Light and lasers for vascular and skin diseases: From bench to clinic – An update

1 Introduction

The laser (light amplification by stimulated emission of radiation) is a device that emits light beams of specific wavelength and is able to transform other energies into electromagnetic radiation [1]. Depending on the medium they use, lasers can be solid-state lasers [ruby or neodymium:yttrium-aluminum garnet (Nd:YAG) lasers], liquid-state lasers (dye lasers), gas lasers (helium, helium-neon and excimer lasers) or semi-conductor lasers (also called diode lasers). The laser’s first medical use was to repair detached retinas by means of spot welding in ophthalmology [2]. However, dermatologists, especially Dr. Leon Goldman, played an important role in the further development and application of medical lasers. Goldman first used the laser in the field of dermatology to treat tattoos using a ruby laser, with 500-ms pulses [3]. As a result, he is often referred to as the “godfather of lasers in medicine and surgery” [4].

Light therapy, also called phototherapy or heliotherapy, classically refers to the use of ultraviolet (UV) light in the management of disease conditions. Phototherapy has been used for centuries to treat skin disorders. Most of the insights into the therapeutic benefit of phototherapy, that have been gained over time, have been related to observed effects of natural sunlight. It was not until the 20th century that artificial light sources were developed to utilize UV light for medical purposes. Niels Finsen was the first person to treat a cutaneous mycobacterial infection of the skin by the focused delivery of UV light for which he was awarded the Nobel Prize [5]. The development continued and in the middle of the 20th century, ultraviolet B (UVB) and psoralen plus ultraviolet A (PUVA) phototherapy were used, primarily for treatment of psoriasis. More recently further research has led to the application of broadband UVB (290–320 nm), narrowband UVB (311–313 nm), 308 nm excimer lasers, and UVA-1 (340–400 nm) irradiation.

Laser and light technology and its use in dermatology is a rapidly advancing field. Laser and light sources are also being used in combination with pharmacological agents to optimize the therapeutic outcome [6]. This issue of Photonics & Lasers in Medicine presents some encouraging efforts in the application of lasers and light-based therapy especially in vascular diseases and dermatophyte fungi. Therefore, the present editorial aims to briefly discuss the use of lasers and light-based therapies for various skin conditions including vascular, fungal infections and other diseases such as inflammatory, premalignant and malignant lesions.

2 Light and lasers on vascular diseases

The treatment of vascular dermatoses presents a particular challenge in dermatology, especially because of their high incidence. In general, vascular dermatoses are clinically differentiated into hemangiomas and vascular malformations. Currently, treatments of vascular dermatoses can be mainly divided into two procedures, one of which is the single laser and photon therapy technology. Since the application of the argon laser in the treatment of superficial skin vascular proliferative diseases in 1981, lasers have become more popular in this field of treatment. Pulsed dye laser (PDL), Nd:YAG, CO₂ and copper-vapor lasers are generally used as light sources. The laser targets the red-colored tissue, which is due to the presence of oxyhemoglobin. The oxyhemoglobin absorbs light energy, which later turns into thermal energy and leads to destruction of the vessels [7]. Each type of laser emits a different wavelength with a different penetration depth. PDL has become the first choice for the treatment of vascular dermatoses due to its excellent therapeutic efficiency and the fact that it has fewer side effects. It is still the “gold standard” for the treatment of port-wine stains (PWS) [8], one form of vascular malformations. Clinically, both the 585-nm and 595-nm PDL are frequently used for treatment [8]. However, of the two the 595-nm PDL is preferred for treatment of deeper vascular lesions due to its wavelength [9]. In contrast, the 532-nm laser is used in superficial vascular lesions, but has possible side effects such as scarring and pigmented anomalies [10]. Another option is the application of intense pulsed light (IPL), which is preferentially used for dilatation of blood vessels and PWS of superficial lesions [11].

Diagnosis and classification should be confirmed before treatment with laser and photon therapy, because the treatment effect strongly depends on the skin thickness, the color and the depth of the lesion, the size of the vessels and the distribution sites of the lesion. This means that different treatment parameters are necessary for different individuals. Laser and photon therapy treatments have been seen to make an effect on vascular dermatoses but as yet have not presented satisfactory results, for example, only 10% of PWS could be completely cured during multiple laser treatments [12] and PDL had no effect on nearly 30% of the lesions.

Photodynamic therapy (PDT) might be a good alternative light-based therapy for vascular dermatoses, having the selective specificity to target tissues. The photosensitizer (PS) accumulates selectively in the lesions, and a photochemical reaction occurs at certain wavelength involving oxygen. The generated substances, such as reactive oxygen, directly or indirectly react with the targeted cells to achieve the therapeutic objective [13]. Compared with other treatments, PDT has a higher selectivity and fewer side effects [14]. As a result, it is gradually becoming one of the first-choice treatments for vascular dermatoses. Usually, an intravenous injection of PS, for example, hematoporphyrin monomethyl ether (HMME), is used for PDT [15]. In this issue, Wei et al. [16] report on effects of a 532-nm continuous laser combined with HMME-PDT compared to 595-nm PDL treatment. The experiments were conducted on chicken combs, a common model for vascular malformations. The authors concluded that both treatment options could damage capillaries in the superficial dermis of combs, with fewer side effects after HMME-PDT but with a lower inefficiency rate if the 595-nm PDL was used [16]. In another contribution, Feng et al. [17] focused on the calibration of a three-dimensional (3D) PDT illumination system and its segmentation assessment for PWS. A checkerboard calibration method using color-coding was proposed to calibrate both projector and camera of the 3D digital PDT illumination system with a broad common field-of-view.

PDT has an excellent effect with sound research having been made with PWS, but further study is required on hemangiomas. Although PDL has advantages, there are still some shortcomings, which need to be overcome, such as a long dark period after treatment and the relatively high cost of treatment, etc. The choice and optimization of both the PS and the light source, and other parameters require further improvement.

3 Light and lasers on fungal infectious diseases

While laser therapy is becoming popular to treat fungal nail infection, it is not widely used for cutaneous infections. There are a number of laser therapy options available for treatment of onychomycosis. Many of these systems have released preliminary clinical trials data to substantiate their efficacy in the treatment of onychomycosis.

Laser light causes local hyperthermia, destruction of pathogenic microorganisms and stimulation of the reparative process. Laser treatment of onychomycosis uses the principle of selective photothermolysis [7]. Laser therapy exploits the differences in laser energy absorption and thermal conductivity between the fungal infection and the surrounding tissue. The absorption of light energy by fungi results in the conversion of energy into heat or mechanical energy [18]. Fungi are heat sensitive above 55°C, so absorption of laser energy that results in sustained photothermal heating of the mycelium (≥10 min) is likely to result in a fungicidal effect [19].

Different types of laser have been studied for their effect on treating onychomycosis, for example, long-pulse, short-pulse and Q-switched Nd:YAG lasers, diode lasers, mode-locked and fractional CO₂ lasers, of which the long-pulse Nd:YAG laser is being used the most. It is suspected that due to its longer wavelength, long-pulse Nd:YAG laser is able to penetrate tissue more deeply and thereby efficiently target fungal overgrowth in the nail bed. Laser treatment for onychomycosis produces satisfactory results. It can be used to treat different types of onychomycosis and is especially suitable for older patients with low immunity, or liver and renal dysfunction, for whom systemic therapy would not be appropriate [20].

Against this background, Spezzia-Mazzocco et al. [21] report on the in-vitro effect of antimicrobial photodynamic therapy (aPDT) with methylene blue (MB) in six dermatophyte fungi of the Trichophyton and Microsporum genera that present a health risk, including a new fungus (T. tonsurans) that has been never treated before with MB in vitro. It was shown that MB is an effective PS to inhibit fungal growth through aPDT, reaching a complete inhibition for most of the fungi tested. For T. tonsurans a repeated exposure to aPDT treatment with low-power light revealed better results than a single exposure with higher power.

4 Light and lasers on acne

Laser and light-based therapies are emerging as alternative treatments for acne patients who do not respond to or cannot be treated with conventional therapy. These therapies work either by killing the Propionibacterium acnes directly or by selectively damaging sebaceous glands, depending on the wavelength of light used [22]. However, targeting both the P. acnes as well as the sebaceous glands appears to be the best approach. UV phototherapy is only used very rarely in the treatment of acne due to the carcinogenic potential [23]. Trials of blue light, blue-red light and infrared radiation have proved to be more successful. Blue and red light may act synergistically in the treatment of acne due to the bactericidal effects of blue light and anti-inflammatory effects of red light. Compared with topical and systemic therapies, laser and light therapies have few, if any, side effects [24] and appear to be safe for use during pregnancy.

5 Light and lasers on skin cancer

Skin cancer is a major and common form of cancer, with non-melanoma types [non-melanoma skin cancer (NMSC)] such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), being the most frequent types. Laser ablation is an alternative, non-surgical treatment modality for skin cancer such as low-risk BCC; however, lack of confirmative tumor destruction or residual tumor presence has been a limiting factor to adoption [25]. Karsai et al. [26] verified that 595-nm PDL is an effective and safe method for treating superficial BCC. However, the occurrence of persistent dyspigmentation still limits the therapy success in terms of an excellent cosmetic outcome. Ortiz et al. [27] put forward that the 1064-nm long-pulsed Nd:YAG laser could offer a safe alternative for treating BCC outside of the face with a prospective, non-randomized, open-label clinical trial. A larger study is required to confirm these preliminary results.

Among all the alternative treatments used for NMSC, also PDT should be highlighted, not only because of its high efficacy but also because of the excellent cosmetic results [28]. Sometimes lasers such as the CO₂ laser can be combined with PDT to remove some refractory lesions, as has been proved in our clinic. However, there are still limitations to PDT. Tumor thickness and hyperkeratosis are the principle obstacles for PS penetration. Different techniques have been used to diminish the tumor size or to increase the penetration of the PS. In our clinical work, we succeeded in increasing the penetration of PS by plum-blossom needle and to enhance the efficacy of PDT [29]. The use of keratolytic agents or curettage before PDT is mandatory for a successful PDT. In addition, studies of new types of PS and new light sources also provide hope to improve PDT effect.

6 Light and lasers on other skin disease

In addition to the above-mentioned indications, there are some other skin targets of light and laser, such as viral skin diseases, mostly for verruca vulgaris. The CO₂ laser is the best ablative approach, producing cure rates for therapy-resistant common warts. Considering non-ablative approaches, PDL can be used for a selective, non-bloody destruction of extragenital and genital warts and may become the treatment of choice especially in the treatment of recalcitrant warts. It is assumed that the success of PDL treatment lies in the fact that warts contain an increased number of dilated blood vessels [30]. In this issue, Bigge and Bigge [31] present results of the treatment of recalcitrant viral warts using a 577-nm wavelength, high-power optically pumped semiconductor laser. Ten out of 12 patients treated for warts showed complete clearance after treatment. One patient had partial clearance and one did not respond at all. No scarring occurred after treatment, and no recurrence of the warts could be observed in the 6-month follow-up.

Laser irradiation treatment also provides a safe and effective alternative for herpetic pain; the most commonly used lasers here are diode and HeNe lasers. Although none of the laser treatment modalities is able to eliminate the virus completely or prevent its recurrence, laser phototherapy appears to strongly decrease both pain and the interval of recurrences without causing any side effects [32].

Photoaging is another hotspot for treatment with light and lasers. Ablative lasers (pulsed CO₂ lasers and erbium laser) and non-ablative lasers (1440–1565 nm) seem to improve photoaging with fewer side effects [33]. IPL therapy is also recognized as one of the most common methods to treat photoaging, as it is safe and effective. Additionally, we could show that IPL-PDT and red-light PDT can achieve a better rejuvenation effect than IPL or red light alone on the skin of the neck [34].

7 Conclusions

There have been rapid developments in the use of laser and light technology in the treatment of vascular and skin diseases, but large-scale clinical trials are still required to compare their efficacy.

This is also the case for other laser applications, three of which are introduced here. Assis et al. [35] investigated the enhancement of muscle regeneration through modulation of inflammatory markers, accentuating possible applications of the low-level laser therapy which can induce physiological reactions when it interacts with cell membranes, cellular organelles and enzymes. In a case series of 32 patients, Bashenow et al. [36] used a 1318-nm Nd:YAG laser for the resection of limited forms of pulmonary tuberculosis and stated a high level of efficacy and excellent aero- and hemostatic properties with a low rate of post-operative complications even though further studies in large groups of patients are needed. Last but by no means least, Gobbo et al. [37] generated expressive results in the treatment of anal cancer patients who had to undergo different anticancer therapies, including radiotherapy, and were suffering from radiodermatitis. Radiodermatitis is a debilitating side effect of radiotherapy, often leading to painful lesions and a suspension of the radiotherapy treatment. Up to now, no widely recognized treatment of radiodermatitis has been available underlining the importance of search for effective treatment options.

We hope that this issue of Photonics & Lasers in Medicine will encourage both scientists and physicians to continue to search for better and effective treatment methods.