Table 1.
Overview of the Treatment Regimen, Outcome, and Side Effects for PDT Treatment of Fungal Infections Articles Cited in This Review
| References | Study Type | Case Number | Fungal Species | PS | Light Source | Light Wavelength (nm) | Light Dose (J/cm2) | Treating Sessions (Interval Time) | Combination Treatment | Outcome | Follow Up | Adverse Effects |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Onychomycosis | ||||||||||||
| de Oliveira GB et al18 | Clinical trial | 7 |
T. rubrum (n=6); Epidermophyton floccosum (n=1) |
16% MAL | LED | NA | NA | 2 sessions (60-day intervals) | Fractional CO2 laser 10.600 nm | 1-year follow-up: MC 100%; ClC 79% (15/19) (nail four quadrants count) 43% (entire nail plate) No relapse. |
30 days; 1 year |
NA |
| Morgado LF et al28 | Clinical trial | 20 included (16 finished) |
NA | AlClPc (entrapped in nanoemulsions) | LED (red light) | 660 | 30.9 | 4.45±1.76 sessions (15-days interval) | No | MC 40% ClC 60% |
1 month | Pain (VAS 2.76±1.87) |
| Tawfik AA et al29 | In vivo experience (rabbit) | 80 | T. mentagrophytes | 3 groups: MB; Gold nanoparticles; MB + gold nanoparticles |
LED (red and green light) | Red (650); Green (530) |
80; 100 |
4 sessions (48-hours intervals) | No | CC: MB 40%; Gold nanoparticles 96%; MB + gold nanoparticles 34% |
48 hours after the 4th session | NA |
| Cronin L et al32 | In vitro study | Spore suspension (A300=0.6) | T. rubrum | Rose Bengal | Laser (green) | 532 | 68; 133; 228 | NA | No | Percentage growth inhibition 15–51% | NA | NA |
| Fekrazad R et al33 | In vitro study | Suspensions (106 cells/ mL) | C.albicans; T.rubrum | Citrus EO; Indocyanine green |
Infrared (IR) laser; Natural and tungsten lights | 810±10 (IR laser) | 55 (IR laser) | NA | No | Cell reduction rates: Citrus EO + natural and tungsten light: 99.99% (C.albicans and T.rubrum); Indocyanine green + IR laser: 91.67% (C.albicans) 74.5% (T.rubrum); Fluconazole + IR laser: 38.5% (T.rubrum) |
NA | NA |
| Smijs TG et al26 | In vitro study | Suspension and spore solution | T. rubrum | Sylsens B; DP mme |
Red light | 600 | 108 | NA | No | Inhibition rates: Suspension cultures: Sylsens B (10μM-50μM): 100% DP mme (30μM): 95%; Microconidia: Sylsens B (1–5μM): 100% DP mme (4–5μM): 80–90% |
2 days; 7 days; 3 months |
NA |
| Tinea pedis (interdigital type) | ||||||||||||
| Sotiriou E et al35 | Clinical trial | 10 |
T. rubrum (n=4); T. mentagrophytes (n=6) |
20% 5-ALA | Red light | 570–670 | 50 | 1 or 3 sessions (2-week intervals) | No | CC after 3 treatments: 60% (6/10) CC at the end of follow-up: 30% (3/10) |
2 months | Burning sensation during irradiation, erythema up to 1 week after therapy. |
| Calzavara-Pinton PG et al36 | Clinical trial | 9 |
T. mentagrophytes (n=4); T. rubrum (n=2); C. albicans (n=3) |
20% 5-ALA | Broadband red light | 575–700 | 75 | 1 or 4 sessions (1-week interval) | No | CC after 1 or 4 treatments: 67% (6/9) CC at the end of follow-up: 22% (2/9) |
4 weeks | Localized erythema and edema during and soon after exposure; pain; desquamation after 3–5 days. |
| Tinea cruris | ||||||||||||
| Sotiriou E et al40 | Clinical trial | 10 | T. rubrum | 20% 5-aminolevulinic acid (ALA) | Red light | 570–670 | 50 | 1–2 sessions (2-week intervals) | No | MC after 1–2 treatments: 80% (8/10) MC at the end of follow-up: 40% (4/10) |
8 weeks | Mild burning and stinging during the exposure; erythema and edema up to 3–4 days after therapy. |
| Tinea Capitis | ||||||||||||
| Lu J et al42 | Case report | 1 | NA | 20% 5- ALA | LED | 630 | 80 | 3 sessions (1-week interval) | Itraconazole 100 mg/day | CC 1/1 No recurrence. |
3 months | Burning sensation during irradiation; temporary edema, erythema, itch, and stinging up to 1 week after therapy. |
| Pityriasis versicolor (PV) | ||||||||||||
| Alberdi E et al43 | Pilot trial | 5 | Malassezia spp. | 2% MB | Red LED lamp | 630±5 | 37 | 6 sessions (2-week intervals) | No | CC: 5/5 No relapse. |
4 weeks; 22 weeks |
Hypopigmentation, no other side effects or pain. |
| Oral candidiasis | ||||||||||||
| Freire F et al47 | In vitro study; in vivo study in a murine model |
107 CFU/mL of suspension (OD570); 15 BALB/c mice |
C. albicans | Methylene blue (MB); new methylene blue (NMB) |
Red diode laser | 660 | 10; 20; 40; 60 J |
5 days of daily treatment | Potassium iodide (KI) | Log reduction of CFU/mL: MB+KI (40 J): 2.31 log NMB (60 J): 1.77 log Reduction of mice bioluminescent photon flux (log10): MB+KI (40J): 2 log NMB (60 J): 1 log |
NA | NA |
| Campos L et al48 | Case report | 1 | Candida spp. | 0.01% MB | Laser | 660 | 178 | 1 session | No | ClC: 1/1 | 72 hours | NA |
| Chibebe JJ et al49 | In vivo experiment in Galleria mellonella model | 16/group |
C. albicans Can14 (wild-type); Can37 (fluconazole-resistant) |
MB (1 mM) | Red light | 660±15 | 0.9 | 1 time | Fluconazole (14 mg/kg) | Can14: MB-PDT prolonged suivival. Can37: MB-PDT reduced fungal burden by 0.2 log; MB-PDT+fluconazole prolonged suivival. |
100 hours - 150 hours | NA |
| Esophageal candidiasis (EC) | ||||||||||||
| Qiu H et al51 | Clinical study | 2 | Candida spp. | Photocarcinorin (PSD-007) | Semiconductor laser | 630 | 135; 270 | 1–3 sessions (1-month and 6-month intervals) | No | Case 1: CC 2/2 EC lesions Case 2: CC 1/1 EC lesions No recurrence in two cases. |
14 months; 24 months |
Substernal pain within 5–7 days after PDT. (both cases) A low-grade fever lasted for 5 days post PDT. (case 1) |
| Vulvovaginal candidiasis (VVC) | ||||||||||||
| de Santi M et al55 | In vivo study in a murine model | 37 | C. albicans | MB (100 μM); PpNetNI (10 μM) |
Laser (MB); LED (PpNetNI) |
660 nm (laser); 630 nm (LED) |
6048 (laser); 85 (LED) |
1 time | No | Reduction of fungal CFUs: 1 order of magnitude (both PSs) |
7 days | No |
| Machado-de-Sena RM et al56 | In vivo study in a murine model | 77 | C. albicans | MB (1 mM) | Red laser | 660 | 18 J; 36 J | 1 or 2 sessions (24-hour intervals) | No | Reduction of fungal CFUs: 1session: 1.62 log (after 24 h) 1.16 log (after 96 h); 2 sessions: 1.66 log (after 24 h) |
24 hours; 96 hours |
NA |
| Chromoblastomycosis (CBM) | ||||||||||||
| Hu Y et al58 | Case report; in vitro study |
1 case; 0.5–2.5×103 conidia/mL (in vitro) |
F. monophora | 20% 5-ALA | LED | 635 | 10 J | Case: 2 sessions (each including 9 times, 1-week interval) |
Case: Terbinafine (250 mg/day) In vitro study: No combination. |
Case: Mycological cure and clinical greatly improvement. In vitro study: Reduce fungal CFUs by 2–4 log. |
Case: 1 year; In vitro study: 7 days |
Hypopigmentation |
| Lyon JP et al59 | In vitro study | Suspension of 1–5×106 CFU/mL | F. pedrosoi; Cladophialophora carrionii | MB (16 μg/mL; 32 μg/mL; 64 μg/mL) | LED | NA | 200 mW/cm2 | 1 time | No | Reduction of fungal CFUs: 4 log approximately (32 μg/mL achieved better result) | 7–10 days | NA |
| Huang X et al60 | In vivo study in Galleria mellonella model | No specific description | F. monophora | 5- ALA | Laser (red light) | NA | NA | 1 session | No | Extend median survival by 2.5 days. Increase hemocyte density by 1.34×103 cells/μL 4h after PDT. |
10 days | No |
| Hu Y et al9 | Case series; in vitro study |
5 cases; Suspension: 0.5–2.5×103 conidia/mL |
F. nubica (n=1); F. pedrosoi (n=2); F. monophora (n=2) |
20% 5- ALA | LED (white light) | 635 | 36.8 mW/cm2 (10 J) | Cases: 4–9 sessions (1- or 2-week intervals) |
Cases: Oral itraconazole 400 mg/day; oral terbinafine 250 mg/day In vitro study: Itraconazole 1μg/mL |
Cases: MC: 3/5 CC: 2/5 Clinical improvement: 3/5 No new lesions. In vitro study: Reduced approximately 2×103 CFUs of F. monophora. |
Cases:6 months - 2 years | Hypopigmentation (n=2) |
| Yang W et al61 | Case report | 1 | F. monophora | 20% 5-ALA | LED (red light) | 630 | 90 | 3 sessions (10-day intervals) | Itraconazole 400 mg/day | CC: 1/1 No relapse. |
3 months | Pain and burning sensation during irradiation; Mild pain, swelling, and exudation whining 3–5 days after PDT. |
| Huang X et al62 | Case report | 1 | F. pedrosoi | 10% ALA | Red light | 633±10 | 80–100 mW/cm2 | 6 sessions (1-week interval) | No | CC: 1/1 No recurrence. |
6 months | NA |
| Lan Y et al63 | Case report | 1 | F. monophora | 20% ALA | Red light | 633±10 | 96 | 4 sessions (1-week interval) | Isotretinoin 20 mg/day; Oral terbinafine 250 mg/day, itraconazole 400 mg/day; CO2 laser. |
MC: 1/1 Clinical improvement. |
4 months | No |
| Sporotrichosis | ||||||||||||
| Gilaberte Y et al66 | Case report and in vitro study | 1 case; Suspension optical density McFarland values 0.5. |
Sporothrix schenkii | Case:1% MB; In vitro study: MAL (0–6 M); MB (1 μM); NMB (1.25 μM); DMMB (1.5 μM) |
LED | 635 nm (case); 639.8±10 nm (in vitro study) |
37 | Case: 3 and 5 sessions (2-week intervals) |
No | Case: Clinical improvement; In vitro study: Reduce fungal cells by 6 log10 CFUs (MB, NMB, DMMB), No change of CFU (MAL). |
NA | Pain during irradiation (score 4 on a VAS) |
| Phaeohyphomycosis | ||||||||||||
| Liu H et al68 | Case report | 1 | Exophiala spinifera | 20% ALA | Red light | 633 | 120 mW/cm2 | 3 sessions (1-week interval) | Oral terbinafine 250 mg/day, itraconazole 200 mg/day | MC: 1/1 Clinical improved greatly. |
3 months | Mild burning and temporary pain during irradiation; hyperpigmentation. |
| Majocchi’s granuloma (MG) | ||||||||||||
| Shi L et al12 | Case report; in vitro study; in vivo study in guinea pig model |
1 case; In vitro study: suspension 1–5×105 CFU/mL |
T. tonsurans | Case: 10% ALA; In vitro study: 5 mM ALA; In vivo study: 10% ALA |
LED | Case: 635 In vitro and in vivo study: 633 |
Case:120; In vitro study: 50, 100, 150, 175, 200; In vivo study: 90. |
Case: 3 sessions (3- or 4-week intervals) | No | Case: CC 1/1; no recurrence. In vitro study: Reduced approximately 4×105 CFU/mL of fungal concentrations. (175 and 200 J/cm2) In vivo study: Reduced the clinical lesions scoring by 6. |
Case: 3 months; In vitro study: 7 days; In vivo study: 14 days |
Case: Inflammatory exudation after 1st PDT. In vivo study: Erythema and exudation 24–48 hours after PDT. Scabs formed on the 8th day. |
| Mucormycosis | ||||||||||||
| Liu Z et al11 | In vitro study | 6 strains; Conidia concentra- tion of 1–3×106 CFU/mL |
R. oryzae | MB (8, 16, and 32 μg/mL) | LED | 635±10 | 12 | 1 time | No | CFU reductions: 1.1 log10 (8 μg/mL MB); 2.2 log10 (16 μg/mL MB); 4.3 log10 (32 μg/mL MB). |
24 hours | NA |
Abbreviations: PS, photosensitizer; PDT, photodynamic therapy; ALA, aminolevulinic acid; MAL, methyl aminolevulinate; MB, methylene blue; NMB, new methylene blue; DMMB, 1.9-dimethylmethylene blue; DP mme, deuteroporphyrin monomethylester; Citrus EO, citrus aurantifolia essential oil; AlClPc, aluminium-phthalocyanine chloride; PpNetNI, Protoporphyrin IX; LED, Light-Emitting Diode; CO2, carbon dioxide; MC, mycological cure; ClC, clinical cure; CC, complete cure; CFU, colony forming unit; VAS, visual analogue scale; NA, not available; T., Trichophyton; C., Candida; F., Foncecaea; R., Rhizopus.