Is Light-Emitting Diode Phototherapy (LED-LLLT) Really Effective?
Author Information
1 Department of Dermatology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
2 Korean Institute for Photomedicine and Photosurgery Research, Goyang, South Korea
Addressee for Correspondence: R Glen Calderhead, Korean Institute for Photomedicine and Photosurgery, Research, 710 Gwanridong Ilsan Technotown, Baekseok, Goyang City, Gyeonggi 1441-1, South Korea, Tel: +82-31-908-3440 / FAX: +82-31-907-3440, email: pj.en.9cc@cgrcod
available at www.jstage.jst.go.jp/browse/islsm
PMID: 24155530 DOI: 10.5978/islsm.20.205
This article has been cited by other articles in PMC.
Abstract
Background: Low-level light therapy (LLLT) has attracted attention in many clinical fields with a new generation of light-emitting diodes (LEDs) which can irradiate large targets. To pain control, the first main application of LLLT, have been added LED-LLLT in the accelerated healing of wounds, both traumatic and iatrogenic, inflammatory acne, and the patient-driven application of skin rejuvenation.
Rationale and Applications: The rationale behind LED-LLLT is underpinned by the reported efficacy of LED-LLLT at a cellular and subcellular level, particularly for the 633 nm and 830 nm wavelengths, and evidence for this is presented. Improved blood flow and neovascularization are associated with 830 nm. A large variety of cytokines, chemokines, and macromolecules can be induced by LED phototherapy. Among the clinical applications, non-healing wounds can be healed through restoring the collagenesis/collagenase imbalance in such examples, and ‘normal’ wounds heal faster and better. Pain, including postoperative pain, postoperative edema, and many types of inflammation can be significantly reduced.
Experimental and clinical evidence: Some personal examples of evidence are offered by the first author, including controlled animal models demonstrating the systemic effect of 830 nm LED-LLLT on wound healing and on induced inflammation. Human patients are presented to illustrate the efficacy of LED phototherapy on treatment-resistant inflammatory disorders.
Conclusions: Provided an LED phototherapy system has the correct wavelength for the target cells, delivers an appropriate power density, and an adequate energy density, then it will be at least partly, if not significantly, effective. The use of LED-LLLT as an adjunct to conventional surgical or nonsurgical indications is an even more exciting prospect. LED-LLLT is here to stay.
Keywords: Grotthus-Draper law, nonhealing wound, photochemical cascade, photophysical reaction, irritant contact dermatitis, dissecting cellulitis, acne rosacea
Introduction
High-level laser treatment (HLLT) means that high levels of incident laser power are used to deliberately destroy a specific target through a light-heat transduction process to induce photothermal damage of varying degrees. HLLT is used in many surgical fields, but probably most commonly in dermatologic, aesthetic, or plastic surgery. On the other hand, when a laser or other appropriate light source is used on the tissue at low incident levels of photon energy, none of that energy is lost as heat but instead, the energy from the absorbed photons is transferred directly to the absorbing cell or chromophore, causing photoactivation of the target cells and some kind of change in their associated activity. In clinical applications, this was termed ‘low-level laser therapy’ (LLLT) by Ohshiro and Calderhead in 1988,1) with ‘photobiomodulation’ or ‘photoactivation’ referring to the activity at a cellular and molecular level.
LED Phototherapy
All this changed in 1998 with the development of the so-called ‘NASA LED’ by Prof Harry Whelan and his group at the NASA Space Medicine Laboratory, which offered clinicians and researchers a useful phototherapy source having less divergence, much higher and more stable output powers, and quasimonochromaticity whereby nearly all of the photons were at the rated wavelength.4) This new generation of LEDs also had its own phenomenon associated with photon intensity, namely photon interference, whereby intersecting beams of LED energy from individual LEDs produced photon interference, increasing the photon intensity dramatically and thus offering much higher photon intensities than the older generation. For LEDs emitting at visible red and near IR wavelengths, the greatest photon intensity was actually seen beneath the surface of the target tissue, due to the combination of the photon interference phenomenon and the excellent tissue scattering characteristics of light at these wavebands.5) This phenomenon, together with quasimonochromaticity, meant that the new generation of LEDs was a clinically viable source for phototherapy.6) ‘Low-level laser therapy’ was therefore renamed by the US photobiologist, Kendric C Smith, as ‘low-level light therapy’, to encompass LED energy.7) Accordingly, useful bioreactions could then be achieved with LEDs through cellular photoactivation without heat or damage, as shown by Whelan and colleagues in their early NASA LED wound healing studies.8)
Although visible and near-infrared light energy induces the same tri-stage process in target cells, namely photon absorption, intracellular signal transduction, and the final cellular photoresponse,9) it should be noted that both wavebands have different primary targets and photoreactions in target cells. Visible light is principally a photochemical reaction, acting directly and mostly on cytochrome-c oxidase, the end terminal enzyme in the cellular mitochondrial respiratory chain,10) and mainly responsible for inducing adenosine triphosphate (ATP) synthesis, the fuel of the cell and indeed the entire metabolism. Infrared light on the other hand induces a primary photophysical reaction in the cell membrane thereby kick-starting the cellular membrane transport mechanisms such as the Na++K++ pump,6) and this in turn induces as a secondary reaction the same photochemical cascade as seen with visible light, so the end result is the same even though the target is different as illustrated schematically in Figure 2.
LED phototherapy at appropriate wavelengths and parameters has now been well-reported in a large number of pan-specialty applications.11) How and where does LED phototherapy work? When we consider investigating how LED phototherapy or LLLT can bring about and influence the molecular mechanism for cell proliferation, we should recognize that LLLT not only has an effect on various signaling processes, but it can also significantly induce the production of cytokines, such as a number of growth factors, interleukins and various macromolecules (Table 2).12)
Applications of LLLT with LEDs
When we confirm in what fields LLLT phototherapy has been most used through a review of the literature, the main application is for pain control, with the pain of almost all aetiologies responding well.11) For example, 830 nm LED phototherapy significantly reduced both acute and chronic pain in professional athletes.13) The first author has been using LED in the control of herpes zoster pain for some time, and also for intractable postherpetic neuralgia, corroborating previous studies with 830 nm LLLT for this indication.14,15) This and other chronic pain entities have been historically very hard to control, but the good efficacy of LED phototherapy has been well recognized. From the large body of work from Rochkind and colleagues in Israel, LED phototherapy can help nerve regeneration, so it has been used for spinal cord injuries,16) and many different types of neurogenic abnormality. In the case of the dental clinic and for the osseointegration of implants and prostheses in maxillofacial surgery, it has been used for guided bone regeneration.17) At present, the research into and development of new applications for LED phototherapy, especially in the processes of inflammatory cell regulation, are being assiduously studied in the dermatology field.
Fast taking over from pain attenuation, and particularly in the dermatology field, wound healing with LED phototherapy has attracted much attention. Reports have shown that, after making uniform burn wounds with a surgical laser, LED phototherapy of experimental wounds induces faster and better-organized healing than in the control unirradiated wounds. This is due to the effect of 830 nm phototherapy on raising the action potential the wound-healing cells, at all three phases of the process, particularly mast cells,18) macrophages19) and neutrophils20) in the inflammatory stage; fibroblasts in the proliferative phase (Personal Communication, Prof. Park, Seoul National University, Seoul, South Korea: unpublished data); and fibroblast-myofibroblast transformation in the remodeling phase.21) As an additional mechanism, it has also been shown that 830 nm phototherapy increased the early vascular perfusion of axial pattern flaps in a controlled speckle flowmetry Doppler trial in the rat model, with actual flap survival significantly better in the irradiated than in the unirradiated control animals.22)
In another very popular indication, studies have reported on the use of LED phototherapy for the rejuvenation of chronologically and photodamaged skin.23,24) Lee and colleagues, in a randomized controlled study, showed that fibroblasts examined with transmission electron microscopy appeared more active, collagen and elastin synthesis was increased and tissue inhibitors of matric metalloproteinases were increased, as a result of which, effective rejuvenation could be achieved which was maintained up to 12 weeks after the final treatment session. Patient satisfaction scores bore these histopathological findings out (Figure 3).24) We must never forget that good skin rejuvenation is firmly based on the wound healing process, particularly neocollagenesis. LED phototherapy has also been reported as being very effective in the prophylaxis against scar formation, due amongst other factors to the response to photomediated interleukin-6 signaling.12) Hair loss is another field where LED phototherapy may well have real efficacy, with red and infrared being the wavelengths of choice.25–27) Figure 4 illustrates schematically the mechanisms already confirmed underlying the three main endpoints of 830 nm LLLT, namely wound healing, the anti-inflammatory response through acceleration, and quenching of the post-wound inflammatory phase, and pain attenuation.
Systemic Effects of LED-LLLT
One of the advantages of LLLT with an LED system as compared with a laser source is that LED-based systems offer large planar arrays so that they can irradiate a large area of the body in a hands-free manner, compared with the point-by-point application of a laser system. In addition, many different cell types can be simultaneously targeted. It may not even be necessary to irradiate every target area. The systemic effect of LED with an 830 nm system (HeaLite II, Lutronic Corp., Goyang, S. Korea, Figure 5) was studied by the first author.28) The systemic effect associated with LLLT has already been suggested as far back as Mester’s pivotal study on non-healing ulcers in 1969, whereby irradiation of one part of the body could induce effects in another unirradiated area.29) To assess this, in the first author’s study controlled wounds on the backs of rodents were created with an ablative fractional laser, and rather than irradiating the laser wounds with LED energy (HeaLite system as above), the animals’ abdomens in the experimental group were irradiated, and sham irradiation was delivered to the control group. The results clearly indicated that the group which had LED treatment of the abdomen demonstrated significantly better healing than the control group (Figure 6). This means that LED phototherapy could very probably have a systemic effect on inflammatory or immune cells in nonadjacent tissues to the target area, as well as those cells in the irradiated tissues.
LED LLLT for Skin Inflammatory Diseases
The anti-inflammatory effect of LED has been generally accepted, but up till now, this has not been well shown well in inflammatory skin diseases such as allergic or irritant contact dermatitis, atopic dermatitis, or rosacea, although a significant degree of success has been demonstrated and reported for inflammatory acne and recalcitrant treatment-resistant psoriasis.30,31) In an experimental animal model study the first author was able to demonstrate that when induced dermatitis in rats was treated with 830 nm LED phototherapy (HeaLite II system, Lutronic Corp, as above) at a dose of 60 J/cm2 in a continuous wave, compared with an untreated control group, the histopathological findings revealed significantly decreased levels of inflammatory cells (Figure 7). Based on the success of that study, treatment-resistant inflammatory contact dermatitis due to a peel compound containing alpha-hydroxy acid (AHA) in a human subject also responded very well to 3 sessions of 830 nm LED therapy, 3 days apart, the irradiance of 100 mW/cm2, 10 min/session, a dose of 60 J/cm2, continuous wave (Figure 8).
Here are another two examples of the clinical success of 830 nm LED phototherapy (continuous wave, 60 J/cm2) in difficult-to-treat conditions. Figure 9 illustrates the dramatic improvement following 830 nm LED phototherapy in a case of dissecting cellulitis of the scalp, a recalcitrant inflammatory problem, treated with 4 sessions over 2 weeks, 20 min/60 J/cm2 per session; and Figure 10 illustrates a typical result 10 weeks after 6 sessions over 6 weeks, 20 min/60 J/cm2 per session, from a clinical trial the first author has conducted on LED therapy for rosacea with neutrophilic dermatitis. This trial is as yet unreported because the full 12-week follow-up time has not yet been reached in all patients. However, preliminary results are very encouraging with no recurrence seen at 10 weeks in those patients who have reached that point.
Conclusions
In conclusion, based on the published data and the authors’ own experience, LED phototherapy is proving to have more and more viable applications in many fields of medicine. However, it must always be remembered that not any old LED will do. In order to be effective, LED phototherapy must satisfy the following 3 criteria.
- The LED system being used must have first of all, and most importantly, the correct wavelength for the target cells or chromophores. At present, the published literature strongly suggests 830 nm for all aspects of wound healing, pain, anti-inflammatory treatment, and skin rejuvenation, with a combination of 415 nm and 633 nm for light-only treatment of active inflammatory acne vulgaris. If the wavelength is incorrect, optimum absorption will not occur and as the first law of photobiology states, the Grotthus-Draper law, without absorption there can be no reaction.
- Secondly, the photon intensity, i.e., spectral irradiance or power density (W/cm2), must be adequate, or once again absorption of the photons will not be sufficient to achieve the desired result. If the intensity is too high, however, the photon energy will be transformed to excessive heat in the target tissue, and that is undesirable.
- Finally, the dose or fluence must also be adequate (J/cm2), but if the power density is too low, then prolonging the irradiation time to achieve the ideal energy density or dose will most likely not give an adequate final result, because the Bunsen-Roscoe law of reciprocity, the 2nd law of photobiology, does not hold true for low incident power densities.
Provided these three criteria are met, LED phototherapy does indeed work and has many useful aspects in clinical practice for practitioners in many surgical specialties. As an exciting extension of the monotherapy approach with LED-LLLT, and even more importantly, the combination of appropriate LED phototherapy as an adjunct to many other surgical or nonsurgical approaches where the architecture of the patient’s skin has been altered will almost certainly provide the clinician with even better results with less patient downtime, in a shorter healing period, and with excellent prophylaxis against obtrusive scar formation.
