Black ceiling tiles reduce occupational ultraviolet light exposure from phototherapy cabinets.

Phototherapy clinics administer ultraviolet (UV) light to patients using phototherapy cabinets. The UV radiation from these cabinets is reflected on the white ceiling tiles of the clinic and is then redirected toward both staff and patients in the area. This is particularly problematic for clinical technologists who must undertake dosimetry in these areas and have a specific time (often as low as 30 min) before they reach their maximum exposure limit. By replacing white tiles with black ones, which absorb any stray radiation, we were able to reduce stray reflection by almost 90%, prolonging the time to maximum exposure by nearly 10 times. We present these findings to encourage other similar clinics to undertake the simple protocols outlined in this article, which will significantly improve staff and patient safety.

Simulating photodynamic therapy for the treatment of glioblastoma using Monte Carlo radiative transport.

Significance: Glioblastoma (GBM) is a rare but deadly form of brain tumor with a low median survival rate of 14.6 months, due to its resistance to treatment. An independent simulation of the INtraoperative photoDYnamic therapy for GliOblastoma (INDYGO) trial, a clinical trial aiming to treat the GBM resection cavity with photodynamic therapy (PDT) via a laser coupled balloon device, is demonstrated. Aim: To develop a framework providing increased understanding for the PDT treatment, its parameters, and their impact on the clinical outcome. Approach: We use Monte Carlo radiative transport techniques within a computational brain model containing a GBM to simulate light path and PDT effects. Treatment parameters (laser power, photosensitizer concentration, and irradiation time) are considered, as well as PDT's impact on brain tissue temperature. Results: The simulation suggests that 39% of post-resection GBM cells are killed at the end of treatment when using the standard INDYGO trial protocol (light fluence = 200 J/cm2 at balloon wall) and assuming an initial photosensitizer concentration of 5 µM. Increases in treatment time and light power (light fluence = 400 J/cm2 at balloon wall) result in further cell kill but increase brain cell temperature, which potentially affects treatment safety. Increasing the p hotosensitizer concentration produces the most significant increase in cell kill, with 61% of GBM cells killed when doubling concentration to 10 µM and keeping the treatment time and power the same. According to these simulations, the standard trial protocol is reasonably well optimized with improvements in cell kill difficult to achieve without potentially dangerous increases in temperature. To improve treatment outcome, focus should be placed on improving the photosensitizer. Conclusions: With further development and optimization, the simulation could have potential clinical benefit and be used to help plan and optimize intraoperative PDT treatment for GBM.

222 nm Far-UVC from filtered Krypton-Chloride excimer lamps does not cause eye irritation when deployed in a simulated office environment.

Far-UVC, from filtered Krypton-Chloride lamps, is promising for reducing airborne transmission of disease. While significant research has been undertaken to investigate skin safety of these lamps, less work has been undertaken on eye safety. There is limited data on human eye safety or discomfort from the deployment of this germicidal technology. In this pilot study, immediate and delayed eye discomfort were assessed in a simulated office environment with deployment of Krypton-Chloride lamps, located on the ceiling and directed downwards into the occupied room. Discomfort was assessed immediately postexposure and several days after exposure using validated, Standard Patient Evaluation Eye Dryness (SPEED) and Ocular Surface Disease Index (OSDI) questionnaires. Our results show no significant eye discomfort or adverse effects from the deployment of Far-UVC in this simulated office environment, even when lamps were operated continuously with participants receiving head exposures of up to 50 mJ cm-2 . In addition, a statistically significant reduction in bacteria and fungi of 52% was observed. Far-UVC in this simulated office environment did not cause any clinically significant eye discomfort and was effective at reducing pathogens in the room. These results contribute an important step to further investigation of the interaction of Far-UVC with the human eye.

Assessing the safety of new germicidal far-UVC technologies.

The COVID-19 pandemic underscored the crucial importance of enhanced indoor air quality control measures to mitigate the spread of respiratory pathogens. Far-UVC is a type of germicidal ultraviolet technology, with wavelengths between 200 and 235 nm, that has emerged as a highly promising approach for indoor air disinfection. Due to its enhanced safety compared to conventional 254 nm upper-room germicidal systems, far-UVC allows for whole-room direct exposure of occupied spaces, potentially offering greater efficacy, since the total room air is constantly treated. While current evidence supports using far-UVC systems within existing guidelines, understanding the upper safety limit is critical to maximizing its effectiveness, particularly for the acute phase of a pandemic or epidemic when greater protection may be needed. This review article summarizes the substantial present knowledge on far-UVC safety regarding skin and eye exposure and highlights research priorities to discern the maximum exposure levels that avoid adverse effects. We advocate for comprehensive safety studies that explore potential mechanisms of harm, generate action spectra for crucial biological effects and conduct high-dose, long-term exposure trials. Such rigorous scientific investigation will be key to determining safe and effective levels for far-UVC deployment in indoor environments, contributing significantly to future pandemic preparedness and response.

Potential harm to the skin from unfiltered krypton chloride 'far-ultraviolet-C' lamps, even below an occupational exposure limit.

Ultraviolet-C (UVC) radiation can effectively inactivate pathogens on surfaces and in the air. Due to the potential for harm to skin and eyes, human exposure to UVC should be limited within the guideline exposure limits produced by the International Commission on Non-Ionising Radiation Protection (ICNIRP) or the American Conference of Governmental Industrial Hygienists (ACGIHs). Both organisations state an effective spectrally weighted limit of 3 mJ cm-2, although the spectral weighting factors of the two organisations diverged following a revision of the ACGIH guidelines in 2022. Using existing published human exposure data, the effective spectrally weighted radiant exposure was calculated for both unfiltered and filtered (to reduce UV emissions above 230 nm) krypton chloride (KrCl*) excimer lamps. The effective radiant exposure of the filtered KrCl* lamp was greater than 3 mJ cm-2when applying ICNIRP or either of the revised ACGIH spectral weightings. This indicates that both guidelines are appropriately conservative for this specific lamp. However, the effective radiant exposure of the unfiltered KrCl* lamp was as low as 1 mJ cm-2with the revised ACGIH weighting function that can be applied to the skin if the eyes are protected. Erythema has therefore been directly observed in a clinical study at an exposure within the revised ACGIH guideline limits. Extrapolating this information means that a mild sunburn could be induced in Fitzpatrick skin types I and II if that particular ACGIH weighting function were applied and an individual received an effective exposure of 3 mJ cm-2. Whilst it is improbable that such an effect would be seen in current deployment of KrCl* lamp technology, it does highlight the need for further research into skin sensitivity and irradiance-time reciprocity for UVC wavelengths.

Far-UVC (222 nm) efficiently inactivates an airborne pathogen in a room-sized chamber.

Many infectious diseases, including COVID-19, are transmitted by airborne pathogens. There is a need for effective environmental control measures which, ideally, are not reliant on human behaviour. One potential solution is Krypton Chloride (KrCl) excimer lamps (often referred to as Far-UVC), which can efficiently inactivate pathogens, such as coronaviruses and influenza, in air. Research demonstrates that when KrCl lamps are filtered to remove longer-wavelength ultraviolet emissions they do not induce acute reactions in the skin or eyes, nor delayed effects such as skin cancer. While there is laboratory evidence for Far-UVC efficacy, there is limited evidence in full-sized rooms. For the first time, we show that Far-UVC deployed in a room-sized chamber effectively inactivates aerosolised Staphylococcus aureus. At a room ventilation rate of 3 air-changes-per-hour (ACH), with 5 filtered-sources the steady-state pathogen load was reduced by 98.4% providing an additional 184 equivalent air changes (eACH). This reduction was achieved using Far-UVC irradiances consistent with current American Conference of Governmental Industrial Hygienists threshold limit values for skin for a continuous 8-h exposure. Our data indicate that Far-UVC is likely to be more effective against common airborne viruses, including SARS-CoV-2, than bacteria and should thus be an effective and "hands-off" technology to reduce airborne disease transmission. The findings provide room-scale data to support the design and development of effective Far-UVC systems.

Turn Up the Lights, Leave them On and Shine them All Around-Numerical Simulations Point the Way to more Efficient Use of Far-UVC Lights for the Inactivation of Airborne Coronavirus.

It has been demonstrated in laboratory environments that ultraviolet-C (UVC) light is effective at inactivating airborne viruses. However, due to multiple parameters, it cannot be assumed that the air inside a room will be efficiently disinfected by commercial germicidal ultraviolet (GUV) systems. This research utilizes numerical simulations of airflow, viral spread, inactivation by UVC and removal by mechanical ventilation in a typical classroom. The viral load in the classroom is compared for conventional upper-room GUV and the emerging "Far-UVC." In our simulated environment, GUV is shown to be effective in both well and poorly ventilated rooms, with greatest benefit in the latter. At current exposure limits, 18 commercial Far-UVC systems were as effective at reducing viral load as a single upper-room GUV. Improvements in Far-UVC irradiation distribution and recently proposed increases to exposure limits would dramatically increase the efficacy of Far-UVC devices. Modifications to current Far-UVC devices, which would improve their real-world efficacy, could be implemented now without requiring legislative change. The prospect of increased safety limits coupled with our suggested technological modifications could usher in a new era of safe and rapid whole room air disinfection in occupied indoor spaces.

Depth Penetration of Light into Skin as a Function of Wavelength from 200 to 1000 nm.

An increase in the use of light-based technology and medical devices has created a demand for informative and accessible data showing the depth that light penetrates into skin and how this varies with wavelength. These data would be particularly beneficial in many areas of medical research and would support the use and development of disease-targeted light-based therapies for specific skin diseases, based on increased understanding of wavelength-dependency of cutaneous penetration effects. We have used Monte Carlo radiative transport (MCRT) to simulate light propagation through a multi-layered skin model for the wavelength range of 200-1000 nm. We further adapted the simulation to compare the effect of direct and diffuse light sources, varying incident angles and stratum corneum thickness. The lateral spread of light in skin was also investigated. As anticipated, we found that the penetration depth of light into skin varies with wavelength in accordance with the optical properties of skin. Penetration depth of ultraviolet radiation was also increased when the stratum corneum was thinner. These observations enhance understanding of the wavelength-dependency and characteristics of light penetration of skin, which has potential for clinical impact regarding optimizing light-based diagnostic and therapeutic approaches for skin disease.

Computer Modeling Indicates Dramatically Less DNA Damage from Far-UVC Krypton Chloride Lamps (222 nm) than from Sunlight Exposure.

This study aims to investigate, with computer modeling, the DNA damage (assessed by cyclobutane pyrimidine dimer (CPD) formation) from far-ultraviolet C (far-UVC) in comparison with sunlight exposure in both a temperate (Harwell, England) and Mediterranean (Thessaloniki, Greece) climate. The research utilizes the published results from Barnard et al. [Barnard, I.R.M (2020) Photodermatol. Photoimmunol. Photomed. 36, 476-477] to determine the relative CPD yield of unfiltered and filtered far-UVC and sunlight exposure. Under current American Conference of Governmental Industrial Hygienists (ACGIH) exposure limits, 10 min of sunlight at an ultraviolet (UV) Index of 4-typical throughout the day in a temperate climate from Spring to Autumn-produces equivalent numbers of CPD as 700 h of unfiltered far-UVC or more than 30 000 h of filtered far-UVC at the basal layer. At the top of the epidermis, these values are reduced to 30 and 300 h, respectively. In terms of DNA damage induction, as assessed by CPD formation, the risk from sunlight exposure greatly exceeds the risk from far-UVC. However, the photochemistry that will occur in the stratum corneum from absorption of the vast majority of the high-energy far-UVC photons is unknown, as are the consequences.

Global verification of a model for determining daylight photodynamic therapy dose.

Daylight photodynamic therapy is an effective treatment for actinic keratoses and relies on a minimum PpIX-effective light exposure dose being delivered during treatment. As such, daylight dosimetry is an important aspect of this treatment. Relatively simple measurements of illuminance may be converted to PpIX-effective irradiance, and subsequently exposure dose, via a conversion model (the O'Mahoney model). This model has been verified against spectral irradiance data from the UK, however the accuracy of the model has not been determined outside the UK. In this work, we test the O'Mahoney model against spectral irradiance measurements from several global locations to within bounds of a median deviation of ±10 %. The median percentage deviations are shown to be independent of location latitude and longitude. The model can be used confidently to determine PpIX-effective irradiance from illuminance measurements irrespective of location and can be widely implemented as an effective and low-cost means of accurately measuring effective light exposure for this important treatment.

Extreme Exposure to Filtered Far-UVC: A Case Study†.

Far-UVC devices are being commercially sold as "safe for humans" for the inactivation of SARS-CoV-2, without supporting human safety data. We felt there was a need for rapid proof-of-concept human self-exposure, to inform future controlled research and promote informed discussion. A Fitzpatrick Skin Type II individual exposed their inner forearms to large radiant exposures from a filtered Krypton-Chloride (KrCl) far-UVC system (SafeZoneUVC, Ushio Inc., Tokyo, Japan) with peak emission at 222 nm. No visible skin changes were observed at 1500 mJ cm-2 ; whereas, skin yellowing that appeared immediately and resolved within 24 h occurred with a 6000 mJ cm-2 exposure. No erythema was observed at any time point with exposures up to 18 000 mJ cm-2 . These results combined with Monte Carlo Radiative Transfer computer modeling suggest that filtering longer ultraviolet wavelengths is critical for the human skin safety of far-UVC devices. This work also contributes to growing arguments for the exploration of exposure limit expansion, which would subsequently enable faster inactivation of viruses.

Development of a Predictive Monte Carlo Radiative Transfer Model for Ablative Fractional Skin Lasers.

It is possible to enhance topical drug delivery by pretreatment of the skin with ablative fractional lasers (AFLs). However, the parameters to use for a given AFL to achieve the desired depth of ablation or the desired therapeutic or cosmetic outcome are hard to predict. This leaves open the real possibility of overapplication or underapplication of laser energy to the skin. In this study, we developed a numerical model consisting of a Monte Carlo radiative transfer (MCRT) code coupled to a heat transfer and tissue damage algorithm. The simulation is designed to predict the depth effects of AFL on the skin, verified with in vitro experiments in porcine skin via optical coherence tomography (OCT) imaging. Ex vivo porcine skin is irradiated with increasing energies (50-400 mJ/pixel) from a CO2 AFL. The depth of microscopic treatment zones is measured and compared with our numerical model. The data from the OCT images and MCRT model complement each other well. Nonablative thermal effects on surrounding tissue are also discussed. This model, therefore, provides an initial step toward a predictive determination of the effects of AFL on the skin. Lasers Surg. Med. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.

Research Techniques Made Simple: Experimental UVR Exposure.

UVR exposure is a widely applied technique in clinical and preclinical studies. Such experimental conditions provide crucial information on the biological responses of skin and cell models, which may then be extrapolated and interpreted, for example, in the context of equivalent daylight exposures. It is therefore important to fully understand the characteristics of UVR and the principles behind correct and appropriate UVR exposure in experimental settings. In this Research Techniques Made Simple article, we discuss the relevant background information and the best practices for accurate, transparent, and reproducible experimentation and reporting of UVR exposure.

SmartPDT®: Smartphone enabled real-time dosimetry via satellite observation for daylight photodynamic therapy.

BACKGROUND: Actinic keratosis (AK) affects one quarter of over 60  year olds in Europe with the risk of transforming into invasive squamous cell carcinoma. Daylight photodynamic therapy (dPDT) is an effective and patient preferred treatment that uses sunlight to clear AK. Currently, there is no standardised method for measuring the light received during treatment. METHODS: SmartPDT® is a smartphone-based application and web-portal, developed by siHealth Ltd, enabling remote delivery of dPDT. It uses satellite imagery and computational algorithms to provide real-time determination of exposure to PpIX-effective solar radiation ("light dose"). The application also provides forecast of expected radiant exposures for 24- and 48-hs prior to the treatment period. Validation of the real-time and forecasted radiant exposure algorithms was performed against direct ground-based measurement under all weather conditions in Chilton, UK. RESULTS: Agreement between direct ground measurements and satellite-determined radiant exposure for 2-h treatment was excellent at -0.1 % ± 5.1 % (mean ±â€¯standard deviation). There was also excellent agreement between weather forecasted radiant exposure and ground measurement, 1.8 % ± 17.7 % at 24-hs and 1.6 % ± 25.2 % at 48-hs. Relative Root Mean Square of the Error (RMSEr) demonstrated that agreement improved as time to treatment reduced (RMSEr = 22.5 % (48 -hs), 11.2 % (24-hs), 5.2 % (real-time)). CONCLUSION: Agreement between satellite-determined, weather-forecasted and ground-measured radiant exposure was better than any existing published literature for dPDT. The SmartPDT® application and web-portal has excellent potential to assist with remote delivery of dPDT, an important factor in reducing risk in an elderly patient population during the Covid-19 pandemic.

Bring the Sunshine Indoors: Easy Dosimetry for Indoor Daylight Photodynamic Therapy.

Daylight photodynamic therapy (DPDT) is an effective and patient preferred treatment for the management of field change actinic keratosis. An important factor in DPDT is light dosimetry, to ensure that patients receive sufficient daylight for effective treatment, and this is the focus of the contribution to this issue by (La Rochelle et al. [2019] Photochem. Photobiol., https://doi.org/10.1111/php.13170). In this work, the authors present an easy-to-use method for obtaining real-time information about patient received light dose during treatment and for determining indoor locations best suited to DPDT.