Patent Publication Number: US-2023145771-A1

Title: Photodynamic therapy illuminator devices and methods

Description:
CROSS-REFERENCE TO RELATED APPLICATION(S) 
     The present application claims priority to U.S. Provisional Application No. 63/276,312 filed Nov. 5, 2021, the entire contents of which are incorporated herein by reference. 
    
    
     FIELD 
     The present disclosure relates generally to devices and methods for photodynamic therapy. 
     BACKGROUND 
     Photodynamic therapy (PDT), photodynamic diagnosis (PD), and/or photochemotherapy generally involve treating and/or diagnosing several types of diseases or disorders relating to the skin or other tissues, such as those in a body cavity. PDT can include administering photoactivatable agents and exposing a patient to photoactivating light to activate the agents and convert them to cytotoxic form, to destroy cells associated with a disease or disorder of the skin. For example, photodynamic therapy or photodynamic diagnosis may be used for treatment or diagnosis of actinic keratosis (AK) of the upper extremities (e.g., the dorsal surface of the hand or forearms), the scalp or facial areas of a patient, among other locations. AK is typically caused by overexposure to ultraviolet (UV) light and may present on the face, head, scalp, ears, shoulders, neck, arms, forearms and hands, for example. 
     In addition, PDT or PD may be used for treatment and diagnosis of other indications (e.g., acne, warts, psoriasis, photo-damaged skin, cancer) and other areas of the patient (e.g., the legs or portions of the arms other than the forearms, the back, the abdomen, the chest, or another portion of a body). PDT using UV or blue light is indicated for the treatment of mild to moderate acne, due to anti-inflammatory effects on skin cells. The combination of a photoactivatable agent and high intensity red light has been found effective, yet can have significant side effects. 
     During a form of photodynamic therapy, a patient is first administered a photoactivatable agent or a precursor of a photoactivatable agent that accumulates in the tissue to be treated. The area to which the photoactivatable agent is administered is then exposed to light, which causes chemical and/or biological changes in the agent. These changes allow the agent to then selectively locate, destroy, or alter the target tissue while, at the same time, causing at most only mild and reversible damage to other tissues in the treatment area. One example of a precursor of a photoactivatable agent is 5-aminolevulinic acid (“ALA” or “5-ALA”), which is commonly used in photodynamic therapy of actinic keratosis. As used herein, the terms ALA or 5-aminolevulinic acid refer to ALA itself, precursors thereof, esters thereof and pharmaceutically acceptable salts of the same, such as aminolevulinic acid hydrochloride (HCl). Photosensitization following application of a topical composition (e.g., a topical solution, an emulsion, a nanoemulsion, a gel) containing ALA occurs through the metabolic conversion of aminolevulinic acid to protoporphyrin IX (“PpIX”). PpIX is a photosensitizer which accumulates in the skin. 
     Illuminators are typically used to provide the proper uniformity of light for treatment purposes. These devices generally include a light source (e.g., a fluorescent tube or light emitting diode (LED)), coupling elements that direct, filter or otherwise conduct emitted light so that it arrives at its intended target in a usable form, and a control system that starts and stops the production of light when necessary. 
     Photodynamic therapy may be carried out using certain compositions, such as ALA, in connection with illuminators. Such compositions and/or illuminators (as well as methods of treatment, dressings, and other details) are disclosed, for example, in (1) U.S. Pat. No. 5,954,703 to Golub, entitled “Method and apparatus for applying 5-aminolevulinic acid,” issued on Sep. 21, 1999, (2) U.S. Pat. No. 6,223,071 to Lundahl et al., entitled “Illuminator for photodynamic therapy and diagnosis which produces substantially uniform intensity visible light,” issued on Apr. 24, 2001, (3) U.S. Pat. No. 10,814,114 to Boyajian et al., entitled “Method and apparatus for applying a topical solution,” issued on Oct. 27, 2020, (4) U.S. Pat. No. 10,589,122 to Boyajian et al., entitled “Adjustable illuminator for photodynamic therapy and diagnosis,” issued on Mar. 17, 2020, (5) U.S. Patent Application Publication No. 2020/0246630 to Boyajian et al, entitled “Adjustable illuminator for photodynamic therapy and diagnosis,” published on Aug. 6, 2020, (6) U.S. Pat. No. 11,179,574 to Boyajian et al., entitled “Method of administering 5-aminolevulinic acid (ALA) to a patient,” issued on Nov. 23, 2021, (7) U.S. Pat. No. 10,603,508 to Boyajian et al., entitled “Adjustable illuminators and methods for photodynamic therapy and diagnosis,” issued on Mar. 31, 2020, and its child, U.S. Patent Application Publication No. 2020/0269063 published Aug. 27, 2020, (8) U.S. Pat. No. 10,357,567 to Lundahl et al., entitled “Methods for photodynamic therapy,” issued on Jul. 23, 2019, and its granted children, U.S. Pat. No. 11,077,192, issued on Aug. 3, 2021 and U.S. Pat. No. 11,135,293 issued on Oct. 5, 2021, and (9) U.S. Patent Application No. 2020/0261580 to Willey entitled “Photodynamic therapy method for skin disorders,” published on Aug. 20, 2020. The entire contents of the foregoing patents and/or patent applications are incorporated herein by reference for background information and the compositions, illuminators, devices, dressings, methods of treatment, processes and techniques relating to photodynamic therapy and diagnosis disclosed therein. 
     SUMMARY 
     The present disclosure describes illuminators for photodynamic therapy and associated techniques and methods of treatment. The illuminators allow improved maneuverability and control for treatment. 
     According to one embodiment, a method of performing photodynamic therapy is provided. The method includes applying, to the skin of a patient, a topical composition. The topical composition includes 5-aminolevulinic acid (ALA) hydrochloride, and a vehicle comprising at least one chelating agent to enhance accumulation of protoporphyrin IX (PpIX) in the skin. The method further includes incubating the topical composition, and following incubation, applying, to the skin, heat from a heat source for at least a first time period. 
     In at least one embodiment, the at least one chelating agent is selected from ethylenediaminetetraacetic acid (EDTA) or a pharmaceutically acceptable salt thereof. In at least one embodiment, the method includes, following incubation, exposing the skin to light from a light source for a second time period, wherein the heat is also applied during the second time period. In at least one embodiment, the incubation occurs for between about 2 hours to about 3 hours, and a sum of the first time period and the second time period is about 13 minutes. In at least one embodiment, light is not applied to the skin prior to applying the heat. In at least one embodiment, applying the heat to the skin for 13 minutes increases an amount of PpIX present in the skin by more than 50%. In at least one embodiment, applying the heat to the skin for 13 minutes increases an amount of PpIX present in the skin by more than 80%. In at least one embodiment, the aminolevulinic acid hydrochloride is present in an amount of 20% w/w of the topical composition, and the at least one chelating agent is ethylenediaminetetraacetic acid (EDTA) present in an amount of about 0.1% to about 0.15% of the topical composition. 
     According to one embodiment, an illuminator is provided with at least one articulated joint which is configured to allow the illuminator panels to be moved approximately 360 degrees in azimuth and then locked into position. In at least one embodiment, two joints are provided to enable 360 degree rotation. According to one embodiment, an illuminator is provided with a control panel or control interface which can be moved relative to the rest of the illuminator. These features allow the illuminator to be positioned in a desired position relative to the patient while allowing a health care provider access to the control panel or interface to administer, control, and monitor treatment. 
     The panels may be arranged in a variety of configurations to provide illumination to the area of the body being treated. Uniform illumination is desirable in order to impart a uniform therapeutic benefit to the area being treated. Embodiments described below provide a uniformity of greater than approximately 70% at approximately 2 to approximately 4 inches from the treatment surface (such that the measured output over the emitting area is within approximately 70% of the measured maximum over a distance of approximately two to approximately four inches). In at least one embodiment, the uniformity may be between approximately 70% and approximately 80%, e.g., between 72.5% and between 77.5%, over a distance of approximately 2 inches to approximately 4 inches. 
     In at least one embodiment, the panels may be unfolded and arranged in a flat or substantially flat arrangement to treat areas such as a back or chest and abdomen of a patient. The panels may also be arranged in a U-shape (corresponding to the letter “U”, or substantially similar to the letter “U”) in which the outer panels are parallel or substantially parallel to each other. The panels are configured to be arranged in a U-shaped orientation during treatment, for example, of the head, face, scalp, neck, arms, forearms, hands, feet and/or legs. The panels may be arranged parallel to the floor, perpendicular to the floor, or any other position with respect to the floor, including to treat other portions of a patient (e.g., the torso or back). The panels may have differing orientations such that a first panel may be parallel to the floor and another panel may be oriented at an incline relative to the floor. In at least one embodiment, the panels may be put in a pre-treatment configuration which is a configuration just prior to treatment, e.g., for the purpose of explication and providing a demonstration, instructions or education to the patient about the treatment taking place, and the panels may then be put in a “patient ready” position corresponding to the orientation conducive for treatment. 
     According to one embodiment, a storage arrangement is provided for an illuminator for photodynamic therapy which allows the illuminator to be folded up into a compact space when not in use. In this embodiment, the illuminator, including arms and panels thereof, when in a stored (stowed) position, does not extend substantially beyond the illuminator base. For example, the illuminator, including arms and panels, when in the stored position, does not extend more than 40%, 30%, 20%, 10%, or 0% beyond the illuminator base. In at least one embodiment, illuminator panels fold around an illuminator pillar in the stored position, thus facilitating a compact storage arrangement. Such a compact storage arrangement is a significant advantage to healthcare providers because the examination and treatment rooms in many medical offices are limited, and the compact storage arrangement provides additional space for patient examination and other types of treatment when the illuminator is not in use. In addition, such a compact arrangement, in conjunction with wheels on the base, allow the illuminator to easily fit through doorways and be moved to other examination and treatment rooms, or other facilities. 
     The illuminator may be configured to accommodate a patient who is standing, sitting, lying down, or in another position. In at least one embodiment, the panels may be adjusted from a first configuration to a second configuration rapidly. For example, the panels may be adjusted from a first configuration which is conducive to treating a patient&#39;s scalp or face to a second configuration which is conducive to treating a patient&#39;s back, or vice versa, within a time period of approximately 20-40 seconds or approximately 30 seconds. The various adjustments of the panels and arms can be accomplished quickly (within 30 to 60 seconds) and without tools. 
     The panels may support, for example, an array of light sources such as light emitting diodes (LEDs). Alternatively, other types of light sources may be used, such as fluorescent or halogen lamps, a non-laser light source, a laser, or other type of light source. The light sources provide illumination which activates a photoactivatable agent as discussed above. 
     The details of one or more embodiments are set forth in the accompanying drawings and the description below. The figures are provided for the purpose of illustrating one or more embodiments with the explicit understanding that they will not be used to limit the scope or the meaning of the claims. It should be noted that the specific embodiments are not intended as an exhaustive description or as a limitation to the broader aspects discussed herein. One aspect described in conjunction with a particular embodiment is not limited to that embodiment and can be practiced with other embodiment(s). 
     The following terms are used throughout this patent specification and are as defined below. 
     As used herein and in the appended claims, singular articles such as “a” and “an” and “the” and similar references in the context of describing the elements (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., “such as”) provided herein, is intended merely to better illustrate the embodiments and does not pose a limitation on the scope of the claims unless otherwise stated. No language in the specification should be construed as indicating any non-claimed element as essential. 
     The terms “incubation time,” “incubation period,” or “incubation” can refer to the time period from a time when a drug (such as ALA) is applied until a time when a treatment period begins, e.g., when illumination occurs. Speaking generally, an incubation time or incubation period can occur prior to a treatment period. For example, incubation time may be an interval from when a drug is applied (e.g., topically) until the commencement of deliberate exposure to targeted illumination by an illuminator (e.g., as opposed to ambient illumination), or commencement of a treatment step such as applying heat (or applying both heat and light). As will be understood by one of skill in the art, incubation may occur in the dark, which is most common. However, incubation may also occur in the presence of light, including daylight (e.g., so-called painless PDT). Incubation, whether in the dark or under light exposure, may take place with or without heat. 
     Any embodiment illustratively described herein may suitably be practiced in the absence of any element or elements. Thus, for example, the terms “comprising,” “including,” “containing,” etc., shall be read expansively and without limitation. Additionally, the terms and expressions employed herein have been used as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the claimed technology. Additionally, the phrase “consisting essentially of” will be understood to include those elements specifically recited and those additional elements that do not materially affect the basic and novel characteristics of the claimed technology. The expression “comprising” means “including, but not limited to.” Thus, other non-mentioned substances, additives, devices or steps may be present. 
     Unless otherwise indicated, all numbers expressing quantities of properties, parameters, conditions, and so forth, used in the specification and claims are to be understood as being modified in all instances by the terms “approximately” or “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and attached claims are approximations. Any numerical parameter should at least be construed in light of the number of significant digits and by applying ordinary rounding techniques. The terms “approximately” or “about” when used before a numerical designation, e.g., temperature, time, amount, and concentration, including range, indicates approximations which may vary by (+) or (−) 10%, 5% or 1%. 
     As will be understood by one of skill in the art, for any and all purposes, particularly in terms of providing a written description, all ranges disclosed herein also encompass any and all possible subranges and combinations of subranges thereof. Any listed range can be easily recognized as sufficiently describing and enabling the same range being broken down into at least equal halves, thirds, quarters, fifths, tenths, etc. As a non-limiting example, each range discussed herein can be readily broken down into a lower third, middle third and upper third, etc. As will also be understood by one skilled in the art all language such as “up to,” “at least,” “greater than,” “less than,” and the like include the number recited and refer to ranges which can be subsequently broken down into subranges as discussed above. Finally, as will be understood by one skilled in the art, a range includes each individual member. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Features, aspects, and advantages of the present invention will become apparent from the following description and the accompanying exemplary embodiments shown in the drawings, which are briefly described below. 
         FIG.  1    shows a front view of an illuminator system according to an exemplary embodiment. 
         FIG.  2    shows a top perspective view of the illuminator system of  FIG.  1   . 
         FIG.  3    shows a front perspective view of the illuminator system of  FIG.  1   . 
         FIG.  4    shows a rear view of the illuminator system of  FIG.  1   . 
         FIG.  5    shows a front perspective view of the illuminator system of  FIG.  1   . 
         FIG.  6    shows a top perspective view of a mounting mechanism of the illuminator system of  FIG.  1   . 
         FIG.  7    shows a side perspective view of a panel of the illuminator system of  FIG.  1   . 
         FIG.  8 A  shows side views of an illuminator of the illuminator system of  FIG.  1   . 
         FIG.  8 B  shows side views of an illuminator of the illuminator system of  FIG.  1   . 
         FIG.  9    shows a back view of an illuminator of the illuminator system of  FIG.  1   . 
         FIG.  10    shows a back view of an illuminator of the illuminator system of  FIG.  1   . 
         FIG.  11    shows a front view of the illuminator system of  FIG.  1    in a stored position. 
         FIG.  12    shows a perspective view of the illuminator system of  FIG.  1    in a stored position. 
         FIG.  13    shows a top view of a panel of the illuminator system of  FIG.  1   . 
         FIG.  14    shows a front view of an interface panel of the illuminator system of  FIG.  1   . 
         FIG.  15    shows a front view of a main power switch of the illuminator system of  FIG.  1   . 
         FIG.  16    shows a front view of a vertical column lock of the illuminator system of  FIG.  1   . 
         FIG.  17    shows a front view of an arm lock of the illuminator system of  FIG.  1   . 
         FIG.  18    shows a cross-sectional side view of a panel of the illuminator system of  FIG.  1   . 
         FIG.  19    shows a perspective view of a fan plenum of a panel of the illuminator system of  FIG.  1   . 
         FIG.  20    shows a detailed cross-sectional view of a fan plenum of the illuminator system of  FIG.  1   . 
         FIG.  21    shows a detailed cross-sectional view of a fan plenum of the illuminator system of  FIG.  1   . 
         FIG.  22    shows a detailed cross-sectional view of a fan plenum of the illuminator system of  FIG.  1   . 
         FIG.  23    shows a touch screen of the illuminator system of  FIG.  1   . 
         FIG.  24    shows a schematic diagram of a controller of the illuminator system of  FIG.  1   . 
         FIG.  25    shows a block diagram of a method of photodynamically diagnosing or treating a patient according to an exemplary embodiment. 
         FIG.  26    depicts graphical results relating to an amount of accumulated PpiX. 
         FIG.  27    depicts graphical results relating to an amount of accumulated PpiX. 
     
    
    
     DETAILED DESCRIPTION 
     Various embodiments are described hereinafter. It should be noted that the specific embodiments are not intended as an exhaustive description or as a limitation to the broader aspects discussed herein. One aspect described in conjunction with a particular embodiment is not limited to that embodiment and can be practiced with any other embodiment(s). 
     Treatment with Photodynamic Therapy Illuminator 
       FIGS.  1 - 4    illustrate at least one embodiment of a configurable illuminator system  105 . Illuminator system  105  includes an illuminator  100 . The illuminator  100  comprises a plurality of panels  10 . The panels  10  are provided with LEDs  60  that are used to emit light for photodynamic therapy for treatment of diseases and disorders of the skin (which may be defined as a multi-layer organ including the epidermis, dermis and subcutaneous tissue, and further including mucous membranes contiguous with the outer skin). The skin to be treated may be, for example, on the surface of the head, face, scalp, neck, arms, legs, torso, genitals, hands or feet, or elsewhere. 
     In particular, according to at least one embodiment, the head, face or neck may be treated using the illuminator  100 . Said treatment of the head, face or neck may occur at a single session all at one time or over multiple sessions over a period of time. The face encompasses, for example, a central portion, eyelids, eyebrows, the periorbital region, the nasal region, lips, chin, mandible, pre-auricular skin, post-auricular skin and sulci. These portions of the face, along with the genitals, hands and feet, may be at a relatively higher risk for developing non-melanoma skin cancer (“NMSC,” which includes all types of skin cancers that are not melanoma, and includes keratinocyte carcinomas). Moderate risk areas include the cheeks, forehead, scalp and neck. For assessing the efficacy of treatment, a lesion count in a given region may be performed in a designated area of the body, such as on the forehead, the left and right cheeks, nose, or chin. 
     Photodynamic therapy may cause certain individuals to experience discomfort and/or pain. In at least one embodiment, the illuminator provides a gentle flow of air tangential to the skin surface to reduce or minimize pain. The air flow may be provided substantially tangential to (that is substantially parallel to) the skin surface (at an angle of approximately 0 degrees with respect to the skin surface). Thus, a gentle flow is imparted across the surface to be treated. In another embodiment, the air is provided at an angle of 45° or less with respect to the skin surface. In at least one embodiment, the angle may be between approximately 25° and approximately 45°, e.g., approximately 29°, approximately 33°, approximately 37°, or approximately 41°. The air flow may be provided in connection with any treatment method set forth in the present disclosure. 
     Such an arrangement avoids the air directly impacting the skin surface. Direct impact on the skin surface has been found to cause pain or tingling due to the sensation (e.g., of contact or pressure) against the skin. In at least one embodiment, the gentle flow of air is provided to alleviate pain and/or discomfort that may be experienced by a patient who has undergone PDT with occlusion via a barrier, such as a low density polyethylene (LDPE) or foil barrier. In particular, the flow of cooled air may mitigate pain following administration of ALA to the patient during a treatment cycle. 
     The following description provides exemplary discussions of how particular areas may be treated using PDT, without limitation. In the following discussion, a distance between a treatment surface and a surface of an illuminator is approximately 2 inches to approximately 4 inches, but it should be appreciated that other distances may be utilized (e.g., between approximately 5 cm to approximately 8 cm). To treat facial lesions, an illuminator as described above may be positioned such that the region to be treated is between approximately 2 to approximately 4 inches from a surface of the illuminator, with the patient&#39;s nose not less than approximately 2 inches from the illuminator surface, and the forehead and cheeks no more than approximately 4 inches from the surface. The sides of the patient&#39;s face and the patient&#39;s ears may be positioned no closer than approximately 2 inches from the illuminator surface, for example. 
     In at least one embodiment, to treat scalp lesions, an illuminator as described above may be positioned such that the region to be treated is between approximately 2 to approximately 4 inches from a surface of the illuminator, with the patient&#39;s scalp not less than approximately 2 inches from the illuminator surface, and no more than approximately 4 inches from the surface. The sides of the patient&#39;s face and the patient&#39;s ears may be positioned no closer than approximately 2 inches from the illuminator surface, for example. 
     In at least one embodiment, to treat lesions on the upper extremities, such as the dorsal surface of the hand or the forearms, an illuminator as described above may be positioned such that the region to be treated is between approximately 2 to approximately 4 inches from a surface of the illuminator. Equipment (e.g., a table) may be used to support the upper extremity during light treatment so as to enhance the patient&#39;s comfort and stabilize the region to be treated. The aforementioned distances may be employed in connection with carrying out treatment according to any of the embodiments of the present disclosure. 
     In at least one embodiment, blue light (e.g., light having a wavelength between about 380 nm and about 500 nm) is applied. In at least one embodiment, blue light having a wavelength of about 417 nm (±5 nm) is applied at an intensity of about 10 mW/cm 2  for 1000 seconds to provide a dose of about 10 J/cm 2 . However, the intensity may be increased (for example, doubled to about 20 mW/cm 2 ) to reduce the treatment time. For example, the intensity may be increased so as to reduce the treatment time by about one-half. In other embodiments, red light (such as red light generated by light emitting diodes (LEDs) at, for example, 635 nm) may be used. The red light can provide a dose of, for example, about 10 to about 75 J/cm 2  (such as 37 J/cm 2 ), e.g., within 10 minutes, or within about 9 to about 11 minutes. The red light may be between about 620 nm and about 750 nm. 
     In at least one embodiment, the illuminator may irradiate the lesions with a uniform intensity red light for a prescribed period. In certain embodiments, the illuminator irradiates the lesions with a uniform intensity blue light for a first prescribed period and then irradiates the lesions with a uniform intensity red light for a second prescribed period. The wavelength of the irradiating light may be selected to match a wavelength which excites the photoactivatable agent, and preferably has low absorption by non-target tissues. For example, in at least one embodiment, the illuminator is configured to irradiate the lesions with a uniform intensity blue light (e.g., about 417 nm) at a low intensity (e.g., about 0.1 J/cm 2  to about 2 J/cm 2 ) to photobleach, for example, protoporphyrin IX (PpIX) present at the surface of the patient&#39;s skin. In at least one embodiment, the illuminator is configured to irradiate the lesions with a uniform intensity red light (e.g., 635 nm) at a high intensity (e.g., about 30 J/cm 2  to about 158 J/cm 2 ) to activate PpIX present at deeper layers of the patient&#39;s skin, thus avoiding potential damage to the upper layers of the patient&#39;s skin. 
     Furthermore, since the total light dose (J/cm 2 ) is equal to irradiance (mW/cm 2 ) multiplied by time (seconds), an additional parameter to be controlled for delivery of the correct treatment light dose is exposure time (among other parameters which may be controlled to influence treatment). This may be accomplished by a timer, which can control the electrical power supplied to the LED arrays appropriately, and which can be set by a healthcare provider. Data has shown that approximately 10 J/cm 2  delivered from a source with an irradiance density of 10 mW/cm 2 , or an irradiance density of approximately 9.3 to approximately 10.7 mW/cm 2 , produces clinically acceptable results for desired treatment areas (e.g., the face, scalp, and extremities). 
     In at least one embodiment, an adjustable illuminator may deliver an irradiance density of approximately 20 mW/cm 2  for an exposure time of approximately 580 seconds (approximately 8 min., 20 sec) to deliver a clinically acceptable light dose of 10 J/cm 2 . In certain embodiments, a lower intensity may be used with a longer exposure time (e.g., approximately 1,000 seconds of exposure time for a light dose of approximately 10 J/cm 2 ). Alternatively, the adjustable illuminator may include higher power ranges, such as approximately 30 mW/cm 2 , over an exposure time, resulting in a light dose of approximately 10 J/cm 2 . A selected light dose may also be administered by additionally or alternatively varying the irradiance density over treatment time. 
     Exemplary Compositions for Photodynamic Therapy 
     In at least one embodiment, a pharmaceutical composition containing a photoactivatable agent is applied using an applicator, or can be applied by other means, such as glove-protected fingers, a gauze pad, a swab, a bandage, or a spatula. The pharmaceutical composition can be applied in, for example, a topical dosage form (e.g., a compound suitable for administering by applying to a surface of a patient&#39;s skin) such as a gel or a solution, and can be applied beyond the lesions to be treated. In at least one embodiment, the photoactivatable agent includes porphyrins or porphyrin precursors. 
     The amount of the photoactivatable agent in the pharmaceutical composition (e.g., in a dosage form suitable for topical delivery) may vary. In at least one embodiment, the photoactivatable agent is ALA which is present in an amount from about 0.1 wt. % to about 75 wt. %. In at least one embodiment, the amount of the photoactivatable agent in the pharmaceutical composition is greater than about 10 wt. %. In at least one embodiment, the amount of the photoactivatable agent in the pharmaceutical composition is about 20 wt. %. In another embodiment, the amount of the photoactivatable agent in the pharmaceutical composition is greater than zero. 
     For example, in at least one embodiment, the ALA may be in a liquid solution including about 20% ALA, or in the form of a 10% ALA gel, or a 20% ALA gel. By way of further example, in at least one embodiment, the photoactivatable agent is provided in a gel comprising 20% aminolevulinic acid hydrochloride. In at least one embodiment, the composition in gel form further includes local anesthetics. The pH of the gel formulation may be in a range of about 4.5 to about 7.5. 
     For example, in at least one embodiment, the composition containing the photoactivatable agent is LEVULAN®, (DUSA Pharmaceuticals, Billerica, Mass.), a topical formulation of 20% 5-aminolevulinic acid hydrochloride, which may be administered via a KERASTICK® applicator. In at least one embodiment, the composition is AMELUZ® (Biofrontera AG, Leverkusen, Germany), a non-sterile topical formulation of 10% 5-aminolevulinic acid hydrochloride (equaling 7.8% of free acid) in a gel-matrix with nanoemulsion. In at least one embodiment, the photoactivatable agent may be a non-porphyrin agent. In at least one embodiment, about one gram (78 mg) of 5-aminolevulinic acid hydrochloride gel (ALA) is administered. 
     In at least one embodiment, the composition containing the photoactivatable agent is a composition disclosed in PCT Application No. PCT/M2022/060058 filed Oct. 19, 2022 and in U.S. patent application Ser. No. 17/968,931 filed Oct. 19, 2022, which are incorporated by reference herein in their entireties for the compositions, compounds and formulae disclosed therein. For example, according to at least one embodiment, the composition containing the photoactivatable agent comprises: 
     a) a 5-carbon aminoketone compound of Formula I 
     
       
         
         
             
             
         
       
     
     or its pharmaceutically acceptable salt 
     b) at least one penetration enhancer, 
     c) at least one chelating agent, and 
     d) optionally, an antifoaming agent. 
     Preferably, the at least one penetration enhancer is selected from a group consisting of dialkyl derivatives of acetamide and formamide, pyrrolidone derivatives, fatty acids, fatty acid esters, glycol derivatives, glycerides, azones, polysorbates, macrogolglycerides, polyethylene glycol derivatives, ethoxylated ether derivatives, bile salts and glycosaminoglycan. More preferably, the topical compositions according to the present disclosure comprises dialkyl derivatives of acetamide and formamide such as dimethyl acetamide, dimethyl formamide, pyrrolidone derivatives such as N-methyl-2-Pyrrolidone, fatty acids such as oleic acid, glycol derivatives such as propylene glycol and its fatty esters such as propylene glycol monocaprylate, propylene glycol monolaurate, azones such as laurocapram or 1-n-dodecyl-azacycloheptan-2-one, polysorbates, such as Tween® (polysorbate) 80, macrogolglycerides such as stearoyl macrogolglycerides, oleoyl macrogolglycerides, lauroyi macrogolglycerides, capryl-caproyl macrogolglycerides, polyethylene glycol derivatives such as polyethylene glycol 400, ethoxylated ether derivatives such as diethyleneglycol monoethyl, diethyleneglycol monomethyl ether; and dipropyleneglycol monomethyl ether, glycosaminoglycan such as chondroitin sulfate, keratan sulfate, dermatan sulfide, heparin sulphate and heparan sulphate as the permeation enhancer. 
     The penetration enhancer is present in the composition in an amount in the range of about 10% w/w to about 50% w/w of the composition, including for example, about 10%, 20%, 30%, 40%, or 50% w/w of the composition and any and all ranges and subranges therein. More preferably, the penetration enhancer is present in the composition in an amount in the range of about 20% w/w to about 40% w/w of the composition, including for example, about 20%, about 30%, or about 40% w/w of the composition and any and all ranges and subranges therein. 
     In at least one other embodiment, the at least one penetration enhancer is selected from a group consisting of glycol derivatives, polyethylene glycol derivatives, and ethoxylated ether derivatives. In another preferred embodiment, the at least one penetration enhancer is selected from a group consisting of propylene glycol, polyethylene glycol, and 2-(2-Ethoxyethoxy)ethanol (Transcutol). Propylene glycol is present in the composition in an amount in the range of about 10% w/w to about 50% w/w of the composition, including for example, about 10%, 20%, 30%, 40%, or 50% w/w of the composition and any and all ranges and subranges therein. Preferably, propylene glycol is present in the composition in an amount in the range of about 20% w/w to about 40% w/w of the composition, including for example, about 20%, about 30%, or about 40% w/w of the composition and any and all ranges and subranges therein. 2-(2-Ethoxyethoxy)ethanol (Transcutol®) when used as a penetration enhancer is present in the composition in an amount in the range of about 2% w/w to about 50% w/w of the composition, including for example, about 2%, 4%, 6%, 8%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, 30%, 32%, 34%, 36%, 38%, or 40% w/w of the composition and any and all ranges and subranges therein. Preferably, 2-(2-Ethoxyethoxy)ethanol is present in the composition in an amount in the range of about 4% w/w to about 10% w/w of the composition, including for example, about 4%, 5%, 6%, 7%, 8%, 9% or 10% w/w of the composition and any and all ranges and subranges therein. 
     In at least one other embodiment, the at least one chelating agent is selected from a group consisting of ethylenediaminetetraacetic acid (EDTA) and its pharmaceutically acceptable salts like disodium edetate, disodium edetate dehydrate, trisodium edetate, di-potassium edetate, dipotassium edetate dehydrate, edetate calcium disodium, diethylenetriamine pentaacetic acid, and organic acid such as citric acid, fumaric acid, malic acid, lactic acid and glycolic acid. Preferably, the at least one chelating agent is disodium edetate. 
     The at least one chelating agent may be present in the composition in an amount in the range of about 0.01% w/w to about 2% w/w of the composition, including for example, about 0.01%, 0.05%, 0.1%, 0.15%, 0.2%, 0.25%, 0.4%, 0.5%, 0.75%, 0.80%, 0.90%, 1.0%, 1.1%, 1.2%, 1.25%, 1.4%, 1.5%, 1.75%, 1.80%, 1.90% or 2.0% w/w of the composition and any and all ranges and subranges therein. Preferably, the at least one chelating agent is present in an amount in the range of about 0.05% w/w to about 1% w/w, including for example, about 0.05%, 0.1%, 0.15%, 0.2%, 0.25%, 0.4%, 0.5%, 0.75%, 0.80%, 0.90% or 1.0% w/w of the composition and any and all ranges and subranges therein. 
     For example, EDTA or its pharmaceutically acceptable salt when used as a chelating agent may be present in the composition in an amount in the range of about 0.01% w/w to about 2% w/w of the composition, including for example, about 0.01%, 0.05%, 0.1%, 0.15%, 0.2%, 0.25%, 0.4%, 0.5%, 0.75%, 0.80%, 0.90%, 1.0%, 1.1%, 1.2%, 1.25%, 1.4%, 1.5%, 1.75%, 1.80%, 1.90% or 2.0% w/w of the composition and any and all ranges and subranges therein. Preferably, an amount in the range of about 0.05% w/w to 1% w/w, including for example, about 0.05%, 0.1%, 0.15%, 0.2%, 0.25%, 0.4%, 0.5%, 0.75%, 0.80%, 0.90% or 1.0% w/w of the composition and any and all ranges and subranges therein. In a most preferred embodiment, EDTA or its pharmaceutically acceptable salt is present in the composition in an amount of about 0.1% w/w to about 0.15% w/w of the composition or in an amount of about 0.1% w/w to about 0.25% w/w of the composition. 
     In at least one embodiment, the 5-carbon aminoketone compound is 5-aminolevulinic acid (ALA) or its pharmaceutically acceptable salt. Preferably, the 5-carbon aminoketone compound is a hydrochloride salt of aminolevulinic acid. 
     The compound of Formula I 
     
       
         
         
             
             
         
       
     
     or its pharmaceutically acceptable salt is present in the composition containing the photoactivatable agent in an amount in the range of about 10% w/w to 70% w/w of the composition, including for example, about 10%, 20%, 30%, 40%, 50%, 60% or 70% w/w of the composition. Preferably the compound or its pharmaceutically acceptable salt is present in an amount in the range about 20% w/w to 50% w/w of the composition, including for example, about 20%, 25%, 30%, 35%, 40%, 45% or 50% w/w of the composition. In a most preferred embodiment, the compound of Formula I or its pharmaceutically acceptable salt is present in an amount of about 20% w/w. 
     The compound of 5-ALA or its pharmaceutically acceptable salt is present in the composition containing the photoactivatable agent in an amount in the range of about 10% w/w to about 70% w/w of the composition, including for example, about 10%, 20%, 30%, 40%, 50%, 60% or 70% w/w of the composition and any and all ranges and subranges therein. Preferably the compound or its pharmaceutically acceptable salt is present in an amount in the range of about 20% w/w to about 50% w/w of the composition including for example, about 20%, 25%, 30%, 35%, 40%, 45% or 50% w/w of the composition and any and all ranges and subranges therein. In a most preferred embodiment, 5-ALA or its pharmaceutically acceptable salt is present in the composition in an amount of about 20% w/w. 
     In at least one embodiment, the composition containing the photoactivatable agent may contain a variety of other inactive ingredients that are conventionally used in given product types. The inactive ingredients may be selected from alcohol, isopropyl alcohol, polyethylene glycol, propylene glycol, glycerine, diethylene glycol monoethyl ether or purified water or combinations thereof. The composition may further comprise a surfactant or a wetting agent and/or a humectant. The surfactant or wetting agent may be selected from the group consisting of laureth-4, sodium lauryl sulphate, sodium dodecyl sulfate, ammonium lauryl sulphate or sodium octech-1/deceth-1 sulfate thereof. The humectant may be selected from the group consisting of polyethylene glycol, propylene glycol, hyaluronic acid or glycerine thereof. 
     In at least one embodiment, the composition containing the photoactivatable agent that may be used according to the present disclosure optionally comprise an anti-foaming agent. Suitable anti-foaming agents may include, but are not limited to polydimethylsiloxanes and other silicones, certain alcohols, stearates and glycols. Preferably, the anti-foaming agent is cyclic polydimethylsiloxane. More preferably, the anti-foaming agent is cyclomethicone. The anti-foaming agent is present in the composition in an amount in the range of about 0.2% w/w to about 1.0% w/w of the composition, including for example about 0.2%, 0.25%, 0.4%, 0.5%, 0.75%, 0.80%, 0.90%, or 1.0% w/w of the composition and any and all ranges and subranges therein. Preferably, the anti-foaming agent is present in the composition in an amount in the range of about 0.2% w/w to about 0.5% w/w of the composition. More preferably, the anti-foaming agent is present in the composition in an amount of about 0.5% w/w of the composition. 
     In at least one embodiment, the composition containing the photoactivatable agent that may be used according to the present disclosure comprises: 
     a) a 5-carbon aminoketone compound of Formula I 
     
       
         
         
             
             
         
       
         
         
           
             or its pharmaceutically acceptable salt, and 
           
         
       
    
     b) a vehicle,
         wherein the vehicle comprises:
           (i) at least one penetration enhancer, and   (ii) at least one chelating agent.   
               

     In at least one embodiment, the vehicle comprises an optional antifoaming agent. 
     In another embodiment, the composition containing the photoactivatable agent that may be used according to the present disclosure comprises: 
     a) a 5-carbon aminoketone compound of Formula I 
     
       
         
         
             
             
         
       
     
     or its pharmaceutically acceptable salt in the form of a dry solid, and 
     b) a vehicle, 
     wherein the vehicle comprises:
         (i) at least one penetration enhancer,   (ii) at least one chelating agent, and   (iii) optionally, an antifoaming agent.       

     In at least one embodiment, the composition containing the photoactivatable agent that may be used according to the present disclosure comprises: 
     a) a 5-carbon aminoketone compound of Formula I 
     
       
         
         
             
             
         
       
     
     or its pharmaceutically acceptable salt in the form of a dry solid, and 
     b) a vehicle, 
     wherein the vehicle comprises:
         (i) at least one penetration enhancer selected from a group consisting of glycol derivatives, polyethylene glycol derivatives, ethoxylated ether derivatives,   (ii) ethylenediaminetetraacetic acid (EDTA) or its pharmaceutically acceptable salts thereof, and   (iii) optionally, an antifoaming agent.       

     In at least one other embodiment, the composition containing the photoactivatable agent that may be used according to the present disclosure comprises: 
     a) 5-ALA or its pharmaceutically acceptable salt, 
     b) propylene glycol, 
     c) EDTA or its pharmaceutically acceptable salt, and 
     d) optionally, an antifoaming agent. 
     In yet at least one other embodiment, the composition containing the photoactivatable agent that may be used according to the present disclosure comprises: 
     a) 5-ALA or its pharmaceutically acceptable salt, in the form of a dry solid, and 
     b) a vehicle, 
     wherein the vehicle comprises:
         (i) propylene glycol,   (ii) EDTA and pharmaceutically acceptable salts, and   (iii) optionally, an antifoaming agent.       

     In yet another embodiment, the composition containing the photoactivatable agent that may be used according to the present disclosure comprises: 
     a) a 5-carbon aminoketone compound of Formula I 
     
       
         
         
             
             
         
       
     
     or its pharmaceutically acceptable salt in the form of a dry solid, and 
     b) a vehicle, 
     wherein the vehicle comprises:
         (i) propylene glycol,   (ii) 2-(2-Ethoxyethoxy)ethanol, and   (iii) disodium edetate, and   (iv) optionally, an antifoaming agent.       

     In at least one embodiment, the composition containing the photoactivatable agent that may be used according to the present disclosure comprises: 
     a) 5-ALA or its pharmaceutically acceptable salt in the form of a dry solid, and 
     b) a vehicle, 
     wherein the vehicle comprises:
         (i) propylene glycol,   (ii) 2-(2-Ethoxyethoxy)ethanol, and   (iii) disodium edetate, and   (iv) optionally, an antifoaming agent.       

     In at least one embodiment, the composition containing the photoactivatable agent that may be used according to the present disclosure comprises: 
     a) a 5-carbon aminoketone compound of Formula I 
     
       
         
         
             
             
         
       
     
     or its pharmaceutically acceptable salt in the form of a dry solid, and 
     b) a vehicle, 
     wherein the vehicle comprises:
         (i) propylene glycol in an amount in the range of about 10% w/w to about 50% w/w,   (ii) 2-(2-Ethoxyethoxy)ethanol in an amount in the range of about 2% w/w to about 50% w/w, and   (iii) disodium edetate, and   (iv) optionally, an antifoaming agent.       

     In at least one other embodiment, the composition containing the photoactivatable agent that may be used according to the present disclosure comprises: 
     a) 5-ALA or its pharmaceutically acceptable salt in the form of a dry solid, and 
     b) a vehicle, 
     wherein the vehicle comprises:
         (i) propylene glycol in an amount in the range of about 10% w/w to about 50% w/w,   (ii) 2-(2-Ethoxyethoxy)ethanol in an amount in the range of about 2% w/w to about 50% w/w, and   (iii) disodium edetate, and   (iv) optionally, an antifoaming agent.       

     In at least one embodiment, the composition containing the photoactivatable agent that may be used according to the present disclosure comprises:
         a) a 5-carbon aminoketone compound of Formula I or its pharmaceutically acceptable salt,       

     
       
         
         
             
             
         
       
         
         
           
             b) propylene glycol, 
             c) 2-(2-Ethoxyethoxy)ethanol, and 
             d) disodium edetate. 
           
         
       
    
     In at least one embodiment, the composition containing the photoactivatable agent that may be used according to the present disclosure comprises: 
     a) 5-aminolevulinic acid in an amount of 20% w/w of the composition, 
     b) propylene glycol in an amount of 20% to 40% w/w of the composition, and 
     c) EDTA in an amount of 0.1% to 0.5% w/w of the composition. 
     In at least one embodiment, the composition containing the photoactivatable agent further comprises 2-(2-Ethoxyethoxy) ethanol in an amount of 4% to 10% w/w of the composition. 
     In at least one other embodiment, the composition containing the photoactivatable agent further comprises cyclomethicone in an amount of 0.2 to 0.5% w/w of the composition. 
     In at least one embodiment, the composition containing the photoactivatable agent that may be used according to the present disclosure comprises:
         a) a 5-carbon aminoketone compound of Formula I       

     
       
         
         
             
             
         
       
         
         
           
             or its pharmaceutically acceptable salt, in an amount of 1-30% w/w, 
             b) propylene glycol in an amount in the range of about 10% w/w to about 50% w/w, 
             c) 2-(2-Ethoxyethoxy)ethanol in an amount in the range of about 2% w/w to about 50% w/w, and 
             d) disodium edetate. 
           
         
       
    
     In at least one embodiment, the composition containing the photoactivatable agent that may be used according to the present disclosure comprises: 
     a) a 5-carbon aminoketone compound of Formula I 
     
       
         
         
             
             
         
       
     
     or its pharmaceutically acceptable salt, 
     b) ethanol, 
     c) Laureth-4 
     d) polyethylene glycol, 
     e) isopropyl alcohol, 
     f) propylene glycol, 
     g) 2-(2-Ethoxyethoxy)ethanol, 
     h) edetate disodium, 
     i) cyclomethicone, and 
     j) purified water. 
     In at least one embodiment, the composition containing the photoactivatable agent that may be used according to the present disclosure comprises: 
     a) a 5-carbon aminoketone compound of Formula I 
     
       
         
         
             
             
         
       
     
     or its pharmaceutically acceptable salt in the form of a dry solid, and 
     b) a vehicle, wherein the vehicle comprises:
         (i) ethanol,   (ii) Laureth-4,   (iii) polyethylene glycol,   (iv) isopropyl alcohol,   (v) propylene glycol,   (vi) 2-(2-Ethoxyethoxy)ethanol,   (vii) edetate disodium,   (viii) cyclomethicone, and   (ix) purified water.       

     In at least one other embodiment, the composition containing the photoactivatable agent that may be used according to the present disclosure comprises: 
     a) 5-ALA or its pharmaceutically acceptable salt, 
     b) ethanol, 
     c) Laureth-4, 
     d) polyethylene glycol, 
     e) isopropyl alcohol, 
     f) propylene glycol, 
     g) 2-(2-Ethoxyethoxy)ethanol, 
     h) edetate disodium, 
     i) cyclomethicone, and 
     j) purified water. 
     In at least one embodiment, the composition containing the photoactivatable agent that may be used according to the present disclosure comprises: 
     a) 5-ALA or its pharmaceutically acceptable salt in the form of a dry solid, and 
     b) a vehicle, wherein the vehicle comprises:
         (i) ethanol,   (ii) Laureth-4,   (iii) polyethylene glycol,   (iv) isopropyl alcohol,   (v) propylene glycol,   (vi) 2-(2-Ethoxyethoxy)ethanol,   (vii) edetate disodium,   (viii) cyclomethicone, and   (ix) purified water.       

     In at least one embodiment, the composition containing the photoactivatable agent that may be used according to the present disclosure comprises:
         a) a 5-carbon aminoketone compound of Formula I or its pharmaceutically acceptable salt in an amount of 20% w/w,       

     
       
         
         
             
             
         
       
         
         
           
             b) ethanol in an amount of 10 to 15% w/w of the composition, 
             c) Laureth-4 in an amount of 5 to 10% w/w of the composition, 
             d) polyethylene glycol in an amount of 1 to 5% w/w of the composition, 
             e) isopropyl alcohol in an amount of 2 to 4% w/w of the composition, 
             f) propylene glycol in an amount of 20 to 40% w/w of the composition, 
             g) 2-(2-Ethoxyethoxy)ethanol in an amount of 2 to 4% w/w of the composition, 
             h) edetate disodium in an amount of 0.1 to 0.25% w/w of the composition, 
             i) cyclomethicone in an amount of 0.2 to 0.5% w/w of the composition, and 
             j) purified water. 
           
         
       
    
     In at least one other preferred embodiment, the composition containing the photoactivatable agent that may be used according to the present disclosure comprises: 
     a) 5-ALA or its pharmaceutically acceptable salt in an amount of 20% w/w, 
     b) ethanol in an amount of 10 to 15% w/w of the composition, 
     c) Laureth-4 in an amount of 5 to 10% w/w of the composition, 
     d) polyethylene glycol in an amount of 1 to 5% w/w of the composition, 
     e) isopropyl alcohol in an amount of 2 to 4% w/w of the composition, 
     f) propylene glycol in an amount of 20 to 40% w/w of the composition, 
     g) 2-(2-Ethoxyethoxy)ethanol in an amount of 2 to 4% w/w of the composition, 
     h) edetate disodium in an amount of 0.1 to 0.25% w/w of the composition, 
     i) cyclomethicone in an amount of 0.2 to 0.5% w/w of the composition, and 
     j) purified water. 
     In at least one embodiment, the composition containing the photoactivatable agent that may be used according to the present disclosure comprises: 
     a) a 5-carbon aminoketone compound of Formula I 
     
       
         
         
             
             
         
       
     
     or its pharmaceutically acceptable salt in the form of a dry solid, and 
     b) a vehicle, 
     wherein the vehicle comprises:
         (i) ethanol in an amount of 10 to 15 w/w of the composition,   (ii) Laureth-4 in an amount of 5 to 10% w/w of the composition,   (iii) polyethylene glycol in an amount of 1 to 5 w/w of the composition,   (iv) isopropyl alcohol in an amount of 2 to 4% w/w of the composition,   (v) propylene glycol in an amount of 20 to 40% w/w of the composition,   (vi) 2-(2-Ethoxyethoxy)ethanol in an amount of 2 to 4% w/w of the composition,   (vii) edetate disodium in an amount of 0.1 to 0.25% w/w of the composition, and   (viii) cyclomethicone in an amount of 0.2 to 0.5% w/w of the composition.       

     Exemplary Treatment Methods 
     In at least one embodiment, heating of the skin is performed to enhance the efficacy of photodynamic therapy. Enhanced efficacy is correlated with a reduction in incubation time for a photoactivatable agent and increased absorption of the photoactivatable agent. In addition, the enhanced efficacy is reflected by an increase in complete incision rates when used for skin cancer. Generally speaking, in at least one embodiment, such results are realized by administering heat to an affected area; administering a therapeutically effective dose of a pharmaceutical composition; and administering a light dose to the affected area to treat a disease or disorder or of the skin. Treatment may be further enhanced through pain alleviation. 
     In at least one embodiment, the time between application of heat to the affected area and application of the ALA may vary. This is known as the “heat-to-drug interval” and may be seconds, minutes, hours or even days. In at least one embodiment, the heat-to-drug interval is about 1 second to about 60 seconds. In at least one embodiment, the heat-to-drug interval is about 1 hour to about 24 hours. In at least one embodiment, the “drug-to-light” interval reflects the period between administration of the photoactivatable agent and the administration of light (e.g., from illuminator  100 ). The “duration of exposure” or “exposure time” is the amount of time the skin is continuously exposed (e.g., to a pharmaceutical composition, to illumination, etc.). 
     The ALA can be applied to the surface to be treated (e.g., directly to lesions to be treated) and to a margin beyond the lesions (such as approximately 5 mm or less than approximately 5 mm, e.g., approximately 2-4 mm). The ALA can be administered to affected areas, without applying the ALA to healthy tissue not containing lesions and/or areas away from the lesions. In certain applications, the ALA may be covered with a barrier, such as a low density polyethylene or foil barrier. The barrier may be provided in a kit with an adhesive, a netting or a mesh to help secure the barrier in place. In at least one embodiment, the ALA may be covered, following its application to the treatment surface, by a material having a degree of occlusion of 65% or more, a material having a degree of occlusion of 75% or more, or 85% or more, or another material. Such material may be provided in order to retain moisture in the tissue and thus improve penetration of the ALA. The low density polyethylene may be characterized by a density of approximately 0.917 g/cm 3  to approximately 0.930 g/cm 3 . 
     As discussed further below, in at least one embodiment, treatment may be carried out on heat-treated skin. To heat the skin, a heating element (e.g., a heat source) may be provided that is separate from or integrated with illuminator  100 . The heat source may be used to heat the region to be treated. According to one embodiment, a method of treatment includes warming up an illuminator so as to cause heat to be emitted from the illuminator, and exposing a treatment site to the illuminator. Heating is believed to increase the rate of porphyrin production in the skin. In particular, the heat accelerates the conversion of ALA to porphyrin (e.g., photoactivatable porphyrin or proto porphyrin). The relationship between temperature exposure and ALA conversion is non-linear, and the enzymatic pathways responsible for the conversion are highly sensitive to temperature. 
     In at least one embodiment, increasing the temperature by approximately 2° C. may approximately double the rate of production of protoporphyrin IX (PpIX), for example. In at least one embodiment, by heating the skin as described herein, the rate of porphyrin production in the skin is increased by about 10%, about 20%, about 30%, about 40%, about 50% or more, about 60% or more, about 70% or more, about 80% or more, or about 85% or more. In at least one embodiment, the rate of porphyrin production in the skin is increased by about 50% or more, about 60% or more, about 70% or more, about 80% or more, or about 85% or more by heating the skin for five minutes followed by heating and a light dose for about eight minutes or about 8 minutes and 20 seconds. For example, as described in more detail below, the amount of PpIX in skin can approximately double with the application of heat to the treatment area compared to when no heat is applied to the treatment area. 
     In at least one embodiment, the heat may be applied before or during illumination with the illuminator  100 . For example, first, the ALA may be applied. Next, the heating element may be activated, to apply heat to the patient&#39;s skin for a first treatment period for a thermal soak, which may be approximately 20 to approximately 30 minutes, for example, or another interval. During the heating, the treatment site may or may not be occluded. The treatment site may be heated while being occluded. In at least one embodiment, the thermal soak may be between approximately 18 minutes and approximately 32 minutes and may or may not be commensurate with the first treatment period. Following the first treatment period, light may be applied for a second treatment period, e.g., about 8 minutes to about 15 minutes. In at least one embodiment, light may be applied for 8 minutes and 20 seconds. The total thermal soak, corresponding to exposure to heat, may be between about 1 minute and about 90 minutes. 
     In at least one embodiment, the skin is heated to a surface temperature of greater than about 37° C. In at least one embodiment, the skin is heated to a surface temperature of greater than about 40° C. 
     The present disclosure thus provides a method for photodynamically treating a surface of a patient (and optionally occluding the patient&#39;s skin as part of treatment). The patient may be illuminated to treat actinic keratosis (AKs), disseminated superficial actinic porokeratosis (DSAP) or refractory disseminated porokeratosis, acne (e.g., cystic acne, inflammatory acne, non-inflammatory acne), photo-damaged skin, skin cancer (e.g., non-melanoma skin cancer (NMSC), nodular basal cell carcinoma, recurrent nodular basal cell carcinoma, infiltrative basal cell carcinoma, multi-focal basal cell carcinoma), warts, psoriasis, or other dermatological conditions. 
     For example, in at least one embodiment, the LEDs of illuminator  100  emit light for photodynamic treatment of cystic acne. In particular, the LEDs may emit red light for carrying out PDT of acne, NMSC, AK, or DSAP on heat-treated skin (e.g., skin that is previously or concurrently heated). In at least one embodiment, cystic acne may be treated by applying 10% ALA gel and delivering a light dose of 37 J/cm 2  of light at 630 nm for approximately one hour, while heating or otherwise maintaining a surface of the patient to be treated (a treatment surface, skin surface, etc.) at a temperature of approximately 40° C. 
     In at least one embodiment, by heating the skin as described herein, a reduction in incubation time needed for ALA may be achieved. Traditional PDT for AK requires a fourteen (14) hour incubation with ALA before exposure to blue light. In at least one embodiment, the incubation period may be drastically reduced. For example, the incubation period may be reduced to less than about 30 minutes, about 30 minutes, about 45 minutes or about 1 hour. A significant quantity of porphyrins is produced after 20 minutes of incubation of 20% ALA gel on skin heated to about 40° C., with even a greater quantity produced after about 30 minutes. The quantity of porphyrins produced after 60 minutes incubation of 20% ALA gel without heat is smaller than for either 20 or 30 minutes with heat. 
     Thus, the reaction to photodynamic therapy is significantly greater for heated skin of a patient than for unheated skin. In at least one embodiment, the heat source may be used for heating for a period of between about 15 to about 60 minutes. In at least one embodiment, the incubation period (e.g., an incubation time, as discussed further herein) may be about 17 minutes for 20% ALA gel with a heat source achieving a skin temperature of between about 38° C. and about 42° C. In at least one embodiment, a one hour incubation period may be employed for 10% ALA, where the heat source is a sodium acetate warming mask used to heat the skin to about 40° C., followed by a light dose of 37 J/cm 2  light at 635 nm (e.g., for treating moderate inflammatory or pustular acne). A reduction in lesion counts was observed nine months following even a single photodynamic therapy treatment session. In at least one embodiment, a one hour incubation period of 20% ALA is performed, where the heat source is a heating pad or a sodium acetate warming pouch. 
     A method of treating skin diseases or disorders using photodynamic therapy (e.g., with red light) on pre-heated skin may be carried out using an illuminator according to the present disclosure. In at least one embodiment, the pharmaceutical composition is a nanoemulsion comprising 10% 5-aminolevulinic acid HCl. In at least one embodiment, the light has a wavelength of between about 620 to about 640 nm, and more particularly, about 630 nm. In one embodiment, the suitable dose of light is about 37 J/cm 2 . 
     For example, a method of treating facial acne in a subject in need thereof may be carried out, including (i) applying heat to an affected area of the subject&#39;s skin using a heat source to achieve a skin temperature of between about 38° C. and about 42° C. for a suitable time; (ii) incubating a pharmaceutical composition comprising a photoactive agent for a period of less than about 14 hours; (iii) applying a therapeutically effective amount of the incubated pharmaceutical composition to the affected area; and (iv) administering light (e.g., red light) to the affected area to treat the facial acne. In at least one embodiment, the acne is mild acne, moderate acne or severe acne. In at least one embodiment, the heat source is a heat mask such as an acetate mask that heats upon crystallization. In at least one embodiment, the affected area is heated for about 60 minutes. 
     In at least one embodiment, the affected area is heated to about 40° C. In at least one embodiment, the incubation period is less than about 3 hours but achieves equivalent efficacy as if the pharmaceutical composition had been incubated for about 3 hours in the absence of applying heat (i.e., without heating) to achieve a skin temperature of between about 38° C. and about 42° C. In at least one embodiment, the incubation period is less than about 1 hour but achieves equivalent efficacy as if the pharmaceutical composition had been incubated for about 1 hour in the absence of heating to achieve a skin temperature of between about 38° C. and about 42° C. In an exemplary embodiment, the incubation period is less than about 15 minutes, less than about 10 minutes, or less than about 5 minutes. 
     In at least one embodiment, the treatment results in a reduction in acne lesion count for a patient suffering from acne. In at least one embodiment, the reduction persists for a period of at least three months. In exemplary embodiments, treatment results in a reduction in acne lesion severity. In at least one embodiment, the reduction persists for a period of at least three months. In at least one embodiment, the side effects of treatment are reduced relative to a method that does not include heating of the skin. 
     In at least one embodiment, a method is provided for treating non-melanoma skin cancers (NMSCs) of the face. The method includes applying heat to achieve a skin temperature of between about 38° C. and about 42° C.; incubating a pharmaceutical composition for less than about 14 hours; applying a therapeutically effective amount of the composition to the affected area, and administering a suitable dose of light (e.g., red light) to the area. In at least one embodiment, the non-melanoma skin cancer is basal cell carcinoma. In at least one embodiment, the non-melanoma skin cancer is a squamous cell carcinoma (SCC). In at least one embodiment, the non-melanoma skin cancer is a basal cell carcinoma, and heat is applied for about thirty minutes or for about twenty minutes. In at least one embodiment, the incubation period is (i) less than about 14 hours but achieves equivalent efficacy as if the pharmaceutical composition had been incubated for about 14 hours in the absence of heating; (ii) less than about 3 hours but achieves equivalent efficacy as if the pharmaceutical composition had been incubated for about 3 hours in the absence of heating; or (iii) less than about ten minutes. 
     In at least one embodiment, a method of treating AKs of the face is provided. The method includes applying heat to achieve a skin temperature of between about 38° C. and about 42° C.; incubating a pharmaceutical composition for less than about 14 hours; applying a therapeutically effective amount of the composition to the affected area, and administering a suitable dose of light (e.g., red light) to the area. In at least one embodiment, the affected area is heated for about 30 minutes. In at least one embodiment, the affected area is heated to about 40° C. In at least one embodiment, the incubation period is (i) less than about 14 hours but achieves equivalent efficacy as if the pharmaceutical composition had been incubated for about 14 hours in the absence of heating, (ii) less than about 3 hours but achieves equivalent efficacy as if the pharmaceutical composition had been incubated for about 3 hours in the absence of heating, (iii) less than about 1 hour but achieves equivalent efficacy as if the pharmaceutical composition had been incubated for about 1 hour in the absence of heating, or (iv) less than about 10 minutes. 
     In at least one embodiment, a method of treating disseminated superficial actinic porokeratosis (DSAP) of the face in a subject in need thereof is provided. The method includes applying heat to achieve a skin temperature of between about 38° C. and about 42° C.; incubating a pharmaceutical composition for less than about 14 hours; applying a therapeutically effective amount of the composition to the affected area, and administering a suitable dose of light (e.g., red light) to the area. In at least one embodiment, the incubation period is (i) less than about 14 hours but achieves equivalent efficacy as if the pharmaceutical composition had been incubated for about 14 hours in the absence of heat, (ii) less than about 3 hours but achieves equivalent efficacy as if the pharmaceutical composition had been incubated for about 3 hours in the absence of heat, (iii) less than about 1 hour but achieves equivalent efficacy as if the pharmaceutical composition had been incubated for about 1 hour in the absence of heat, or (iv) less than about 10 minutes. 
     In at least one embodiment, the ALA is incubated simultaneously with application of heat to the skin or within a few seconds or minutes prior to heating of the skin, or after heating of the skin has commenced. The following discussion sets forth illustrative examples of how treating a disease or disorder of the skin may be carried out using an exemplary illuminator, e.g., for performing photodynamic therapy, in combination with heat. 
     Examples—Effect of Heat on PpIX Levels in Skin 
     A study was conducted to evaluate the effect of heat application on PpIX levels in skin after a photoactivatable agent is applied to the skin. More specifically, the study was performed on porcine test subjects to investigate the pharmacokinetic profiles of 5-ALA and PpIX for enhanced topical formulations using Levulan® (i.e., Levulan® as enhanced, for example, with a chelating agent as discussed herein). Three compositions were tested, including (i) Levulan® (DUSA Pharmaceuticals, Inc., Billerica, Mass.), (ii) Levulan® with 0.1% ethylenediaminetetraacetic acid (EDTA) present in an amount of about 0.1% w/w of the topical composition and (iii) Levulan® with EDTA present in an amount of about 0.15% w/w of the topical composition. 
     Each formulation was prepared for application via the Levulan® Kerastick® applicator. The same batch of each formulation (e.g., same batch number, manufacturing date, and expiration date) was used for each respective porcine test subject. The formulations were stored at temperatures between 20° C. to 25° C. (68°-77° F.). Testing was performed on thirty-six (36) test subjects ( Sus scrofa domesticus ), allowing for three test subjects per time point (two hours or three hours) per formulation, with heat and without heat. PpIX was evaluated after each time point (i.e., after two hours and after three hours of incubation). 
     The test subjects were kept in an environment having a temperature between 18° C. to 28° C. with a humidity between 30%-70%. In the day when treatment was performed, the test subjects were exposed to approximately 12 hours of darkness and approximately 12 hours of light. The test subjects were protected from light during the test incubation period (of either two or three hours). 
     The test subjects were divided into 12 groups as shown Table 1: 
     
       
         
           
               
             
               
                 TABLE 1 
               
               
                   
               
               
                 Study groups 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                   
                 Group 1 
                 3 test subjects: Levulan ®; no heat; 2 hrs 
               
               
                   
                 Group 2 
                 3 test subjects: Levulan ®; no heat; 3 hrs 
               
               
                   
                 Group 3 
                 3 test subjects: Enhanced 0.1% EDTA; no heat; 
               
               
                   
                   
                 2 hrs 
               
               
                   
                 Group 4 
                 3 test subjects: Enhanced 0.1% EDTA; no heat; 
               
               
                   
                   
                 3 hrs 
               
               
                   
                 Group 5 
                 3 test subjects: Enhanced 0.15% EDTA; no heat; 
               
               
                   
                   
                 2 hrs 
               
               
                   
                 Group 6 
                 3 test subjects: Enhanced 0.15% EDTA; no heat; 
               
               
                   
                   
                 3 hrs 
               
               
                   
                 Group 7 
                 3 test subjects: Levulan ®; with heat; 2 hrs 
               
               
                   
                 Group 8 
                 3 test subjects: Levulan ®; with heat; 3 hrs 
               
               
                   
                 Group 9 
                 3 test subjects: Enhanced 0.1% EDTA; with heat; 
               
               
                   
                   
                 2 hrs 
               
               
                   
                 Group 10 
                 3 test subjects: Enhanced 0.1% EDTA; with heat; 
               
               
                   
                   
                 3 hrs 
               
               
                   
                 Group 11 
                 3 test subjects: Enhanced 0.15% EDTA; with heat; 
               
               
                   
                   
                 2 hrs 
               
               
                   
                 Group 12 
                 3 test subjects: Enhanced 0.15% EDTA; with heat; 
               
               
                   
                   
                 3 hrs 
               
               
                   
                   
               
            
           
         
       
     
     A portion of the dorso-lateral trunk skin of each test subject area was divided into ten blocks for dose application, where each block was approximately 2 cm×2 cm, with four cm of space between blocks. The test sites were cleaned with ethanol prior to dose application. 
     Each dose (of the three formulations) was applied topically per Levulan® dosing instructions to different blocks. A single dose included two applications using the Kerastick® applicator of approximately 15 seconds each, with an interval of approximately two minutes between applications. The duration of treatment was confined to a single dose. 
     Following application of the dose, heat was applied to the skin of test subjects in groups 7-12. Heat was applied at approximately 39° C. to approximately 41° C. for approximately thirteen minutes after the respective group of test subjects were dosed. More particularly, test subjects of groups 7-12 were subjected to heat application for about 13 minutes after formulation application and the designated incubation time. Infrared (IR) lamps were used to provide the heat. 
     After 2 hours of incubation, dermis and epidermis samples were taken from the test subjects designated for the 2 hour time point (e.g., groups 1, 3, 5, 7, 9, and 11) and tested for amounts of PpIX. After 3 hours of incubation, dermis and epidermis samples were taken from the test subjects designated for the 3 hour time point (e.g., groups 2, 4, 6, 8, 10, and 12) and tested for amounts of PpIX. 
     The epidermis and dermis layers were separated approximately 10-20 minutes after harvesting the stratum corneum of the subjects. To separate the epidermis and the dermis, the skin samples were then kept in a hot air oven for 5-10 minutes at 60° C.-62° C. in a closed aluminum foil. The epidermis layer was separated from the dermis layer manually. The dermis and epidermis layers were collected in separate centrifuge containers. The container was weighed before and after adding the skin layer. The difference in weight was calculated to determine the weight of the skin layer. Skin samples were flash frozen immediately after skin layer separation using liquid nitrogen to stop continued production of PpIX in the samples. The samples remained frozen for at least 24 hours prior to processing for analysis. The aforementioned processes were carried out under monochromatic light (i.e., a sodium vapor lamp). A homogenization solution was added to the containers containing the skin tissues to prepare 4% w/v tissue homogenate, and the skin tissue homogenate was prepared using homogenizer under constant cooling using an ice bath. After every run, a probe of the homogenizer was washed and dried. The tissue homogenate samples were analyzed for 5-ALA and PpIX. 
     As shown in  FIGS.  26 - 27   , exposing the formulations to heat resulted in higher PpIX levels at 3 hours of incubation. For example, application of the reference Levulan® with no heat applied produced about 0.628 mcg/g of PpIX after 3 hours of incubation. Application of Levulan® with approximately 13 minutes of heat applied produced about 0.966 mcg/g of PpIX after 3 hours of incubation. As such, the treatment with the heat resulted in over a 50% increase in the amount of PpIX produced that the treatment without heat. 
     For another example, application of the Levulan® enhanced with 0.1% EDTA with no heat applied produced about 0.771 mcg/g of PpIX after 3 hours of incubation. Application of the Levulan® enhanced with 0.1% EDTA with 13 minutes of heat applied produced about 1.776 mcg/g of PpIX after 3 hours of incubation. As such, the treatment with the heat resulted in over double the amount of PpIX than the treatment without heat. 
     Application of the Levulan® enhanced with 0.15% EDTA with no heat applied produced about 1.186 mcg/g of PpIX after 3 hours of incubation. Application of the Levulan® enhanced with 0.15% EDTA with 13 minutes of heat applied produced about 2.146 mcg/g of PpIX after 3 hours of incubation. As such, the treatment with the heat resulted in over an 80% increase in the amount of PpIX produced than the treatment without heat. 
     This surprising increase in PpIX with such a short duration of heating has not been previously achieved and was not expected previously. The short duration of heating according to the techniques of the present disclosure overcomes a major drawback of PDT generally, namely, the necessity for a patient to be exposed to an illuminator for a long period of time. 
     The foregoing examples are believed to allow for dramatic reductions in total treatment time to be realized, with concomitant reduction in pain. 
     In particular, the compositions described above may be utilized to treat patients in accelerated PDT protocols. For example, in at least one embodiment, a method of performing PDT (e.g., for treatment of a dermatological disorder) can be carried out in which topical composition is applied to skin and incubated for a predetermined incubation period. 
     In at least one embodiment, a topical composition as enhanced with the at least one chelating agent is applied to the skin, e.g., with an applicator. The topical composition may comprise ALA (e.g., ALA HCl) as enhanced with at least one chelating agent in accordance with any of the embodiments of the present disclosure, such as EDTA in an amount of about 0.1% w/w to about 0.15% w/w of the composition. 
     Following topical application, the incubation period may be about 30 minutes to about 3 hours, which in some embodiments, may be between about 2 hours to about 3 hours. Optionally, the skin may be occluded during all or part of the incubation. In some embodiments, the skin is occluded with a barrier, such as a low density polyethylene (LDPE) barrier or foil barrier, following application of ALA as enhanced with at least one chelating agent. 
     After a predetermined incubation period, the skin is exposed to heat from a heat source, and, in some embodiments, light (e.g., from a light source). For example, heat may be applied during an initial part of treatment, followed by both light and heat being applied during a final part of treatment. Optionally, a flow of air may be directed to the skin during the initial and/or final parts of treatment which may alleviate associated pain. For example, a gentle flow of air may be provided during at least the initial part of treatment (e.g., a first time period). 
     In some embodiments, the patient may be exposed to about 5 minutes of heat, followed by about 8 minutes of both light and heat. In some embodiments, 8 minutes and 20 seconds of light and heat may be administered. Thus, a sum of the initial part of treatment and the final part of treatment may be about 13 minutes. The light can be, e.g., blue light applied at an intensity of 20 mW/cm 2  or about 30 mW/cm 2 . In some embodiments, blue light may be applied at an intensity of 10 mW/cm 2 . The blue light may be supplied for a sufficient time period to provide a dose of about 10 J/cm 2 . In some embodiments, red light may be applied to achieve a dose of about 10 J/cm 2  to about 75 J/cm 2 , e.g., within less than 10 minutes. In some embodiments, the patient may be exposed to both blue and red light. Any combination of the light dosages, durations and/or intensities set forth in the present disclosure may be utilized. 
     In some embodiments, a patient may be exposed to heat for a duration of about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19 or about 20 minutes in the initial part of the treatment. Following the initial treatment, the patient may be exposed to both heat and light for the final part of the treatment, which may be for a duration of about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19 or about 20 minutes. In some embodiments, the total heating time may be from between about 10 minutes to about 30 minutes. 
     In some embodiments, the illumination can be performed with an illuminator according to the disclosed embodiments described herein. In some embodiments, a kit is provided including the illuminator, the heat source and at least one applicator having a topical composition according to the foregoing embodiments. 
     Illuminator Panel Configuration 
     Returning to  FIGS.  1 - 4   , in at least one embodiment, the illuminator  100  preferably has five panels  10  (namely, panels  10   a - 10   e ). The panels  10  may vary in size. For example, a first panel  10   a  may be a first size, a second panel  10   b  may be a second size, a third panel  10   c  may be a third size, a fourth panel  10   d  may be the second size, and a fifth panel  10   e  may be the first size. In at least one alternative embodiment, the panels may be of equivalent size. 
     In conventional adjustable illuminators, the panels are equally sized by width and length and are typically driven at the same power level. The panels are further joined at their edges. Owing to this construction, light is not emitted from a “gap” between the light sources. The lack of light emitting from such areas, together with the uniform supply of power to the panels, can cause optical “dead space” in certain portions of the target treatment area. These portions, in turn, receive less overall light, resulting in a lower dose of treatment in those portions. In some instances, the dose of treatment can be lowered by as much as a factor of five when compared with those areas receiving a desired amount of light. 
     At least one embodiment of the present disclosure includes a plurality of panels  10 , wherein at least one panel  10  is of a different width than the other panels. This panel is positioned between two other panels and, in a way, acts as a “lighted hinge” to provide enough “fill-in” light to reduce or eliminate the optical dead spaces when the panels are bent into a certain configuration. Preferably, five panels in total may provide for a desirable increase in the total size of possible treatment areas. Two of the panels (e.g., panels  10   b  and  10   d  in  FIG.  2   ) are preferably of a smaller width than the other three larger panels (e.g., panels  10   a ,  10   c  and  10   e  in  FIG.  2   ). The panels are positioned in an alternating manner such that each of the smaller-width panels is situated in between two of the three larger panels to allow for both adjustability and increased uniformity. 
     In at least one embodiment, each panel  10  contains an array of light emitting diodes (LEDs)  60 , which may be configured in an evenly or unevenly spaced pattern across a face of the panel  10 . In at least one embodiment, three adjacent panels may be illuminated (e.g., the three inner panels) and two panels may be non-illuminated for a given period, such that illumination may be carried out with a small number of panels than the total number of panels present in the illuminator  100 . The number of individual LEDs arranged in a given array is not particularly limited. The panels  10  are configured to uniformly illuminate a treatment surface of a patient via the LEDs. Thus, a substantially homogenous distribution of light may be imparted to the treatment surface. 
     Preferably, the LEDs may be distributed across a plurality of arrays, where each array of LEDs  60  extends as far to the edges of the panels  10  as possible. In addition, the arrays of LEDs  60  are preferably dimensioned to provide an overall lighted area for a given treatment area based on a range from the 5th percentile of corresponding sizes of female subjects to the 95th percentile of corresponding sizes of male subjects for that particular treatment area. The LEDs  60  emit light at an appropriate wavelength according to the intended treatment or to activate the particular photoactivatable agent used in treatment or diagnosis. For example, when ALA is used as a precursor of a photoactivatable agent for the treatment of AK, the LEDs  60  preferably emit blue light having wavelengths at or above 400 nanometers (nm), for example, about 430 nm, about 420 nm or, for example, 417 nm. However, the LEDs  60  may also emit visible light in other ranges of the spectrum, such as in the green and/or red ranges between 400 and 700 nm, for example, about 625 nm to 640 nm or, for example, 635 nm. For example, the LEDs  60  may also emit light having wavelengths of 510 nm, 540 nm, 575 nm, 630 nm, or 635 nm. In addition, the LEDs  60  may be configured to emit light continuously or may be configured to flash the diodes on and off based on a predetermined interval. Furthermore, the LEDs  60  may be configured such that only one wavelength of light (e.g., blue) is emitted. Alternatively, the LEDs  60  may be configured such that two or more wavelengths of light are emitted from the arrays. For example, the LEDs  60  may be configured to alternately emit blue light and red light. 
     In at least one embodiment, the LEDs  60  on each of the panels  10  are individually configurable to provide specific power output to certain areas on the panels  10  to compensate for decreased uniformity. For example, the power outputted to each individual diode in an array of LEDs  60  may be individually adjusted. In more detail, the LED arrays may be divided into three general areas, which may be described as “addressable strings.” The current to each area is adjusted in order to adjust the intensity of light emitting from each of the areas. For example, a higher current may be supplied to a given area associated with a particular string or strings, so that it produces a higher intensity of light than another area associated with another string or other strings. Alternatively or in addition, the LEDs  60  may be operated at a higher power level. 
     In addition, individually regulating power to the LEDs  60  can contribute to the reduction or elimination of optical dead spaces that may otherwise occur where typical illuminator panels are connected. Specifically, power output and/or the emitted light intensity may be increased close to the edges of arrays of LEDs  60  to compensate for the lack of light emitting from an area where neighboring panels meet or adjoin. The narrower panels  10   b ,  10   d  are preferably operated at a higher power level and/or at a higher emitted light intensity compared to the wider panels  10   a ,  10   c ,  10   e  in order to provide additional “fill-in” light. In this manner, the LEDs  60  are controllable such that a higher intensity of light is emitted overall from the edges of the panels  10 , which may allow for a reduction in any fall-off effect. Thus, such a configuration provides a more uniform illumination output than one in which power and/or intensity are equal across all panels. In at least one embodiment, the illuminator may be configured to adjust each individual diode present in a given LED array, allowing for further calibration. 
     In at least one alternative embodiment, other types of light sources may be used, such as fluorescent or halogen lamps, instead of or in addition to LEDs. 
     Illuminator Structure and Operation 
     The illuminator may be arranged with a folding apparatus designed to allow maneuverability and reconfigurability of the illuminator panels. In at least one embodiment, the illuminator is adjustable via a main post. The main post is supported by a hydraulic cylinder according to at least one embodiment. The hydraulic cylinder allows raising and/or lowering with manual force applied by a user&#39;s digit(s) and/or hands. The cylinder is optionally outfitted with a valve to lock the cylinder in position. Other constructions may be utilized, e.g., instead of a hydraulic cylinder, a spring may be used. 
     For example, in at least one embodiment, the illuminator is provided with a vertical post which are optionally provided with one or more supports arms. The one or more support arms are configured to support illuminator panel(s) whose height is adjustable. The post may be pushed down into a body of the illuminator or pulled up out of the illuminator. The illuminator may be provided with one or more air cylinders (with at least one check valve and/or at least one spring) to allow the post to be moved with minimal force (e.g., finger pressure). These aspects allow the illuminator to be readily maneuverable and usable under various conditions. 
     In at least one embodiment, the illuminator uses a ducting arrangement to draw air in via an air distributor (e.g., a fan) at the back of an illuminator panel and output the air via a J-shaped ducting arrangement such that the air gently flows (for example, a laminar flow or similar even, uniform flow) substantially parallel to the front surface (the surface that emits light) of a panel and substantially tangentially to the skin surface. A controller allows a healthcare provider or the patient to control the fan speed at different speeds (for example, slow and fast) in accordance with an observation of the healthcare provider and/or a desire expressed by the patient. The air may be room temperature air (for example approximately 68° F. to approximately 75° F. or approximately 65° F. to approximately 72° F.). 
     In particular, whether or not the skin is pre-heated as described above, the flowing air is nonetheless cooler than the treatment surface. The temperature is significantly lower than body temperature, and thus feels cooling to the patient. The air may also be cooled below room temperature, in at least one embodiment. The air flow may provide evaporative cooling that reduces the perception or sensation of pain. The air speed can be, for example, approximately 3 to approximately 6 knots, e.g., approximately 3 knots, approximately 4 knots, approximately 5 knots or approximately 6 knots. Such air distributors may have an air flow rate of about 7.5 CFM to about 12 CFM, about 14 CFM, about 5 CFM to about 15 CFM or about 5 CFM to about 20 CFM. Enhancing patient comfort in this manner may influence the willingness of a patient to complete a course of treatment, among other benefits. 
     The illuminator may be equipped with a thermal management system having additional components beyond those described above. For example, additional air distributors may direct waste heat away from electronic components to the external environment. 
     Further, in at least one embodiment, the illuminator can be provided with sensors that detect the size of the treatment area positioned in front of the illuminator. In at least one embodiment, information from the sensors can be used (e.g., by a controller) determine the correct light dosing parameters based on the sensed treatment area. In at least one embodiment, the sensors are configured to detect the adjusted position of the illuminator manually set by the user. The detected position of the illuminator may then be used to indicate the intended treatment area. Appropriate light dosing parameters for the specific treatment area may be provided based on the detected position set by the user. 
     Referring again to  FIGS.  1 - 4   , in at least one embodiment, each panel  10  contains at least one vent  68 . The vent  68  may be configured to actively (e.g., push/pull) or passively (e.g., provide a path) expel air from the panel  10 . In at least one embodiment, the panel  10  may include a plurality of vents  68 . For example, the panel  10  may include a first vent  68  and a second vent  68 . The first vent maybe disposed at or proximate to a first end of the panel  10 , and the second vent  68  may be disposed at or proximate to a second end of the panel  10 . Each panel  10  may also contain at least one fan  70 . The fan  70  may be configured to draw air into the panel  10  or to expel air from inside the panel  10 . A fan  70  may be disposed on a back side of the panel  10 . The fan  70  may be disposed at a central location of the panel  10 . In at least one embodiment, a panel  10  includes a plurality of fans  70 . For example, panel  10   c  includes a first fan  70  disposed proximate a first end of the panel  10   c  and a second fan  70  disposed proximate a second end of the panel  10   c.    
     Each panel  10  may contain a distance sensor  11 . The distance sensor  11  may detect a distance between the panel  10  and a treatment surface (an affected area) disposed in front of the panel  10 . The distance sensor  11  may be automatically turned on when the associated panel  10  is turned on. Detecting the distance between the panel  10  and the treatment surface can facilitate individual adjustment of each panel  10  such that each panel  10  is at a desired distance from the treatment surface. 
     As shown in  FIG.  6   , in at least one embodiment, the panels  10  may be coupled together via a hinge  58  or other adjustable connection point to facilitate movement of the panels  10  with respect to each other. For example, the panels  10  may be connected in a rotatable manner via nested hinges  58 . The illuminator  100  may be configured to fold and unfold via the hinges  58  depending on use. For example, the panels  10  can be in an unfolded (e.g., flat) arrangement when treating areas such as a back, chest or abdomen of a patient. The panels  10  can be in a folded (e.g., U-shaped) arrangement, when treating areas such as a face, scalp, arm, or leg. For example, the outermost panels  10  may face each other (at least in part). The panels  10  can also be in a folded arrangement when in a stowed position. For example, the panels  10  may be wrapped around at least a portion of the illuminator system  105  (e.g., the vertical column  82 ) when the illuminator  100  is not in use. The hinges  58  may include torque inserts to maintain a position of the panels  10  without using an additional lock. The hinges  58  may also include hard stops that prevent the panels  10  of the illuminator  100  from having an undesired configuration. For example, the hinges  58  may prevent the panels  10  from being fully unfolded (e.g., flat), or from bending beyond the flat configuration (e.g., a U-shape in an opposite direction). 
     As shown in  FIG.  3   , the illuminator system  105  may include a moveable stand  80 . The movable stand  80  may simplify movement of the illuminator system  105  between various locations and orientations. For example, the moveable stand  80  may include a vertical column  82  coupled to a base  81 . The vertical column  82  may extend perpendicular to the base  81 . The base  81  may provide support for the vertical column  82  and other components of the illuminator system  105  that are coupled with the vertical column  82 . The base  81  may be movable. For example, the base  81  may include a plurality of wheels, shown as casters  87 . For example, the base  81  may include four casters  87 . The casters  87  may facilitate rolling of the illuminator system  105  from a first location to a second location, or from a first orientation to a second orientation. 
     As shown in  FIG.  3   , in at least one embodiment, the illuminator system  105  includes one or more hooks  83 . For example, the illuminator may include a first hook  83   a  and a second hook  83   b . The first hook  83   a  and the second hook  83   b  may be disposed on a first side of the vertical column  82 . The first hook  83   a  may be disposed above the second hook  83   b . The hooks  83  may be rotatably coupled with the vertical column  82 . The illuminator system  105  may also include a handle  84  (e.g., a stabilization arm). The handle  84  may be disposed around three sides of the vertical column  82 . For example, the handle  84  may extend from a first side of the vertical column  82 , wrap around a second side of the vertical column  82 , and connect to the vertical column  82  via a third side of the vertical column  82 . Apart from a first and second connection point disposed on the first and third side of the vertical column  82 , the handle  84  may be spaced apart from the vertical column  82 . 
     As shown, for example, in  FIGS.  1 - 4   , the illuminator system  105  may further comprise an extension member  86 . The extension member  86  may be partially disposed within the vertical column  82 . The vertical column  82  and the extension member  86  may be configured as a telescoping structure wherein the extension member  86  can extend or slide into the vertical column  82  and extend or slide vertically out of the vertical column  82  between different positions. The extension member  86  may be configured to adjust a height of the illuminator  100 . For example, when the extension member  86  is in a retracted position (a low position) and a majority of the extension member  86  is generally disposed in the vertical column  82 , as shown in  FIGS.  1 - 2   , the illuminator is in a low position. Conversely, when the extension member  86  is in an extended position (an expanded position, or an elevated position) and a majority thereof is disposed generally outside of the vertical column  82 , as shown in  FIGS.  3 - 4   , the illuminator  100  is in a high (raised or elevated) position. The different positions may be based on a use of the illuminator  100 , taking into account one or more of: (i) patient characteristics (e.g., a relatively shorter versus a relatively taller person), (ii) patient orientation (e.g., a standing versus sitting position) or (iii) location of an area to be treated (e.g., the back versus the forearms). The position of the extension member  86  may be adjusted either manually or automatically (e.g., by power). The extension member  86  may be configured to maintain any position between a top position (e.g., fully extended) and a bottom position (e.g., fully retracted). 
     As seen in  FIG.  2   , a top of the extension member  86  may be coupled with or be integral with (e.g., for a single component) a connecting arm  85 . The connecting arm  85  extends horizontally from the top of the extension member  86 . The connecting arm  85  is configured to move with the extension member  86  as the extension member  86  moves relative to the vertical column  82  (e.g., as the extension member  86  moves into or out of the vertical column  82 ). The connecting arm  85  can include a material of sufficient strength to support other components of the illuminator system  105  (e.g., the illuminator  100 ). 
     The connecting arm  85  has a joint, shown as pivot point  89 . The pivot point  89  divides the connecting arm  85  into two portions, a first portion and a second portion. The first portion can be a stationary portion  97  and the second portion can be a movable portion  98 . The movable portion  98  can extend from an end of the stationary portion  97 . The movable portion  98  is rotatably coupled with the stationary portion  97 . For example, the movable portion  98  can pivot around the pivot point  89 . For example, the movable portion  98  can rotate vertically about the pivot point  89 . In at least one embodiment, the movable portion  98  rotates approximately 90 degrees around the pivot point  89  (so as to be rotatable within a range from 0° to approximately 90°). 
     For example, the stationary portion  97  may define a horizontal plane. The movable portion  98  may rotate between a horizontal position (e.g., parallel with the stationary portion  97  and disposed in the horizontal plate) and a vertically downward position (e.g., perpendicular to the stationary portion  97  and extending downward)). The horizontal position may be a use position or treatment position. The vertically downward position may be a stowed position. In at least one embodiment, the movable portion  98  may rotate approximately up to 180 degrees around the pivot point  89  (e.g., in a range from approximately zero to 180 degrees). For example, movable portion  98  may rotate between the vertically downward position and a vertically upward position (e.g., perpendicular to the stationary portion  97  and extending upward). The vertically upward position may be a use position or treatment position. The movable portion  98  may also be configured to remain at any other angle relative to the stationary portion  97 . 
     In at least one embodiment, the illuminator system  105  includes an arm lock  22 , as shown in  FIGS.  1  and  17   , among others. The movable portion  98  may be folded into a vertical position, for example, when the illuminator system  105  is not in use or is being stored. The movable portion  98  may be rotated into a horizontal position, for example, when the illuminator system  105  is being used for treatment. The arm lock  22  may be disposed at a location where the movable portion  98  couples with the stationary portion  97 . For example, the arm lock  22  may be disposed at the pivot point  89 . The pivot point  89  may be disposed approximate to a midpoint of the connecting arm  85  such that the arm lock  22  may be disposed approximate to the midpoint of the connecting arm  85 . The arm lock  22  may be activated when no force is applied. To unlock or release the movable portion  98 , the arm lock  22  may be depressed. The arm lock  22  may automatically lock the movable portion  98  in a position when the movable portion  98  reaches the use position or the fully stowed position. 
     The connecting arm  85  is configured to support the illuminator  100  at the various positions described herein. The movable portion  98  is coupled with the illuminator  100  via a mounting mechanism  40 , as shown in  FIGS.  4 - 6   . The mounting mechanism  40  may include a bracket  42  coupled with the movable portion  98 . The bracket  42  defines a first rotational axis, shown as bracket axis  44 . The bracket  42  may extend from a first side of the movable portion  98 . For example, the bracket  42  may extend from a bottom side of the movable portion  98  when the movable portion  98  is in a horizontal position. The mounting mechanism  40  may further include a plate  46 . The plate  46  couples with at least one of the plurality of panels  10  of the illuminator  100 . The plate  46  preferably couples with a central panel (e.g., panel  10   c ) of the illuminator  100 . The plate  46  is preferably positioned at a central location of the backside of the panel  10 . The plate  46  defines a second rotational axis, shown as plate axis  48 . The plate axis  48  maybe perpendicular, or substantially perpendicular, to the bracket axis  44 . 
     In at least one embodiment, the plate  46  includes at least one projection  50 . The projection  50  extends from the plate  46  to couple with the bracket  42 . In at least one embodiment, the plate  46  includes two projections  50 . Coupling the plate  46  with the bracket  42  via the projections  50  facilitates securing of the illuminator  100  to the movable stand  80 . The projections  50  are rotatably coupled with the bracket  42  such that the projections  50  and the plate  46  can rotate about the bracket axis  44 . With the illuminator  100  coupled with the plate  46 , the illuminator  100  can rotate about the bracket axis  44 . For example, the illuminator can tilt approximately ±90 degrees from a stowed position (e.g., with the center panel  10  facing the floor). The bracket  42  may utilize one or more torque inserts that are capable of holding the illuminator  100  at any position without an additional lock. The movable portion  98  may remain stationary while the illuminator  100  rotates or tilts. 
     As shown in  FIG.  7   , the illuminator  100  may rotate or tilt about the bracket axis  44 . Rotation about the bracket axis may facilitate placement of the illuminator  100  for treatment. For example, the illuminator  100  may be rotated about the bracket axis  44  such that the illuminator  100  is disposed below the connecting arm  85  (e.g., a stowed or neutral position) with the movable portion  98  in a horizontal position. In such an embodiment, the panels  10  may be facing toward a floor (or ground) where the illuminator system  105  sits. The central panel  10  of the illuminator may be oriented horizontally. 
     The illuminator  100  may be rotated about the bracket axis  44  such that the illuminator  100  is disposed on a side of the connecting arm  85 . For example, the illuminator  100  may be rotated approximately 90 degrees such that the panels  10  face toward a wall. In such an embodiment, the central panel  10  of the illuminator may be oriented vertically. The illuminator  100  can rotate approximately 90 degrees (e.g., in a range from approximately zero degrees up to approximately 90 degrees) to either the left or right side of the movable portion  98 , as shown by the arrows of  FIG.  7   . As such, the illuminator  100  can rotate approximately up to 180 degrees around the bracket axis  44  (e.g., in a range from approximately zero to 180 degrees). The one or more torque inserts can hold the illuminator  100  at any position through the permitted 180 degree range of motion. 
     The plate  46  may be rotatably coupled to the panel  10  such that the panel  10 , and the other panels  10  of the illuminator  100  can rotate about the plate axis  48  relative to the plate  46 . For example, as shown in  FIGS.  5  and  6   , the illuminator  100  may rotate approximately 90 degrees from a stowed or neutral position (e.g., the center panel  10  is aligned with the stationary portion  97  of the connecting arm  85 ). In at least one embodiment, the mounting mechanism  40  includes a positioning guide  52  on the plate  46  and a position indicator  54  on the panel  10 . The positioning guide  52  indicates the rotation range of the illuminator  100  (e.g., approximately 90 degrees). The position indicator  54  indicates where within the rotation range the illuminator  100  is currently positioned. For example, as shown in  FIG.  6   , the positioning guide  52  may indicate that the illuminator  100  can rotate as long as the position indicator  54  aligns with a portion of the positioning guide  52 . As the illuminator  100  rotates, the position indicator  54  may travel around the positioning guide  52 . When the position indicator  54  reaches an end of the positioning guide  52 , the mounting mechanism  40  may prevent the illuminator  100  from rotating any further in that direction. For example, the mounting mechanism  40  may have a detent at each end of the positioning guide  52  to lock the illuminator  100  into position. The position of the illuminator  100  may be locked into a position for treatment when the position indicator  54  aligns with an end of the positioning guide  52 . 
     The illuminator  100  can rotate such that the position indicator  54  moves from a first position aligned with a first end of the positioning guide  52  to a second position aligned with a second end of the positioning guide  52 . The movement between the first position and the second position can include a rotation of the illuminator  100  of approximately 90 degrees. To move between the first and second positions, the illuminator  100  can move approximately 90 degrees to the left (e.g., clockwise) or 90 degrees to the right (e.g., counter clockwise). The illuminator  100  may also move to any intermediate position disposed between the first and second ends of the positioning guide  52 . The illuminator  100  is configured to remain at any desired angle during operation. For example, the position indicator  53  may be disposed between the first and second ends of the positioning guide  52  when the illuminator  100  is being used. 
     As shown in  FIGS.  8 A- 13   , the illuminator  100  may rotate about both the bracket axis  44  and the plate axis  48  regardless of the position of the movable portion  98  of the connecting arm  85  or the height of the extension member  86 . For example, in  FIG.  8 A , the extension member  86  is in a low (retracted) position, the movable portion  98  of the connecting arm  85  is in a horizontal position, the illuminator  100  is rotated about the bracket axis  44  such that the illuminator  100  is disposed on a left side of the connecting arm  85 , and the illuminator  100  is rotate such that the panels  10   a - 10   e  are disposed in a horizontal orientation. In  FIG.  8 B , the extension member  86  is the same low position, movable portion  98  is in the same horizontal position, and the panels  10   a - 10   e  are still oriented in the same horizontal orientation, but the illuminator  100  is rotated about the bracket axis  44  in the opposite direction such that the illuminator  100  is disposed on a right side of the connecting arm  85 . For example, the illuminator  100  rotated under the connecting arm  85  to switch from the left side to the right side. The same movements can be made when the extension member  86  is extended from, and not fully disposed in, the vertical column  82 . 
     In  FIG.  9   , the illuminator  100  is still disposed on the right side of the connecting arm  85  (as viewed from the right of the figure), but the illuminator  100  is rotated about the plate axis  48  such that the panels  10   a - 10   e  are disposed in a vertical orientation. In  FIG.  10   , the movable portion  98  is oriented vertically and the illuminator  100  may still rotate about either the plate axis  48  or the bracket axis  44  to a desired orientation. The orientation of the panels  10  with respect to each other can also be modified in any position. For example, with the movable portion  98  in the vertical position, the panels  10  may move between a flat configuration and a folded configuration. For example,  FIG.  10    shows the movable portion  98  in a vertical position with the panels  10  in a flat configuration.  FIGS.  11 - 12    show the movable portion  98  still in the vertical position, but with the panels  10  in a folded configuration.  FIG.  13    shows the movable portion  98  in a horizontal position with the panels  10  in a folded configuration. 
     The components of the illuminator system  105  described herein facilitate movement of the illuminator  100  to provide uniform light to a desired treatment area. The illuminator  100  can move between a fully stowed position and various operational positions, and various intermediate positions in between. In the fully stowed position, (i) the extension member  86  is in its lowest position (e.g., a majority of the extension member  86  is disposed in the vertical column  82 ), (ii) the movable portion  98  of the connecting arm  85  is in a vertically downward position (perpendicular to the stationary portion  97 ), and (iii) the central panel  10  of the illuminator  100  is aligned with the movable portion  98  (e.g., vertical and at the neutral position relative to both the bracket axis  44  and the plate axis  48 ). Further, when the illuminator  100  is fully stowed, the panels  10  of the illuminator  100  are configured to be maintained in a U-shaped arrangement and to surround at least a portion of the vertical column  82 . The panels  10  of the illuminator  100  are foldable within the contours of the base  81  and the vertical column  82 . 
     In at least one embodiment, an operational position includes the extension member  86  extending at least partially from the vertical column  82  (the vertical column lock  21  can lock the vertical column  82  at any height), the movable portion  98  of the connecting arm  85  being horizontal and parallel with the stationary portion  97 , the illuminator  100  disposed at any orientation relative to the bracket axis  44  and the plate axis  48 , and the panels  10  of the illuminator  100  in any configuration to provide light to the desired treatment area. Regarding the plate axis  48 , the illuminator  100  may be substantially parallel with the movable portion  98  of the connecting arm  85  or may rotate approximately 90 degrees to be substantially perpendicular to the movable portion  98 . The illuminator  100  may also be at any angle between 0 and 90 degrees with respect to the plate axis  48 . Regarding the bracket axis  44 , the illuminator  100  may be in the neutral position and be in the same vertical plane as the stationary portion  97  of the connecting arm  85 , or may either (i) rotate up to approximately 90 degrees (e.g., in a range from approximately zero to 90 degrees) in a first direction to be disposed on a first side of the movable portion  98  (out of the plane of the stationary portion  97 ) or (ii) rotate up to approximately 90 degrees (e.g., in a range from approximately zero to 90 degrees) in a second direction to be disposed on a second side of the movable portion  98  (also out of the plane of the stationary portion  97 ). 
     Referring now to  FIG.  15   , illuminator system  105  includes a main power switch  96 . The main power switch  96  may control when power is supplied to the illuminator system  105 . The main power switch  96  may be a two-position rocker switch that can toggle between two positions. For example, a first position can activate (e.g., turn on power to) the illuminator system  105  and the second position can deactivate (e.g., disconnect all electrical components of) the illuminator system  105 . The first position can place the illuminator system  105  in a stand-by mode. At least one emitter (e.g., an LED  60 ) may be disposed adjacent to the main power switch  96 . The emitter is configured to provide illumination when the illuminator system  105  is in the stand-by mode. The main power switch  96  may be located on the base  81  adjacent to a socket for a removable power cord (e.g., a medical grade power cord). 
     As shown in  FIG.  16   , the illuminator system  105  includes a vertical column lock  21 . The vertical column lock  21  may be disposed below the handle  84 . The vertical column lock  21  may be moved between a first position and a second position. The first position may be an up position that unlocks the vertical column  82  such that the extension member  86  can move in and out of the vertical column  82  and the height of the illuminator  100  can be adjusted. A bezel adjacent to the vertical column lock  21  may be a first predetermined color (e.g., green or another color) when the vertical column lock  21  is in the up position to indicate the vertical column  82  is unlocked. The second position may be a down position that locks the vertical column  82  such that the extension member  86  is fixed at its current position. The bezel adjacent to the vertical column lock  21  may be a second predetermined color (e.g., red or another color) when the vertical column lock  21  is in the down position to indicate the vertical column  82  is locked. 
     Illuminator Sensor Configuration and Interface 
     As shown in  FIGS.  1  and  14   , the illuminator system  105  may include an interface panel  90 . The interface panel  90  may be supported by the vertical column  82 . The interface panel  90  may be coupled with the vertical column  82  and may be removable from the vertical column  82 . The interface panel  90  may include any number of buttons, switches, or other control mechanisms that control aspects of the illuminator system  105 . For example, the interface panel  90  may include a power button  91   a  and a status indicator  91   b . The power button  91   a  may control a setting of the illuminator system  105 . For example, the power button  91   a  may load one of two pre-programmed treatment cycles to the illuminator system  105 . For example, the last treatment cycle used (e.g., 10 mW or 20 mW) may be loaded and a time is displayed (e.g.,  16 : 40  or  8 : 20 ). 
     The status indicator  91   b  may indicate a status of the illuminator system  105 . For example, different colors or frequencies of the status indicator  91   b  may have different meanings. For example, a first color (e.g., blue) may indicate a first status (e.g., normal operation) and a second color (e.g., amber) may indicate a second status (e.g., fault condition). A flashing first color may indicate a third status and a solid first color may indicate a fourth status. Actuating the power button  91   a  (e.g., pressing the button) at predetermined times may cause predetermined actions. For example, pressing the power button  91   a  while a treatment cycle is “paused” may cancel the treatment cycle to clear the time displayed. Pressing the power button  91   a  with a main power switch  96  (described in more detail below) activated may toggle to load or clear a treatment cycle for the illuminator system  105 . 
     The status indicator  91   b  may include an array of LEDs disposed around the power button  91   a  (e.g., in an annular pattern or a different pattern). The status indicator  91   b  displays a status of the illuminator system  105 . In at least one embodiment, at a beginning of a treatment, the status indicator  91   b  may illuminate a steady blue (or another color) to indicate that control electronics of the illuminator system  105  are functioning normally and that associated software is ready for use. The status indicator  91   b  may change from the steady blue to a slow flashing blue (or another color) when the illuminator system  105  is placed into a pause mode. In at least one embodiment, another color or other colors may be used. The status indicator  91   b  may return to a steady blue when the cycle resumes. The status indicator  91   b  may illuminate a steady amber or flashing amber (or another color) if a fault condition is detected (i.e., in response to detecting a fault). 
     The interface panel  90  may include time adjuster  92 . For example, the time adjuster  92  may be a button configured to control a treatment time of the panels  10  (e.g., the time the illuminator is activated). A maximum treatment time may be predetermined. For example, a maximum treatment time may be set at thirty minutes. The time adjuster  92  may be used to adjust an exposure time manually or automatically turn off the LEDs of the panels  10  after a set exposure time has lapsed. The time adjuster  92  may include an up button  92   a  and a down button  92   b  to increase or decrease the time, respectively. When first depressed, the up button  92   a  and the down button  92   b  change a displayed reading relatively slowly (e.g., within a first predetermined time period, such as over fifteen seconds, etc.). When the up button  92   a  or the down button  92   b  remain depressed, the displayed reading changes more quickly (e.g., within a second predetermined time period that is shorter than the first time period, e.g., within five seconds). Depressing and releasing the up and down buttons  92   a ,  92   b  quickly allows for an adjustment to the displayed time. For example, each depression may adjust the time by a given interval (e.g., by one second). 
     The interface panel  90  may include a level adjuster  93 . For example, the level adjuster  93  may be a button configured to adjust an intensity or power setting (e.g., power level) of the illuminator  100 . For example, the level adjuster  93  may switch the power between two settings (e.g., 10 mW and 20 mW). The power level may be selected after pressing the power button and status indicator  91  to load one of the pre-programmed cycles. The time adjuster  92  may automatically set the correct time for the power level selected. The power level selected may be displayed above the level adjuster  93 . For example, the 10 mW setting may be displayed as “10” and the 20 mW setting may be displayed as “20.” 
     The interface panel  90  may include a comfort adjuster (comfort controller, patient settings controller)  94 . For example, the comfort adjuster  94  may be a button or other interface configured to control a patient comfort fan. For example, the comfort adjuster  94  may be a button or other interface configured to switch a setting of a fan between off, low, and high. The patient comfort fan may be controllable by the healthcare provider or patient upon pressing the power button and status indicator  91  to load the treatment cycle. The comfort adjuster  94  can be used to cycle through the three settings. The patient cooling fans may automatically shut off when a cycle timer reaches zero during treatment. 
     The interface panel  90  may include a start/stop button  95 . For example, the start/stop button may be configured to initiate the programmed treatment cycle, pause an active treatment cycle, or restart a paused treatment cycle. Pressing the start/stop button  95  while the treatment cycle is active may cause one or more of the following: (i) pausing or cessation of the treatment cycle, (ii) switching off of LEDs, and (iii) terminating a count-down performed by the timer. The power button and status indicator  91  may flash a predetermined color to indicate that the system is paused. The illuminator system  105  may automatically return to stand-by mode when left paused for a predetermined time or more. For example, the illuminator system  105  may automatically return to stand-by mode if left paused for over 5 minutes. Pressing the start/stop button  95  while the system is paused may cause the treatment cycle to resume, the LEDs to illuminate, and the timer to resume counting down. The power button and status indicator  91  may display a steady predetermined color to indicate normal operating status (e.g., a steady blue color, or another color). 
     As shown in  FIG.  23   , the illuminator system  105  may include a touch screen  200 . The touch screen  200  may be a part of the interface panel  90 , the controller  115 , or some other independent device (e.g., a user device). The touch screen  200  may allow a user to control, monitor, and adjust settings of the illuminator system  105 . For example, the touch screen  200  may include at least one of the power button  91   a , the status indicator  91   b , the time adjuster  92 , the lever adjuster  93 , the comfort adjuster  94 , and/or the start/stop button  95 . The touch screen  200  may include additional features (e.g., buttons, displays, notifications, etc.) for a user to monitor and control the settings. 
     For example, the touch screen  200  may provide a heat controller  201  to control the heat directed to the patient for pain management. The touch screen  200  may provide a notification window  202  to provide notifications or alerts to the user. The touch screen  200  may provide a time indicator  203 . The time indicator  203  may display a time remaining for the treatment. The time displayed on the time indicator  203  may change as time progresses and may change as adjusted via the time adjuster  92 . In at least one embodiment, the remaining exposure time is displayed in minutes and seconds. Prior to pushing the start/stop button  95 , the exposure time indicator displays the amount of exposure time set. When the start/stop button  95  is pressed, the exposure time indicator  203  counts down the amount of exposure time remaining. The exposure time indicator  203  may turn off automatically when the display reaches zero. The interface panel  90  may include some or all of these additional features, even if the interface panel  90  does not include the touch screen  200 . 
     The illuminator system  105  may include one or more sensors  110 . In at least one embodiment, the illuminator system  105  may include a sensor  110  configured to detect a size of a treatment area of a patient. In at least one embodiment, the illuminator system  105  may include a sensor  110  configured to detect a position of the illuminator  100 . The position of the illuminator  100  may include the height of the extension member  86 , the orientation of the illuminator  100  (e.g., vertical, horizontal, to the right or left of the connecting arm  85 ), or the configuration of the panels  10  (e.g., U-shaped, flat, etc.). The position of the illuminator  100  and the size of the treatment area can be used to determine the correct light dosing parameters for the treatment. The sensor  110  can be disposed on any component of the illuminator system  105 . For example, a sensor  110  may be disposed on the vertical column  82 , a panel  10 , and/or the connecting arm  85 , among others. The sensor  110  can be any type of sensor configured to detect data indicative of the position of the illuminator. 
     The illuminator system  105  may include a controller  115 . As shown in  FIG.  24   , the controller  115  may be configured to monitor and control various components of the illuminator system  105 . For example, the controller  115  may be configured to control the heat source currents to accommodate differing tissue geometries and to provide differing power levels, including varying the current over time to modulate a patient&#39;s pain tolerance. The variation in current may be in response to input from sensors such as a distance sensor or a sensor that indicates the relative position of the panels. 
     In at least one embodiment, the controller  115  may also be configured to transition the illuminator system  105  between a curved geometry and a flat geometry and maintain uniformity and power throughout the transition. The controller  115  may also include a processing circuit  116 . The processing circuit  116  may include a processor  117  and a memory  118 . The memory  118  (e.g., storage device) may include one or more devices (e.g., RAM, EPROM, optical disk storage, magnetic disk storage flash memory, hard disk storage, or any other medium) for storing data and/or computer code for completing or facilitating the various processes and functions described in the present disclosure. The memory  118  may be or include transitory memory or non-transitory memory, and may include any type of information structure for supporting the various activities and information structures described in the present disclosure. 
     According to at least one embodiment, the memory  118  is communicably connected with the processor  117  and includes computer code for executing (e.g., by the processor  117 ) the processes described herein. The processor  117  may be a general purpose single-chip or multi-chip processor, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), or other programmable logic device, discrete gate or transistor logic, discrete hardware components, or any combination thereof designed to perform the functions described herein. A general purpose processor may be a microprocessor or any typical processor, controller, microcontroller, or state machine. The processor  117  may also be implemented as a combination of computing devices, such as a combination of a DSP and a microprocessor, a plurality of microprocessors, one or more microprocessors in conjunction with a DSP core, or any other such configuration. In at least one embodiment, particular processes and methods may be performed by circuitry designed for a given function. 
     In at least one embodiment, the memory  118  may include a dosing parameter database  119 . The dosing parameter database  119  may include relationships between dosing quantities (including exposure time), light intensities, distances between the panels and the treatment surface, and size of the treatment surface, among other data associated with treatment via the illuminator system  105 . For example, a specific duration of exposure to light from the illuminator  100  can be associated with a specific light intensity, a specific distance between the panels and the treatment surface, and a specific size of the target surface. The processor  117  can use the data stored in the dosing parameter database  119  to determine the appropriate dosing parameters for a treatment session for a patient. 
     In at least one embodiment, the controller  115  may include an input/output (I/O) circuit  120 . The I/O circuit  120  may be configured to receive signals or data from external devices and transmit signals or data to external devices. 
     In at least one embodiment, the controller  115  may include a user interface  121 . The user interface  121  may be a touch screen. The user interface  121  may be configured to display the information received by the controller  115  via the I/O circuit  120  or retrieved from the memory  118 . The user interface  121  may be configured to receive input from a user. For example, the user interface  121  may have interactive sections with which a user can interact with and provide information. The interactive sections may be buttons, switches, or input fields, among others. The controller  115  may receive the user input via the I/O circuit  120  and may be configured to store the user input in the memory  118  or use the user input to generate an output. For example, the user interface  121  may be configured to provide a display that shows the orientation and position of the illuminator  100  based on information received from the distance sensors  11  and the sensors  110 . For example, when the illuminator  100  is in a use configuration, the user interface  112  may show the illuminator  100  in its current position. The display may include a current distance of each panel  10  from the treatment area detected by the distance sensors  11 . 
     In at least one embodiment, the controller  115  may be communicably coupled with one or more components of the illuminator system  105 . For example, the controller  115  may be communicably coupled with a distance sensor  11 . The distance sensor  11  may be configured to transmit a signal to the controller  115  indicative of the distance between the panel  10  and the treatment area. The controller  115  may be communicably coupled with a sensor  110 . The sensor  110  may be configured to transmit a signal to the controller  115  indicative of the position or orientation of the illuminator  100 . The controller  115  may be communicably coupled with the mounting mechanism  40 . The controller  115  may be configured to transmit a command to the mounting mechanism  40  to orient the illuminator  100  in a desired position. The controller  115  may be communicably coupled with the panels  10  of the illuminator  100 . The controller  115  may be configured to transmit a command to the panels  10  to orient the panels  10  in a desired configuration (e.g., U-shaped). The controller  115  may be communicably coupled with the components via a wired or wireless connection. 
     Illuminator Cooling System and Method 
     As shown in  FIGS.  18 - 23   , at least one of the panels  10  of the illuminator system  105  (e.g., panel  10   c ) may include a patient cooling fan system  66 . The patient cooling fan system  66  may be configured to blow air across a surface of the panel  10  such that the air is tangential to a patient&#39;s skin to provide a soothing effect to the patient. The patient cooling fan system  66  includes a fan plenum  74 . The fan plenum  74  may define a serpentine path for air to flow, shown as air path  75 . For example, the fan plenum  74  may include a body  78  and a neck  79 . The body  78  defines a cavity for receiving the air. The cavity can have a first thickness. The body  78  transitions to the neck  79  that has a second thickness. The first thickness is larger than the second thickness. The neck  79  can define a serpentine air path  75  for the airflow  76  until the air reaches the plenum outlet  77 . 
     In at least one embodiment, the fan plenum  74  may be disposed within the panel  10 . The patient cooling fan system  66  may include a fan  70 . The fan  70  may be configured to draw air in from the environment and push the air into the fan plenum  74 . The fan  70  can push the air through the air path  75  of the fan plenum  74  to a plenum outlet  77 . The air path  75  and the plenum outlet  77  are configured to generate an airflow  76  that moves parallel, or substantially parallel, to the face of the panel  10 . 
     In at least one embodiment, the panel  10  may include a plurality of fan plenums  74 . For example, a first fan plenum  74  may be disposed at a first end of the panel  10  and a second fan plenum  74  may be disposed at a second end of the panel  10 . The first and second fan plenums  74  may generate an airflow  76  that is parallel, or substantially parallel, to the face of the panel  10 , but a first airflow  76  from the first fan plenum  74  may be directed in a first direction and a second airflow  76  from the second fan plenum  74  may be directed in a second direction. The second direction may be opposite the first direction. For example, the first airflow  76  may move down the face of the panel  10  and the second airflow  76  may move up the face of the panel  10 . 
     In at least one embodiment, the heat source may be provided separately from the illuminator  100  or integrated therein. In at least one embodiment, the heat source (a thermal delivery device) may be an infrared (IR) quartz heater. In at least one embodiment, the heat source may comprise frame mounted resistance tape heaters or a plurality of heaters, including at least one selected from the group including IR LEDs, resistance cartridge heaters, positive temperature coefficient heaters, or IR quartz heaters, as mentioned above. The heat may be deliberately generated and directed towards the area to be treated, as opposed to ambient heat in the clinical setting or byproduct heat from one or more operating mechanisms of the illuminator. In at least one embodiment, the heat is intentionally generated and directed toward the patient and the patient is still further heated by ambient and/or byproduct heat. In at least one embodiment, the heat is administered in the form of a heat mask, such as a sodium acetate mask configured to heat upon crystallization. In at least one embodiment, the heat source is a heating pad. 
     Thus, components or operating mechanisms of the illuminator can be configured to generate heat that can be deliberately targeted toward the patient. For example, the illuminator may include one or more fans that draw air across such components or mechanisms to deliver heat to the patient. The heat may alleviate pain or discomfort experienced by the patient. And, as noted above, heating additionally accelerates the conversion of ALA to porphyrin. 
     Referring now to  FIG.  25   , a method  250  of providing photodynamic therapy is shown, according to an exemplary embodiment. Method  250  may include detecting a position of the illuminator (step  251 ), identifying a treatment area (step  252 ), determining a dosing parameter (step  253 ), and beginning treatment (step  254 ). In particular, the method can include detecting the position of the illuminator  100 , e.g., when the illuminator is in a neutral position or a rotated position of up to 90° relative to an axis. 
     At step  251 , one or more processors and/or sensors may detect a position of an illuminator  100 . For example, the controller  115  may receive a signal from a sensor  110  indicating a position of a panel  10  of the illuminator  100 . For example, the sensor  110  may be a distance sensor or a sensor that indicates a relative position of the panels  10  of the illuminator  100 . The controller  115  may receive a signal from a plurality of sensors  110  indicating a position of a corresponding panel  10 . The controller  115  may determine the position of the illuminator  100  based on the plurality of signals. Step  251  may include at least one of detecting a height of an extension member  86 , detecting an orientation of the movable portion  98  of the connecting arm  85  (e.g., vertically down, vertically up, horizontal), detecting an orientation of the illuminator  100  (e.g., rotation angle around at least one of the bracket axis  44  and the plate axis  48 ), and/or detecting an arrangement of the plurality of panels  10  of the illuminator  100  (e.g., U-shaped, flat). 
     At step  252 , one or more processors or sensors may identify characteristics of a treatment area. For example, the controller  115  may identify or infer a location, shape or size of treatment area based on the position of the illuminator  100 . For example, the signals received by the controller  115  may indicate that the panels  10  of the illuminator  100  are positioned vertically, in a U-shape, and are disposed at a specific height. Based on data from the signal and/or sensors, the controller  115  may identify that a face of a patient as the treatment area. Identifying the treatment area may also include determining a shape or size of the treatment area. For example, the controller  115  may determine the size of the treatment area based on signals received from the sensors  11 ,  110 . In some embodiments, a panel position sensor may be used to identify characteristics of the treatment area based on, for example, a look up table. In some embodiments, an active optical or ultrasonic sensor could be used to identify characteristics of the treatment area. 
     In at least one embodiment, the detection of the position of the illuminator and/or the identification of the treatment area, such as its location, shape or size, may be determined in furtherance of enhancing photodynamic therapy provided using the illuminator  100 . For example, by using sensors to detect the shape of the surface to be treated, the LED arrays can be individually configured to emit more intense light to only those areas that require it. Additionally, the sensors can be used to detect the orientation of one or more panels (e.g., whether a panel is angled or folded flat) and may be used to configure the LEDs to emit more or less intense light in areas as desired. 
     In particular, in at least one embodiment, at least one sensor detects an orientation of at least one panel and provides detection information (a detection result) to the controller  115 . The sensors may include one or more encoders, such as one or more angle encoders, which are provided at one or more locations on the panels. In at least one embodiment, at least one sensor is a microswitch configured to sense a position of at least one panel. In at least one embodiment, a plurality of sensors may include an encoder, a microswitch, or combinations thereof. The sensors are communicated with the controller  115  and are configured to provide information about the panel orientation, such as an angle at which a panel is disposed, to the controller  115 . The controller then controls the intensity of light in accordance with a detection result. In at least one embodiment, a plurality of sensors provides information to the controller so that the controller may carry out a determination as to whether the illuminator has a configuration that is one of a plurality of preset configurations. For example, the controller may store, in a memory, information relating to one or more preset configurations (e.g., for a bent illuminator, a flat illuminator, etc.). 
     When the controller receives information transmitted from the sensors, the controller may compare the sensed information to the preset configurations to determine a match between the sensed information and one or more preset configurations. The controller may further store a protocol for altering intensity which is executed upon determining a match between the sensed information and the preset configuration. For example, if the illuminator is detected to be in a U-shaped configuration, the controller implements a light intensity output which is correlated to the preset protocol for a U-shaped illuminator. The controller may further compare an existing intensity to an intensity associated with a particular configuration and determine whether the intensity should be adjusted. This allows for an increase in uniformity of light exposure in an efficient manner as power output and/or light intensity is increased to only certain diodes, in accordance with need. In at least one embodiment, a plurality of preset configurations may be presented to a healthcare provider, e.g., on a touch screen, who may then select the preset configuration corresponding to the physical arrangement of the illuminator in the treatment or clinical environment. 
     At step  253 , one or more processors may determine a dosing parameter. For example, the controller  115  may compare the data received from the sensors  11 ,  110  with the data stored in the dosing parameter database  119 . Based on the comparison, the controller  115  may determine a dosing parameter suitable for treatment for a given position of the illuminator  251  and a given treatment area. The dosing parameter may be a duration of exposure or a light intensity, among others. 
     The one or more processors may detect an adjusted position of the illuminator  100 . In such an embodiments, steps  251 - 253  can be repeated until a final position of the illuminator  100  is established. 
     At step  254 , one or more processors may initiate a treatment cycle. For example, the controller  115  may initiate a treatment cycle based on the determined dosing parameter. The controller  115  may actuate the LEDs  60  of the panels  10  of the illuminator  100  at a specified intensity based on the dosing parameter. The controller  115  may set a treatment duration based on the dosing parameter. The controller  115  may actuate the patient cooling fan system  66 . 
     Thus, the controller allows a healthcare provider to control one or more of the following aspects: (i) the treatment cycle, (ii) LED actuation, (iii) LED intensity, (iv) treatment duration, and (v) cooling (i.e., fan-induced cooling) of the patient (among other aspects of treatment). The healthcare provider may adjust any or all of (i)-(v) throughout treatment using the controller  115 . In particular, the controller  115  may be used (e.g., manipulated by a healthcare provider or the patient) to operate the patient cooling fan system  116  to cause cooled air to be directed to the patient. The cooling air may thus be delivered in response to an input from the controller  115  as it is operated during treatment. For example, by providing cooling air to the patient via the patient cooling fan system  116 , a sensation of pain or discomfort experienced by the patient may be alleviated. 
     It should be noted that the term “example” as used herein to describe various embodiments is intended to indicate that such embodiments are possible examples, representations, and/or illustrations of possible embodiments (and such term is not intended to connote that such embodiments are necessarily extraordinary or superlative examples). 
     As utilized herein, the term “substantially” and similar terms are intended to have a broad meaning in harmony with the common and accepted usage by those of ordinary skill in the art to which the subject matter of this disclosure pertains. It should be understood by those of skill in the art who review this disclosure that these terms are intended to allow a description of certain features described and claimed without restricting the scope of these features to the precise numerical ranges provided. Accordingly, these terms should be interpreted as indicating that insubstantial or inconsequential modifications or alterations of the subject matter described and claimed are considered to be within the scope of the invention as recited in the appended claims. 
     The terms “coupled,” “connected,” and the like as used herein mean the joining of two members directly or indirectly to one another. Such joining may be stationary (e.g., permanent) or moveable (e.g., removable or releasable). Such joining may be achieved with the two members or the two members and any additional intermediate members being integrally formed as a single unitary body with one another or with the two members or the two members and any additional intermediate members being attached to one another. 
     While this specification contains specific implementation details, these should not be construed as limitations on the scope of any embodiment or of what may be claimed, but rather as descriptions of features specific to particular implementations of particular embodiments. Certain features described in this specification in the context of separate implementations can also be implemented in combination in a single implementation. Conversely, various features described in the context of a single implementation can also be implemented in multiple implementations separately or in any suitable subcombination. Moreover, although features may be described above as acting in certain combinations and even initially claimed as such, one or more features from a claimed combination can in some cases be excised from the combination, and the claimed combination may be directed to a subcombination or variation of a subcombination. For example, the implementations described herein can be used in conjunction with (and applied to) the compositions, illuminators, devices, dressings, methods of treatment, processes and techniques set forth in the patents and/or patent applications cited above. 
     The construction and arrangement of the various exemplary embodiments are illustrative only. Recognizing that one or more embodiments have been described in detail in this disclosure, those skilled in the art who review this disclosure will further appreciate that many modifications are possible (e.g., variations in sizes, dimensions, structures, shapes and proportions of the various elements, values of parameters, mounting arrangements, orientations, etc.) without materially departing from the novel teachings and advantages of the subject matter described herein. Other substitutions, modifications, changes and omissions may also be made in the design, operating aspects and arrangement of the various exemplary embodiments without departing from the scope of the instant disclosure.