Probe
Cholesteatoma	1-2 W	20-40 ms	50-100 ms	Otology Probe
Rhinologic Surgery
Turbinate Reduction	5-6 W	1 sec	1 sec	Surgical handpiece, 80 mm cannula
Scar band lysis	4-5 W	CW	-	Surgical handpiece, 80 mm cannula

D: Reported settings in laryngeal surgery (Hess et al., 2018)

• Disclosure: Dr. Hess and Dr. Fleischer collaborated in development of the 445-nm laser
• Photoangiolysis of Vocal Fold Ectasia (General anesthesia with transoral flexible laser surgery)
  • 10 W, 40 ms pulses, 250 ms pauses, 400 µm fiber
  • Staggered approach: beginning at 4 mm away and slowly approaching until photoangiolysis achieved
• Photoangiolysis and Photocoagulation (debulking) of RRP (General anesthesia)
  • 10 W, 20–40 ms pulses, 300 ms pauses, 400 µm fiber
  • Staggered approach: beginning at 4 mm and approaching until photoangiolysis
• Excision of ventricular fold cyst (General anesthesia)
  • General anesthesia with suspension microlaryngoscopy
  • 10 W, 40 ms pulses, 250 ms pauses, 400 µm fiber, close-to-contact mode, lateral speed 5 mm/s
• Divsion of interarytenoid synechia (General anesthesia)
  • 10 W, 40 ms pulses, 300 ms pause, 400 µm fiber
• Office-based surgery: Photoangiolysis of papilloma
  • Topical anesthesia
  • 10 W, 20 ms pulse duration, 300 ms pauses, 400 µm fiber
  • Staggered approach
• Authors noted that most sensitive variables for tissue damage were distance-to-tissue and lateral speed (speed of movement across tissue) of laser tip.
  • Increased distance from tip to tissue caused the laser beam to spread over a larger area, thus decreasing the fluence.
  • Contact or close-to-contact mode provided the most focused beam with the smallest area of adjacent tissue damage.
  • Lateral speed of tip: slow, steady movement increased energy delivery to target tissue (vs. faster speeds, which decreased energy delivery).
  • “Clinically useful” speed of 5 mm/s suggested.
• Reported capacity to achieve outcomes similar to KTP V, 1, 2, 3, 4
• Visualization during surgery allows for evaluation of immediate tissue effects
  • Pulses of light caused camera to “auto-darken” following each pulse. 
    • Pulses exceeding 3-4 per second caused an effective “blinding” of the camera system due to constant auto-darkening.
  • Did not mention potential “color confounding” effects of protective eyewear (as reported previously with KTP laser).

E. Reported settings for In-Office Blue Light Laser procedures (Miller et al., 2021)

• Topical anesthesia: Spray 2.5 mL 5% lidocaine/5% phenylephrine plus 10 sprays of 10% oral xylocaine. Visualize epiglottis and larynx and spray additional 2.5 mL lidocaine/phenylephrine.
• Recommended setting:
  • 10 W, continuous superpulse, 60 ms on, 120 ms off. Fire laser from 1-4 mm from target.
  • Provides blend of photoangiolysis and cutting.
  • For biopsy: blue laser may devascularize pedicle before removal with cold steel.
• 29 patients, 36 in-office procedures using blue light laser:
  • 14 RRP, 9 benign lesions, 4 biopsy, 2 debulking of subglottic granulations
  • One instance of early vocal cord bleeding after treatment of telangiectasia and hemorrhagic polyp (bleeding occurred at area distinct from operative site).

F. Reported settings in dentistry and oral surgery (Fornaini 2016; Frentzen 2016)

• Fornaini et al., 2016: Removal of lip fibroma - 1W, CW (continuous wave), 320 μm fiber, contact mode, speed 5 mm/s
  • Patient received topical anesthetic (lidocaine-prilocaine) and reported no pain during the procedure
• Frentzen et al., 2016: Gingivectomy – 2W, CW, 320 μm fiber

Conclusion

• Blue light laser combines cutting and photoangiolytic properties in a compact, portable system for office or operating room (Hess et al., 2018).
• However, it is a new technology with limited documented literature (Hess et al., 2018).
• Areas for further investigation:
  • Targeting of darker tissue resulted in higher absorption and faster carbonization (Hess et al., 2018).
  • No micromanipulator available yet.

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