The Importance of Your Light Source for Photodynamic Therapy

PDT

Photodynamic therapy (PDT) has been used for a variety of dermatologic conditions for many years. In the United States, PDT is considered an effective first-line therapy for treatment of skin with actinic keratoses (AK). PDT is a common therapeutic option in dermatology practices. The most commonly used photosensitizer is aminolevulinic acid (ALA). Sold under  several different brand names worldwide and a variety of formulations, ALA, and variations/derivatives, is considered today’s safest and most effective PDT photosensitizing drug.1,2 

Mechanism of Action

Conventional PDT for the treatment of AKs, and in Europe basal cell carcinoma (BCC) and nonmelanoma skin cancer, involves the photoactivation of protoporphyrin IX (PpIX). This occurs after prodrug ALA application and uptake, PpIX selectively accumulates in the atypical, dysplastic, or malignant cells. Upon illumination, photoactivation and photobleaching of PpIX occurs, generating oxidative stress and free radical reactive oxygen species (ROS). This initiates inflammation and ensuing cytotoxicity, resulting in preferential apoptosis and necrosis of abnormal cells.

To generate a therapeutic effect, the spectral output of the light source should correspond to the excitation peaks of the photosensitizer. PpIX has 2 important therapeutic peaks, 404 to 420 nm in the violet-blue spectrum, and 633 nm in the red wavelength region. The depth of light penetration into the skin increases with longer wavelengths. Although blue light allows sufficient tissue penetration for the treatment of superficial AKs, red light penetrates much deeper into skin (up to 8-mm deep) and is more effective for the treatment of thicker lesions such as BCCs when combined with ALA.3 

Updates on Photosensitizer and Light Sources

Compared with the US market, more photosensitizer options for PDT are available in Europe. For example, most photosensitizers are approved for, and used with, red light PDT. Levulan Kerastick (DUSA Pharmaceuticals, Inc) was the first ALA photosensitizer to gain FDA approval in the United States. Ameluz (Biofrontera) has recently entered the US market as a new ALA photosensitizer in nanoemulsion. Ameluz uses a red light-emitting diode (LED) system with a compact LED array named BF-RhodoLED. DUSA markets a U-shaped fluorescent bulb blue light source, aptly named the BLU-U, for PDT in conjunction with its ALA Kerastick. 

Other light sources are available in the US market that use the same wavelength of blue light as with the DUSA device and the same red light as with the Biofrontera device and offer dermatologists additional applications beyond just ALA-PDT. The leading commercially-available LED system worldwide is the Omnilux LED System (GlobalMed Technologies). The Omnilux device (Figure) is modular, and includes: red (633 nm), blue (415 nm), and infrared (830 nm) wavelength-specific light heads that are used for a wide variety of dermatologic applications, including blue light or red light PDT (although this is considered an off-label use by the FDA.)

Practice Implications

Practically speaking, how can dermatologists integrate visible light phototherapy into their practice now, and what are some of the key benefits for patients? LEDs represent a very interesting technological advance in dermatology. LED-based systems are exciting as they represent cost-effective methods to deliver light-based energy efficiently to skin that can allow for a large area to be treated depending on the device used. Several key advantages to using the Omnilux light source for PDT, and specifically the red LED light wavelength-based array, includes: less ROS generated by LED red light compared with blue light, increased depth of penetration, cost of unit, and modular ability to add or decrease array heads based on physician, practice, and patient needs. LEDs also have greater longevity and a more convenient small form factor compared with fluorescent bulb light arrays and can offer greater peak power.

The Omnilux red light system has been studied in combination with Ameluz and demonstrated good efficacy in Ameluz phase 3 studies, and the Omnilux LED red light system (PhotoMedex) generated similar improvements in AKs to the BF-RhodoLED light.4

The Omnilux LED red light system has several advantages that make it an ideal light source:

  • The FDA-cleared professional Omnilux LED System has been clinically studied by Biofrontera in 2 phase 3 clinical trials and demonstrated to yield equivalent clinical results in reduction of AKs.
  • The treatment field size is significantly larger than other systems and can cover an entire face, allowing for a full face to be treated in a single 10-minute irradiation session.
  • The adjustable panels also allow for the treatment of curved areas of the body.
  • The modular nature allows for updating and swapping of LED panels to enable the system to be used for other applications, many without photosensitizers. These include acne treatment, skin rejuvenation, wound healing, and in conjunction with commonly used aesthetic procedures such as injections, chemical peels, laser resurfacing, and microneedling to reduce skin trauma and promote healing.

The Omnilux System has been studied extensively for many years and validated in more than 30 controlled clinical studies published in peer-reviewed journals.5 

Conclusion

PDT has safely been used for many years and is considered an effective treatment for a range of indications. Scientific research has led to a greater understanding of the pharmacokinetics and is leading to the development of more effective photosensitizers. Light sources are often overlooked—but play an important role in the delivery and success of PDT treatment. LEDs are considered by most experts to be reliable and are the preferred method of light delivery for PDT. It is important to consider many aspects and factors when selecting the LED light source that best fits your clinical practice.

In the United States, PDT applications have previously been limited by lack of photosensitizer options and remained mainly for treatment of AKs. However, the introduction of Ameluz in the United States for AKs and the renaissance of red light PDT in the United States provides advantages for dermatologists and patients. LEDs offer dermatologists a proven, validated light source for use in PDT applications and many other dermatologic uses. 

 

jagdeoDr Jagdeo is an associate professor of dermatology at University of California, Davis in Davis, CA. 

 

Disclosure: Dr Jagdeo’s disclosures include: honorarium (Nutrafol, L’Oreal/SkinCeutifcals, GlobalMed Technologies), speaker (L’Oreal/SkinCeuticals), Scientific Advisory Board (Heliocare, GlobalMed Technologies), Consultant (Biofrontera).

 

References

1. Pariser DM, Houlihan A, Ferdon MB, Berg JE; PDT-AK Investigational Group. Randomized vehicle-controlled study of short drug incubation aminolevulinic acid photodynamic therapy for actinic keratoses of the face or scalp. Dermatol Surg. 2016;42(3):296-304. 

2. Reinhold U, Dirschka T, Ostendorf R, et al. A randomized, double-blind, phase III, multicentre study to evaluate the safety and efficacy of BF-200 ALA (Ameluz®) vs. placebo in the field-directed treatment of mild-to-moderate actinic keratosis with photodynamic therapy (PDT) when using the BF-RhodoLED® lamp. Br J Dermatol. 2016;175(4):696-705.

3. Biofrontera announces 12-month follow-up results of phase III trial evaluating Ameluz® for basal cell carcinoma [press release]. Leverkusen, Germany: Biofrontera AG; October 20, 2016. http://adhoc.pressetext.com/news/20161020019. Accessed January 26, 2018.

4. Dirschka T, Radny P, Dominicus R, et al; AK-CT002 Study Group. Photodynamic therapy with BF-200 ALA for the treatment of actinic keratosis: results of a multicentre, randomized, observer-blind phase III study in comparison with a registered methyl-5-aminolaevulinate cream and placebo. Br J Dermatol. 2012;166(1):137-46.

5. Bibliography for acne (mild to moderate acne vulgaris). Omnilux website. http://omniluxled.com/bibliography/. Accessed January 26, 2018.