Innovations in noninvasive procedures keep dermatology on cutting edge

Noninvasive procedural dermatology has evolved at a dizzying pace, and continues to do so.

In addition to an array of procedures for skin tightening, skin resurfacing, and fat reduction, emerging technologies such as complex feedback devices, nanotechnology, and stem cell–based therapies promise to keep dermatology at the forefront of the cosmetic and esthetic realm, according to Dr. Murad Alam.

In an article featured in the March issue of Seminars in Cutaneous Medicine and Surgery, Dr. Alam of Northwestern University, Chicago, makes several predictions about the future of these technologies (Semin. Cutan. Med. Surg. 2013;32:61-63).

For example, like modern vehicles equipped with computer chips that can change steering and braking in response to environmental conditions, dermatologic devices will soon include technology that uses precise feedback to make automated setting changes, he said.

"Over time, the reduced cost of microelectronics, feedback controls, and computing power is simplifying the capacity of devices to analyze intraoperative information and adjust the procedure to compensate. For instance, certain laser and energy devices already have tips that are able to sense the temperature in the microenvironment and adjust power output to maintain site-specific temperature within a narrow band," he explained.

This technology could increase effectiveness and improve the safety of devices by reducing the level of operator time and expertise needed, and by making setting changes faster than humanly possible.

Autonomous nanotechnology devices are another advance described by Dr. Alam.

Miniaturization will become more feasible and affordable, and eventually devices will become "so exceedingly small that they will be mostly disposable and deployed in large numbers to the treatment site," he said.

The concept of hundreds of minuscule machines deployed to resurface skin or repair a wound may sound like science fiction, but the rapid advances in nanotechnology could make it a reality that could lead to the creation of new procedures such as ways to treat scars that can’t be corrected using currently available technologies, he added.

Dr. Alam’s other predictions for the future of noninvasive procedural dermatology included:

• Optimization of minimally invasive procedures for fat reduction and skin tightening, which currently provide only mild to modest results and longevity.

• The use of stem cells for augmentation of tissue layers, which could provide genuine rejuvenation rather than simply repair and concealment.

• The improvement of artificial dermal substitutes that can develop many of the functions of live skin, and can be grafted without inducing contractures.

• The development of rapid treatments for pigmentation using nanotechnology and cellular therapies, which will allow for precise melanocyte and melanosome transfer and automatic recoloration of discolored skin.

While these technologies continue to emerge, plenty of others have already established their places in the dermatology arena. The many and varied applications of one of these – low-level laser therapy, or LLLT – are described in another article in the March issue of Seminars in Cutaneous Medicine and Surgery (Semin. Cutan. Med. Surg. 2013;32:42-54).

"LLLT involves exposing cells or tissue to low levels of red and near-infrared light. ... Recently, medical treatment with LLLT at various intensities has been found to stimulate or inhibit an assortment of cellular processes," wrote Dr. Pinar Avci of Massachusetts General Hospital, Boston, and his colleagues, noting that the mechanism associated with the cellular photobiostimulation by LLLT is not yet fully understood, but appears to have a wide range of effects at the molecular, cellular, and tissue levels.

Describing LLLT as "possibly the ultimate noninvasive approach to treating the skin," the researchers highlighted numerous existing or emerging applications for the technology, outlined below.

Skin rejuvenation

Many modalities developed to reverse the dermal and epidermal signs of photoaging and chronological aging depend on the removal of the epidermis and the induction of a controlled form of skin wounding to promote collagen biosynthesis and dermal matrix remodeling. Examples include retinoic acid, dermabrasion, chemical peels, and ablative laser resurfacing.

These modalities require intensive posttreatment care and prolonged down time, and are associated with a risk of numerous complications, the researchers said.

LLLT represents an alternative that is known to increase microcirculation and vascular perfusion in the skin. Data from previous studies have shown that LLLT increased collagen and improved wrinkles and skin laxity with less down time and risk than that of other treatments.

In one study, for example, 300 patients treated with only a light-emitting diode (LED) LLLT device set at 590 nm, 0.10 J/cm², were compared with 600 patients who received the LED therapy in combination with a thermal-based photorejuvenation procedure. Of those who received LED therapy alone, 90% reported softer skin and less roughness and fine lines. The changes ranged from subtle to significant.

Those who received thermal photorejuvenation laser treatment reported a reduction in posttreatment erythema and an overall impression of increased efficacy with the additional LED treatment – an effect that could be attributed to anti-inflammatory effects of LLLT, they noted.

In another study, more than 90% of 90 patients receiving eight LED treatments over 4 weeks experienced favorable results, improving by at least one Fitzpatrick photoaging category. In addition, 65% of patients experienced global improvement in facial texture, fine lines, background erythema, and pigmentation, with results peaking 4-6 months after completion.

Acne treatment

LLLT in the red to near-infrared (NIR) spectral range (630-1000 nm) and with nonthermal power (less than 200 mW) has been shown in several studies to improve acne vulgaris. In one study, a significant reduction in active acne lesions occurred after 12 twice-weekly sessions using 630 nm red-spectrum LLLT with a fluence of 12 J/cm² in conjunction with 2% topical clindamycin. No significant effects were seen using an 890-nm laser. Other studies have demonstrated that the combination of blue and red light is synergistic for treating acne.

Photoprotection

Recent suggestions that infrared exposure might have protective effects against ultraviolet light–induced skin damage are based on the theory that the exposure might trigger protective or repair responses to UV irradiation. While controversial, this view is supported by data suggesting potential mechanisms of action. For example, some data suggest a role of p53, a sensor of gene integrity involved in cell apoptosis and repair mechanisms. In one study, the response to infrared (IR) irradiation was shown to be p53 dependent, suggesting the IR irradiation prepares cells to resist and/or repair further UV-induced DNA damage. Data from another study showed that IR irradiation induced the protective protein ferritin, which is involved in skin repair.

Data from yet another study suggested that nerve growth factor (NGF) production induced by LLLT using the helium neon semiconductor laser diode (HeNe, 633 nm) might explain the photoprotective effects of LLLT. In that study, NGF – a major paracrine maintenance factor for melanocyte survival in skin, was shown to protect melanocytes from UV-induced apoptosis by upregulating the level of Bcl-2 (an antiapoptotic protein) in the cells.

Herpesvirus lesion treatment

New therapies are needed to shorten recurrent herpesvirus episodes and reduce related pain and inflammation. LLLT has been suggested as an alternative to current medications. In one study of 50 patients with recurrent perioral HSV infection, LLLT at 690 nm, 80 mW/cm², 48 J/cm² daily for 2 weeks during recurrence-free periods decreased the frequency of herpes labialis episodes, the authors said.

In another study with similar parameters, patients achieved a significant prolongation of remission intervals from 30 to 73 days.

The mechanism of action remains unclear, but an indirect effect of LLLT on cellular and humoral components of the immune system may be involved in antiviral responses, as opposed to a direct virus-inactivating effect, the researchers noted.

Vitiligo treatment

Modest efficacy seen with the low-energy HeNe laser (632 nm, 25 mW/cm²) for the treatment of 18 vitiligo patients led to speculation that LLLT could serve as an alternative effective treatment for this typically treatment-resistant condition. (Repigmentation was observed in 64%, and some follicular repigmentation was observed in the remaining patients).

In a subsequent study of local administration of the HeNe laser light at 3 J/cm², 1.0 mW, 632.8 nm in patients with segmental type vitiligo, marked perilesional and perifollicular repigmentation of more than 50% was observed in 60% of patients.

"Both NGF and (basic fibroblast growth factor) stimulate melanocyte migration, and deficiencies of these mediators may participate in the development of vitiligo," the researchers wrote.

Depigmentation

During tests of red and blue light for acne, researchers unexpectedly found that patients treated with both red and blue light experienced an overall decrease in melanin.

Based on instrumental measurement results, blue light exposure (415 nm, 40 mW/cm², 48 J/cm²), increased the melanin level by 6.7, whereas red light exposure (633 nm, 80 mW/cm², 96 J/cm²) decreased the melanin level by 15.5.

"This finding may have some relationship with the laser’s brightening effect of the skin tone, which 14 of 24 patients spontaneously reported after the treatment period. However, as of today, no other studies investigated or reported a similar decrease in melanin levels after red light irradiations," the researchers said.

Hypertrophic scar and keloid eradication

LLLT has shown promise for preventing hypertrophic and keloid scars in patients who undergo scar revision by surgery or CO₂ laser. The use of daily near-infrared LED (NIR-LED) treatment on one of the two bilateral sites safely reduced the risk of scar development in that lesion, compared with the untreated lesion in three patients with bilateral scars. One underwent surgical revision/excision for preauricular linear keloids that developed after a face-lift procedure, one underwent CO₂ resurfacing for hypertrophic acne scars on the chest, and one underwent CO₂ resurfacing after excision of hypertrophic scars on the back. No significant treatment-related adverse effects were reported.

LLLT may work in these types of scars through an inhibitory effect on interleukin-6 mRNA levels and the modulating of platelet derived growth factor, transforming growth factor–beta, interleukins, and MMPs, which are associated with abnormal wound healing, the researchers noted.

Burn treatment

LED exposure was shown to provide benefit for the treatment of acute sunburn in a study of 10 patients.

Treatment once or twice daily for 3 days on half of the affected area decreased symptoms of burning, redness, swelling, and peeling compared with the untreated half. Decreased MMP-1 was noted on the treated side through immunofluorescence staining in one patient, and real-time polymerase chain reaction gene expression analysis showed a significant decrease in MMP-1 gene expression at both 4 and 24 hours after the UV injury on the treated side.

In another study, LED treatment was effective compared with control for speeding the healing process of laser treatment–related burns. In nine patients with second-degree burns from nonablative laser devices, LED therapy once daily for 1 week was associated with 50% faster healing based on both patient and physician accounts.

LED treatment also was shown in a pilot study to accelerate re-epithelialization of a forearm injury induced by a CO₂ laser; identical test sites were treated with daily dressing changes and polysporin ointment, but the site with faster re-epithelialization had also received the LED treatment (a computer pattern generator was used to deliver the identical CO₂ treatment to both sites).

Psoriasis

LLLT also shows promise for the treatment of plaque psoriasis. In a preliminary study, the combined use of sequential NIR (830 nm) and visible red light (630 nm) led to resolution of psoriasis in patients who were resistant to conventional therapy. The patients received treatment in two 20-minute sessions, 48 hours apart, for 4 or 5 weeks. No adverse side effects occurred.

Despite the variety of potential applications for the technology, LLLT remains somewhat controversial due to "uncertainties about the fundamental molecular and cellular mechanisms responsible for transducing signals from the photons incident on the cells to the biological effects that take place in the irradiated tissue" and because "there are significant variations in terms of dosimetry parameter: wavelength, irradiance or power density, pulse structure, coherence, polarization, energy, fluence, irradiation time, contact versus noncontact application, and repetition regimen," the researchers said.

They noted, however, that problems that have been experienced with LLLT – as well as negative study results – could be the result of inappropriate parameters, skin preparation, and/or device maintenance.

"LLLT appears to have a wide range of applications in dermatology, especially in indications where stimulation of healing, reduction of inflammation, reduction of cell death, and skin rejuvenation are required," they noted, but added that the lack of agreement on important parameters (particularly whether red, NIR, or a combination of both is optimal for a given application) has created a credibility gap that must be overcome before LLLT is routinely applied in every dermatologist’s office.

Once LLLT does become so widely accepted, however, it may be time for dermatologists to move on to the next big thing, Dr. Alam said in his article on the future of procedural dermatology.

"For several decades, dermatologists have worked closely with start-up companies to commercialize new devices and technologies ... when new toxins, fillers, and energy devices have been marketed, dermatologists have been early adopters," he said. "Over time, each device or procedure has diminished in cost and exclusivity as other physicians and nonphysicians have entered the market, and dermatologists have moved on to greener pastures. In all likelihood, this cycle will continue," he noted. "Dermatologists cannot prevent the dissemination of stable technologies, but they can continue to innovate and create new ones."

In fact, he added, continued success in this arena will rest largely on clinicians’ ability to nurture innovation to ensure a healthy pipeline of novel technologies.

The authors of the articles had no financial conflicts to disclose.

Noninvasive procedural dermatology has evolved at a dizzying pace, and continues to do so.

In addition to an array of procedures for skin tightening, skin resurfacing, and fat reduction, emerging technologies such as complex feedback devices, nanotechnology, and stem cell–based therapies promise to keep dermatology at the forefront of the cosmetic and esthetic realm, according to Dr. Murad Alam.

In an article featured in the March issue of Seminars in Cutaneous Medicine and Surgery, Dr. Alam of Northwestern University, Chicago, makes several predictions about the future of these technologies (Semin. Cutan. Med. Surg. 2013;32:61-63).

For example, like modern vehicles equipped with computer chips that can change steering and braking in response to environmental conditions, dermatologic devices will soon include technology that uses precise feedback to make automated setting changes, he said.

"Over time, the reduced cost of microelectronics, feedback controls, and computing power is simplifying the capacity of devices to analyze intraoperative information and adjust the procedure to compensate. For instance, certain laser and energy devices already have tips that are able to sense the temperature in the microenvironment and adjust power output to maintain site-specific temperature within a narrow band," he explained.

This technology could increase effectiveness and improve the safety of devices by reducing the level of operator time and expertise needed, and by making setting changes faster than humanly possible.

Autonomous nanotechnology devices are another advance described by Dr. Alam.

Miniaturization will become more feasible and affordable, and eventually devices will become "so exceedingly small that they will be mostly disposable and deployed in large numbers to the treatment site," he said.

The concept of hundreds of minuscule machines deployed to resurface skin or repair a wound may sound like science fiction, but the rapid advances in nanotechnology could make it a reality that could lead to the creation of new procedures such as ways to treat scars that can’t be corrected using currently available technologies, he added.

Dr. Alam’s other predictions for the future of noninvasive procedural dermatology included:

• Optimization of minimally invasive procedures for fat reduction and skin tightening, which currently provide only mild to modest results and longevity.

• The use of stem cells for augmentation of tissue layers, which could provide genuine rejuvenation rather than simply repair and concealment.

• The improvement of artificial dermal substitutes that can develop many of the functions of live skin, and can be grafted without inducing contractures.

• The development of rapid treatments for pigmentation using nanotechnology and cellular therapies, which will allow for precise melanocyte and melanosome transfer and automatic recoloration of discolored skin.

While these technologies continue to emerge, plenty of others have already established their places in the dermatology arena. The many and varied applications of one of these – low-level laser therapy, or LLLT – are described in another article in the March issue of Seminars in Cutaneous Medicine and Surgery (Semin. Cutan. Med. Surg. 2013;32:42-54).

"LLLT involves exposing cells or tissue to low levels of red and near-infrared light. ... Recently, medical treatment with LLLT at various intensities has been found to stimulate or inhibit an assortment of cellular processes," wrote Dr. Pinar Avci of Massachusetts General Hospital, Boston, and his colleagues, noting that the mechanism associated with the cellular photobiostimulation by LLLT is not yet fully understood, but appears to have a wide range of effects at the molecular, cellular, and tissue levels.

Describing LLLT as "possibly the ultimate noninvasive approach to treating the skin," the researchers highlighted numerous existing or emerging applications for the technology, outlined below.

Skin rejuvenation

Many modalities developed to reverse the dermal and epidermal signs of photoaging and chronological aging depend on the removal of the epidermis and the induction of a controlled form of skin wounding to promote collagen biosynthesis and dermal matrix remodeling. Examples include retinoic acid, dermabrasion, chemical peels, and ablative laser resurfacing.

These modalities require intensive posttreatment care and prolonged down time, and are associated with a risk of numerous complications, the researchers said.

LLLT represents an alternative that is known to increase microcirculation and vascular perfusion in the skin. Data from previous studies have shown that LLLT increased collagen and improved wrinkles and skin laxity with less down time and risk than that of other treatments.

In one study, for example, 300 patients treated with only a light-emitting diode (LED) LLLT device set at 590 nm, 0.10 J/cm², were compared with 600 patients who received the LED therapy in combination with a thermal-based photorejuvenation procedure. Of those who received LED therapy alone, 90% reported softer skin and less roughness and fine lines. The changes ranged from subtle to significant.

Those who received thermal photorejuvenation laser treatment reported a reduction in posttreatment erythema and an overall impression of increased efficacy with the additional LED treatment – an effect that could be attributed to anti-inflammatory effects of LLLT, they noted.

In another study, more than 90% of 90 patients receiving eight LED treatments over 4 weeks experienced favorable results, improving by at least one Fitzpatrick photoaging category. In addition, 65% of patients experienced global improvement in facial texture, fine lines, background erythema, and pigmentation, with results peaking 4-6 months after completion.

Acne treatment

LLLT in the red to near-infrared (NIR) spectral range (630-1000 nm) and with nonthermal power (less than 200 mW) has been shown in several studies to improve acne vulgaris. In one study, a significant reduction in active acne lesions occurred after 12 twice-weekly sessions using 630 nm red-spectrum LLLT with a fluence of 12 J/cm² in conjunction with 2% topical clindamycin. No significant effects were seen using an 890-nm laser. Other studies have demonstrated that the combination of blue and red light is synergistic for treating acne.

Photoprotection

Recent suggestions that infrared exposure might have protective effects against ultraviolet light–induced skin damage are based on the theory that the exposure might trigger protective or repair responses to UV irradiation. While controversial, this view is supported by data suggesting potential mechanisms of action. For example, some data suggest a role of p53, a sensor of gene integrity involved in cell apoptosis and repair mechanisms. In one study, the response to infrared (IR) irradiation was shown to be p53 dependent, suggesting the IR irradiation prepares cells to resist and/or repair further UV-induced DNA damage. Data from another study showed that IR irradiation induced the protective protein ferritin, which is involved in skin repair.

Data from yet another study suggested that nerve growth factor (NGF) production induced by LLLT using the helium neon semiconductor laser diode (HeNe, 633 nm) might explain the photoprotective effects of LLLT. In that study, NGF – a major paracrine maintenance factor for melanocyte survival in skin, was shown to protect melanocytes from UV-induced apoptosis by upregulating the level of Bcl-2 (an antiapoptotic protein) in the cells.

Herpesvirus lesion treatment

New therapies are needed to shorten recurrent herpesvirus episodes and reduce related pain and inflammation. LLLT has been suggested as an alternative to current medications. In one study of 50 patients with recurrent perioral HSV infection, LLLT at 690 nm, 80 mW/cm², 48 J/cm² daily for 2 weeks during recurrence-free periods decreased the frequency of herpes labialis episodes, the authors said.

In another study with similar parameters, patients achieved a significant prolongation of remission intervals from 30 to 73 days.

The mechanism of action remains unclear, but an indirect effect of LLLT on cellular and humoral components of the immune system may be involved in antiviral responses, as opposed to a direct virus-inactivating effect, the researchers noted.

Vitiligo treatment

Modest efficacy seen with the low-energy HeNe laser (632 nm, 25 mW/cm²) for the treatment of 18 vitiligo patients led to speculation that LLLT could serve as an alternative effective treatment for this typically treatment-resistant condition. (Repigmentation was observed in 64%, and some follicular repigmentation was observed in the remaining patients).

In a subsequent study of local administration of the HeNe laser light at 3 J/cm², 1.0 mW, 632.8 nm in patients with segmental type vitiligo, marked perilesional and perifollicular repigmentation of more than 50% was observed in 60% of patients.

"Both NGF and (basic fibroblast growth factor) stimulate melanocyte migration, and deficiencies of these mediators may participate in the development of vitiligo," the researchers wrote.

Depigmentation

During tests of red and blue light for acne, researchers unexpectedly found that patients treated with both red and blue light experienced an overall decrease in melanin.

Based on instrumental measurement results, blue light exposure (415 nm, 40 mW/cm², 48 J/cm²), increased the melanin level by 6.7, whereas red light exposure (633 nm, 80 mW/cm², 96 J/cm²) decreased the melanin level by 15.5.

"This finding may have some relationship with the laser’s brightening effect of the skin tone, which 14 of 24 patients spontaneously reported after the treatment period. However, as of today, no other studies investigated or reported a similar decrease in melanin levels after red light irradiations," the researchers said.

Hypertrophic scar and keloid eradication

LLLT has shown promise for preventing hypertrophic and keloid scars in patients who undergo scar revision by surgery or CO₂ laser. The use of daily near-infrared LED (NIR-LED) treatment on one of the two bilateral sites safely reduced the risk of scar development in that lesion, compared with the untreated lesion in three patients with bilateral scars. One underwent surgical revision/excision for preauricular linear keloids that developed after a face-lift procedure, one underwent CO₂ resurfacing for hypertrophic acne scars on the chest, and one underwent CO₂ resurfacing after excision of hypertrophic scars on the back. No significant treatment-related adverse effects were reported.

LLLT may work in these types of scars through an inhibitory effect on interleukin-6 mRNA levels and the modulating of platelet derived growth factor, transforming growth factor–beta, interleukins, and MMPs, which are associated with abnormal wound healing, the researchers noted.

Burn treatment

LED exposure was shown to provide benefit for the treatment of acute sunburn in a study of 10 patients.

Treatment once or twice daily for 3 days on half of the affected area decreased symptoms of burning, redness, swelling, and peeling compared with the untreated half. Decreased MMP-1 was noted on the treated side through immunofluorescence staining in one patient, and real-time polymerase chain reaction gene expression analysis showed a significant decrease in MMP-1 gene expression at both 4 and 24 hours after the UV injury on the treated side.

In another study, LED treatment was effective compared with control for speeding the healing process of laser treatment–related burns. In nine patients with second-degree burns from nonablative laser devices, LED therapy once daily for 1 week was associated with 50% faster healing based on both patient and physician accounts.

LED treatment also was shown in a pilot study to accelerate re-epithelialization of a forearm injury induced by a CO₂ laser; identical test sites were treated with daily dressing changes and polysporin ointment, but the site with faster re-epithelialization had also received the LED treatment (a computer pattern generator was used to deliver the identical CO₂ treatment to both sites).

Psoriasis

LLLT also shows promise for the treatment of plaque psoriasis. In a preliminary study, the combined use of sequential NIR (830 nm) and visible red light (630 nm) led to resolution of psoriasis in patients who were resistant to conventional therapy. The patients received treatment in two 20-minute sessions, 48 hours apart, for 4 or 5 weeks. No adverse side effects occurred.

Despite the variety of potential applications for the technology, LLLT remains somewhat controversial due to "uncertainties about the fundamental molecular and cellular mechanisms responsible for transducing signals from the photons incident on the cells to the biological effects that take place in the irradiated tissue" and because "there are significant variations in terms of dosimetry parameter: wavelength, irradiance or power density, pulse structure, coherence, polarization, energy, fluence, irradiation time, contact versus noncontact application, and repetition regimen," the researchers said.

They noted, however, that problems that have been experienced with LLLT – as well as negative study results – could be the result of inappropriate parameters, skin preparation, and/or device maintenance.

"LLLT appears to have a wide range of applications in dermatology, especially in indications where stimulation of healing, reduction of inflammation, reduction of cell death, and skin rejuvenation are required," they noted, but added that the lack of agreement on important parameters (particularly whether red, NIR, or a combination of both is optimal for a given application) has created a credibility gap that must be overcome before LLLT is routinely applied in every dermatologist’s office.

Once LLLT does become so widely accepted, however, it may be time for dermatologists to move on to the next big thing, Dr. Alam said in his article on the future of procedural dermatology.

"For several decades, dermatologists have worked closely with start-up companies to commercialize new devices and technologies ... when new toxins, fillers, and energy devices have been marketed, dermatologists have been early adopters," he said. "Over time, each device or procedure has diminished in cost and exclusivity as other physicians and nonphysicians have entered the market, and dermatologists have moved on to greener pastures. In all likelihood, this cycle will continue," he noted. "Dermatologists cannot prevent the dissemination of stable technologies, but they can continue to innovate and create new ones."

In fact, he added, continued success in this arena will rest largely on clinicians’ ability to nurture innovation to ensure a healthy pipeline of novel technologies.

The authors of the articles had no financial conflicts to disclose.

Noninvasive procedural dermatology has evolved at a dizzying pace, and continues to do so.

In addition to an array of procedures for skin tightening, skin resurfacing, and fat reduction, emerging technologies such as complex feedback devices, nanotechnology, and stem cell–based therapies promise to keep dermatology at the forefront of the cosmetic and esthetic realm, according to Dr. Murad Alam.

In an article featured in the March issue of Seminars in Cutaneous Medicine and Surgery, Dr. Alam of Northwestern University, Chicago, makes several predictions about the future of these technologies (Semin. Cutan. Med. Surg. 2013;32:61-63).

For example, like modern vehicles equipped with computer chips that can change steering and braking in response to environmental conditions, dermatologic devices will soon include technology that uses precise feedback to make automated setting changes, he said.

"Over time, the reduced cost of microelectronics, feedback controls, and computing power is simplifying the capacity of devices to analyze intraoperative information and adjust the procedure to compensate. For instance, certain laser and energy devices already have tips that are able to sense the temperature in the microenvironment and adjust power output to maintain site-specific temperature within a narrow band," he explained.

This technology could increase effectiveness and improve the safety of devices by reducing the level of operator time and expertise needed, and by making setting changes faster than humanly possible.

Autonomous nanotechnology devices are another advance described by Dr. Alam.

Miniaturization will become more feasible and affordable, and eventually devices will become "so exceedingly small that they will be mostly disposable and deployed in large numbers to the treatment site," he said.

The concept of hundreds of minuscule machines deployed to resurface skin or repair a wound may sound like science fiction, but the rapid advances in nanotechnology could make it a reality that could lead to the creation of new procedures such as ways to treat scars that can’t be corrected using currently available technologies, he added.

Dr. Alam’s other predictions for the future of noninvasive procedural dermatology included:

• Optimization of minimally invasive procedures for fat reduction and skin tightening, which currently provide only mild to modest results and longevity.

• The use of stem cells for augmentation of tissue layers, which could provide genuine rejuvenation rather than simply repair and concealment.

• The improvement of artificial dermal substitutes that can develop many of the functions of live skin, and can be grafted without inducing contractures.

• The development of rapid treatments for pigmentation using nanotechnology and cellular therapies, which will allow for precise melanocyte and melanosome transfer and automatic recoloration of discolored skin.

While these technologies continue to emerge, plenty of others have already established their places in the dermatology arena. The many and varied applications of one of these – low-level laser therapy, or LLLT – are described in another article in the March issue of Seminars in Cutaneous Medicine and Surgery (Semin. Cutan. Med. Surg. 2013;32:42-54).

"LLLT involves exposing cells or tissue to low levels of red and near-infrared light. ... Recently, medical treatment with LLLT at various intensities has been found to stimulate or inhibit an assortment of cellular processes," wrote Dr. Pinar Avci of Massachusetts General Hospital, Boston, and his colleagues, noting that the mechanism associated with the cellular photobiostimulation by LLLT is not yet fully understood, but appears to have a wide range of effects at the molecular, cellular, and tissue levels.

Describing LLLT as "possibly the ultimate noninvasive approach to treating the skin," the researchers highlighted numerous existing or emerging applications for the technology, outlined below.

Skin rejuvenation

Many modalities developed to reverse the dermal and epidermal signs of photoaging and chronological aging depend on the removal of the epidermis and the induction of a controlled form of skin wounding to promote collagen biosynthesis and dermal matrix remodeling. Examples include retinoic acid, dermabrasion, chemical peels, and ablative laser resurfacing.

These modalities require intensive posttreatment care and prolonged down time, and are associated with a risk of numerous complications, the researchers said.

LLLT represents an alternative that is known to increase microcirculation and vascular perfusion in the skin. Data from previous studies have shown that LLLT increased collagen and improved wrinkles and skin laxity with less down time and risk than that of other treatments.

In one study, for example, 300 patients treated with only a light-emitting diode (LED) LLLT device set at 590 nm, 0.10 J/cm², were compared with 600 patients who received the LED therapy in combination with a thermal-based photorejuvenation procedure. Of those who received LED therapy alone, 90% reported softer skin and less roughness and fine lines. The changes ranged from subtle to significant.

Those who received thermal photorejuvenation laser treatment reported a reduction in posttreatment erythema and an overall impression of increased efficacy with the additional LED treatment – an effect that could be attributed to anti-inflammatory effects of LLLT, they noted.

In another study, more than 90% of 90 patients receiving eight LED treatments over 4 weeks experienced favorable results, improving by at least one Fitzpatrick photoaging category. In addition, 65% of patients experienced global improvement in facial texture, fine lines, background erythema, and pigmentation, with results peaking 4-6 months after completion.

Acne treatment

LLLT in the red to near-infrared (NIR) spectral range (630-1000 nm) and with nonthermal power (less than 200 mW) has been shown in several studies to improve acne vulgaris. In one study, a significant reduction in active acne lesions occurred after 12 twice-weekly sessions using 630 nm red-spectrum LLLT with a fluence of 12 J/cm² in conjunction with 2% topical clindamycin. No significant effects were seen using an 890-nm laser. Other studies have demonstrated that the combination of blue and red light is synergistic for treating acne.

Photoprotection

Recent suggestions that infrared exposure might have protective effects against ultraviolet light–induced skin damage are based on the theory that the exposure might trigger protective or repair responses to UV irradiation. While controversial, this view is supported by data suggesting potential mechanisms of action. For example, some data suggest a role of p53, a sensor of gene integrity involved in cell apoptosis and repair mechanisms. In one study, the response to infrared (IR) irradiation was shown to be p53 dependent, suggesting the IR irradiation prepares cells to resist and/or repair further UV-induced DNA damage. Data from another study showed that IR irradiation induced the protective protein ferritin, which is involved in skin repair.

Data from yet another study suggested that nerve growth factor (NGF) production induced by LLLT using the helium neon semiconductor laser diode (HeNe, 633 nm) might explain the photoprotective effects of LLLT. In that study, NGF – a major paracrine maintenance factor for melanocyte survival in skin, was shown to protect melanocytes from UV-induced apoptosis by upregulating the level of Bcl-2 (an antiapoptotic protein) in the cells.

Herpesvirus lesion treatment

New therapies are needed to shorten recurrent herpesvirus episodes and reduce related pain and inflammation. LLLT has been suggested as an alternative to current medications. In one study of 50 patients with recurrent perioral HSV infection, LLLT at 690 nm, 80 mW/cm², 48 J/cm² daily for 2 weeks during recurrence-free periods decreased the frequency of herpes labialis episodes, the authors said.

In another study with similar parameters, patients achieved a significant prolongation of remission intervals from 30 to 73 days.

The mechanism of action remains unclear, but an indirect effect of LLLT on cellular and humoral components of the immune system may be involved in antiviral responses, as opposed to a direct virus-inactivating effect, the researchers noted.

Vitiligo treatment

Modest efficacy seen with the low-energy HeNe laser (632 nm, 25 mW/cm²) for the treatment of 18 vitiligo patients led to speculation that LLLT could serve as an alternative effective treatment for this typically treatment-resistant condition. (Repigmentation was observed in 64%, and some follicular repigmentation was observed in the remaining patients).

In a subsequent study of local administration of the HeNe laser light at 3 J/cm², 1.0 mW, 632.8 nm in patients with segmental type vitiligo, marked perilesional and perifollicular repigmentation of more than 50% was observed in 60% of patients.

"Both NGF and (basic fibroblast growth factor) stimulate melanocyte migration, and deficiencies of these mediators may participate in the development of vitiligo," the researchers wrote.

Depigmentation

During tests of red and blue light for acne, researchers unexpectedly found that patients treated with both red and blue light experienced an overall decrease in melanin.

Based on instrumental measurement results, blue light exposure (415 nm, 40 mW/cm², 48 J/cm²), increased the melanin level by 6.7, whereas red light exposure (633 nm, 80 mW/cm², 96 J/cm²) decreased the melanin level by 15.5.

"This finding may have some relationship with the laser’s brightening effect of the skin tone, which 14 of 24 patients spontaneously reported after the treatment period. However, as of today, no other studies investigated or reported a similar decrease in melanin levels after red light irradiations," the researchers said.

Hypertrophic scar and keloid eradication

LLLT has shown promise for preventing hypertrophic and keloid scars in patients who undergo scar revision by surgery or CO₂ laser. The use of daily near-infrared LED (NIR-LED) treatment on one of the two bilateral sites safely reduced the risk of scar development in that lesion, compared with the untreated lesion in three patients with bilateral scars. One underwent surgical revision/excision for preauricular linear keloids that developed after a face-lift procedure, one underwent CO₂ resurfacing for hypertrophic acne scars on the chest, and one underwent CO₂ resurfacing after excision of hypertrophic scars on the back. No significant treatment-related adverse effects were reported.

LLLT may work in these types of scars through an inhibitory effect on interleukin-6 mRNA levels and the modulating of platelet derived growth factor, transforming growth factor–beta, interleukins, and MMPs, which are associated with abnormal wound healing, the researchers noted.

Burn treatment

LED exposure was shown to provide benefit for the treatment of acute sunburn in a study of 10 patients.

Treatment once or twice daily for 3 days on half of the affected area decreased symptoms of burning, redness, swelling, and peeling compared with the untreated half. Decreased MMP-1 was noted on the treated side through immunofluorescence staining in one patient, and real-time polymerase chain reaction gene expression analysis showed a significant decrease in MMP-1 gene expression at both 4 and 24 hours after the UV injury on the treated side.

In another study, LED treatment was effective compared with control for speeding the healing process of laser treatment–related burns. In nine patients with second-degree burns from nonablative laser devices, LED therapy once daily for 1 week was associated with 50% faster healing based on both patient and physician accounts.

LED treatment also was shown in a pilot study to accelerate re-epithelialization of a forearm injury induced by a CO₂ laser; identical test sites were treated with daily dressing changes and polysporin ointment, but the site with faster re-epithelialization had also received the LED treatment (a computer pattern generator was used to deliver the identical CO₂ treatment to both sites).

Psoriasis

LLLT also shows promise for the treatment of plaque psoriasis. In a preliminary study, the combined use of sequential NIR (830 nm) and visible red light (630 nm) led to resolution of psoriasis in patients who were resistant to conventional therapy. The patients received treatment in two 20-minute sessions, 48 hours apart, for 4 or 5 weeks. No adverse side effects occurred.

Despite the variety of potential applications for the technology, LLLT remains somewhat controversial due to "uncertainties about the fundamental molecular and cellular mechanisms responsible for transducing signals from the photons incident on the cells to the biological effects that take place in the irradiated tissue" and because "there are significant variations in terms of dosimetry parameter: wavelength, irradiance or power density, pulse structure, coherence, polarization, energy, fluence, irradiation time, contact versus noncontact application, and repetition regimen," the researchers said.

They noted, however, that problems that have been experienced with LLLT – as well as negative study results – could be the result of inappropriate parameters, skin preparation, and/or device maintenance.

"LLLT appears to have a wide range of applications in dermatology, especially in indications where stimulation of healing, reduction of inflammation, reduction of cell death, and skin rejuvenation are required," they noted, but added that the lack of agreement on important parameters (particularly whether red, NIR, or a combination of both is optimal for a given application) has created a credibility gap that must be overcome before LLLT is routinely applied in every dermatologist’s office.

Once LLLT does become so widely accepted, however, it may be time for dermatologists to move on to the next big thing, Dr. Alam said in his article on the future of procedural dermatology.

"For several decades, dermatologists have worked closely with start-up companies to commercialize new devices and technologies ... when new toxins, fillers, and energy devices have been marketed, dermatologists have been early adopters," he said. "Over time, each device or procedure has diminished in cost and exclusivity as other physicians and nonphysicians have entered the market, and dermatologists have moved on to greener pastures. In all likelihood, this cycle will continue," he noted. "Dermatologists cannot prevent the dissemination of stable technologies, but they can continue to innovate and create new ones."

In fact, he added, continued success in this arena will rest largely on clinicians’ ability to nurture innovation to ensure a healthy pipeline of novel technologies.

The authors of the articles had no financial conflicts to disclose.