Effectiveness & Safety of PDT
In the following paragraphs, the results and the findings of various studies relating to the effectiveness and safety of Photodynamic Therapy are presented and discussed.
In one study the effectiveness of PDT using topical ALA was examined for the treatment of acne vulgaris. A total number of 22 patients with acne at their back participated and they followed treatment in four sites with ALA plus red light, ALA alone, light alone or no treatment. More specifically 20% ALA was applied with 3 hours occlusion and half of the subjects were treated once while the other half four times. The researchers concluded that the combination of ALA and red light resulted in clinically and statistically significant decrease of inflammatory acne. This improvement was evident for at least 20 weeks following multiple therapeutic sessions and for at least 10 weeks following one treatment session.
The use of red light (635 nm) either with or without the application of a photosensitiser has also been investigated in a study with the participation of ten patients with mild to moderate acne. According to the results, statistically significant reduction of inflammatory lesions was evident after the second therapeutic session using red light for 10 minutes and ALA 20% cream in occlusion for 3 hours. However, there was no statistically significant reduction neither in relation to P. acnes number nor in relation to sebum excretion. Therefore, the researchers conclude that PDT using ALA does not cause direct damage to the sebaceous glands and it does not eliminate completely P. acnes.
Similar results regarding PDT mechanism of action in relation to acne have also been demonstrated in another more recent study. More specifically, in this study fifteen participants were examined, who followed treatment using ALA-PDT. Although statistically significant improvement in terms of acne severity was noticed following the end of treatment, sebum excretion was not affected and the number of P. acnes was not reduced.
In another randomised controlled trial both effectiveness and tolerability of MAL-PDT were assessed using red light at 635-nm for the treatment of moderate to severe inflammatory facial acne. A total number of thirty patients participated and, according to the results, MAL-PDT led to statistically significant reduction of the number of inflammatory lesions compared to PDT plus placebo at 12 week, with a mean reduction of 54% for the MAL-PDT group versus 20% for the placebo-PDT group. In addition to this, ΜAL-PDT was related to more severe pain during treatment, although intensity of pain was reduced with repeated treatment.
The purpose of another recent study was to compare the efficacy and tolerability of therapy using red light only, or red light in combination with PDT (MAL-PDT) in patients with mild to moderate facial acne. The study was controlled and the researchers were blind to the treatment regimen, which followed by the total number of thirty six patients participating in the study. MAL cream was applied on the face for 90 minutes and then red light was applied with mean wavelength of 635 nm. The researchers concluded that both therapeutic interventions reduced acne severity significantly at week 10, with the group following MAL-PDT showing quicker clinical response as compared to the group receiving treatment with red light only. However, MAL-PDT was related to more severe pain and erythema than therapy with red light only.
As far as the effectiveness of the combination of PDT and red light at 633 nm and ALA is concerned, similar findings were also shown by another study. The researchers concluded that the combination of a low dose of ALA and red light constitutes a safe and effective method for the treatment of moderate to severe acne.
Various studies have also focused on the comparison between photodynamic therapy using ALA and MAL. In a comparative study with the participation of fifteen patients with acne on the face PDT was applied on one half of the face using MAL and on the other half PDT was applied using ALA. Although no statistically significant differences were found between the two photosensitisers in terms of effectiveness, PDT using ALA led to more prolonged and serious adverse events, such as erythema and flaking. Moreover, the patients in both groups evaluated pain as moderate to severe during illumination.
In a recent retrospective study conducted with the participation of twenty dermatology clinics of Italy PDT using MAL was evaluated for various indications, among which acne vulgaris was included. As far as acne treatment is concerned, the researchers underline that more than 75% reduction was evident for the majority of the patients (72.8%).
As already mentioned, ΜAL cream itself is not a photosensitiser. Porphyrins are the active photosensitisers in ΜΑL-PDT. When MAL cream is applied to the skin it results in the selective accumulation of porphyrins. MAL cream, the methyl ester of ALA has been shown by certain studies to penetrate more easily into target lesions and be more selective in the accumulation of porphyrins.
According to the analysis of the results, acne severity was significantly decreased after the completion of the necessary treatment sessions. This finding is consistent with many of the results of the studies discussed in the present article. In addition to this, other studies of MAL-PDT using red light studies have shown a reduction of inflammatory lesions between 60 and 70% three months after the completion of treatment.
Improvement in terms of acne severity may have been further enhanced by the combined use of blue and red light, which seem to work synergistically. This has been proposed by other research studies too and it could be explained by the combination of the antibacterial and anti-inflammatory actions. The application of two sources of light following a 20-min interval was performed due to the different penetration depth of blue and red light at 750 μm and 2000 μm respectively and in order to allow the necessary time interval for the re-oxygenation of photosensitised tissues, where the photosensitizing agent has been applied.