Diffey BL

E. Eadie

M. Khazova

P. O'Mahoney

S. Ibbotson

English

O'Mahoney, Paul

Khazova, Marina

Ibbotson, Sally

Eadie, Ewan

University of Dundee Online Publications

                                                                    University of DundeeThe effects of sunscreen use and window glass on daylight photodynamic therapydosimetryO'Mahoney, Paul; Khazova, Marina; Ibbotson, Sally; Eadie, EwanPublished in:British Journal of DermatologyDOI:10.1111/bjd.17895Publication date:2019Document VersionPeer reviewed versionLink to publication in Discovery Research PortalCitation for published version (APA):O'Mahoney, P., Khazova, M., Ibbotson, S., & Eadie, E. (2019). The effects of sunscreen use and window glasson daylight photodynamic therapy dosimetry. British Journal of Dermatology, 181(1), 220-221.https://doi.org/10.1111/bjd.17895General rightsCopyright and moral rights for the publications made accessible in Discovery Research Portal are retained by the authors and/or othercopyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated withthese rights. • Users may download and print one copy of any publication from Discovery Research Portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain. • You may freely distribute the URL identifying the publication in the public portal.Take down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Download date: 27. Apr. 2021The effects of sunscreen use and window glass on daylight photodynamic therapy dosimetry Paul O’Mahoney1,2,3, Marina Khazova4, Sally Ibbotson1,2,3 and Ewan Eadie1,2 1. Photobiology Unit, NHS Tayside, Ninewells Hospital, Dundee, United Kingdom 2. The Scottish Photodynamic Therapy Centre, Dundee, United Kingdom 3. University of Dundee, Dundee, United Kingdom 4. Public Health England, Didcot, United Kingdom Funding sources: P.O’M. is funded by Medi-lase (registered charity SC 037390) and the Alfred Stewart Trust. Conflicts of interest: S.I. has received honoraria and travel expenses from Galderma and Spirit Healthcare. P.O’M. has received travel expenses from Galderma. Word Count: 750  Daylight photodynamic therapy (dPDT) is a widely used treatment in the management of field-change actinic keratoses (AK).1 Daylight PDT relies on natural daylight activating photosensitisers (typically protoporphyrin-IX, PpIX) in diseased tissue to initiate PDT effects. During the delivery of dPDT, it is recommended that a minimum PpIX-effective light dose is delivered to the treatment site.2 PpIX-effective light dose is the product of the spectral irradiance of the light source and the normalised PpIX absorption spectrum, integrated over the treatment duration. The current European guidelines suggest a minimum PpIX-effective dose of 8 J cm-2, though other research suggests that this may be lower.3–5 Daylight PDT may be undertaken using daylight through window glass in situations where there is ample daylight, but the outdoor conditions are unfavourable. Standard practice in dPDT involves application of a high SPF sunscreen on all exposed sites prior to pro-drug application and subsequent sun exposure. It is recommended that organic (chemical) sunscreens are used, which filter only the ultraviolet (UV) part of the spectrum.1 However, the absorption spectrum of PpIX extends into the UVA (<400 nm), and therefore some sunscreens may attenuate light that might otherwise activate PpIX. This means that in published literature the reported dose may be higher than the actual dose delivered to the skin, depending upon the sunscreen used. We would like to initiate discussion, considering the following. A spectral irradiance measurement is taken in clear skies (13:00 GMT 14/05/14, Chilton, UK). This measurement is weighted for PpIX absorption, and then weighted for either the transmission spectra of double-glazed window glass or one of several commercial sunscreens (Figure 1, sunscreen transmission measured with Labsphere UV1000 (Labsphere, New Hampshire), 2 mg cm-2 density on Transpore tape and quartz slide).6 The resultant PpIX-weighted dose values are compared for a 2 or 2.5-hour treatment duration in dPDT and conservatory-based dPDT respectively. The reduction in PpIX-weighted dose through different sunscreens varied, between a 38% and 92% reduction, while through window glass the PpIX dose was reduced by 22%. All sunscreens measured have some visible light attenuation (>400 nm), and critically at the 408 nm absorption peak of PpIX.7 One of the first published studies on dPDT compared the PpIX and P20 SPF20 (Riemann A/S, Denmark) absorption spectra, which at the time had a formulation with significant UVA transmission.2 However, the formulation has updated in the intervening years to attenuate more UVA resulting in a theoretically lower PpIX dose. Additionally, Actinica® (Galderma, Switzerland), one of the most commonly used sunscreens in dPDT, absorbed heavily in the UVA and reduced the PpIX dose to 35% of the unfiltered dose. This may explain, in part, our own experience with dPDT, which has tended to show lower efficacy rates than those in published studies following single dPDT treatments.8 UVA and visible light attenuation by sunscreens may in part explain this difference, with particular relevance at more northerly latitudes with less daylight and thus more likely to deliver below the minimum dose threshold. A reduction in dose is also seen for conservatory-based dPDT, which is accounted for with longer recommended treatment times, but there remains a lower reduction in dose compared with sunscreens. Our results highlight the large differences in PpIX-effective dose depending on the sunscreen used and, therefore, careful consideration of the choice of sunscreen is important. Ideally the spectral transmission of the sunscreen should be known; our results show that simply relying on organic sunscreens may not be adequate (from Figure 1, 5 of 9 sunscreens contain only organic filters). In our clinic, sunscreen is applied by trained nurses, however with variation in application and considering self-administered dPDT, higher doses to the skin may result than presented here. Previous published literature has not always considered the absorption of different sunscreens and their impact on PpIX-effective dose and therefore it may be that simple comparisons between studies are not always applicable. Daylight PDT is still an effective treatment however, perhaps due to centres typically performing dPDT in favourable weather conditions, therefore avoiding the minimum dose by delivering high doses of light. Daylight PDT continues to evolve, and with more diverse methodology comes a need for more detailed understanding of dosimetry. It is important that the dosimetry underlying effective dPDT is detailed in order to provide confidence to practitioners that effective doses are delivered. Awareness that both sunscreen choice and use, and window glass reduce the effective dose of light delivery by a variable, yet significant amount is helpful in determining dose regimes to compensate and avoid potential loss of efficacy.  1 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 Dermatology Venereol 2015; 29:1718–23. 2 Wiegell SR, Haedersdal M, Eriksen P, Wulf HC. Photodynamic therapy of actinic keratoses with 8% and 16% methyl aminolaevulinate and home-based daylight exposure: a double-blinded randomized clinical trial. Br J Dermatol 2009; 160:1308–14. 3 Rubel DM, Spelman L, Murrell DF, et al. Daylight photodynamic therapy with methyl aminolevulinate cream as a convenient, similarly effective, nearly painless alternative to conventional photodynamic therapy in actinic keratosis treatment: a randomized controlled trial. Br J Dermatol 2014; 171:1–8. 4 O’Gorman SM, Clowry J, Manley M, et al. Artificial White Light vs Daylight Photodynamic Therapy for Actinic Keratoses. JAMA Dermatology 2016; 152:1–7. 5 Lerche C, Heerfordt I, Heydenreich J, Wulf HC. Alternatives to Outdoor Daylight Illumination for Photodynamic Therapy—Use of Greenhouses and Artificial Light Sources. Int J Mol Sci 2016; 17:309. 6 Diffey BL, Robson J. A new substrate to measure sunscreen protection factors throughout the ultraviolet spectrum. J Soc Cosmet Chem 1989; 133:127–33. 7 Prahl S. Protoporphyrin IX dimethyl ester [WWW Document]. URL http://omlc.org/spectra/PhotochemCAD/html/149.html [accessed on 25 July 2016]. 8 Cordey H, Valentine R, Lesar A, et al. Daylight photodynamic therapy in Scotland. Scott Med J 2017; 62:48–53.      Figure 1. a) Sunscreen and window glass spectral transmission data. Sunscreen transmission data only available up to 450 nm, transmission above 450 nm assumed to be spectrally flat. Sunscreens categorised by labelled SPF rating, and whether they contain organic (O) and/or inorganic (I) filters. b) PpIX dose (± standard deviation) is calculated for each sunscreen transmission (mean for five transmission measurements on each sample) and through window glass for a representative daylight spectrum (350-800 nm) and treatment duration, and the resultant percentage reduction in dose is displayed.  

The effects of sunscreen use and window glass on daylight photodynamic therapy dosimetry

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                                                                    University of DundeeThe effects of sunscreen use and window glass on daylight photodynamic therapydosimetryO'Mahoney, Paul; Khazova, Marina; Ibbotson, Sally; Eadie, EwanPublished in:British Journal of DermatologyDOI:10.1111/bjd.17895Publication date:2019Document VersionPeer reviewed versionLink to publication in Discovery Research PortalCitation for published version (APA):O'Mahoney, P., Khazova, M., Ibbotson, S., & Eadie, E. (2019). The effects of sunscreen use and window glasson daylight photodynamic therapy dosimetry. British Journal of Dermatology, 181(1), 220-221.https://doi.org/10.1111/bjd.17895General rightsCopyright and moral rights for the publications made accessible in Discovery Research Portal are retained by the authors and/or othercopyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated withthese rights. • Users may download and print one copy of any publication from Discovery Research Portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain. • You may freely distribute the URL identifying the publication in the public portal.Take down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Download date: 03. Sep. 2023The effects of sunscreen use and window glass on daylight photodynamic therapy dosimetry Paul O’Mahoney1,2,3, Marina Khazova4, Sally Ibbotson1,2,3 and Ewan Eadie1,2 1. Photobiology Unit, NHS Tayside, Ninewells Hospital, Dundee, United Kingdom 2. The Scottish Photodynamic Therapy Centre, Dundee, United Kingdom 3. University of Dundee, Dundee, United Kingdom 4. Public Health England, Didcot, United Kingdom Funding sources: P.O’M. is funded by Medi-lase (registered charity SC 037390) and the Alfred Stewart Trust. Conflicts of interest: S.I. has received honoraria and travel expenses from Galderma and Spirit Healthcare. P.O’M. has received travel expenses from Galderma. Word Count: 750  Daylight photodynamic therapy (dPDT) is a widely used treatment in the management of field-change actinic keratoses (AK).1 Daylight PDT relies on natural daylight activating photosensitisers (typically protoporphyrin-IX, PpIX) in diseased tissue to initiate PDT effects. During the delivery of dPDT, it is recommended that a minimum PpIX-effective light dose is delivered to the treatment site.2 PpIX-effective light dose is the product of the spectral irradiance of the light source and the normalised PpIX absorption spectrum, integrated over the treatment duration. The current European guidelines suggest a minimum PpIX-effective dose of 8 J cm-2, though other research suggests that this may be lower.3–5 Daylight PDT may be undertaken using daylight through window glass in situations where there is ample daylight, but the outdoor conditions are unfavourable. Standard practice in dPDT involves application of a high SPF sunscreen on all exposed sites prior to pro-drug application and subsequent sun exposure. It is recommended that organic (chemical) sunscreens are used, which filter only the ultraviolet (UV) part of the spectrum.1 However, the absorption spectrum of PpIX extends into the UVA (<400 nm), and therefore some sunscreens may attenuate light that might otherwise activate PpIX. This means that in published literature the reported dose may be higher than the actual dose delivered to the skin, depending upon the sunscreen used. We would like to initiate discussion, considering the following. A spectral irradiance measurement is taken in clear skies (13:00 GMT 14/05/14, Chilton, UK). This measurement is weighted for PpIX absorption, and then weighted for either the transmission spectra of double-glazed window glass or one of several commercial sunscreens (Figure 1, sunscreen transmission measured with Labsphere UV1000 (Labsphere, New Hampshire), 2 mg cm-2 density on Transpore tape and quartz slide).6 The resultant PpIX-weighted dose values are compared for a 2 or 2.5-hour treatment duration in dPDT and conservatory-based dPDT respectively. The reduction in PpIX-weighted dose through different sunscreens varied, between a 38% and 92% reduction, while through window glass the PpIX dose was reduced by 22%. All sunscreens measured have some visible light attenuation (>400 nm), and critically at the 408 nm absorption peak of PpIX.7 One of the first published studies on dPDT compared the PpIX and P20 SPF20 (Riemann A/S, Denmark) absorption spectra, which at the time had a formulation with significant UVA transmission.2 However, the formulation has updated in the intervening years to attenuate more UVA resulting in a theoretically lower PpIX dose. Additionally, Actinica® (Galderma, Switzerland), one of the most commonly used sunscreens in dPDT, absorbed heavily in the UVA and reduced the PpIX dose to 35% of the unfiltered dose. This may explain, in part, our own experience with dPDT, which has tended to show lower efficacy rates than those in published studies following single dPDT treatments.8 UVA and visible light attenuation by sunscreens may in part explain this difference, with particular relevance at more northerly latitudes with less daylight and thus more likely to deliver below the minimum dose threshold. A reduction in dose is also seen for conservatory-based dPDT, which is accounted for with longer recommended treatment times, but there remains a lower reduction in dose compared with sunscreens. Our results highlight the large differences in PpIX-effective dose depending on the sunscreen used and, therefore, careful consideration of the choice of sunscreen is important. Ideally the spectral transmission of the sunscreen should be known; our results show that simply relying on organic sunscreens may not be adequate (from Figure 1, 5 of 9 sunscreens contain only organic filters). In our clinic, sunscreen is applied by trained nurses, however with variation in application and considering self-administered dPDT, higher doses to the skin may result than presented here. Previous published literature has not always considered the absorption of different sunscreens and their impact on PpIX-effective dose and therefore it may be that simple comparisons between studies are not always applicable. Daylight PDT is still an effective treatment however, perhaps due to centres typically performing dPDT in favourable weather conditions, therefore avoiding the minimum dose by delivering high doses of light. Daylight PDT continues to evolve, and with more diverse methodology comes a need for more detailed understanding of dosimetry. It is important that the dosimetry underlying effective dPDT is detailed in order to provide confidence to practitioners that effective doses are delivered. Awareness that both sunscreen choice and use, and window glass reduce the effective dose of light delivery by a variable, yet significant amount is helpful in determining dose regimes to compensate and avoid potential loss of efficacy.  1 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 Dermatology Venereol 2015; 29:1718–23. 2 Wiegell SR, Haedersdal M, Eriksen P, Wulf HC. Photodynamic therapy of actinic keratoses with 8% and 16% methyl aminolaevulinate and home-based daylight exposure: a double-blinded randomized clinical trial. Br J Dermatol 2009; 160:1308–14. 3 Rubel DM, Spelman L, Murrell DF, et al. Daylight photodynamic therapy with methyl aminolevulinate cream as a convenient, similarly effective, nearly painless alternative to conventional photodynamic therapy in actinic keratosis treatment: a randomized controlled trial. Br J Dermatol 2014; 171:1–8. 4 O’Gorman SM, Clowry J, Manley M, et al. Artificial White Light vs Daylight Photodynamic Therapy for Actinic Keratoses. JAMA Dermatology 2016; 152:1–7. 5 Lerche C, Heerfordt I, Heydenreich J, Wulf HC. Alternatives to Outdoor Daylight Illumination for Photodynamic Therapy—Use of Greenhouses and Artificial Light Sources. Int J Mol Sci 2016; 17:309. 6 Diffey BL, Robson J. A new substrate to measure sunscreen protection factors throughout the ultraviolet spectrum. J Soc Cosmet Chem 1989; 133:127–33. 7 Prahl S. Protoporphyrin IX dimethyl ester [WWW Document]. URL http://omlc.org/spectra/PhotochemCAD/html/149.html [accessed on 25 July 2016]. 8 Cordey H, Valentine R, Lesar A, et al. Daylight photodynamic therapy in Scotland. Scott Med J 2017; 62:48–53.      Figure 1. a) Sunscreen and window glass spectral transmission data. Sunscreen transmission data only available up to 450 nm, transmission above 450 nm assumed to be spectrally flat. Sunscreens categorised by labelled SPF rating, and whether they contain organic (O) and/or inorganic (I) filters. b) PpIX dose (± standard deviation) is calculated for each sunscreen transmission (mean for five transmission measurements on each sample) and through window glass for a representative daylight spectrum (350-800 nm) and treatment duration, and the resultant percentage reduction in dose is displayed.  

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The effects of sunscreen use and window glass on daylight photodynamic therapy dosimetry

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