Medical Policy



Subject: Laser Treatment for Onychomycosis
Document #: SURG.00138 Current Effective Date:    03/29/2017
Status: Reviewed Last Review Date:    02/02/2017

Description/Scope

This document addresses the proposed use of laser treatment for onychomycosis. Onychomycosis is a common and persistent fungal infection of the nail bed and plate, which is often challenging to treat. Conventional therapeutic options are either topical or systemic antifungal agents. However, topical therapies are seldom effective since it is difficult to achieve local therapeutic concentrations, and individual adherence to long-term therapy is low. Systemic antifungal agents are more effective, with approximately 50% of individuals achieving significant improvement or cure. However, systemic agents are associated with higher rates of complications, including liver and kidney damage in some individuals with comorbidities. As a result, laser treatment has been introduced as an alternative, noninvasive treatment modality.

Position Statement

Investigational and Not Medically Necessary:

Laser treatment of onychomycosis is considered investigational and not medically necessary.

Rationale

A search of the peer-reviewed medical literature for studies related to laser treatment for onychomycosis identified four randomized, controlled trials (RCTs) and several nonrandomized, uncontrolled studies. Zhang and colleagues (2012) evaluated the effect of the Pinpointe Footlaser long-pulse Nd:YAG 1064-nm laser (PinPointe USA, Inc; Chico, CA) (n=33; 154 nails) in individuals with clinically and mycologically proven onychomycosis. Participants were randomly assigned to 2 groups (group 1 and group 2) of varying treatment duration. All participants were also divided into 3 sub-groups (II degree, III degree, and IV degree) according to the Scoring Clinical Index of Onychomycosis (SCIO). Group 1 participants (n=15; 78 nails) were given 8 weekly sessions, and group 2 participants (n=18; 76 nails) were given 4 weekly sessions. In group 1, the effective rates at 8 weeks, 16 weeks, and 24 weeks were 63%, 62%, and 51%, respectively; the effective rates in group 2 were 68%, 67%, and 53% respectively. The treatment effect was not significantly different between any sub-group pair. No safety issues were reported by the study authors. Limitations of this study include the small sample size; lack of blinded participants and assessors; lack of placebo controls, sham controls, or conventional treatment comparators; and the lack of clearly defined and clinically relevant endpoints for post-treatment clinical outcomes. Randomization was performed on an individual basis, while analysis was done on a per nail basis, which introduced a potential for bias. In addition, self-reported outcomes were not based upon a validated tool or instrument, which is particularly important given the subjective nature of self-reported data.

In a second RCT, Landsman and colleagues (2010) evaluated the Noveon instrument (Nomir Medical Technologies, Inc.; Waltham, MA), a dual wavelength near-infrared diode laser to treat onychomycosis in 36 individuals with mycologically confirmed onychomycosis. Participants were blinded to treatment group, and outcome assessments were performed by unblinded investigators who conducted clinical examinations. In addition, an independent blinded expert panel reviewed photographic outcomes. Participants were randomized to either laser treatment (n=26) or sham treatment (n=10). A treatment course consisted of 4 individual sessions, each session occurring on day 1, 14, 42, and 120. Each session consisted of an initial exposure for 4 minutes at 870- and 930-nm wavelengths, followed by a second exposure for 2 minutes at 930-nm wavelengths. The sham group received the same number of sessions as the treatment group, but the laser power was set to zero. At 180 days of follow-up, 85% of treated toenails were improved by clear nail linear extent, 65% showed at least 3 mm, and 26% showed at least 4 mm of clear nail growth. Of 16 toes with moderate to severe involvement, 10 improved, as shown by clear nail growth of at least 3 mm. Simultaneous negative culture and periodic acid-Schiff were noted in 30% of nails at 180 days of follow-up. It is worth noting that the Noveon laser has not been approved by the U.S. Food and Drug Administration (FDA) for the specific treatment of onychomycosis.

Subsequently, Landsman and Robbins (2012) reported follow-up results of the original trial published in 2010. At 270 days, 15 of 40 (38%) of the treated toes had negative culture and microscopy, qualifying as mycological cures. Only 2 of 13 (15%) of control toes achieved both negative culture and microscopy (P value not reported). Despite the statistically significant improvements observed at 180 days in the Landsman and Robbins (2010) study, findings were weakened by several limitations, including lack of blinded assessments, manufacturer financial sponsorship, and the use of a surrogate outcome measure, such as clear nail growth, as a substitute for a more clinically meaningful endpoint, such as rates of cure or functional improvement.

An RCT conducted by Hollmig (2014) reported lack of efficacy of laser treatment for onychomycosis. Investigators compared 1064-nm neodymium: yttrium-aluminum garnet laser with no treatment (n=27; 125 affected nails). At 3 and 12 months, no significant differences were observed for any outcome measure.

In another RCT, Xu (2014) evaluated the combined treatment of oral terbinafine and long-pulsed 1064-nm Nd:YAG laser treatment for onychomycosis compared with either treatment alone (n=53). Participants were randomized to 3 treatment groups: oral terbinafine alone (T group); Nd:YAG laser alone (L group); and the combination of Nd:YAG and terbinafine therapy (T+L group). Outcomes included the mycological clearance rate (MCR) and the clinical clearance rate (CCR). Participants in the combination treatment group (T+L) experienced significantly higher rates of MCR and CCR than participants in the T group and L group at weeks 8, 12, 16, and 24 (p<0.05 for each time point). No significant side effects were reported. Study authors concluded that combined treatment shows greater efficacy than laser or terbinafine drug therapy alone.

Lesser quality evidence derived from several nonrandomized, uncontrolled studies generally reported consistent results following laser treatment using several types of laser instruments. Carney and colleagues (2013) conducted a four-part in vitro and in vivo study to determine thermal response and optical effects of a submillisecond neodymium:yttrium-aluminum-garnet (Nd:YAG) 1064-nm laser on common fungal nail pathogens, and the clinical efficacy and safety of the Nd:YAG 1064-nm laser on onychomycotic toenails. In vivo treatment of toenails showed no improvement in the Onychomycosis Severity Index score (OSIS). Study authors reported that laser treatment of onychomycosis was not related to thermal damage or direct laser effects; moreover, in vivo treatment did not result in onychomycosis cure. Kimura and colleagues (2012) conducted a small trial of 37 toes treated with Nd:YAG laser. Participants were followed for 16 weeks. Treatment was well tolerated by the participants and no adverse events were reported. Of the 37 toenails treated, 30 (81%) had "moderate" to "complete" clearance at an average of 16 weeks post-final treatment. Nineteen toenails (51%) were completely clear and all tested negative for fungal infection on direct microscopic analysis; 7 (19%) toenails had significant clearance, and 4 (11%) had moderate clearance. The authors concluded that the preliminary results demonstrated the laser treatment to be safe and effective in the short term. Hochman (2011) reported the findings of a study in which 8 subjects with onychomycosis were treated with 2 to 3 sessions with a 0.65 millisecond pulsed 1064-nm laser. Seven of the 8 participants had negative post-treatment cultures after the second or third session.

A number of Nd:YAG laser systems have been cleared by the FDA for marketing for the temporary increase of clear nail in individuals with onychomycosis. The regulatory 510K clearance of device systems by the FDA are made on the basis of "substantial equivalence" to the technical specifications of pre-existing devices already approved for marketing for onychomycosis, not on the basis of clinical trials data. These laser devices are not FDA approved as a treatment for onychomycosis.

No relevant clinical practice guidelines or position statements were identified during the literature search.

In summary, laser treatment for onychomycosis may offer some advantages over standard medication therapy because the short-term treatment duration may increase compliance and eliminate the risk of adverse events caused by systemic therapies. However, additional well-designed RCTs with appropriate control or comparator groups, using FDA-approved devices, are necessary before definitive conclusions can be made regarding the safety and efficacy of laser treatment. Long-term follow-up periods are also necessary to ascertain the durability of treatment effect, (particularly since full clearance of infection can take up to 1 year), and rates of recurrence associated with use of laser devices. Although published studies thus far indicate that laser treatment has a favorable safety profile, additional research is needed to explore the possibility of late adverse events following laser treatment.

Background/Overview

Onychomycosis (also known as dermatophytic onychomycosis or tinea unguium) is a fungal infection of the nail. Most toenail onychomycosis is caused by dermatophytes; however, many cases of fingernail onychomycosis are due to yeast. This condition may affect toenails or fingernails, although toenails are more likely to be infected. One or more of the toenails or fingernails may be involved, but seldom are all involved (Becker, 2013).

Onychomycosis is very common, accounting for half of all nail disorders, and is considered the most common nail disease in adults. Its incidence ranges from 2% to 13% in North America. It has been reported that 30% of individuals with a cutaneous fungal infection also have onychomycosis. Onychomycosis has been reported to occur in 2.6% of children (younger than 18 years of age), and in 90% of the elderly. Even with optimal diagnosis and treatment, 1 in 5 individuals with onychomycosis fail to achieve full clearance and cure with current topical and systemic therapies. The long-term recurrence rates of onychomycosis are relatively high, and range from 20% to 50% (de Morais, 2013).

Risk factors that have been associated with onychomycosis include older age, swimming, tinea pedis, psoriasis, diabetes, immunodeficiency, genetic predisposition, and living with family members who have onychomycosis. Onychomycosis is usually asymptomatic. Individuals frequently initially seek treatment for cosmetic reasons without any physical complaints. However, as the disease progresses, onychomycosis may interfere with wearing shoes, standing, walking, and exercising. In more severe cases, individuals may report paresthesia, pain, discomfort, and loss of dexterity. They may also report loss of self-esteem and lack of social interaction. Providers may suggest treating toenail onychomycosis in individuals with a history of ipsilateral lower extremity cellulitis and in individuals with diabetes who have additional risk factors for cellulitis (that is, prior cellulitis, venous insufficiency or edema) (Gupta, 2012, 2013).

Onychomycosis is frequently treated with either systemic or topical antifungal medications, or a combination of both systemic and topical medications. However, because the infection is embedded within the nail and is difficult to reach, full resolution of symptoms is slow and may take a year or more, since a new nail must grow and entirely replace the infected nail. Also, some of the medications used to treat onychomycosis are associated with serious adverse events, including hepatotoxicity (Gupta, 2012, 2013).

Researchers are currently investigating the use of various laser systems in the clinical setting as a relatively noninvasive treatment for onychomycosis. Laser therapy has the potential to be an ideal treatment option with respect to its ability to deliver a high concentration of energy to a relatively small area, limiting systemic side effects, while enhancing its ability to penetrate more deeply into the nail plate.

Definitions

Distal subungual onychomycosis: Fungal infection of the distal nail plate.

Fungal melanonychia: An uncommon form of onychomycosis caused by fungal species capable of producing melanin.

Proximal subungual onychomycosis: A relatively uncommon form of onychomycosis that affects the proximal portion of the nail in the vicinity of the cuticle and extends outward. It usually occurs in individuals with a severely compromised immune system and is often a marker for Acquired Immune Deficiency Syndrome (AIDS).

White superficial onychomycosis: A fungal infection caused by T. mentagrophytes, characterized by the appearance of dull white spots on the surface of the nail plate of one or several nails.

Yeast onychomycosis: A common cause of fingernail onychomycosis caused by yeast, particularly in previously damaged nails. Candida albicans is most often the causative organism.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services are Investigational and Not Medically Necessary:

CPT    
17999 Unlisted procedure skin, mucous membrane and subcutaneous tissue [when specified as laser treatment of onychomycosis]  
96999 Unlisted special dermatological services or procedures [when specified as laser treatment of onychomycosis]  
     
ICD-10 Diagnosis  
  All diagnoses including, but not limited to the following:  
B35.1 Tinea unguium
   
References

Peer Reviewed Publications: 

  1. Becker C, Bershow A. Lasers and photodynamic therapy in the treatment of onychomycosis: a review of the literature. Dermatol Online J. 2013; 19(9):19611.
  2. Bristow IR. The effectiveness of lasers in the treatment of onychomycosis: a systematic review. J Foot Ankle Res. 2014; 7:34.
  3. Durme DJ. Ch 4 Disease of the skin. In: Bope & Kellerman: Conn's Current Therapy 2013, 1st ed. Saunders. St. Louis, MO. 2012; 242-244.
  4. Carney C, Cantrell W, Warner J, Elewski B. Treatment of onychomycosis using a submillisecond 1064-nm neodymium:yttrium-aluminum-garnet laser. J Am Acad Dermatol. 2013; 69(4):578-582.
  5. de Morais OO, Costa IM, Gomes CM, et al. The use of the Er:YAG 2940nm laser associated with amorolfine lacquer in the treatment of onychomycosis. An Bras Dermatol. 2013; 88(5):847-849.
  6. El-Tatawy RA, Abd El-Naby NM, El-Hawary EE, Talaat RA. A comparative clinical and mycological study of Nd-YAG laser versus topical terbinafine in the treatment of onychomycosis. J Dermatolog Treat. 2015; 26(5):461-464.
  7. Gupta AK, Simpson FC. Laser therapy for onychomycosis. J Cutan Med Surg. 2013; 17(5):301-307.
  8. Gupta AK, Simpson F. Newly approved laser systems for onychomycosis. J Am Podiatr Med Assoc. 2012; 102(5):428-430.
  9. Hochman LG. Laser treatment of onychomycosis using a novel 0.65-millisecond pulsed Nd:YAG 1064-nm laser. J Cosmet Laser Ther. 2011; 13(1):2-5.
  10. Hollmig ST, Rahman Z, Henderson MT, et al. Lack of efficacy with 1064-nm neodymium:yttrium-aluminum-garnet laser for the treatment of onychomycosis: a randomized, controlled trial. J Am Acad Dermatol. 2014; 70(5):911-917.
  11. Hoy NY, Leung AK, Metelitsa AI, Adams S. New concepts in median nail dystrophy, onychomycosis, and hand, foot, and mouth disease nail pathology. ISRN Dermatol. 2012; 2012:680163.
  12. Karsai S, Jager M, Oesterhelt A, et al. Treating onychomycosis with the short-pulsed 1064-nm-Nd:YAG laser: results of a prospective randomized controlled trial. J Eur Acad Dermatol Venereol. 2017; 31(1):175-180.
  13. Kim TI, Shin MK, Jeong KH, et al. A randomized comparative study of 1064 nm Neodymium-doped yttrium aluminum garnet (Nd:YAG) laser and topical antifungal treatment of onychomycosis. Mycoses. 2016; (Epub ahead of print).
  14. Kimura U, Takeuchi K, Kinoshita A, et al. Treating onychomycoses of the toenail: clinical efficacy of the sub-millisecond 1,064 nm Nd: YAG laser using a 5 mm spot diameter. J Drugs Dermatol. 2012; 11(4):496-504.
  15. Landsman AS, Robbins AH. Treatment of mild, moderate, and severe onychomycosis using 870- and 930-nm light exposure: some follow-up observations at 270 days. J Am Podiatr Med Assoc. 2012; 102(2):169-171.
  16. Landsman AS, Robbins AH, Angelini PF, et al. Treatment of mild, moderate, and severe onychomycosis using 870- and 930-nm light exposure. J Am Podiatr Med Assoc. 2010; 100(3):166-177.
  17. Ledon JA, Savas J, Franca K, et al. Laser and light therapy for onychomycosis: a systematic review. Lasers Med Sci. 2014; 29(2):823-829.
  18. Nenoff P, Grunewald S, Paasch U. Laser therapy of onychomycosis. J Dtsch Dermatol Ges. 2014; 12(1):23-28.
  19. Ortiz AE, Avram MM, Wanner MA. A review of lasers and light for the treatment of onychomycosis. Lasers Surg Med. 2014; 46(2):117-124.
  20. Xu Y, Miao X, Zhou B, Luo D. Combined oral terbinafine and long-pulsed 1,064-nm Nd: YAG laser treatment is more effective for onychomycosis than either treatment alone. Dermatol Surg. 2014; 40(11):1201-1207.
  21. Zhang R, Wang D, Zhuo F, et al. Long-pulse Nd: YAG 1064-nm laser treatment for onychomycosis. Chin Med J (Engl). 2012; 125(18):3288-3291.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. Ameen M, Lear JT, Madan V, et al. British Association of Dermatologists' guidelines for the management of onychomycosis. 2014. Br J Dermatol. 2014; 171(5):937-958.
  2. National Horizon Scanning Centre (NHSC). Infrared lasers for treating onychomycosis. Horizon Scanning Review. Birmingham, UK: National Horizon Scanning Centre (NHSC); September 2011.
  3. U.S. Food and Drug Administration (FDA). 510(k) Premarket Notification Database. Yag lasers. Updated December 26, 2016. Available at: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm. Accessed on December 28, 2016.
Websites for Additional Information
  1. American Academy of Dermatology (AAD). New generation of laser and light therapies could provide future treatment options for skin, hair and nail conditions. 2012. Available at: http://www.aad.org/stories-and-news/news-releases/new-generation-of-laser-and-light-therapies-could-provide-future-treatment-options-for-skin-hair-and-nail-conditions. Accessed on December 28, 2016.
Index

ClearSense
GenesisPlus
Long pulse laser
Modelocked Laser Systems
Nd:YAG laser
Near Infrared Diode Lasers
Noveon
Pinpointe Footlaser
Q-Switched laser
Short pulse laser
VARIABreeze

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

Document History
Status Date Action
Reviewed 02/02/2017 Medical Policy & Technology Assessment Committee (MPTAC) review. References were updated.
Reviewed 02/04/2016 MPTAC review. References were updated. Removed ICD-9 codes from Coding section.
Reviewed 02/05/2015 MPTAC review. Updated Description, Rationale, and References sections.
New 02/13/2014 MPTAC review. Initial document development.