Collegues: I would like to take the opportunity to present some basics in laser/tissue interctions, so that Podiatric Physicians can

read and better understand some of the photobiology involved in the issues being discussed, with potential onychomycosis therapy with lasers. A free running pulsed (FRP) Nd:YAG laser is capable of pulse durations in the millionths of a second (10-6 sec), that allow for very high peak powers (1-2 thousand watts/pulse) for safe and rapid ablation of tissues. Exploiting this laser-tissue interaction, a clinician using a FRP Nd:YAG has the ability to apply an intense burst of laser energy, for a very short time interval, to effect a desired outcome. As previously described, this has been successfully peer-reviewed and applied in vitro for photo-disinfection experiments, (2, 3, 4) and in humans for periodontal therapy. (1)

1) Harris, D., Gregg, RH., McCarthy DK. et al, Laser-assisted new attachment procedure in private practice, General Dentistry, Sept-Oct 2004, Vol52 No 5, pp396-403 2) Harris DM and M Yessik: Therapeutic ratio quantifies laser antisepsis: Ablation of Porphyromonas gingivalis with dental lasers. Lasers Surg Med 35:206-213, 2004. 3) Harris DM: Laser antisepsis of Phorphyromonas gingivalis in vitro with dental lasers. SPIE Proceedings 5313-22, 2004. 4) Harris DM, SE Jacques: Monte Carlo Simulation of depth of kill of P. gingivalis in dentin based on experimental damage threshold. Abstract presented at ASLMS, Orlando, FL, April 2005.

A continuous wave (CW) or gated diode laser (such as the Noveon device- Nomir Medical Technologies) does not have the high peak power or microsecond pulse abilities of the FRP Nd:YAG. A CW Diode laser has far longer pulse durations in milliseconds (10-3 sec or thousandths of a sec), with far less peak power, that will not reach the ablation threshold in soft tissues. (5, 6) 5) ALD (The Academy of Laser Dentistry). Featured wavelength: diode the diode Laser in dentistry (Academy report) Wavelengths 2000: 8: 13. 6) Bornstein E, Near-infrared dental diode lasers. Scientific and photobiologic principles and applications, Dent Today. 2004 Mar;23(3):102-8

The abilities of the FRP: Nd:YAG can cause quick, safe and precise ablation of soft tissues involved, (7, 8) as long as the physician performing the procedure is particularly careful not to employ a manual method called pulse stacking. Pulse stacking is an overlapping localization of laser pulses (going over the same small spot more than once) that occurs from the inconsistent manual aiming of small to medium laser spot sizes over large areas of tissue. This can lead to excessive heating of areas of treatment, and potentially ablate healthy tissues.(9).

In careful hands, this can be avoided and pulse stacking is not partial to the Nd:YAG laser, but is a phenomenon associated with all micro-pulsed lasers such as the Er:YAG, CO2, Homium:YAG and Nd:YAG (9) This issue is the same universally based on Photo-physics with micropulsed lasers. I am not knocking Nd:YAG lasers.

7) Marjaron B, Plestenjak P, Luka CM: Thermo-mechanical laser ablation of soft biological tissue: modeling the micro-explosions. Applied Physics B 69:71-80, 1999. 8) Venugopalan V, Nishioka NS, Mikic BB: The thermodynamic response of soft biological tissues to pulsed infrared-laser irradiation. Biophysical Journal 70:29812993, 1996. 9) Dawson E, Willey A, LEE K: Adverse events associated with nonablative cutaneous laser, radiofrequency, and light-based devices. Semin Cutan Med Surg 26:15-21, 2007.

The Noveon (Diode laser) works on a completely different mechanism of action. This device expands the laser/spot size to 1.5 cm diameter (vs 1mm for most FRP systems through a fiber), to cover the entire nail area simultaneously, in a hands free manner, vs a spot by spot manual procedure with a FRP laser. With the Noveon, the device can make use of the non-ablative ability, to stay below the Thermal Threshold in the treatment of skin and nail. The Thermal Threshold Power Density for near-IR laser energy (W/cm2), that will produce Thermal Interactions with tissues and will permanently alter the tissues, is

about 10 W/cm 2 (This is 2-3 Log less than ablative lasers). According to Henriques (10) and Eichler and Seiler (11) and Dewhirst (12) producing voluminous data, it can be deduced that as long as the tissue temperature being irradiated (with any system) is at or below about 45 C (113 F), there is little chance of Irreversible Tissue Damage. The Noveon therapy, in peer-reviewed publications and under IRB guideance does not go over 101 F when treating human nails. (13, 14) Hence, to separate out (non thermal) unique photo-biological effects of 870nm/930nm, the Noveon has a Power Density that is below the 10 W/cm2 threshold, so that the photobiology of the wavelength can be the dominant interaction, instead of thermal tissue changes. This is the basis for the noveon therapy. (13, 14) 10) Henriques and Moritz, Am. J. Path., 23,. 531-549 (1947) 11) Eichler and Sieler, Lasertichnik in der Medizin, Springer, Berlin (1991) 12) Dewhirst MW, et al. Basic principles of thermal dosimetry and thermal thresholds for tissue damage from hyperthermia. Int J Hyperthermia. 2003 MayJun;19(3):267-94. Review. 13) Bornstein E., Hermans W., Gridley S., and Manni J. Near infrared Photoinactivation of bacteria and fungi at physiologic temperatures. Photochemistry and Photobiology 14) Bornstein ES: A Review of Current Research in Light-Based Technologies for Treatment of Podiatric Infectious Disease States Journal of the American Podiatric Medical Association Volume 99 Number 4 348-352 2009 With the Noveon device, there is: 1) 2) 3) 4) no ablation, no manual moving of a fiber handpiece or holding an individual toe, no worry of pulse stacking, and no skill involved.

The device delivers the same therapy every time, at the same dose, to four toes simultaneously, independent of the user. The Noveon Device has finished its Pivotal FDA study, and the FDA is currently reviewing the data under the 510(k) application process.

Eric Bornstein Chief Science Officer Nomir Medical Technologies ebornstein@nomirmedical.com