A consensus on the use of daylight photodynamic therapy in the UK

Figures & data

Figure 1. Wavelength-dependent penetration of blue, green, yellow and red light in PDT. Arrows indicate the approximate 50% optical penetration depth in human skin. Reproduced with permission (34).

Figure 2. Meteorological data for the UK, showing the daily average light irradiances throughout the year between 09:00 and 18:00 (Panel a) and the days with >1.0 mm precipitation (Panel b; personal communication). The threshold above which efficacy appears to be independent of light irradiance (130 W/m²) (24) is indicated by the dashed line.

Table 1. Information on average UK weather conditions 1986–2005 (personal communication).

Average UK weather conditions for d-PDT
• Average temperatures were above 10 °C from March to November in the south (below 53°L – south of Nottingham), and from April to October in the north (above 53°L).
• Average light irradiances were above 130 W/m^2 (and hence were sufficient for d-PDT) from March to September in the north and from March to October in the south (Figure 2(a)).
• On average, 30–35% of days experience some rain between March and October (Figure 2(b)). However, the time and duration of the rainfall were not specified, i.e. it may have been brief or at night, bearing in mind that d-PDT requires a two-hour rain-free exposure.

Table 2. d-PDT Protocol considerations.

Protocol consideration	UK expert comment
Acceptable characteristics of sunscreen	In order to block only UV (but allow visible light to activate PpIX), a chemical sunscreen without reflective filters must be used.
Skin preparation	Using an emollient prior to treatment could be sufficient instead of more formal preparation as long as the lesions were thin. Otherwise, standard preparation as for c-PDT (light curettage, using a disposable ring curette, without local anaesthesia or any surface bleeding, is standard practice prior to conventional PDT, if there is surface crust or hyperkeratosis).
Quantities of MAL to use	For simplicity, one tube per area. Clinical studies have shown that dose (i.e. thickness of layer) does not influence outcomes and less is required compared with c-PDT (36). One tube is sufficient to treat the face or scalp.
Time before exposure	Exposure within 30 min is ideal, longer time before exposure can result in increased discomfort due to PpIX accumulation.
Weather	Treatment must be given in the recommended months (Figure 2) but otherwise the weather should not affect the decision to treat unless it is too cold or wet for the patient to be outside. If treatment is interrupted by rain before the patient has received 30 min exposure, the MAL should be removed and the patient's treatment should be rescheduled for another day. If the patient has received >30 min exposure, response should be assessed against the exposure time achieved.
Impact of indoor breaks during daylight exposure	Ideally, exposure should be continuous, and indoor breaks should be kept to a minimum to avoid further PpIX accumulation, which is associated with an increased risk of discomfort.
Removal of MAL	It does not appear to matter how removal is achieved but, for simplicity, the use of emollient or water and drying with towels is suggested.
Follow-up	- Follow-up telephone call the next day to establish that treatment was successfully undertaken and to ask about adverse effects may be advisable.
	- Cover the treated area to avoid UV exposure for 24 h.
	- Immunocompetent patients – Next appointment usually six weeks to three months depending on extent and severity of disease treated.
	- Immunocompromised patients – Usually 4–6 weeks.

Figure 3. European consensus protocol for daylight photodynamic therapy (d-PDT) compared with protocol for conventional PDT (c-PDT). Adapted from (11,36).

Table 3. Patient understanding for treatment with d-PDT.

Key concepts patients should understand to undertake d-PDT:

- Why AKs are usually treated

- Other treatment options available for AKs

- How d-PDT works using visible light (not UV)

- How long it takes

- The risks and side effects of treatment and how to deal with them (e.g. information on cooling/flannels, moisturiser, no anti-inflammatories)

- How to choose the setting for their treatment (e.g. at home, hospital site, suitable off-site space) and the potential benefits of undertaking d-PDT such as undertaking outdoor activities during the sun exposure phase

Patients should also understand the protocol, in particular:

- The necessity to protect normal skin with appropriate chemical sunscreen to limit UV exposure (as d-PDT only requires visible light) with a healthy message regarding sun protection practices in general

- Include a clear message on suitable weather conditions and what to do regarding interruptions

- Dose/thickness of cream

- The necessity to limit the incubation time prior to daylight exposure to 30 min maximum if possible to minimise discomfort during the illumination phase

- The need to avoid covered time/time indoors during the two hours of daylight exposure

- The need to avoid applying MAL to certain areas of the face (eyes/mouth etc.)

- The need to cover the area and avoid further exposure to natural daylight or intense internal lighting for 24 h after completing treatment

- The option to be available for a follow-up call the next day to record information on treatment and adverse effects should be considered

Table 4. Summary of recommendations.

Summary of recommendations

1. Patients suitable for d-PDT may be those with:

- AKs Grades I and II on the face and scalp

- Multiple and widespread AKs (field areas)

- With good surface preparation using a disposable ring curette, it may be feasible to undertake successful PDT for Grade III AK, but this would be off licence use and we would not recommend this as a treatment of choice

2. Patients who choose to remain at the hospital for the duration of the procedure should be provided with:

- An outdoor area, which has been risk assessed, and/or an appropriate indoor area for daylight exposure in case it rains

- Supervision during the exposure period; groups of patients could be treated at the same time to minimise pressure on staff

3. Patients who choose to leave the hospital following application of MAL should be provided with:

- Careful instructions about the importance of beginning daylight exposure within 30; the duration of the exposure period; what to do in the event of rain or other interruption, and how to remove MAL at the end of the exposure period

4. Patient education and advice

- A simple video/animation explaining the treatment and protocol would be helpful for discussion with patients (and could ultimately be available online for patients to refer to if they are completing care at home)

- General information on the treatment

- A free patient advice line to give patients access to advice (especially in the event that home treatment becomes possible) could also be helpful

- Future sun exposure and photoprotection advice for patients with AKs and with skin cancer

Sakamoto FH, Torezan L, Anderson RR. Photodynamic therapy for acne vulgaris: a critical review from basics to clinical practise: Part II. Understanding parameters for acne treatment with photodynamic therapy. J Am Acad Dermatol. 2010;63:195–211.

 PubMed Web of Science ®Google Scholar

Wiegell SR, Fabricius S, Stender IM, et al. A randomised, multicentre study of directed daylight exposure times of 1½ vs. 2½ h in daylight-mediated photodynamic therapy with methyl aminolaevulinate in patients with multiple thin actinic keratoses of the face and scalp. Br J Dermatol. 2011;164:1083–90.

 PubMed Web of Science ®Google Scholar

Morton CA, Wulf HC, Szeimies RM, et al. Practical approach to the use of daylight photodynamic therapy with topical methyl aminolevulinate for actinic keratosis: a European consensus. J Eur Acad Dermatol Venereol. 2015;29:1718–23.

 PubMed Web of Science ®Google Scholar

Metvix SPC [Internet] [cited 2015 May 2]. Available from http://www.medicines.org.uk/emc/medicine/11913.

 Google Scholar