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Efficacy of laser therapy combined with topical antifungal agents for onychomycosis: a systematic review and meta-analysis of randomised controlled trials

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Abstract

Introduction

Onychomycosis is a common fungal infection of the nail. Laser and topical antifungal agent combination therapy is an emerging treatment for onychomycosis. The objective of this study was to systematically evaluate the efficacy and safety of laser and topical antifungal agent combination therapy for onychomycosis.

Methods

The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang and VIP databases were searched from inception to November 2021. Randomised controlled trials (RCTs) on laser therapy combined with topical antifungal agents for onychomycosis were included. The Cochrane Collaboration tool was used to assess the risk of bias, and Revman 5.3 software was used in the meta-analysis.

Results

Twelve studies involving 869 patients were included in this meta-analysis. The results showed that compared with topical antifungal agents alone, laser and topical antifungal agent combination therapy was superior in terms of the complete cure rate (RR 6.04,95% CI (2.17, 16.85), P = 0.0006), mycological cure rate (RR 1.27, 95% CI (1.10, 1.48), P = 0.001), clinical effective rate (RR 1.38, 95% CI (1.20, 1.57), P < 0.00001) and patient satisfaction rate (RR 1.47,95% CI (1.17, 1.84), P = 0.0009).The subgroup analysis of outcome indicators, including mycological cure rate and clinical effective rate, demonstrated that both carbon dioxide (CO2) laser therapy combined with topical antifungal therapy and 1064-nm neodymium-doped:yttrium aluminium garnet (Nd:YAG) laser therapy combined with topical antifungal therapy showed better results than topical antifungal therapy alone. No adverse events were identified except for three studies reporting transient burning sensation without treatment and mild to moderate pain, both of which were well tolerated.

Conclusion

The present study indicated that laser and topical antifungal agent combination therapy is effective for onychomycosis. However, more large-scale and well-designed RCTs are warranted.

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References

  1. Lipner SR, Scher RK (2019) Onychomycosis: clinical overview and diagnosis. J Am Acad Dermatol 80(4):835–851. https://doi.org/10.1016/j.jaad.2018.03.062

    Article  PubMed  Google Scholar 

  2. Gupta AK, Stec N, Summerbell RC, Shear NH, Piguet V, Tosti A, Piraccini BM (2020) Onychomycosis: a review. J Eur Acad Dermatol Venereol 34(9):1972–1990. https://doi.org/10.1111/jdv.16394

    Article  CAS  PubMed  Google Scholar 

  3. Ghannoum MA, Hajjeh RA, Scher R, Konnikov N, Gupta AK, Summerbell R, Sullivan S, Daniel R, Krusinski P, Fleckman P, Rich P, Odom R, Aly R, Pariser D, Zaiac M, Rebell G, Lesher J, Gerlach B, Ponce-De-Leon GF, Ghannoum A, Warner J, Isham N, Elewski B (2020) A large-scale North American study of fungal isolates from nails: the frequency of onychomycosis, fungal distribution, and antifungal susceptibility patterns. J Am Acad Dermatol 43(4):641–648. https://doi.org/10.1067/mjd.2000.107754

    Article  Google Scholar 

  4. Lipner SR, Scher RK (2014) Onychomycosis: current and investigational therapies. Cutis 94:E21–E24

    PubMed  Google Scholar 

  5. Crawford F, Young P, Godfrey C, Bell-Syer SE, Hart R, Brunt E, Russell I (2002) Oral treatments for toenail onychomycosis: a systematic review. Arch Dermatol 138(6):811–816. https://doi.org/10.1001/archderm.138.6.811

    Article  CAS  PubMed  Google Scholar 

  6. Ameen M, Lear JT, Madan V, Mohd Mustapa MF, Richardson M (2014) British Association of Dermatologists’ guidelines for the management of onychomycosis. Br J Dermatol 171(5):937–958. https://doi.org/10.1111/bjd.13358

    Article  CAS  PubMed  Google Scholar 

  7. Aggarwal R, Targhotra M, Kumar B, Sahoo PK, Chauhan MK (2020) Treatment and management strategies of onychomycosis. J Mycol Med 30(2):100949. https://doi.org/10.1016/j.mycmed.2020.100949

    Article  CAS  PubMed  Google Scholar 

  8. Elewski BE, Rich P, Pollak R, Pariser DM, Watanabe S, Senda H, Ieda C, Smith K, Pillai R, Ramakrishna T, Olin JT (2013) Efinaconazole 10% solution in the treatment of toenail onychomycosis: two phase III multicenter, randomized, double-blind studies. J Am Acad Dermatol 68(4):600–608. https://doi.org/10.1016/j.jaad.2012.10.013

    Article  CAS  PubMed  Google Scholar 

  9. Gupta AK, Venkataraman M, Anbalagan N, Guenin EP (2021) One size does not fit all: the need for individualized treatment based on factors that may affect the therapeutic outcome of efinaconazole 10% solution for the treatment of toenail onychomycosis. Int J Dermatol 60(10):1296–1302. https://doi.org/10.1111/ijd.15739

    Article  CAS  PubMed  Google Scholar 

  10. Yeung K, Ortner VK, Martinussen T, Paasch U, Haedersdal M (2019) Efficacy of laser treatment for onychomycotic nails: a systematic review and meta-analysis of prospective clinical trials. Lasers Med Sci 34(8):1513–1525. https://doi.org/10.1007/s10103-019-02802-8

    Article  PubMed  Google Scholar 

  11. FDA. (2016) Medical devices and clinical trial design for the treatment or improvement in the appearance of fungally-infected nails; draft guidance for Industry and Food and Drug Administration Staff; Availability. 81(44):29

  12. Gupta AK, Mays RR, Versteeg SG, Shear NH, Piguet V (2018) Update on current approaches to diagnosis and treatment of onychomycosis. Expert Rev Anti Infect Ther 16(12):929–938. https://doi.org/10.1080/14787210.2018.1544891

    Article  CAS  PubMed  Google Scholar 

  13. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151(4):264–269, W64. https://doi.org/10.7326/0003-4819-151-4-200908180-00135

  14. Han Y, Wang Y, Zhang XR, Chen J, Li XD (2021) The effects of CO2 laser and topical agent combination therapy for onychomycosis: a meta-analysis. Dermatol Ther 34(6):e15136. https://doi.org/10.1111/dth.15136

    Article  CAS  PubMed  Google Scholar 

  15. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (2019) Cochrane handbook for systematic reviews of interventions, 2nd edn. John Wiley & Sons, Chichester

    Book  Google Scholar 

  16. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, Norris S, Falck-Ytter Y, Glasziou P, DeBeer H, Jaeschke R, Rind D, Meerpohl J, Dahm P, Schunemann HJ (2011) GRADE guidelines:1. Introduction-GRADE evidence profles and summary of fndings tables. J Clin Epidemiol 64(4):383–394. https://doi.org/10.1016/j.jclinepi.2010.04.026

    Article  PubMed  Google Scholar 

  17. Wang JH, Jia YQ, Chen YL, Wang YP (2019) Effect of lattice carbon dioxide laser combined with local medication on treating onychomycosis. J Clin Med Pract 23(7):32–36

    CAS  Google Scholar 

  18. Jing WW, Liang YH, Zhou YA (2018) Clinical efficacy of fractional CO2 laser combined with naftifine hydrochloride and ketoconazole cream for the treatment of onychomycosis. China Med Cosmet 263(11):46–49. https://doi.org/10.15909/j.cnki.cn61-1347/r.002686

    Article  Google Scholar 

  19. Bonhert K, Dorizas A, Sadick NS (2019) Efficacy of combination therapy with efinaconazole 10% solution and 1064 nm Nd:YAG laser for treatment of toenail onychomycosis. J Cosmet Laser Ther 21(3):179–183. https://doi.org/10.1080/14764172.2018.1502451

    Article  PubMed  Google Scholar 

  20. Bunyaratavej S, Wanitphakdeedecha R, Ungaksornpairote C, Kobwanthanakun W, Chanyachailert P, Nokdhes YN, Patthamalai P, Tantrapornpong P, Suphatsathienkul P, Kiratiwongwan R, Limphoka P, Leeyaphan C (2020) Randomized controlled trial comparing long-pulsed 1064-Nm neodymium: Yttrium-aluminum-garnet laser alone, topical amorolfine nail lacquer alone, and a combination for nondermatophyte onychomycosis treatment. J Cosmet Dermatol 19(9):2333–2338. https://doi.org/10.1111/jocd.13291

    Article  PubMed  Google Scholar 

  21. Song ZJ, Li Z (2016) Clinical efficacy of long-pulsed 1064nm laser combined with amorolfine hydrochloride in the treatment of patients with onychomycosis. China Pharm 19(10):1919–1921

    Google Scholar 

  22. Zhang XL, Zhang HP, Yang LJ (2016) Observation of efficacy of CO2 laser combined with amorolfine hydrochloride liniment in treatment of 27 patients with onychomycosis. China Med Cosmet 25(5):74–76. https://doi.org/10.15909/j.cnki.cn61-1347/r.001157

    Article  Google Scholar 

  23. Kim TI, Shin MK, Jeong KH, Suh DH, Lee SJ, Oh IH, Lee MH (2016) A randomised comparative study of 1064 nm neodymium-doped yttrium aluminium garnet (Nd:YAG) laser and topical antifungal treatment of onychomycosis. Mycoses 59(12):803–810. https://doi.org/10.1111/myc.12534

    Article  CAS  PubMed  Google Scholar 

  24. Rajbanshi B, Shen L, Jiang M, Gao Q, Huang X, Ma J, Wang J, Hu Y, Lv H, Wu X, Zhao J (2020) Comparative study of traditional ablative CO2 laser-assisted topical antifungal with only topical antifungal for treating onychomycosis: a multicenter study. Clin Drug Investig 40(6):575–582. https://doi.org/10.1007/s40261-020-00914-6

    Article  CAS  PubMed  Google Scholar 

  25. Liu Q, Zheng KP, Jiang S, Ling P (2021) Clinical efficacy of CO2 fractional laser combined with topical amorolfine cream in the treatment of superficial white onychomycosis and distal and lateral subungual onychomycosis. Cnki.net. https://kns.cnki.net/kcms/detail/42.1677.R.20210930.1324.001.html. Accessed 07 October 2021. https://doi.org/10.14188/j.1671-8852.2021.0263

  26. Bi XD, Song MA, Zhai L (2015) The efficacy of 1064nm long-pulse laser combined with amorolfine regimen for patients with onychomycosis. China J Derm Venereol 29(5):475–477. https://doi.org/10.13735/j.cjdv.1001-7089.201408134

    Article  Google Scholar 

  27. Zaki AM, Abdo HM, Ebadah MA, Ibrahim SM (2020) Fractional CO2 laser plus topical antifungal versus fractional CO2 laser versus topical antifungal in the treatment of onychomycosis. Dermatol Ther 33(1):e13155. https://doi.org/10.1111/dth.13155

    Article  CAS  PubMed  Google Scholar 

  28. Zhang J, Zhang Y, Qin J, Lu S, Cai W, Li J, Huang H, Yang S, Xi L (2021) Comparison of a fractional 2940-nm Er:YAG laser and 5% amorolfine lacquer combination therapy versus a 5% amorolfine lacquer monotherapy for the treatment of onychomycosis: a randomized controlled trial. Lasers Med Sci 36(1):147–152. https://doi.org/10.1007/s10103-020-03054-7

    Article  PubMed  Google Scholar 

  29. Dars S, Banwell HA, Matricciani L (2019) The use of urea for the treatment of onychomycosis: a systematic review. J Foot Ankle Res 12:22. https://doi.org/10.1186/s13047-019-0332-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Morais OO, Costa IM, Gomes CM, Shinzato DH, Ayres GM, Cardoso RM (2013) The use of the Er:YAG 2940nm laser associated with amorolfine lacquer in the treatment of onychomycosis. An Bras Dermatol 88(5):847–849. https://doi.org/10.1590/abd1806-4841.20131932

    Article  PubMed  PubMed Central  Google Scholar 

  31. Shi J, Li J, Huang H, Permatasari F, Liu J, Xu Y, Wu D, Zhou BR, Luo D (2017) The efficacy of fractional carbon dioxide (CO 2) laser combined with terbinafine hydrochloride 1% cream for the treatment of onychomycosis. J Cosmet Laser Ther 19(6):353–359. https://doi.org/10.1080/14764172.2017.1334925

    Article  PubMed  Google Scholar 

  32. Gupta AK, Foley KA, Versteeg SG (2017) Lasers for onychomycosis. J Cutan Med Surg 21(2):114–116. https://doi.org/10.1177/1203475416677722

    Article  PubMed  Google Scholar 

  33. Zhang RN, Zhao JY, Li LF (2020) Morphological and transcriptome analyses provide insights into growth inhibition of trichophyton rubrum caused by laser irradiation. Evid Based Complement Alternat Med 2020:6052461. https://doi.org/10.1155/2020/6052461

    Article  PubMed  PubMed Central  Google Scholar 

  34. El-Tatawy RA, Aliweh HA, Hegab DS, Talaat RAZ, Shams Eldeen MA (2019) Fractional carbon dioxide laser and topical tioconazole in the treatment of fingernail onychomycosis. Lasers Med Sci 34(9):1873–1880. https://doi.org/10.1007/s10103-019-02789-2

    Article  PubMed  Google Scholar 

  35. Kreutz T, de Matos SP, Koester LS (2019) Recent patents containing permeation enhancers for nail delivery. Recent Pat Drug Deliv Formul 13(3):203–218. https://doi.org/10.2174/1872211313666191030155837

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Guan XH, Xu TH, Chen X, Mu QS, Suo JF, Xu RX, Chen J, Xiao T, Hua GX, Chen HD (2021) Fractionated carbon dioxide (CO2) laser treatment contributes to trans-nail penetration of rhodamine B and changes of cytokine microenvironment. Lasers Med Sci 36(8):1619–1623. https://doi.org/10.1007/s10103-020-03232-7

    Article  PubMed  Google Scholar 

  37. Imrigha NAA, Bidin N, Lau PS, Musa N, Zakaria N, Krishnan G (2017) Photobiomodulation therapy on wound treatment subsequent to Q-switched Nd: YAG laser tattoo removal in rat model. J Biophotonics 10(10):1287–1291. https://doi.org/10.1002/jbio.201600295

    Article  CAS  PubMed  Google Scholar 

  38. Nestor M, Andriessen A, Berman B, Katz BE, Gilbert D, Goldberg DJ, Gold MH, Kirsner RS, Lorenc PZ (2017) Photobiomodulation with non-thermal lasers: mechanisms of action and therapeutic uses in dermatology and aesthetic medicine. J Cosmet Laser Ther 19(4):190–198. https://doi.org/10.1080/14764172.2017.1293828

    Article  PubMed  Google Scholar 

  39. Elewski BE, Ghannoum MA, Mayser P, Gupta AK, Korting HC, Shouey RJ, Baker DR, Rich PA, Ling M, Hugot S, Damaj B, Nyirady J, Thangavelu K, Notter M, Parneix-Spake A, Sigurgeirsson B (2013) Efficacy, safety and tolerability of topical terbinafine nail solution in patients with mild-to-moderate toenail onychomycosis: results from three randomized studies using double-blind vehicle-controlled and open-label active-controlled designs. J Eur Acad Dermatol Venereol 27(3):287–294. https://doi.org/10.1111/j.1468-3083.2011.04373.x

    Article  CAS  PubMed  Google Scholar 

  40. Ricardo JW, Lipner SR (2020) Safety of current therapies for onychomycosis. Expert Opin Drug Saf 19(11):1395–1408. https://doi.org/10.1080/14740338.2020.1829592

    Article  CAS  PubMed  Google Scholar 

  41. Ma W, Si C, Kasyanju Carrero LM, Liu HF, Yin XF, Liu J, Xu Y, Zhou B (2019) Laser treatment for onychomycosis: a systematic review and meta-analysis. Medicine (Baltimore) 98(48):e17948. https://doi.org/10.1097/MD.0000000000017948

    Article  Google Scholar 

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Funding

This work was supported by the Tianjin Municipal Health Commission-Research Projects in Key Areas of Traditional Chinese Medicine (grant no.2019002), Tianjin Municipal Health Commission Health Science and Technology Project (grant no. zc20127).

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Authors and Affiliations

  1. Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China

    Jianfeng Zhang, Peng Lin, Junchen Li & Chenqi Guo

  2. Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China

    Jingbo Zhai

  3. Department of Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, 300120, China

    Yu Zhang

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  1. Jianfeng Zhang
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Zhang, J., Lin, P., Li, J. et al. Efficacy of laser therapy combined with topical antifungal agents for onychomycosis: a systematic review and meta-analysis of randomised controlled trials. Lasers Med Sci 37, 2557–2569 (2022). https://doi.org/10.1007/s10103-022-03561-9

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