The Two Faces of Fractionated Photodynamic Therapy: Increasing Efficacy With Light Fractionation or Adjuvant Use of Fractional Laser Technology

November 2016 | Volume 15 | Issue 11 | Original Article | 1324 | Copyright © November 2016

Margit L.W. Juhasz MD,a,b Melissa K. Levin MD,a and Ellen S. Marmur MDa,c

aMarmur Medical, New York, NY bIcahn School of Medicine at Mount Sinai, New York, NY cThe Mount Sinai Hospital, New York, NY

“Fractionated photodynamic therapy (PDT)” is a new term being used by dermatologists to describe advances in PDT technology including fractionated light or the adjuvant use of fractional lasers. Although dermatologists have used PDT since the early 1990s for the treatment of photodamage and precancerous lesions, newer developments in technology have allowed for the treatment of non-melanoma skin cancers (NMSCs), in ammatory disorders, and even uses in the eld of anti-aging. Recent developments in fractionated light therapy have allowed for PDT with dark intervals and two-fold illumination schemes to increase cellular damage and apoptosis. Combining PDT with fractional laser technology has allowed for enhanced dermal penetration of topical photosensitizers including 5-aminolevulinic acid (ALA) and methyl aminolevulinate (MAL), as well as increased ef cacy of treatment. These advances in PDT technology will allow for increased convenience, decreased treatment time, only one application of topical photosensitizer, and decreased cost to the patient and dermatologist. J Drugs Dermatol. 2016;15(11):1324-1328.


Since its introduction in the 1990s, photodynamic therapy (PDT) has become a staple for the treatment of cutaneous pre-cancerous and cancerous lesions, as well as photorejuvenation. The application of topical hematoporphyrin derivatives, such as 5-aminolevulinic acid (ALA) or its methylated counterpart methyl aminolevulinate (MAL), and exposure to a light source, allows metabolically active cells to endogenously produce protoporphyrin IX (PpIX), a photosensitizer, which results in the destruction of these cells through formation of reactive oxygen species (ROS). Success of PDT treatment depends on a variety of factors including type of photosensitizer, duration of exposure to topical photosensitizer, penetration of the topical photosensitizing agent into the skin or lesion, concentration of PpIX formed (if it even reaches therapeutic levels), type of light source, and length of exposure to said light source. All these factors can be modified in various ways to increase efficacy of the treatment including destruction of epidermal barriers or decreasing the thickness of the treatable lesion (topical keratolytic agents, curettage, dermabrasion, tape-stripping, micro needling, etc.) to allow for further penetration of the photosensitizing compound, increasing exposure to the light source, and accumulating more endogenous PpIX during the treatment session. This review will focus on two novel methods to increase PDT efficacy.

Fractionation Two Ways

As with many entities in the medical field, the terminology used becomes rather ambiguous when referring to “fractionated” or “fractional” PDT. For instance, in a landmark paper by Hass et al, the term “fractionated” refers to the PDT light source as a two-fold illumination scheme with a dark interval of two hours between each light treatment. In essence, these authors are referring to a “fractionated” light delivery system.1 However, in another ground-breaking paper by Ruiz-Rodriquez et al, these authors refer to “fractional” PDT in which a fractional resurfacing laser device is used as an adjuvant therapy to allow for deeper penetration of topical photosensitizer. In other words, this use of “fractional” refers to a separate laser device used prior to administration of PDT.2 It is important as dermatologists to understand the differences and advantages of both of these methods as they both improve PDT outcomes but by different means.

Fractional Light Delivery (Two-Fold Illumination) and PDT

Background of light fractionationIn the early 1990s, it was noted that tumors treated with fractionated X-ray irradiation fared significantly better than those treated with a single-dose.3 Given this remarkable finding, researchers applied this theory to other sources of waves on the electromagnetic spectrum, including PDT. Preliminary research in vitro showed that meta-tetrahydroxyphenylchorin (mTHPC) and the methyoxy-PEG2000 water soluble version (mTHPC-MD) combined with fractionated light (652 nm, 0.05 s duration) applied in on-off cycles with a 30-60 s dark period,