PHYSIOLOGICAL EFFECTS: LIGHT EFFECTS ON SKIN CELLS CAN CAUSE PREMATURE AGING

• The skin cells are attached to the electrode then put the resistance of cell in 10-15 hours to reach a steady state as the same condition as skin cell in the human body.
• After reaching the cell confluence, the lights were exposed to an on/off series with gradually increasing time intervals of 1 to 2.5 hours.
• The lights are made of 8 LED with different RGB colors as visible light spectrum equipped with its control setup, thermocouples, eight well ten electrodes (8W10E) ECIS culture chip, thermocouples, and PC (data-acquisition system) with a software interface.

• The visible light spectrum has blue-460 nm, green-530 nm, red-625 nm, and white light radiation.
•  Cells were exposed to intermittent, mild, and intense radiation with the timing from 1 to 180 minutes light with on/off cycles, using blue, green, red, and white light.

• How certain are the scientists with this work: The scientists were certain with this work to the extent that this research advanced the understanding of the different color light-induced degenerative process.
• The study can help in the development of new therapeutic strategies.

• Visible light can cause premature aging on the skin cells.

• Outcome metrics using LED glare to human cells: Blue light exposure shows a significant decrease in cell viability at 150 minutes. The research found that about 12% of the cells died after 150 minutes of exposure.
• Quality of evidence: Another study stated that the uses of LED lighting as a visible light spectrum to the human body is promising because it has the same effect and it can cause physiological damage directly and lead to various health problems. It also stated that blue light may also contribute to skin aging similar to UVA.

• More time exposure of visible light spectrum to skin cells is equivalent to more dead skin appearance.

• Type of application on the human body: skin cells 

NEURAL EFFECT: VISIBLE LIGHT SPECTRUM, ESPECIALLY BLUE LIGHT, CAN DAMAGE RETINA NEURON CELL

• In this study, the researcher used rat retinal cells, those were isolated from four eyes of one-day-old rats for each experiment. The retina cells were isolated then incubated for 20 minutes in a media with trypsin to dissociate the cells.
• The retinal cells were maintained in the dark or exposed to white light (900 lux, 1500 lux), or blue light (900 lux, 1500 lux) for about 2 hours then transferred to a dark incubator for incubation, the cells were taken at 2h, 24h, and 48h.
• The short term blue light is achieved by an LED system in a cellular incubator where the cells were maintained under culture conditions. This LED cellular system produces a low radiant heat output, avoiding hyperthermic disturbance.

•  Blue light (450–495 nm) with the radiation of 900 lux impairs cell viability and induces cell apoptosis in retinal neurocytes in vitro.

• How certain is the scientist with this work: Based on the findings, the researchers are convinced and certain with their work and declared no conflict of interest.
• The researchers were sure that their study provides new insights into the mechanisms of the effect of blue light on the retina.

• Visible light spectrum, especially blue light, can cause retinal damage.

• Outcome metrics: Blue light-induced changes in the integrity of retina thickness that when the retina is exposed to blue light, the thickness is 227.1 ± 9.7, * p < 0.001. While when in the control visible light spectrum, the thickness is 266.5 ± 6.38. The thickness is different and it was stated that blue light exposure can induce severe retinal damage.
• Positive cells damaged in white visible light spectrum is only 2% while on the blue light is 35.3%. This finding shows that DNA assay shows severe DNA damage in the retinal neuron at 2 hours after blue light treatment.
• Quality evidence: A study with the title "Does rat retina make relevant model for discussing exposure limit values applicable to humans?", answered that there's no clear consensus of rat model and undermines the validity of exposure calculations, unless the values can be justified by biological measurement.
• But a study with living human cell justified that blue visible light spectrum distorts plasma membrane on retina phospholipid, phosphatidylinositol 4,5 bisphosphate (PIP2), and disrupt its function.
• Another evidence shows that visible light spectrum makes a large number of mitochondria in retinal ganglion cells when exposed to visual light of 400–850 nm and the blue lights negatively affects mitochondrial function causing stress and decreased cell survival.

• More blue light is equivalent to more damage on retina cell.

• Type of application on the human body: eyes 

How Ultraviolet Light Affects The Human Body

• Increased expression of beta endorphin in the keratinocytes is demonstrated in skin biopsies of adults exposed to UVB radiation.
• Among cultured human keratinocytes exposed to UVA or UVB and UVA radiation: the cells exposed to UVA and UVB radiation had a marked increase in the expression and production of beta-endorphin compared to cells exposed only to UVA radiation.
• UVB radiation is believed to play an important role in controlling cellular circadian activity (a natural, internal process that regulates the sleep-wake cycle and repeats roughly every 24 hours).
• Most of the biologically relevant chromophores, such as compounds with a benzene ring, including aromatic amino acids, biogenic amines, or proteins containing corresponding amino acids, pyrimidines, and purines with their derivatives alone or in nucleic acids, trans-urocanic acid (UCA), quinones, melatonin, indoles, melanin monomers, polymers and precursors, unsaturated lipids and 7-dehydrocholesterol as examples, absorb UVC and UVB with surprisingly high absorption spectra in the UVC range.
• UV radiation can directly activate keratinocytes and other cells to release inflammatory mediators such as cytokines and chemokines, cause redistribution and release of sequestered autoantigens from UV-damaged cells, alter self-proteins to make them more immunogenic, enhance the immunogenicity of externally applied molecules, and chemically alter systemically administered medications whose distribution includes the skin.
• UVB radiation is generally considered to be more effective than UVA.
• UVC radiation has the ability to damage DNA in cells. This causes the cell to either arrest division or undergo apoptosis. This method could be used to treat cancerous cells.
• When it comes to normal interaction with UVC, like lamps, the absorption length of UVC radiation in human skin is extremely short so that almost no UVC radiation can reach the living cells in the skin; all the absorption occurs in the dead cell layers.
• High level exposure to UVC can cause serious burns. Chronic exposure to UVC can cause eye damage, premature aging and skin cancer.
• Far-UVC light is also known as a potent bactericidal and commonly used for sterilization of water, surfaces and air.

1. Proposed Mechanisms and Magnitude

• NB-UVB (311–313nm)
• PUVA (320-400 nm)
• Broadband UVB (280–320 nm)
• Narrowband UVB (311–313nm). Narrowband UVB is often more effective and safer than broadband.
• UVA1 (340–400 nm)
• It was proposed that 222-nm UVC to be safe and not induce mutagenic or cytotoxic DNA lesions in mammalian cells; however, effect of chronic irradiation with a high dose of 222-nm UVC has not been determined.
• Weighing the type of disease being treated, the depth of disease pathology, and the risk of skin carcinogenesis helps to determine the best phototherapy treatment modality for a particular patient.
• Once the appropriate modality has been chosen, the treatment is then individualized based upon the patient’s minimal erythema dose (MED).
• MED is defined as the minimum amount of radiation that produces erythema 24 hours after exposure.
• The maximum dose of broadband UV-B is 0.5 Joules per treatment.
• The maximum dose for narrowband UV-B is 3 Joules per treatment.

2. Certainty

Skin Diseases:

• NB-UBV and PUVA are valuable tools for dermatological treatments.
• The use of NB-UBV and PUVA for skin diseases can be highly effective, well tolerated, safe, cost saving and reduce the need for topical therapies.
• The main indication is for psoriasis, but it can be used for atopic dermatitis, vitiligo, cutaneous T-cell lymphoma (CTLC) and other conditions.
• PUVA is the gold standard of photochemotherapy modalities, mainly for topical psoriatic plaques.

Well Being

• The inclusion of UVA wavelengths within treatment protocols for SAD disorder has been shown to be ineffective.
• Some studies have shown that the UV spectrum does not increase the antidepressant response of light therapy.
• Studies about the effect of UV lights' on mood disorders and well-being are still inconclusive due to small groups, biased studies, non-blinded trials, experimental studies, among other issues.

UVC

• Due to its hazardous nature and the fact that humans don't naturally interact with it, there is still no consensus about the safety, intensity and duration of UVC light directly interacting with the human body (not far-uvc light), with most studies still requiring further investigation.

3. Types of Effects

• UV radiation causes local and systemic immunosuppression by disrupting Langerhans cell function, inducing the formation of the cis isomer of urocanic acid, inducing anergy or deletion of Th1 cells, and promoting the influx of IL-10-secreting macrophages.
• Ultraviolet radiation induces keratinocytes and other cells to produce a variety of cytokines, including IL-1β and TNF-α.
• A non-blinded trial with patients with high MS risk found that the participants who received phototherapy self-assessed that they felt better. UVR exposure may otherwise have reversed a deficiency of monoamines, particularly serotonin and noradrenalin, and normalized the hypothalamic-pituitary-adrenal-axis.
• A recent study on rodents (but with correlation to human conditions) found that UV irradiation of the skin can decrease hippocampal neurogenesis and synaptic signaling, leading to mood changes.
• Chronic UV irradiation results in addiction to UV light in rodents due to β-endorphin production.
• A recent study proposes that solar ultraviolet radiation limits diet-induced weight gain, increases liver triglycerides, and prevents the early signs of cardiovascular disease in mice; however, they still don't know enough to apply it to humans without risks.
• UVC light can be used in cancer treatment since it has the ability to damage DNA cells and decrease the division rate.
• There are studies looking into the use of 222-nm UVC light as a tool to reduce SSI incidence in patients and hospital staff.
• The combination of UVC therapy with an ultra-short course of direct anti-virus agents may provide the ability to prevent transmission altogether, allowing expansion of transplantation using HCV+ organs.
• UVC can also increase inflammatory genes expression such as COX-2 that results in elevated oxidative stress that plays a role in the radiation-induced bystander effect.

4. Outcome Metrics vs Quality of Evidence

4.1 Mood:

• A study conducted in the Netherlands reviewed research made about the effect of ultraviolet light on mood, depression and well-being. (Source 1)
• They started by analyzing 677 studies and clinical trials and from there they eliminated until they could find studies that had control groups, mood measurements, practical outcomes, and exposure to UV light as an intervention. After that, only 7 studies were regarded as eligible and even among those there are concerns about bias.

 Gambichler Study 

• Whole Body UVA
• Skin 2x week, 10-15 min
• Results: UVA-exposed volunteers were more balanced (P = .01), less nervous (P = .03), more strengthened (P = .009) at T3 in comparison with T1, 2. UVA-exposed volunteers showed more robustness and strength (P = .011) and more satisfaction with their own appearance (P = .04) at T3 in comparison with T1.

 Taylor Study 

• Patients with fibromyalgia syndrome
• 4% UVB, 96% UVA
• Skin
• Results: Changes in being active, enthusiastic, alert, attentive or sad were not significant before and after UV–exposure.

 Edstrom Study 

• Patients with dermatological conditions
• Group 1: WBI (Whole body irradiation) UVA/UVAB/PUVA, Group 2: PUVA on hands/feet volunteers, Group 3: WBI (UVB/UVA), Group 4: Placebo
• Skin: 2 & 3/wk
•  Highly significant improvement in MADRS score in patients with WBI (P < .001), tendency toward improvement in the healthy group with WBI(P = .08). Both patients and volunteers divided in groups: UVA, UVB, UVAB: Significant improvement in UVB and UVAB group in MADRS.

 Knippenberg Study 

• Patients with MS
• Skin and eyes
• Personally reported sun exposure was inversely associated with depression scores (β:−.26 (95% CI −0.40, −0.12)), P ≤ .001. When both 25 (OH) D and sun exposure were included in the model, the magnitude of sun exposure remained stable (β: −.26 (95% CI −0.40, −0.11)) P = .001, 25 (OH) D remained non-significant P = .667.

 Lam Study 

• Patients with recurrent major depression, Seasonal pattern
• A. 1 wk: 2500 luxcool-white fluorescent
• Light with UVA By non-response/relapse:
• B. 1 wk: 2500 lux cool-white fluorescent light By non-response/relapse:
• C. 500 lux cool-white fluorescent light
• Eyes (three 1-wk intervals, 2 h per d)
• A. Dim light (500 Lux) had a small, not statistically significant effect onHAM-D, BDI and ATYP scores
• B. UV light condition produced a statistically significant effect on HAM-D, BDI, ATYP compared with other two conditions, resp. P < .003, P < .02, P < .008
• C. The UV-blocked condition produced significant improvement only in atypical symptoms of depression P < .02

 Pudikov Study 

• Cross-over clinical trial, N = 24, Patients with seasonal depression
• Light therapy with full spectrum lenses
• Group 1: UV-blocked condition
• Group 2: UVA condition
• Eye (2 wk, 2 h per d)
• 1. The analysis of SIGH-SAD scores did not find significant effect of condition (P < .70), nor condition-by-time (P < .70).
• 2. Analysis of BDI didn’t find significant effects of condition (P < .25), nor condition –by-time (P < .20).
• 3. Both analysis have found only a significant effect of time (P < .0001)

 Quality of Evidence 

• According to a study conducted by the University Medical Center Leiden, the results of the reviewed studies above, the available knowledge on UV light mechanisms, and the neural, endocrine, and immune regulation of mood, provide sufficient information to warrant further research in this area.
• 6 out of the 7 studies show positive outcomes for the use of UV light for mood enhancement; however, the study still didn't consider those findings to be conclusive.
• They also state that the small number of studies, their heterogeneity and the small number of participants in some studies, the existing bias, and the sub optimal study designs make it difficult to draw general conclusions about the effect of UV light on mood and depressive disorders.
• The same study points out a need for better methods of measure as well as studies in the general population, as well as in cohorts of people with depressive disorders.

4.2 Immune System Modulation

• Several types of UV light treatments are being tested or used as a way for Immune System Modulation.
• As UV radiation, especially UVC, present a direct bactericidal effect, it was directly used for the treatment of a cutaneous infection caused by antibiotic-resistant bacteria.
• In 2014, a 9-year-old girl was treated for wounds and infections relating to burns with UVC irradiation after antibiotics did not present the proper results.
• Repeat cultures of the wounds grew colonies of P. aeruginosa, Protease mirabilis and Klebsiella pneumoniae.
• She was treated with ultraviolet light exposure, of wavelength 32–40 nm/W/cm2, 6-8 hours, for 8 days.
• After the UVC phototherary, the girl recovered from the infection and showed no side effects.
• Another study conducted used UV light C irradiation (254 nm) for the disinfection of surgical wounds during total joint arthroplasty procedures.
• Two different UV light C irradiances, 0.1 and 0.3 mW/cm2 were used. The average bacterial CFU in wounds was reduced by 87% with 0.1 mW/cm2 and 92% with 0.3 mW/cm2, compared with controls no exposed to UV light.

Quality of Evidence

• More studies need to be performed to clarify this point and to allow the establishment of new treatments using UV light for cutaneous infections produced by antibiotic-resistant bacteria. (S18)
• Another study showed that histological analysis demonstrated that small numbers of CPD-expressing cells were detected only in hyperkeratotic stratum corneum after chronic irradiation with a high dose of 254-nm UVC, and that significant hyperplasia and intercellular edema were also induced in the epidermis of mice.
• Despite these effects being attenuated after a further 2 days of treatment, affected skin lesions were exacerbated following re-irradiation with 254-nm UVC for a further 3 consecutive days.

5. Dose-response relationship

• The intensity and duration of applications of NB-UBV and PUVA are carefully measured to ensure minimum risks, considering that higher exposure to UV light treatments can results in greater increase in the risk of cancer and other advervise reactions and they are usually kept at a minimum level.
• Some studies are testing if a higher dosage of irradiation of UVC light would in fact decrease the division rate of cancerous cells; however, the thesis is not yet completely confirmed.
• There also seems to be a difference in how cells react to 254 nm UVC vs 222 nm UVC, with the later being considered safer.

6. Type of Application

• Humans exclusively come into contact with UV (UVB, UVA and UVC) via their skin and eyes.

Findings

A. Physiological/Neural Effects of NIL When Applied to the Human Body

1. Proposed Mechanisms

• One of the reports we found discussed proposed mechanisms with respect to NIL in stating: "[T]he mechanisms underlying the therapeutic benefits of NILT appear to depend upon the absorption of NIR photons in the wavelength range of 600–1,200 nm by cytochrome c oxidase in the mitochondria."
• Mechanisms stated in another report we consulted included the following: (1) "Mitochondria and cytochrome c oxidase;" (2) "Reactive oxygen species, nitric oxide, blood flow;" (3) "Light sensitive ion channels and calcium;" (4) "Signaling mediators and activation of transcription factors;" and (5) "Biphasic dose response and effect of coherence."

2. Magnitude

• The magnitude of NIR ranges from "0.78~3.0 μm."

3. Types of Effects Observed/Outcome Metrics

• One of the uses of NIL is through Photobiomodulation (PBM), which many authors suggest results in "increases in cerebral blood flow, greater oxygen availability and oxygen consumption, improved ATP production and mitochondrial activity." Light exposure from that treatment has yielded fourteen or more signaling mediators and transcription factors.
• Effects that have been observed from NIL include "modulat[ion of] reactive oxygen species, activat[ion of] mitochondrial DNA replication, increase[d] early-response genes, increase[d] growth factor expression, induce[d] synaptogenesis, and stimulate[d] cell proliferation."
• Effects resulting from NIL applied via "a fluence range of 0.9 – 36 J/cm2" included "decreased expression of pro-apoptotic genes, increased expression of anti-apoptotic genes, and increased expression of neurotrophic factors, such as nerve growth factor and brain-derived neurotrophic factor."

4. Quality of Evidence/Certainty

• One study described human studies involving treatments with NIL as "inconsistent, but promising."
• A study described the mechanisms with respect to NIL as "not fully understood."
• Studies of NIL treatment (NILT) for "stroke yielded mixed results." One reason that might have explained that was "the physical parameters of NILT in these clinical trials may have delivered insufficient fluence to cortical tissues to be effective." Those studies used a "continuous wave NIR light of 808 nm wavelength with infrared energy densities of 0.9 J/cm2 was applied to the human scalp for a total of 40 minutes."
• Photobiomodulation (PBM) treatments, some of which use NIL, hold promise for potentially treating brain diseases and disorders. The success with such is, in part, dependent on whether LED helmets can be made available at an affordable price. If that occurs, the researchers noted that a significant quantity of patients could be benefited through such treatment.

5. Dose-Response Relationship

• The dose-response relationship with respect to Photobiomodulation (PBM) treatments was described in a study as follows: "There are many reports of PBM following a biphasic dose response (sometimes called obeying the Arndt-Schulz curve). A low dose of light is beneficial, but raising the dose produces progressively less benefit until eventually a damaging effect can be produced at very high light. It is often said in this context that 'more does not mean more.'"

6. Type of Application

• One application of NIL we found in a research study about Photobiomodulation (PBM) was the forehead. The reason that NIL is frequently "applied to the forehead [is] because of the better penetration (no hair, longer wavelength)."
• We also read that NIL has been applied to the skin and the scalp.

B. Physiological/Neural Effects of FIL/FIR When Applied to the Human Body

1. Proposed Mechanisms

• A proposed mechanism for promoting the outgrowth of neurite, with respect to FIL, was via the AKT1 pathway.
• The "inhibiting [of] neointimal hyperlsia" was proposed as a mechanism for FIL therapy as a way to "improve[] vascual restenosis progression in patients with ESRD." This is due to "the growth of VSMCs [which] increases the risk of vascular access stenosis in HD patients."

2. Magnitude

• The magnitude of far-infrared radiation (FIR) ranges from "50.0~1000.0 μm."

3. Types of Effects Observed/Outcome Metrics

• Studies of far-infrared radiation conducted on animals showed that it was effective in promoting repair of nerves.
• An effect of far-infrared radiation is that it can effectively reduce bacteria with regard to "both Staphylococcus aureus and Escherichia coli at 99.9 %, and showed a reduction of Klebsiella pneumoniae by 34.8 %."
• A study of 20 patients who had facial wrinkles that ranged from "mild to moderate" were given FIR treatments on a daily basis ("9–10 × 106 nm") over a six-month span. The majority of the patients (between 51% and 75%) experienced positive changes with the roughness and texture of their skin, while some patients saw moderate improvement in the tone of their skin, as between 25% and 50% reported such.
• With regard to the aforementioned study, all groups that took part in the treatment noted a significant increase with respect to their elastic fibers and collagen. Further, the results found "an increase of TIMP-1 and 2. RT-PCR results showed the mRNA levels of IL-1ss, TNF-alpha, ICAM-1, and Cx43 increased after LED phototherapy whereas that of IL-6 decreased."
• Another study that utilized "830 nm LEDs" found results comparable to the aforementioned study.
• Another effect noted about FIR treatments is that they "may be closely related to the increased expression of endothelial nitric oxide synthase as well as nitric oxide production and may modulate the profiles of some circulating miRNAs."
• The effects of FIR radiation have included both non-thermal and thermal ones, as observed by prior studies. Some of those effects observed include "increasing artery blood flow and peripheral blood circulation, improving endothelial function, alleviating fatigue and pain, reducing blood pressure, and promoting capillary dilatation."
• Further, FIR rays have been shown to "enhance blood flow and improve ischemic areas."

4. Quality of Evidence/Certainty

• One study concluded that "FIR therapy can be applied to enhance neural regeneration for further clinical applications."
• A study found that "[i]ncreasing evidence suggests that convenient and non-invasive far-infrared (FIR) rays, a vital type of physiotherapy, improve the health of patients with cardiovascular disease, diabetes mellitus, and chronic kidney disease. Nevertheless, the molecular mechanisms by which FIR functions remain elusive."
• A study noted that FIR "may be a beneficial complement to treatments for some chronic diseases that yields no adverse effects."
• A research study explained that the researchers "speculate that FIR rays positively affect pericytes after ischemia."

5. Dose-Response Relationship

• With regard to dose-response relationship involving FIR, it was stated that "[t]he effects of FIR in promoting neurite outgrowth were dose dependent, and higher power density of FIR provided more effects for improving neurite outgrowth."
• Further, that same study explained that "[t]he neurite outgrowth-enhancing effect of FIR irradiation was more obvious when lower NGF concentration (1 ng/ml and 10 ng/ml) was added into the medium."

6. Types of Application

• Applications of FIR cited in research studies included the skin and face.
• Applications of FIR are also applied through "[t]he use of far-infrared saunas for medical treatment [which] is based on deep skin-penetration of the radiation to restore homeostasis of thermal regulation."

Your research team applied the following strategy:

TECHNOLOGIES/PRODUCTS ASSOCIATED WITH LIGHT

UVA

1. Daavlin ML24000: Full Body UVA-1

• Daavlin, a leading manufacturer of phototherapeutic products, developed the Daavlin ML24000: Full Body UVA-1.
• This device produces a UVA-1 output through a combination of high-pressure lamps and special filters.
• It is a full body device used as a phototherapy solution for the treatment of psoriasis and vitiligo.
• Daavlin claims that the treatment of photo-responsive skin diseases will take significantly less time or receive a 30% to 40% boost due to their proprietary lamp and filtering system that absorbs infrared output and limits spectral emission to the UVA-1 range.

2. Waldmann UV Therapy System UV 182

• This product was developed by Waldmann, a developer, and manufacturer of light products for industrial, office, care, and health applications.
• It uses UVA emitting compact lamps in its system and is fully interactive.
• The Waldmann UV Therapy System UV 182 is a device used for multiple phototherapy solutions.
• Waldmann claims that their product will provide a more therapeutic effect to targeted areas due to their controlled interactive system which adjusts the light intensity and eliminates stray radiation.

UVB

1. SolRx 1000-Series UVB-Narrowband Full Body Panel

• This product was developed by Solarc, a developer and manufacturer of home phototherapy solutions.
• It uses either 4, 6, 8, or 10 Philips UVB-Narrowband bulbs which are also used by phototherapy clinics.
• The SolRx 1000-Series UVB-Narrowband Full Body Panel is a full body device used for multiple phototherapy solutions in skin disorders.
• Solarc claims that their product will provide an efficient full-body treatment to skin patients, as the device is using the same UVB-Narrowband bulbs as large clinical booths.

2. DermaLume 2X

• DermaLume 2X was developed by National Biological, a known developer and manufacturer of phototherapy solutions.
• It is a handheld device that uses UVB Narrowband light to treat skin conditions such as psoriasis or vitiligo.
• National Biological claims that they can treat skin conditions such as psoriasis or vitiligo without the use of drugs, but through their product alone.

UVC

1. ARTZ 2.0 Mobile Room UVC Germicidal Solutions for Healthcare

• This product was developed by American Ultraviolet, a leading developer and manufacturer of UVC Germicidal Fixtures.
• It is a medical UV lamp that uses high-output UVC flux which is used to disinfect a room.
• American Ultraviolet claims that their product delivers a balanced and uniform UVC flux to surfaces and the atmosphere, which significantly reduces pathogens within the area.

2. PearlAqua UV-C LED Water Treatment

• This product was developed by Aquisense, a developer and manufacturer of UV-C LED systems.
• It is a product that uses UV-C LED to disinfect water.
• Aquisense claims that their product will disinfect water for any consumption use without utilizing chemicals or mercury-based UV lamps.

NEAR IR LIGHT

1. Joovv Elite

• Joovv Elite was developed by Joovv, a trusted manufacturer of red light therapy devices.
• It is a product that uses near-infrared light for a variety of light therapy treatments.
• Joovv claims that their product will provide full body treatment, as well as benefits such as increased energy levels, collagen production in the skin, and anti-inflammation.

2. Faraday

• Faraday was developed by SaunaSpace, a developer and manufacturer of sauna solutions that uses near-infrared light.
• This device uses low-EMF Incandescent near-infrared bulbs for thermal light therapy.
• SaunaSpace claims that their product will make users feel more energized and induces the cellular detoxification response.

FAR IR LIGHT

1. Qi-Point Thermal Patch-QPU50

• This product was developed by TherMedic, a developer and manufacturer of far infrared light based products.
• This device is a thermal patch that uses far infrared light emission to provide pain relief to targeted areas.
•  TherMedic claims that the product provides acupuncture like pain relief that stimulates the removal of waste and toxins that cause pain.

2. Promolife Far Infrared Dome Sauna

• This product was developed by Promolife, a manufacturer of multiple health-related products.
• It is a dome-like product that uses black carbon far infrared light technology for sauna solutions.
• Promolife claims that this product improves circulation and oxygenation of the body.

RESEARCH STRATEGY

EYES

Chronic Central Serous Chorioretinopathy

• A randomized, observer-masked comparison study was conducted to “compare the efficacy and the detrimental effects of half-drug dose and half-laser light fluence of photodynamic therapy (PDT) for the treatment of chronic central serous chorioretinopathy” which is a disease where fluid accumulates under the retina, causing it to detach. [1]
• 40 patients with chronic central serous chorioretinopathy were equally divided into 2 groups. 
• The first group received only half the standard dose of verteporfin infusion (3 mg/m2) (an eye drop) and were exposed to 83 seconds of laser light.
• The second group received the standard dose of verteporfin infusion (6 mg/m2) and only 42 seconds of laser light.
• Both the first and the second group showed the PDT was similarly effective in improving both the ability to see and the amount of fluid under the retina.
• Both types of modification of PDT were also able to cause post-laser choroidal hypoperfusion (a smaller amount of blood flow to the eye).
• Summary — light can be used to treat fluid buildup behind the retina.

Prospective Evaluation Of Intense Pulsed Light And Meibomian Gland Expression Efficacy On Relieving Signs And Symptoms Of Dry Eye Disease Due To Meibomian Gland Dysfunction

• The aim of this study was to estimate the efficacy of intense pulsed light (IPL), followed by gland expression (MGX) for reducing the number and severity of signs and symptoms of dry eye disease (DED).
• Each treatment included the administration of 10–15 pulses of IPL on the cheeks and nose, followed by MGX of the upper and lower eyelids.
• Intense Pulsed Light combined with gland expression reduced the number and severity of symptoms and signs of dry eye disease.
• Summary — Light in the eyes can be used to treat dry eye disease.

SKIN

Evaluation Of Rosacea Before And After Intense Pulsed Laser Treatment Using Reflectance Confocal Microscopy: Case Report

• This is a case study of a 50-year-old female with rosacea on her cheeks that would periodically intensify with exercise and heat that was treated with light therapy due to its previous effectiveness.
• Reflectance confocal microscopy (a real-time non-invasive diagnostic imaging technique used in the field of dermatology) was performed on the cheek in order to confirm the diagnosis and assess characteristics.
• An RCM image taken of the cheek prior to any treatment. These findings are consistent with rosacea.
• After two rounds of IPL, RCM imaging showed a response to the treatment, showing a “decreased number of capillary loops and a decreased diameter of the pilosebaceous ducts”.
• Inflammatory cells were still present, although sparse.
• Summary — Intense Pulse Light Therapy is an appropriate therapy for some forms of rosacea.

Bright Light Therapy For Sleep Disturbance In Dementia Is Most Effective For Mild To Moderate Alzheimer's Type Dementia (AD): A Case Series

• Sleep problems in people with dementia are common. The administration of bright light therapy (BLT) in the morning is a non‐pharmacological treatment that was expected to treat sleep disorders in patients with dementia by reprogramming the circadian rhythm to decrease disturbances to the normal sleep–wake cycle.
• In this study, the effectiveness of BLT in the treatment of 17 participants was explored. Patients sat in front of the light box for 1 h/day from 0900 to 1000. The patients underwent treatment every day for 2 weeks.
• BLT led to the improvement of sleep disturbance in all four Alzheimer participants who showed a shorter duration of illness and/or had mild to moderate AD.
• Summary — light on the body can be used to improve nighttime sleep patterns

EARS

Light-Driven Contact Hearing Aid for Broad-Spectrum Amplification: Safety and Effectiveness Pivotal Study

• Forty-three patients with mild-to-severe hearing impairment were fitted with a light-driven contact hearing aid made up of a Tympanic Lens (Lens) with a customized platform that encodes sound into light pulses which wirelessly deliver signal and power to the Lens using both omnidirectional and directional microphones.
• There were no serious device, procedure-related adverse events, or unanticipated adverse events. The average speech-recognition threshold improvement over the unaided case for the Hearing in Noise Test was positive.
• Summary: light can be used to assist hearing.

In-ear photoplethysmography for central pulse waveform analysis in non-invasive hemodynamic monitoring

• In recent years, the analysis of the photoplethysmographic (PPG) pulse waveforms has attracted a lot of interest. In laymen’s term, it is those little things you see at the end of a person’s finger when they are in the hospital that use light to measure blood oxygen.
• The problem has been that for patients who suffer from reduced peripheral circulation (the blood isn’t traveling well to the extremities) waveform analysis using the normal fingertip appliance is not feasible.
• Because the ear canal is not affected by cardiovascular centralization, the authors have developed a new system that uses the same light transmission technology in the ear and provides highly accurate photoplethysmographic measurements.
• The results show that the system provided highly accurate PPG recordings in the ear canal facilitating sophisticated pulse waveform analysis.
• Furthermore, they demonstrated that the pulse decomposition analysis is also applicable to in-ear PPG recordings.
• Summary — light can be used in the ear to monitor blood oxygen.

COMPARISONS

• Vision:
• Both artificial and natural light affect a person's vision.
• Biorhythms, melatonin and sleep:
• Both lights affect the circadian rhythm of a person and have an energizing or relaxing impact.
• Exposure to both artificial and natural light affects melatonin secretion, which is cyclic throughout the day: its secretion is high at night (in the dark) and low during daytime. Light exposure in the evening, at night and in the morning affected the circadian phase of melatonin levels, as exposure to light suppresses the hormone's secretion, thereby altering the sleep patterns of the person.
• "Exposure to blue light from both natural and artificial light in the morning advances the circadian clock, so may help people who want to move their sleep to an earlier time."
• Natural light affects an individual's mood and artificial light can be used to do so as well:
• Natural light has also been reported to have a positive effect on a person's mood, comfort and efficiency.
• A group of depressed adults with bipolar I or II disorder that were treated with bright white light experienced a significantly higher remission rate and significantly lower depression scores compared to the placebo group. This is an indication of the efficacy of midday bright light (artificial light) therapy for bipolar depression.

• Productivity:
• Natural light in a building has a positive impact on the occupants’ performance, productivity and health when daylighting systems are properly put in place. Healthy people are more productive. Students also had better performance and productivity when placed in classrooms that had windows allowing in daylight.
• Employees in work environments with only artificial lighting recorded higher absenteeism and lower productivity.
• Biological effect
• Exposure to artificial light at night alters the length perception of a day, making it seem longer. This triggers a psychological condition called longer-day-length-like. As a result, humans living in polar regions are exposed to the risk of the so-called ‘polar T3 syndrome', characterized by chronically low levels of blood T3.
• Polar T3 syndrome and seasonal affective disorders (SADs) experienced by people exposed to more artificial lighting than daylight are usually associated with psychological disorders such as depression and increased aggression. People exposed to adequate and regular daylight have little or no risk of these syndromes.
• Melatonin and sleep:
• Night-shift workers and day workers in windowless workspaces have been studied and found to have lower levels of melatonin, "a hormone that regulates sleep, enhances immune function and may prevent some forms of cancer". These two groups also slept worse than their counterparts who had access to daylight.
• Activity:
• A human is more active in daylight, as opposed to when exposed to artificial lighting.

MELATONIN SUPPRESSION DUE TO LIGHT EXPOSURE

• Light pulses of various duration and intensity, administered in the nighttime, can subdue melatonin levels in humans and some vertebrae.
• This is not the case for reptiles such as lizards and turtles. Light pulses delivered at night does not reduce their melatonin levels.

COGNITIVE EFFECTS

• The main cognitive effects of light on humans seems to be that their alertness increases, a metric normally measured by conducting a reaction time task. Studies on the effect light has on humans suggest that light increases subjective ratings of alertness.
• In mice, however, studies investigating "the effects of light on tone-cued fear conditioning in mice, found that light enhances freezing responses in wild-type mice." Being exposed to bright light had a negative effect on the "spatial navigation performance on a water maze task in BALB/c mice," which was connected to heightened anxiety and raised corticosterone levels.

MASKING BY LIGHT

• Humans are more active in daylight and less active in artificial lighting, meaning they are more active during the day and their activity is not significantly affected by light at night.
• However, "light at night causes positive masking in diurnal animals (activity increase), and negative in nocturnal animals (decrease in their activity)."

SENSITIVITY TO UV LIGHT

• The mouse retina contains three visual pigments which include the ultraviolet sensitive (UVS) cone opsins. "A subset of cones express just the UVS opsin" and are dispersed across the whole retina.
• Because of this UVS visual pigment, mice are more sensitive to UV light than humans. Therefore, exposing mice to UV light during dark cycle would cause a circadian disruption and result in them being active in their dark phase.

SENSITIVITY TO LONGER WAVELENGTH LIGHT

• Mice lack a long wavelength sensitive opsin and are therefore less sensitive to longer wavelength light compared to humans. An example would be if both humans and mice were exposed to a red light stimulus at 600 nm, the mouse eyes would be 12 times less sensitive based on the visual pigments of the retina.
• Humans are therefore able to have visual perception under dim red light without causing a circadian disruption in the mice and potentially influencing their behavior.

RESEARCH STRATEGY

COMMON EMOTIONAL AND PERCEPTUAL HUMAN RESPONSES

• Light is a cognitive map able to guide and direct the individual in the exploration and discovery of the surrounding environment.
• Light may stimulate our perceptual apparatus through type and range of exposure to a lighting source and its colors, inducing specific emotional states or behavior in the human.
• Light acts as a specific type of stimulus that is able to move, excite, impress, communicate, heal, communicate, and generate wellness, creating a sense of harmony and syntony with the surrounding environment.
• Light is able to induce dynamism, privacy, relaxation, visual clarity, productivity, excitation, efficiency, but also stress, sadness, sleepiness, agitation, anxiety, restlessness, depending on its intensity, saturation, and modulation.
• Light can affect mood state in the long-term.
• Human emotion, regardless if the emotion is positive or negative, is felt more intensely under bright light.
• Modification to any lighting modes—namely, bright/dim, uniform/non-uniform, central/perimeter, and warm/cool—would result in a change to the human response with respect to their perception of the space.
• Light can induce negative emotions and unpleasant physical sensations that often accompany a migraine.

EMOTIONAL RESPONSES TO DIFFERENT LIGHTS

• Non-uniform intense direct light from above induces tension in people.
• Non-uniform lower overhead lighting with some warm-colored lighting tones at room perimeter relaxes people.
• Uniform bright light on workplane with less light at the perimeter, cooler color tones, and wall lighting induces work/visual clarity.
• Uniform bright light with lighting on walls and possibly ceiling creates a feeling of spaciousness.
• A non-uniform low-light level at activity space with a little perimeter lighting and dark areas in the rest of the space gives a feeling of privacy or intimacy.
• Ambient light modulates ongoing cognitive brain function, including working memory, attention, updating, and sensory processing, within a few tens of seconds.
• Ambient light influences the brain processing of emotional stimuli.
• All light colors, except green, result in migraine sufferers feeling intense emotional responses, such as anger, hopelessness, nervousness, depression, sadness, anxiety, and fear.

RESEARCH STRATEGY

DERMATOLOGY & AESTHETICS

• The Dermatology Laser and Cosmetic Center at Massachusetts General Hospital is involved in the application of photomedicine in dermatology & aesthetics in collaboration with the Wellman Center for Photomedicine.
• Low-level laser (light) therapy (LLLT) is used in aesthetic dermatology for a wide range of procedures like primarily cosmetic, which is used for treating for several dermatological conditions.
• The most successful commercially application of LLLT is in the treatment of alopecia (hair loss). LLLT is also applied in other procedures like lipoplasty and liposuction.
• Research by Dr. Michael Hamblin of Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts and Mossum Sawhney, published in ResearchGate provided scientific evidence supporting the application of photomedicine in dermatology & aesthetics.

PAIN MANAGEMENT & WOUND HEALING

•  Macedon Ranges Laser Therapy, Australia is involved in the application of photomedicine in pain management and wound healing.
• Neuronal activity changes have been found to be useful in providing pain relief through laser biostimulation (LLLT). Its applications include the treatment of chronic neck pain, tendonitis, chronic joint disorders, musculoskeletal pain, and chronic pain.
• Cells affected by wound “respond to light induced reactive oxygen species (ROS)” resulting in increased generation of blood vessels and less inflammation, thereby promoting wound healing.
• Research by Dr. Michael Hamblin of Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, Ying-Ying Huang of Department of Dermatology, Harvard Medical School, and Pawel Mroz of Department of Pathology, Feinberg School of Medicine, Northwestern University, Feinberg, published in ResearchGate provided scientific evidence supporting the application of photomedicine in dermatology & aesthetics.

ONCOLOGY

• UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania is involved in the application of photomedicine in oncology.
• LLLT is used in oncology for the treatment of oral mucositis which is a typical side effect of cancer therapy.
• LLLT is applied to tissues to reduce the swelling and redness of the mouth and promote healing. It works by increasing the energy of the cells, induce repair and reduce the free radicals which are dangerous molecules.
• Research by several authors published by National Institutes for Health provided scientific evidence supporting the application of photomedicine in oncology.

OPHTHALMOLOGY

•  Lourdes Ophthalmology Surgery/Laser Treatment Center, New York is involved in the application of photomedicine in ophthalmology.
• Lasers have been applied in the treatment of eye conditions since the 1960’s. A laser beam focused on the eye can eliminate diseased tissue or stop degenerative eye issues from getting worse.
• The application of laser in the treatment of eye diseases is referee to as “laser photocoagulation” or “laser photoablation”, it can be used in the treatment of eye conditions like proliferative diabetic retinopathy, macular oedema, chronic open-angle glaucoma, retinal tears, and retinopathy of prematurity in babies.
• Research by The Diabetic Retinopathy Study Research Group as well as several studies published by National Institutes for Health provided scientific evidence supporting the application of photomedicine in ophthalmology.

DENTISTRY

•  Go Dental Clinic, Dubai, UAE is involved in the application of photomedicine in dentistry.
• LLLT has found practical applications in dental procedures including treatment of the soft and hard tissues of the oral cavity.
• Soft dental tissue applications include herpetic lesions, aphthous/traumatic ulcers, post oncology mucositis, edema, and Sinusitis. Hard dental tissue applications include temporomandibular disorders, orthodontic treatment, dentinal hypersensitivity, bone remodelling, erosion, and implants.
• Research by several authors published by National Institutes for Health provided scientific evidence supporting the application of photomedicine in dentistry.

RESEARCH STRATEGY