Laser treatment
One systematic review and meta-analysis reported mycological cure rates of 63% with 1064-nm Nd:YAG laser and 74.0% with CO₂ lasers in patients with onychomycosis.[60]Ma W, Si C, Kasyanju Carrero LM, et al. Laser treatment for onychomycosis: a systematic review and meta-analysis. Medicine (Baltimore). 2019 Nov;98(48):e17948.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890331
http://www.ncbi.nlm.nih.gov/pubmed/31770202?tool=bestpractice.com
A Cochrane review reported that treatment with 1064‐nm Nd:YAG laser therapy may be of little or no difference to sham treatment or no treatment with respect to mycological cure at 52 weeks.[61]Foley K, Gupta AK, Versteeg S, et al. Topical and device-based treatments for fungal infections of the toenails. Cochrane Database Syst Rev. 2020 Jan 16;(1):CD012093.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012093.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/31978269?tool=bestpractice.com
Potential adverse effects include pain and bleeding.[60]Ma W, Si C, Kasyanju Carrero LM, et al. Laser treatment for onychomycosis: a systematic review and meta-analysis. Medicine (Baltimore). 2019 Nov;98(48):e17948.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890331
http://www.ncbi.nlm.nih.gov/pubmed/31770202?tool=bestpractice.com
More randomised controlled studies are required.
Systemic second-generation azole antifungals
Reserved primarily for the treatment of invasive opportunistic fungal infections, particularly in immunocompromised patients. Second-generation triazoles (e.g., voriconazole, posaconazole, ravuconazole) have broad-spectrum antifungal activity. Clinical trials indicate efficacy in patients with onychomycosis.[62]Elewski B, Pollak R, Ashton S, et al. A randomized, placebo- and active-controlled, parallel-group, multicentre, investigator-blinded study of four treatment regimens of posaconazole in adults with toenail onychomycosis. Br J Dermatol. 2012 Feb;166(2):389-98.
http://www.ncbi.nlm.nih.gov/pubmed/21967490?tool=bestpractice.com
[63]Sigurgeirsson B, van Rossem K, Malahias S, et al. A phase II, randomized, double-blind, placebo-controlled, parallel group, dose-ranging study to investigate the efficacy and safety of 4 dose regimens of oral albaconazole in patients with distal subungual onychomycosis. J Am Acad Dermatol. 2013 Sep;69(3):416-25.
http://www.ncbi.nlm.nih.gov/pubmed/23706639?tool=bestpractice.com
[64]Watanabe S, Tsubouchi I, Okubo A. Efficacy and safety of fosravuconazole L-lysine ethanolate, a novel oral triazole antifungal agent, for the treatment of onychomycosis: a multicenter, double-blind, randomized phase III study. J Dermatol. 2018 Oct;45(10):1151-9.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220848
http://www.ncbi.nlm.nih.gov/pubmed/30156314?tool=bestpractice.com
The systemic bioavailability of fosravuconazole, a prodrug of ravuconazole, enables a short duration of therapy of 3 months.[64]Watanabe S, Tsubouchi I, Okubo A. Efficacy and safety of fosravuconazole L-lysine ethanolate, a novel oral triazole antifungal agent, for the treatment of onychomycosis: a multicenter, double-blind, randomized phase III study. J Dermatol. 2018 Oct;45(10):1151-9.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220848
http://www.ncbi.nlm.nih.gov/pubmed/30156314?tool=bestpractice.com
[65]Noguchi H, Matsumoto T, Kimura U, et al. Fosravuconazole to treat severe onychomycosis in the elderly. J Dermatol. 2021 Feb;48(2):228-31.
http://www.ncbi.nlm.nih.gov/pubmed/33099769?tool=bestpractice.com
Second-generation azoles may have a role in the management of onychomycosis resistant to standard antifungal agents. However, they are associated with rare but severe adverse effects.