Photobiomodulation with fluorescent light

Dr. Irina Matricoti, DVM, European Specialist in Veterinary dermatology, Dip ECVD

What is bioluminescence

Bioluminescence is a photobiomodulation technique that, like laser therapy and phototherapy, uses photons of certain wavelengths to activate specific biological mechanisms in tissues. In particular, bioluminescence uses the energy produced by fluorescent light: this is generated by a chromophore gel applied to the skin to be treated when illuminated by a blue light lamp. The fluorescent light generated in this way is transferred to the skin tissue without excessive heat development, activating various biological mechanisms. In particular, immunohistochemical studies have shown that in the treated tissues there is a reduced production of pro-inflammatory cytokines such as IL-6 and TNFalpha, while tissue growth and regeneration factors such as EGF, FGF, Coll I and Coll III and other chemical mediators are overexpressed (1). In the treated areas, at the cellular level, an increase in the size of the mitochondria, the organelles that supply energy to the cell, is observed, which appear more elongated and oval compared with untreated areas (2).

Scope and method of application

Bioluminescence is therefore applied to treat various dermatological diseases, given its proven anti-inflammatory and tissue regenerating effects, such as superficial folliculitis, deep pyoderma, traumatic skin wounds, chronic pododermatitis, pyotraumatic dermatitis, perianal fistulas and cutaneous calcinosis. The treatment consists of irradiating the diseased area with two weekly applications. After cleaning with physiological saline and applying a layer of chromophore gel, the area is illuminated for 2 minutes with a lamp that generates blue light and promotes the fluorescence of the gel. Recently, the effectiveness of the so-called ‘back-to-back’ treatment, i.e. two consecutive cycles of two minutes each, about one minute apart, in the same session once a week, has been evaluated. In the comparison studies that were carried out between the two methods (two sessions per week of one cycle or one session per week two consecutive cycles) no significant differences were observed, so two consecutive irradiation cycles once a week may be more suitable to promote compliance.

Published studies in veterinary dermatology

The efficacy of bioluminescence in superficial folliculitis was proven in a small randomised study in which patients were treated with antibiotic therapy or bioluminescence alone once or twice a week, without the use of other therapies, either topical or systemic (3). Regardless of treatment frequency, bioluminescence proved effective in treating enrolled subjects. In another randomised trial in deep pyoderma, the efficacy of antibiotic therapy alone was compared with antibiotic therapy combined with bioluminescence (4). Patients treated with the two combined therapies recovered statistically faster than those treated with antibiotic therapy alone. In a subsequent study of patients with deep pyoderma (11 subjects) or interdigital furunculosis (5 subjects) caused by multiresistant bacteria, bioluminescence proved effective as monotherapy (5).

In the course of interdigital furunculosis, patients treated with antibiotics alone and patients treated with bioluminescence (with two applications per week in a first study and with two consecutive applications in a single session in a second study) in combination with antibiotics were compared. Patients treated with the combination of antibiotic therapy and bioluminescence showed a shorter healing time than those treated with antibiotic therapy alone (6).

In a small study of five patients with perianal fistulas, the lesions were treated exclusively with bioluminescent therapy with two consecutive applications in the same session (7). The patients enrolled all showed a clear reduction in lesion area at 4 weeks. After 6 weeks, 4 out of 5 showed enough improvement to discontinue the course of therapy, while the fifth subject needed more treatment. All subjects remained in remission for a follow-up period of 6 months.

A case report was recently published on the use of bioluminescence in the course of cutaneous calcinosis due to iatrogenic hypercortisolism (8). The patient was treated with systemic antibiotic, local disinfection and bioluminescence once a week (two consecutive applications). Phototherapy was only applied to certain areas, covering the control areas not to be irradiated with gauze. Although clinically no differences were observed between the treated and non-treated areas, those irradiated with bioluminescence showed cytologically faster healing of the bacterial infection.

Finally, bioluminescence was used effectively and without adverse effects in two subjects with traumatic skin lesions with tissue loss and appeared to accelerate and improve clinical skin healing in patients with surgical wounds following mastectomy (9,10).

Bioluminescence and quality of life

In a collection published in 2023, the impact of this phototherapy on the quality of life of patients and their owners was analysed (11). Thirty-five dogs with various diseases (interdigital furunculosis, deep pyoderma, skin wounds, pyotraumatic dermatitis, perianal fistulas) were treated. In the majority of patients (86%) bioluminescent therapy was effective alone or in combination with local antiseptic therapy. Only in 5 subjects was it necessary to use other therapies in combination (3 of 13 patients with interdigital furunculosis and in both 2 patients enrolled with perianal fistulas). The therapy appears to be a promising method both clinically and in improving the quality of life of patients and owners.

In conclusion

From the studies published so far, biolumiscence appears to be an innovative approach in the treatment of numerous dermatoses that often require prolonged antibiotic or immunomodulatory therapy, so its use may be effective in reducing the use of antibiotics or immunosuppressive drugs. However, it should be noted that most of these studies were performed on a small number of patients and that some of these studies were not randomised and controlled. Furthermore, in vitro studies have not currently shown proven antibacterial efficacy, despite the fact that in in vivo studies, bioluminescence has been shown to be effective in the treatment of bacterial dermatitis (12). It is therefore possible that there may be a synergistic effect between bioluminescence and other antiseptic therapies.

Bibliography

1. Scapagnini, G., Marchegiani, A., Rossi, G., Zago, M., Jowarska, J., Wael, M., ... & Spaterna, A. (2019, March). Management of all three phases of wound healing through the induction of fluorescence biomodulation using fluorescence light energy. In Photonic Diagnosis and Treatment of Infections and Inflammatory Diseases II (Vol. 10863, pp. 147-163). SPIE.

2. Salvaggio, A., Magi, G. E., Rossi, G., Tambella, A. M., Vullo, C., Marchegiani, A.. & Palumbo Piccionello, A. (2020). Effect of the topical Klox fluorescence biomodulation system on the healing of canine surgical wounds. Veterinary Surgery, 49(4), 719-727.

3. Marchegiani, A., Spaterna, A., Fruganti, A., & Cerquetella, M. (2023). Exploring fluorescent light energy as management option for canine superficial bacterial folliculitis. Frontiers in Veterinary Science, 10, 1155105.

Marchegiani, A., Fruganti, A., Spaterna, A., Cerquetella, M., Tambella, A. M., & Paterson, S. (2021). The effectiveness of fluorescent light energy as adjunct therapy in canine deep pyoderma: a randomised clinical trial. Veterinary Medicine International, 2021.

5. Marchegiani, A., Fruganti, A., Bazzano, M., Cerquetella, M., Dini, F., & Spaterna, A. (2022). Fluorescent Light Energy in the Management of Multi Drug Resistant Canine Pyoderma: A Prospective Exploratory Study. Pathogens, 11(10), 1197.

6. Marchegiani, A., Spaterna, A., Cerquetella, M., Tambella, A. M., Fruganti, A., & Paterson, S. (2019). Fluorescence biomodulation in the management of canine interdigital pyoderma cases: a prospective, single-blinded, randomized and controlled clinical study. Veterinary dermatology, 30(5), 371-e109.

7. Marchegiani, A., Tambella, A. M., Fruganti, A., Spaterna, A., Cerquetella, M., & Paterson, S. (2020). Management of canine perianal fistula with fluorescence light energy: preliminary findings. Veterinary Dermatology, 31(6), 460-e122.

Apostolopoulos, N., & Mayer, U. (2020). Use of fluorescent light energy for the management of bacterial skin infection associated with canine calcinosis cutis lesions. Veterinary Record Case Reports, 8(4), e001285.

9.Marchegiani, A., Spaterna, A., Palumbo Piccionello, A., Meligrana, M., Fruganti, A., & Tambella, A. M. (2020). Fluorescence biomodulation in the management of acute traumatic wounds in two aged dogs. Veterinární medicína, 65(5), 215-220.

10. Marchegiani, A., Troisi, A., Bazzano, M., Spaterna, A., & Fruganti, A. (2024). A Prospective, Blinded, Open-Label Clinical Trial to Assess the Ability of Fluorescent Light Energy to Enhance Wound Healing after Mastectomy in Female Dogs. Animals, 14(8), 1250.

11. Mosca, M., Briand, A., Carrasco, I., Luciani, L., & Fantini, O. (2023). Impact of Fluorescent Light Energy on the Quality of Life of Dogs with Dermatologic Disease and Their Owners. Open Journal of Veterinary Medicine, 13(7), 122-135.

12. Marchegiani, A., Spaterna, A., & Cerquetella, M. (2021). Current applications and future perspectives of fluorescence light energy biomodulation in veterinary medicine. Veterinary Sciences, 8(2), 20.