Intense Pulsed Light: From the Past to the Future

Abstract

Background:

For 20 years, intense pulsed light (IPL) technology has been used to treat various medical problems. IPL has since developed rapidly, becoming popular among patients worldwide. Recently, IPL has been used mainly for cosmetic purposes. Researchers are constantly seeking new applications of IPL to meet the increasing needs of patients. Objective: This review summarizes the development of IPL devices, discusses the current literature on the clinical application of IPL to increase our understanding of IPL, and provides guidance for broadening its clinical applications.

Materials and methods:

We performed a systematic search of electronic databases, including MEDLINE and PubMed and the authors experience on IPL to divide IPL development into three stages: germination, growth, and relative maturity.

Results:

Studies established the classical indications of IPL, including vascular lesions, pigmented lesions, hair growth, and photo rejuvenation. However, trials showed IPL has limited effects for complicated skin problems. Many studies explored rational combination therapies by IPL and laser or other cosmetic technologies.

Conclusions:

Based on previous research and the new generation of IPL devices, in the future, we predict wider and more effective clinical applications of IPL through the further improvement of IPL devices and their combined treatment.

Introduction

In 1989, Morgan Gustavsson produced the concept of a high-intensity flashlamp. The first intense pulsed light (IPL) device was exhibited in December 1990 at an annual medical conference in Stockholm.¹ That same year, Goldman also proposed this concept. The original light spectrum came only from a plain filtered flashlamp. After animal experiments, the more formal IPL treatment equipment was introduced to treat patients in 1994.² Thus, it has been only 20 years since IPL technology began to be used to treat various medical problems. Since then, IPL technology has developed rapidly and has become increasingly popular with patients worldwide. Recently, IPL has been used mainly for cosmetic purposes.

IPL devices are nonlaser, high-intensity light sources that use high-output flashlamps to produce a broad wavelength output of noncoherent light, usually ranging from 500 to 1200 nm.³ Lasers are known to interact with the skin in four possible ways: reflection, absorption, scattering, or transmission. Effects on tissue are only achieved if the light is absorbed, which results in the release of photons.⁴ Based on the light wavelength, the endogenous or exogenous chromophores within the skin are targeted and will absorb those photons, subsequently releasing thermal energy, which heats the target chromophores, leading to destruction of the target tissue by thermocoagulation. This theory is called selective photothermolysis, which was proposed by Anderson and Parish in 1983.⁵ Although not actually a laser, IPL functions by the same principles: when polychromatic light is delivered, the three main chromophores in our skin, hemoglobin, melanin, and water, can be targeted simultaneously, leading to thermotropy.⁶ The final overall changes resulting from the superposition of various tiny effects were encouraging.

UVC (200–290 nm) radiation can be absorbed by all cells, while UVB (290–320 nm) and UVA (320–400 nm) wavelengths have long been thought to be the factors responsible for the damaging effects of solar radiation.⁷ Intense shorter wavelengths can more easily increase the epidermal temperature; however, wavelengths of 400–1000 nm can only be absorbed by a few biomolecules (mainly the endogenous chromophores in the skin: hematoidin, hemoglobin, and melanin). Thus, most IPL devices incorporate various cutoff filters by which the lower wavelengths can be eliminated, These cutoff filters usually allow light transmission from 515, 550, 560, 570, 590, 615, 645, 690, or 755 nm up to 1200 nm to avoid epidermal damage.⁸

Suitable cutoff filters are usually chosen based on patient skin type and current skin condition. The Fitzpatrick Skin Phototype Classification is most commonly used to determine the skin's response to ultraviolet rays (UVR) and the skin's ability to tan.⁹ More side effects have been documented for darker skin types. The higher filters can decrease light absorption by epidermal melanin and prevent adverse effects, such as lasting erythema, crusting, blistering, and hyperpigmentation.¹⁰ In addition to skin type, the choice of the filter is also based on the position in the skin of the target chromophores that the treatment is designed to destroy.⁵ The derma of different body areas present different characteristics, and thus, we should choose the appropriate filter and other parameters according to the target structure localization. For example, the face presents more resistant characteristics to luminous radiations than the neck and décolleté areas. There are references for choosing suitable filters to treat different skin problems (Table 1).

Table 1.

Filter Options for Clinical Applications (Lumenis Company)

Wavelength (nm)	Application
515–1200	Rosacea, facial telangiectasia
515,560–1200	Light pigment lesions
560,590–1200	Rejuvenation, moderate pigment lesions
590,615–1200	Winkles, coarse pores
640,695–1200	Superficial varicose veins
695–1200	Hemangioma, hair removal

After light absorption, the fluence must ensure the delivery of adequate thermal energy to the target tissue. The exposure time should be less than the thermal relaxation time to prevent thermal damage via heat diffusion into adjacent tissue.⁴ Therefore, the light pulse duration should be set to fit the size of the target, whereas the pulse shape should be as square as possible to ensure uniform energy throughout the full pulse length.¹¹

Some exogenous chromophores in the skin, such as the porphyrins generated by the Propionibacterium acne bacterium, allow the etiological agents of acne vulgaris to be targeted indirectly, while others, such as professional tattoos and post-traumatic accidental tattoos, are not recommended to be treated by IPL because of serious side effects. There are various cooling techniques that can be used to protect the epidermis, such as cryogen spray, forced refrigerated air, or contact cooling; however, these methods can be insufficient for patients with tanned or dark skin. In addition, using refrigerated (6°C–10°C) IPL coupling gels on the skin serves to control discomfort and to provide a light-coupling medium between the light guide and the skin surface.

All IPL devices have a high potential to cause eye injury because the eye also contains hemoglobin and melanin. Therefore, treatment areas near the eye should be avoided as much as possible; special eye protection goggles are necessary for all individuals present in the therapy room.¹² The current clinical flexibility of IPL devices requires more expert knowledge than do laser systems with restricted indications. This versatility is advantageous for skilled and experienced physicians; however, for untrained users, it raises the risk of side effects caused by nonspecific thermal damage.

To date, IPL has passed through stages of germination, growth, and relative maturity, and this progress has been driven by constant upgrades to the IPL equipment. The ability of IPL to treat skin problems depends mainly on whether the spectrum output is sufficiently well controlled to target the tissue precisely. One or more chromophores may be targeted, and their positions in the skin maybe different during the same treatment. Therefore, with more accurate output spectrum control, energy is delivered more effectively and better potential curative effects can be achieved. Thus, the speed of the development of this technology has been affected mainly by device optimization, and each stage exhibited distinct characteristics in the effects on different target chromophores according to the device in that stage (Table 2).

Table 2.

The Developmental History of Intense Pulsed Light (on the Basis of Information from Lumenis)

Time	Name	Advantages	Disadvantages	Application	General features
1994	First-generation IPL	Noninvasive compared with lasers	Single wide spectrum; with short wavelength light; single pulse; no cooling system	Hemoglobin—vascular lesions	Uncontrolled IPL output spectrum
				Melanin—Hair removal	Severe pain
					Epidermal burns
				PhotoDerm VL	Easily hyperpigmentation
1998	Second-generation IPLVascuLight VL	High peak power; short pulses; Nd:YAG therapeutic head	Complicated filter system; single pulse; no cooling system	Hemoglobin—vascular lesions	Partly controlled IPL output spectrum
				Melanin—hair removal	Severe pain
					Epidermal burns
				Pigment lesions	Easily hyperpigmentation
2000	Third-generation IPL	Cooling system; reasonable filter wavelength; more simply designed	The pulse has an initial energy peak and energy attenuation; single spot size (8 × 34 mm); filters bound with therapy head	Water(collagen)—photorejuvenation	Moderate pain
					Reduction of skin damage
				Quantum SR	Reduction of hyperpigmentation
2004	Fourth-generation IPLLumenis One	More filters; big and small spot sizes; OPT technology; multiple pulses; cooling system	Weight of hand piece	Classical indicationsMultiple chromophores as simultaneous targets—acne and keloids	Fully controlled IPL output spectrumPrecisely controlled spectrumEndurable painNo damage to the epidermis

IPL, intense pulsed light; Nd:YAG, neodymium-doped yttrium aluminum garnet; OPT, optimal pulse technology.

The Preliminary Stage (1989–1997): Uncontrolled IPL Output Spectrum

Before this stage, various lasers, especially the flashlamp pulsed dye laser (PDL), had been used to treat vascular lesions, with good results; however, the post-treatment side effects, such as severe purpura and hyperpigmentation that faded only rarely and with difficulty, seriously disturbed the patients. To explore better treatment methods, in 1989, Gustavsson proposed the new concept of a nonablative treatment utilizing a high-intensity flashlamp to emit IPL. Subsequently, in 1994, the first-generation formal IPL, named PhotoDerm VL, was produced by the EMC company under the guidance of Goldman and began to be used to treat patients.² The output spectrum of this device included the absorption peak of hemoglobin, and several studies have demonstrated its beneficial effects in the treatment of vascular lesions.

In 1996, Goldman and Eckhouse used this IPL device to treat 159 patients with 369 various vascular lesions and found it to be safe and effective to treat leg veins with diameters ranging from 0.1 to 3 mm.¹³ Thereafter, Raulin et al. used a large spot size IPL to treat essential telangiectasias, with good effects.¹⁴ They praised IPL for having equal effects but greater safety compared with lasers. Patient compliance was excellent because the cosmetically relevant side effects were considerably smaller for IPL than they were for lasers. In 1997, Raulin and Goldman¹⁵ reported a new application of IPL in the treatment of port wine stains (PWSs), which are formed by the dilation and malformation of dermal capillaries without endothelial proliferation.

Two years later, Raulin et al.¹⁶ performed a retrospective study, including 37 patients, with 40 PWSs. This study showed that an average of 4.2 sessions was required to achieve 70–100% clearance when treating PWSs with IPL. The parameters were usually set as follows: 515 or 550 nm filter; pulse duration of 2.5–5.0 ms; and fluence ranging from 24 to 30 J/cm². Although side effects were observed, including purpura (76%), superficial blisters (8%), crusting (20%), transient pigmentation changes (10.8%), hypopigmentation (8.1%), and hyperpigmentation (2.7%), no scarring was observed. The author affirmed that IPL was a safe and effective tool to treat PWSs, especially purple PWSs, based on the final effect.

Angermeier¹⁷ used the PhotoDerm VL and various treatment parameters to treat patients with facial veins, including telangiectasia, facial hemangiomas, rosacea, and PWSs. A total of 174 cases achieved 75–100% clearance after one to four treatment sessions, representing 188 patient visits. Mark made a quantitative determination of the change in rosacea-associated erythema after treatment with the PhotoDerm VL: the results showed a 30% decrease in blood flow, a 29% decrease in the area of cheek telangiectasia, and a 21% decrease in erythema intensity, as determined by scanning laser Doppler.¹⁸ The results were not particularly satisfactory, however, they could be improved by further treatment sessions.

In 1997, Raulin et al.¹⁹ reported successful hair removal treatment of two transsexual patients (male to female) in the perioral and mandibular area. Two days after the treatment, the hair in the treatment area was epilated easily using forceps. Biopsies showed follicle atrophy. Six months later, there were no local recurrences and no adverse effects. In the same year, Gold et al.²⁰ verified the long-term epilation efficacy and safety of the Epilight broadband IPL hair removal system. Successful hair removal via IPL demonstrated that it could target melanin well because the hair shaft was black.

In this germination stage, the first-generation IPL devices were taking shape, and the output spectrum remained uncontrolled. Although the spectrum could target hemoglobin and melanin, shorter wavelengths could not be filtered, and no effective measures were in place to protect tissue adjacent to the target or darker skin types; therefore, these devices produced many side effects, such as severe pain and epidermal burns. There was limited research during this initial phase, and the further progress of IPL was in doubt; however, the positive results of these studies had opened a door for further exploration.

The Growth Stage (1998–2003): Partially Controlled IPL Output Spectrum

In 1998, a second-generation IPL device, named VascuLight VL, was created. The device had high peak power, short pulses, and a filter system, which increased its multifunctional applications. An Nd:YAG (neodymium-doped yttrium aluminum garnet; Nd:Y3al5O12) laser therapeutic head was also included, meaning that the output spectrum of the IPL was partly controlled. Thus, IPL could be used safely for a wider variety of pigment damage and hair removal treatments by targeting melanin in addition to vascular lesions. In the same year, Bitter used the new IPL device to eliminate facial hair and found that the patient's face appeared younger; this result introduced the new concept of “Photo Rejuvenation” via IPL.²¹

Light absorption by tissue water increases at longer wavelengths. The longer wavelength portion of the broad spectrum emitted by IPL indirectly targeted the collagen of the dermis via heat conduction because it is closely integrated with tissue water. This photothermal stimulation led to the regeneration and rearrangement of collagen, thereby improving the skin texture. Since then, the classical indications of IPL were preliminarily established; it can simultaneously target the three main chromophores in human skin, hemoglobin, melanin, and water. To improve the effect of this type of simultaneous therapy, in 2000, the third-generation IPL device, the Quantum SR, was introduced. This no-downtime device was designed to be simpler and included a cooling system, which greatly reduced the occurrence of side effects.

At this stage, researchers showed great interest in actively seeking new indications for IPL and also conducted some research into its mechanisms.

Classical indications of IPL

Based on the research of the previous stage and the new generation of IPL devices, Weiss et al.²² evaluated the effects of IPL on the disruption of hair growth; the results showed that hair clearance was 64% after the double treatment protocol, 42% 8 weeks after treatment, and 33% after 6 months. Thus, it seemed that the effect decreased over time and that longer term effects were not achieved. Bjerring et al.²³ compared the effectiveness of IPL with a ruby laser for hair removal. Their data showed that IPL was 3.94 times more effective than the ruby laser was for epilation. However, the therapeutic result could not be improved significantly in the chin and neck region by more than three treatments, which indicated that the effect varied with treatment area. Lor et al.²⁴ evaluated patient satisfaction with hair removal by IPL and reported it to be a reliable and practical solution for the long-term removal of unwanted hair, especially for patients with skin irritation and ingrown hair.

In his case report on the use of IPL to treat hirsutism, Johnson and Dovale²⁵ indicated that IPL could be used to treat very dark skin types, if the proper parameters were selected. However, Radmanesh et al. found that leukotrichia could develop after IPL-or-laser-based hair removal therapy. It was proposed that the light absorbed and the heat produced by melanin might be sufficient to destroy or impair the function of melanocytes, but was insufficient to damage hair follicle cells.²⁶ White hair absorbs less light than black hair, and the resulting heat conduction is not strong enough to destroy the follicles. In general, people began to accept using IPL for hair removal at this time.

Gold et al.²⁷ used IPL with a 590 nm filter to treat nevus spilus successfully. Following this case, Bjerring and Christiansen²⁸ tried to treat benign pigmented lesions with IPL in a study that included lentigo solaris (18 cases) and melanocytic nevi (8 cases). After one IPL treatment, 96% of the patients exhibited pigment reduction, and the average clearances of lentigo solaris and melanocytic nevi were 74.2% and 66.3%, respectively. Kawada et al. performed a similar study 2 years later and demonstrated the same positive results. The explanation given was that with the absorption spectrum for melanin, IPL induced the injury of melanin-containing epidermal cells via photothermal effects.^29,30

Remington and Remington³¹ even used IPL with a 590 nm filter to treat facial lentigines successfully in a 10-year-old girl with Peutz–Jeghers syndrome. A study by Moreno Arias and Ferrando³² not only showed that IPL could treat superficial melanocytic lesions, such as ephelides, epidermal melasma, nevus spilus, and café-au-lait macules, but also inferred that such deep melanocytic lesions should be improved by repeated treatment sessions. At this stage, it seemed that IPL yielded promising results in the treatment of melanocytic lesions.

The aging of human skin includes intrinsic aging and photoaging, characterized by a thinning epidermis. Collagen fibers become thickened and fragmented with increasing age, with a higher ratio of collagen III to collagen I.³³ Thus, rhytid improvement requires dermal collagen remodeling. Laser ablation resurfacing to treat facial rhytids has associated complications and limitations. People prefer nonablative approaches, which can deliver enough energy to improve rhytids while avoiding epidermal damage. Since Bitter introduced the concept of “Photo Rejuvenation” with IPL,²¹ several studies have demonstrated it to be a genuine effect.

Goldberg and Cutler evaluated the efficacy and complication rate of IPL in the treatment of rhytids. Thirty subjects received up to four treatments with an IPL device, and changes were assessed after 6 months. Twenty-five subjects showed different degrees of improvement in skin quality, but no subject exhibited a total resolution of the rhytids. The mechanism is presumed to act through nonspecific dermal injury, which is considered to stimulate the synthesis of new collagen without epidermal damage.³⁴ Goldberg and Samady also compared the effectiveness and safety of IPL with those of the Nd:YAG laser in the treatment of facial rhytids. Although both devices could improve facial rhytids in a nonablative manner, the Nd:YAG laser was better tolerated than IPL and resulted in fewer side effects.³⁵ Of course, that result was partly because the second generation of IPL devices had no effective protective devices for the epidermis.

Two years later, Negishi used a third-generation IPL device with a 560 nm filter and integrated a contact-cooling system to accomplish full-face photorejuvenation, including the reversal of various photoaging symptoms in Asian patients. Seventy-three patients received five or more full-face IPL treatments at 3- to 4-week intervals. After a series of treatments, 80% of the patients showed more than 60% improvement in pigmentation fading telangiectasia reduction, smoother skin texture, and overall appearance. Histological examination showed strong staining for type I and type III collagen. The patients were also satisfied with the minor and transitory complications compared with those of other invasive modalities.³⁶

Weiss et al. reviewed 80 randomly selected patients who received IPL treatment, with an average of three treatments during 1996 and 1997, and evaluated long-term clinical effects 4 years after the initial treatment by examining photorejuvenation improvements on the face, neck, and chest. The results showed improvement in skin texture (83% of patients), telangiectasias (82% of patients), and pigmentation (79% of patients), with side effects including temporary mild crusting (19% of patients), erythema (15%), and purpura (6%). Therefore, the signs of photoaging could be improved by IPL with long-lasting results. Smoother skin texture, although not easily quantified, is an additional long-term benefit.³⁷

Many studies helped to establish the classical IPL indications at this stage, including vascular lesions, pigment lesions, hair removal, and photoaging rejuvenation. Although its ability to improve wrinkles was limited, the overall change that resulted from the superposition of various tiny effects was encouraging.

New applications

IPL became a highly active research area because of its special properties, such as nonablative operation, short downtime, and minor side effects. People were not content with the known indications and continued to discover new opportunities. For example, poikiloderma of Civatte had always been difficult to treat effectively because it was necessary to eliminate both vascular and pigment damage simultaneously. IPL seemed to be the ideal treatment, offering a broad-spectrum output that delivered many wavelengths with adjustable pulse durations and sequencing.

Studies by both Goldman and Weiss indicated that poikiloderma could be treated well by IPL, eliminating 50–75% of telangiectasias and hyperpigmentation, while the incidence of side effects was only 5%.^38,39 Adatto attempted to use IPL to treat hyperpigmentation on the forearms of a 55-year-old patient. The case reported more than 90% clearance of the hyperpigmentation. These results showed that treating hyperpigmented lesions with IPL on areas other than the face was effective and safe.⁴⁰ Moreover, Ho et al. treated postburn hyperpigmentation successfully in Asian patients, and Kontoes and Vlachos found that IPL could improve erythema and hyperpigmentation caused by laser resurfacing in the periorbital area.^41,42

Moreno-Arias et al. even used IPL to treat a facial repigmented hairy intradermal melanocytic nevus that had relapsed postshave excision, achieving complete pigment clearance and hair removal. The effect was maintained for 6 months, during which no repigmentation or hair regrowth was observed.⁴³ However, because the hairy intradermal melanocytic nevus had relapsed postshave excision, the observation time should have been extended to years after the IPL treatment to ensure that it was cleared completely; unfortunately, no subsequent report was available.

Although IPL had a demonstrated capability to disrupt veins without damaging the overlying skin, Miyake et al. performed a study to improve the procedure. He used an industrial thermometer equipped with a laser-aiming system adapted to the IPL hand piece to measure skin temperature during IPL treatments. The results showed that the average temperature was 35°C–45°C (skin types I–IV), which caused skin lesions, and darker skin types tolerated smaller temperature increases. The author indicated that skin type could predict the cutaneous reaction to IPL.⁴⁴ Thus, the energy values should be lowered to treat darker skin types to ensure the therapeutic safety of IPL.

The Relatively Mature Stage (2004–): Fully Controlled IPL Output Spectrum

Initially, IPL devices were cumbersome, difficult to operate and control, and were only accepted by a few practitioners. After a decade of development, in 2004, the fourth-generation IPL systems were introduced with more favorable beam characteristics. These systems offered “square pulse” beams, meaning that an even spectral distribution was delivered over the entire width of a pulse.⁴⁵ This technology, called optimal pulse technology (OPT), is considered the greatest innovation in the development of IPL.

The former spiked pulse more easily led to instant thrombosis and vascular rupture, while the new square pulse eliminated the initial energy peak and avoided the energy attenuation at the end of the pulse. Thus, IPL with a square pulse resulted in few purpuras under rational operation. In addition, the pulse duration, the delivery of double or multiple pulses, and the pulse width all contributed to more reasonable and accurate parameter setting combinations and enabled the simultaneously treatment of several target chromophores at different positions in the skin. This approach complies with the concept of medical precision.

At this stage, the use of IPL had gradually spread worldwide, and more therapists and patients had accepted this type of treatment, which led to a large supply of reliable clinical data. Studies during this stage also focused on a more rational evaluation of the effects of IPL, apart from the undesired side effects.

New Progress for Classical Indications

Target chromophore: hemoglobin

During this period, several articles studied the details of using IPL to treat vascular lesions. Kassir et al. analyzed 102 patients with mild to severe rosacea who received IPL treatment. From these data, the author attempted to optimize the parameter settings to achieve beneficial effects with minimal side effects. They found that the use of IPL, with a 530/420 nm filter; double, triple, or quadruple pulses with 20–30 ms of delay time; a pulse width of 2.5–5 ms; and fluence ranging from 10 to 30 J/cm²), could be safe and effective.⁴⁶ Sufficient clinical experience is also required to adjust the parameters appropriately for different patients. Lim et al.'s study supported the efficacy of IPL treatment for patients with erythematotelangiectatic rosacea (ETR) and showed that IPL might be more effective in patients with more severe ETR and in younger patients.⁴⁷

The new generation of IPL devices was equipped with a small spot size (6.35 mm) that could contact the skin in contoured areas. Tsunoda et al. recommended using this novel small spot sized IPL along with shorter wavelengths (500–635 nm) to treat facial telangiectasia, because it permitted the use of a high fluence that provided better efficacy.⁴⁸ Nymann compared the effects and side effects of long-pulse dye laser (LPDL) and IPL in the treatment of facial telangiectasias and reported that LPDL offered advantages.⁴⁹ In addition, PDL was regarded as the gold standard to treat PWSs. A comparative study showed that PDL (65%) was more effective than IPL (30%) to treat PWSs.⁵⁰ However, Babilas et al. found that IPL showed additional lesion clearance of PWSs that were resistant to PDL therapy. The author explained that cases resistant to laser therapy usually had deeper and smaller diameter vessels. While the single wavelength and narrow pulse width both inhibited penetration, the laser penetrated sufficiently to target some smaller diameter vessels. However, the latest generation of IPL devices (Lumenis One) with a large spot size could increase penetration and decrease light scattering. In addition, the tunable pulse width aided the targeting of different diameter vessels.⁵¹

In a clinical study by Li et al., most of the PWSs faded significantly, including those resistant to other therapies. Further, the author found that adult lesions were easier to remove by IPL than were lesions in younger individuals.⁵² Wang et al. used IPL (560 nm, single pulse with a pulse width of 6 ms, and a fluence of 20–24 J/cm², 5 sessions at an interval of 4–5 weeks) to treat 29 Chinese patients with neck PWSs. Over 60% of the patients achieved more than 50% improvement, and half of the patients were satisfied with the effect.⁵³ No studies have compared IPL with other lasers in the treatment of PWSs in the neck area. Taken together, these studies have shown that IPL is an alternative method for treating most PWS lesions.

Determining the effectiveness of infantile hemangioma therapy takes a long time. PDL has been used successfully to treat superficial hemangiomas. As the new generation of IPL devices with OPT provided safe therapy, Li et al. reviewed its application to infantile hemangioma and showed that 76% of patients achieved more than an 80% clearance of infantile hemangioma, while only 5% of the treatments led to mild adverse events.⁵⁴ Caucanas et al. also performed a retrospective cohort study in Caucasian children and confirmed the safety and effectiveness of IPL to treat infantile hemangioma.⁵⁵

Target chromophore: melanin

For pigment lesions, Wang et al. compared a Q-switched alexandrite laser (QSAL) and IPL to treat facial freckles and lentigines in Asian patients and found that QSAL was superior to IPL for freckle treatment.⁵⁶ However, for complex dyspigmentation, Park et al. suggested that a combination treatment using both IPL and a Q-switched ruby laser (QSRL) was safer and more effective than the individual therapies alone.⁵⁷ Rusciani et al. spent 7 years studying the treatment of poikiloderma of Civatte using IPL and observed satisfactory long-term effects.⁵⁸

The actual effects of IPL seemed to be different or limited in the treatment of various pigment lesions. Pigmented lesions with clear demarcation lines could be identified easily and resulted in better effects when treated with IPL, compared with those of less well-demarcated lesions. Kawasaki tried to treat poorly demarcated pigment lesions, such as seborrheic keratosis, with IPL by marking them with a carbon-based ink pen. All the marked patients showed better improvement in their pigmented lesions than did the unmarked patients.⁵⁹ The study cleverly destroyed the real target tissue indirectly by utilizing artificial colors as a direct target via heat conduction. This method is expected to be very useful.

IPL has also been used to treat striae distensae (SD) in recent years. Shokeir et al. found that both PDL and IPL could reduce the striae width and improve the skin texture through collagen stimulation.⁶⁰ Aldhalimi and Abo Nasyria showed that a wavelength of 590 nm was more effective than a wavelength of 650 nm to treat SD with IPL.⁶¹

However, IPL and all the lasers used to treat melasma have had minimal results. Transient results have been observed for the epidermal subtype; however, the dermal and mixed type of melasma, which constitute the majority of melasma in pigmented skin, are difficult to treat.⁶² Figueiredo Souza and Trancoso Souza used single-session IPL combined with a stable, fixed-dose, triple combination of IPL, bleaching agents, and broad-spectrum sunscreens to treat refractory mixed and dermal melasma effectively.⁶³ Cunha et al. suggested that treating refractory melasma with laser Q-switched Nd:YAG followed by IPL was the best therapy for hyperpigmentation produced by melasma.⁶⁴ Yun et al. reported similar results in their study on Korean melasma patients.⁶⁵

In addition, there is a novel technique named fractionated IPL (E-toning, Union Medical Co., Seoul, Korea), which uses a microsecond-domain pulse-in-pulse (PIP) mode, where multiple fractionated subpulses exist in one pulse width. In two studies, this fractionated IPL showed moderate efficacy. The author stated that PIP IPL increased the temperature of the target tissue gradually and did not induce any microcrusts, suggesting greater safety compared conventional IPL. The author found it to be an effective tool, especially for the treatment of melasma, and that it could be applied every other week.^66,67

However, Sardana et al. postulated that melasma is most likely a natural compensation for the high ambient ultraviolet flux in tropical countries and that any method of removal would probably lead to minimal results and rapid recurrence.⁶⁸ Melasma is a complex multifactorial disorder, whose pathogenesis is not well understood;⁶² therefore, Kabir's theory applies to patients in local areas. Many studies have lacked long-term follow-up data. The limitations of the current literature include the heterogeneity of study designs, small sample sizes, and poor follow-up rates. Thus, this topic remains a challenge requiring further exploration.

In this phase, a new understanding of hair removal via IPL was achieved. In comparative studies, the alexandrite laser was more effective than IPL for reducing facial hirsutism in women with polycystic ovary syndrome (PCOS).⁶⁹ However, Rezvanian suggested that combining metformin with IPL in women with PCOS could improve the cosmetic effects of hair removal.⁷⁰ Cameron et al. found that diode (810 nm) laser (DL) therapy was more effective than IPL for hair removal in a comparative study.⁷¹ Several other comparative studies have reported that both DL and IPL treatments are highly effective, long lasting, and safe, and that DL was more effective and less time-consuming, but more painful, than IPL therapy.^72
–74

However, IPL has its own advantages, such as a large light guide that can treat larger areas more quickly, as well as efficacy in almost any bodily area where smoother, younger looking, hair-free skin is desired. IPL works equally well with lighter or darker hair and skin, and it is suitable for almost all skin types. At the same time, home-use IPL appeared at this stage, which offered efficacy in addition to convenience. In a study by Emerson and Town of home-use IPL devices, 84% of participants showed a mean of 51% (range, 25–86%) epilation at the 6-month follow-up point.⁷⁵

Target chromophore: water(collagen)

The exploration of skin rejuvenation by IPL continued. In a randomized controlled split-face trial, it was reported that three IPL treatments improved telangiectasia, pigmentation, and skin texture, but showed no efficacy on rhytids.⁷⁶ In a study by El-Domyati et al., neither the clinical assessment of patients nor the histological changes of matrix proteins for facial wrinkles showed noticeable changes after IPL treatment.⁷⁷ To some extent, the effect was limited when IPL was used alone. The studies in this phase were more inclined to turn to combination therapy for improved effects. Some studies have attempted the additional use of 5-aminolevulinic acid (ALA) to treat facial photoaging with IPL and showed greater improvements of the photodamage.^78,79 Further, the addition of polyphenolic antioxidants to an IPL regimen improved the observed clinical, biochemical, and histological changes compared with those of IPL treatment alone.⁸⁰

Multiple chromophores as simultaneous targets

It is difficult to achieve good results in acne treatment. IPL can damage blackheads and allow hair follicles to secrete unobstructed; it can also activate protoporphyrin, kill propionic acid acne bacilli, eliminate red marks, and aid in dermal collagen regeneration and rearrangement. Thus, acne could be improved by IPL because it can target several chromophores simultaneously.

To enhance the curative effects, many studies have combined IPL and light photodynamic therapy (PDT). PDT is an effective method to treat acne vulgaris, usually using ALA. Taub's study compared the activation effect of ALA by blue light, IPL alone, and IPL combined with RF, and reported that ALA-PDT with activation by IPL showed more consistent improvement than did the other two methods in the treating of moderate to severe acne.⁸¹ Kumaresan and Srinivas indicated that the burst-pulse mode was more controllable than the single-pulse mode when treating facial acne with IPL.³⁶ Choi et al. compared the effects of PDL and IPL to treat acne and found that PDL resulted in a more sustained effect.⁸²

A new technology combining IPL with negative pressure, called photopneumatic technology, also attracted interest. Lee et al. used this technology to treat acne vulgaris and found that it could reduce effectively the number of acne lesions.⁸³ Moreover, Omi demonstrated that photopneumatic therapy was effective for both acne vulgaris and rejuvenation in a clinical study.⁸⁴

Keloids and hypertrophic scars are prevalent and psychologically distressing dermatological conditions. Various treatment modalities have been explored, but without complete success using any one method.

Erol et al. showed that IPL is helpful in improving the appearance of keloids and hypertrophic scars, regardless of their origin, mainly by reducing the height, redness, and hardness of the scars.⁸⁵ Another study showed the effect of IPL on immature burn scars. The therapy was tolerated well by patients, produced an early decrease in scar vascularity, reduced scar height, increased the pliability of immature burn scars, and prevented the development of hypertrophic scars.⁸⁶

Shamsi Meymandi et al. used IPL combined with corticosteroid injection and showed that this combined therapy improved the recovery level of hypertrophic and keloid scars greatly.⁸⁷ Kim et al. also showed that this combination therapy could increase the recovery level of skin hydration status in terms of the skin barrier function.⁸⁸ Hultman et al. reported that patients subjectively considered IPL an effective treatment for burn scar dyschromia, but they neglected the potential for morbidity. The author did not recommend IPL for the routine treatment of burn scars, because it provided only minimal improvement, but raised the potential for complications, and the willingness to pay was lower than was the cost of providing care.⁸⁹

The formation of scars is complicated; scars require combined treatments to achieve an improved appearance, and IPL could be one component of an effective therapy. Perhaps the best approach would be to evaluate the condition of a scar correctly and to determine the optimal time for therapy.

Exploring new applications

Meibomian gland dysfunction (MGD) is the main cause of evaporative dry eye disease. Chronic inflammation leads to abnormal blood vessel growth, called telangiectasias, surrounding the meibomian glands, as well as the secretion of inflammatory mediators that cause gland malfunction.

Various measures have been used to treat MGD, with only slight improvements. As IPL could improve vascular lesions, it was used near the eye lid to close the abnormal blood vessels and prevent the secretion of inflammatory mediators.⁹⁰ A clinical study by Craig and Yen-Heng demonstrated the therapeutic potential of IPL for MGD by improving tear film quality and reducing the symptoms of dry eye.⁹¹ These results were only preliminary, and a multisite clinical trial with a larger sample size and comparison treatment groups is expected, as well as other randomized controlled trials.

Aberrant Mongolian spots (AMSs) distal to the lumbosacral region are thought to be more persistent than typical sacral Mongolian spots. Shirakawa et al. was the first to treat AMSs with IPL. The patients were satisfied with the effect, and all of them exhibited improvement to different degrees and were willing to accept the next treatment.⁹² Tawfik studied the efficacy of IPL to treat nail psoriasis. The patients received a mean of 8.63 ± 3.6 IPL sessions. The nail bed showed a mean improvement of 71.2%, but the improvement of the nail matrix was only 32.2%. Patient follow-up revealed relapse in three patients after 6 months; IPL provided a long period of remission.⁹³

Advances in mechanistic studies

The therapeutic mechanism of targeting hemoglobin and melanin to treat vascular and pigment lesions has been made relatively clear. At this stage, IPL was popular mainly for its contribution to photorejuvenation. Therefore, researchers focused on the antiaging mechanism of IPL. Various hypotheses have been proposed to explain the probable mechanisms of IPL effects. The most recognized explanation is that selective and mild thermal damage to dermal collagen can stimulate the collagen to regenerate and rearrange.⁹⁴ Several animal experiments have supported this hypothesis.

Iyer et al. observed procollagen I deposition after IPL treatments in a porcine model and showed that the increase in procollagen was greater with a fluence of 40 J/cm² than it was with 30 J/cm².⁹⁵ In study by Wang et al., 15 SD rats were exposed to IPL in three dermal regions with triple pulses (duration of 4, 5, and 6 ms) at an energy density of 34 J/cm². The results showed an increase of transforming growth factor beta 1 (TGF-β1) mRNA expression only in the IPL-exposed skin areas, and not in the unexposed regions.⁹⁶ TGF-β is a multifunctional cytokine that can upregulate the cell growth, differentiation, and biosynthesis of extracellular connective tissue. The TGF-β1 signaling pathway regulates the appearance of the features of H₂O₂-induced premature senescence.⁹⁷ Therefore, this study suggested that TGF-β1 plays an important role in the dermal remodeling of photorejuvenation.

In Luo's rat experiment, IPL irradiation induced mRNA transcription of type I and III procollagen and promoted the synthesis of collagen protein in a time-dependent manner, as well as causing rearrangement of collagen fibers. IPL could also downregulate the mRNA expressions of the MMP-1 and MMP-2 genes in a time-dependent manner.⁹⁸ Matrix metalloproteinases (MMPs) are generated by skin fibroblasts and can degrade specifically almost all components of the extracellular matrix (ECM), including collagen, thereby playing an important role in skin aging.⁹⁹

Cuerda-Galindo et al. found that human skin fibroblasts proliferate at a fast rate and that hyaluronic acid and versican production increased after irradiation with IPL using a filtered spectrum of 800–1200 nm. Moreover, the mRNA levels of collagen type I, collagen type III, and MMP-1, as determined by reverse transcription–polymerase chain reaction, were increased.³³ Cuerda-Galindo et al. compared the effects of different IPL parameters and showed that collagen and hyaluronic synthesis exhibited an equivalent rise. The results also showed that a 550 nm filter caused more decorin and versican synthesis than did an 800 nm filter. Thus, it seemed that the wavelength could affect the differential synthesis of ECM proteins.¹⁰⁰

An investigation by Wong et al. showed similar results. IPL reduced the protein levels of MMP-2, especially the active form MMP-2. Meanwhile, the mRNA levels of MMP-2, MMP-14, and TIMP-2 were also downregulated.¹⁰¹ The MMP activity is regulated by a family of molecules known as tissue inhibitors of metalloproteinases (TIMPs). TIMP-2 can assist MMP-14 to activate pro-MMP-2 on the plasma membrane.¹⁰² Decreased expression levels of both MMP-14 and TIMP-2 could impede MMP-2 activation. IPL downregulated their mRNA expression levels in a time-dependent manner, suggesting that IPL irradiation cannot degrade the ECM protein components as UV irradiation can. This property is also very helpful in preventing skin aging. Therefore, the author stated that IPL irradiation could not only enhance new collagen production but also decrease collagen degradation through photorejuvenation mechanisms in mouse skin.⁹⁸ Shin et al. observed that vimentin protein expression was upregulated in human dermal microvascular endothelial cells after exposure to UV irradiation but that was downregulated when treated with IPL. This study aided the identification of aging-related proteins. The study also showed increased expression of HSP71; however, because UV radiation is known to cause cellular damage directly, this expression was not considered to be a biological marker of skin aging¹⁰³ (Fig. 1).

FIG. 1.

The antiaging mechanism of IPL. IPL irradiation induced the mRNA transcription of type I and III procollagen and promoted the synthesis of collagen protein, as well causing rearrangement of collagen fibers (orange). IPL reduced the mRNA levels of MMP-2 and MMP-14 generated by skin fibroblasts, which can degrade collagen (green). ECM, extracellular matrix; IPL, intense pulsed light; MMPs, matrix metalloproteinases; TIMPs, tissue inhibitors of metalloproteinases.

Side effects

The disadvantages of IPL should also be mentioned. Nowadays, the most common side effect of IPL treatment is pain.² Most people can endure it, but it sometimes requires the use of topical analgesic creams or lowering the energy density. Lask et al. showed that pneumatic skin flattening (PSF) with negative pressure could reduce pain during IPL hair removal treatment.¹⁰⁴ Empathy is often required to determine appropriate therapeutic parameters, and means of pain control should be flexible.

One study indicated that burns and their sequelae, including leukotrichia, paradoxical hypertrichosis, and folliculitis, are four major side effects of IPL hair removal therapy.¹⁰⁵ In the past, erythema, blisters, and cutaneous pigmentary alterations were also common when various skin lesions were treated by IPL. Currently, the new generation of IPL devices, which can be fully controlled and have largely decreased the risks of these side effects, can occasionally cause side effects; however, the effects are usually mild and can be recovered from.

Asian patients, usually with skin types III-V, still have a high risk of post-treatment hyperpigmentation after the treatment of pigment lesions, especially melasma. Negishi et al. used UV photography to help diagnose patients with subtle epidermal melasma; these patients were then treated with mild IPL parameters, and no secondary hyperpigmentation was induced.¹⁰⁶ Haedersdal recommended the following to achieve safe laser and IPL treatments: optimal preoperative information, examination, and patient selection; optimal therapy performance; and optimal postoperative wound care.^107,108

Most potential risks can be avoided if the new IPL devices are used cautiously and reasonably. Hammes et al. performed a survey of 50 patients affected by treatment errors that were caused by inexperienced medical personnel. The identified sources of error (multiple answers were possible) were as follows: 62.8% excessively high energy, 39.5% incorrect device for the indication, 20.9% treatment of patients with darker or markedly tanned skin, 7% no cooling, and 4.6% incorrect information. The causes of malpractice suggested insufficient training, inadequate diagnostic abilities, and promises of unrealistic results.¹⁰⁹

In addition, some studies have examined whether IPL treatment has carcinogenic potential. A study by El-Domyati et al. showed an increase in epidermal p53 expression after IPL treatment, which the author said could increase the risk of skin neoplasia via IPL-induced DNA damage, possibly leading to the dysregulation of apoptosis and initiation of skin cancer.¹¹⁰ However, another researcher declared that IPL rejuvenation has no intrinsic carcinogenic potential and does not influence UV-induced carcinogenesis. Meanwhile, UV exposure influences the occurrence of relevant side effects after IPL rejuvenation in an animal model.¹¹¹ In another study, the author verified that the repeated use of IPL did not cause any toxicity in mice.¹¹² In addition, it has been only two decades since the first clinical application of IPL, and some patients require annual long-term treatment. Longer term observations are required to confirm these results (Table 3).

Table 3.

Case Reports of Applications and Side Effects of Intense Pulsed Light

Time	Application	Author
1989–1997	Venous-lake angioma	Jay and Borek¹¹⁴
1998–2003	Chronic facial erythema of systemic lupus erythematosus	Levy¹¹⁵
	Angioma serpiginosum	Cheng-Sheng et al.¹¹⁶
	Tufted angioma	Poenitz et al.¹¹⁷
2004–	Angiokeratomas of Fabry	Morais et al.¹¹⁸
	Refractory facial atopic dermatitis	Oh et al.¹¹⁹
	Faun tail nevus¹²⁰	Lee et al.
	Idiopathic cutaneous hyperchromia of the orbital region	Sasaya et al.¹²¹
	Solar lentigines of the hands	Cymbalista and Prado de Oliveira¹²²
	Peaud's orange cellulite	Fink et al.¹²³
	Pyogenic granuloma (satellitosis after carbon dioxide laser vaporization	Paradela et al.¹²⁴
	Hand warts	Kalil et al.¹²⁵
	Pigmented actinic lichen planus	Santos-Juanes et al.¹²⁶
	Lupus pernio	Rosende et al.¹²⁷
	Microstomia in scleroderma	Comstedt et al.¹²⁸
	Scrotal angiokeratomas	Ichikawa and Furue¹²⁹
	Dowling-Degos disease	Gupta and Huilgol¹³⁰
	Behcet's disease with superficial vascular involvement	Fioramonti et al.¹³¹
	Corneal deposition of pigments from cosmetic contact lenses	Sojin et al.¹³²
Side effects	IPL-induced iritis following treatment for a medial canthal capillary malformation	Crabb et al.¹³³
	Popular hyperplasia of the follicular infundibulum	Maria Leticia et al.¹³⁴
	Vitiligo	Shin et al.¹³⁵
	Sarcoidal granulomatous reaction to old cosmetic tattoos	Tourlaki et al.¹³⁶

Conclusions

IPL has become increasingly popular, especially in medical cosmetology, because it is noninvasive, allows multiple treatment targets, and produces good effects. Although the equipment is constantly improving, IPL hand pieces remain cumbersome because of the required integration of the lamp, filters, and cooling device. Operating a heavy hand piece leads to inflexibility and difficulty in maintaining uniform pressure on local skin areas during each pulse. Future research is expected to simplify the equipment further to produce small, portable devices.

Future devices should also provide more filter choices, such as two-way filters, or perhaps multiple filters that can control output wavelengths more precisely by omitting the shorter wavelengths and emitting a relatively narrow spectrum. Cooling systems could be designed to combine a variety of cooling methods to ensure that the skin temperature remains at a safe level and to improve the comfort of the procedure. In addition, an increasing number of patients require IPL treatment for areas other than the face. However, different areas of the skin have different thicknesses and structures, which require the development of more sophisticated pulse parameter settings. Local and overall treatment could be combined to supplement each other and improve efficacy, which is analogous to the concept of international medical precision.

IPL therapy alone is not sufficient to treat patients with complex skin problems. Photosensitizers are special chemicals that can be activated by absorbing photons; they then transmit the light energy to a target tissue that is not sensitive to visible light or they increase the photosensitive properties of the tissue. Thus, a photosensitizer can improve the precision of IPL chromophore targeting. The combination of IPL and PDT has been used successfully to treat acne, photoaging, PWS, and hair removal.^10,84,113

Other techniques, such as PSF and marking pigment lesions with a carbon-based ink pen, can also assist IPL and improve its efficacy. In the future, we expect the advent of more auxiliary methods. IPL can also be combined with other medical cosmetology technologies for rejuvenation, such as lasers and light source devices, radiofrequency, botulinum toxin, and fillers. The main question is the rational approach to applying combination therapies and choosing optimal treatment parameters. Further research will produce more favorable findings in the future.

All of the above approaches require professional diagnosis and operation by specialized physicians or operators who have been trained to avoid subjective error. We also expect further research to provide more long-term data about IPL applications.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

References

Gustavsson

. American Medical Bio Care. 1989. Available at: www.medicalbiocare.com/html/corporate.html (Last accessed March 22, 2016 ).

Goldman

. Treatment of benign vascular lesions with the photoderm VL high-intensity pulsed light source. Adv Dermatol, 1997; 13:503–521.

Patil

, Dhami

. Overview of lasers. Indian J Plast Surg, 2008; 41:S101–S113.

Herd

, Dover

, Arndt

. Basic laser principles. Dermatol Clin, 1997; 15:355–372.

Anderson

, Parish

. Selective photothermolysis: precise microsurgery by selective absorption of pulsed radiation. Science, 1983; 220:524–527.

Goldberg

. Laser- and light-based hair removal: an update. Expert Rev Med Devices, 2007; 4:253–260.

Battie

, Verschoore

. Cutaneous solar ultraviolet exposure and clinical aspects of photodamage. Indian J Dermatol Venereol Leprol, 2012; 78(Suppl 1):S9–S14.

Wat

, Wu

, Rao

, Goldman

. Application of intense pulsed light in the treatment of dermatologic disease: a systematic review. Dermatol Surg, 2014; 40:359–377.

Roberts

. Skin type classification systems old and new. Dermatol Clin, 2009; 27:529–533, viii.

10.

Ciocon

, Andreas

, Goldberg

. Intense pulsed light: what works, what's new, what's next. Facial Plast Surg, 2009; 25:290–300.

11.

Caerwyn

, Godfrey

, Peter

. Relevance of the structure of time-resolved spectral output to light-tissue interaction using intense pulsed light (IPL). Lasers Surg Med, 2008; 40:83–92.

12.

Adamic

, Troilius

, Adatto

, Drosner

, Dahmane

. Vascular lasers and IPLS: guidelines for care from the European Society for Laser Dermatology (ESLD). J Cosmet Laser Ther, 2007; 9:113–124.

13.

Goldman

, Eckhouse

. Photothermal sclerosis of leg veins. Dermatol Surg, 1996; 22:323–330.

14.

Raulin

, Weiss

, Schönermark

. Treatment of essential telangiectasias with an intense pulsed light source (PhotoDerm VL). Dermatol Surg, 1997; 23:941–945.

15.

Raulin

, Goldman

, Weiss

. Treatment of adult port-wine stains using intense pulsed light therapy (PhotoDerm VL): brief initial clinical report. Dermatol Surg, 1997; 23:594–597.

16.

Raulin

, Schroeter

, Weiss

, Keiner

, Werner

. Treatment of port-wine stains with a noncoherent pulsed light source: a retrospective study. Arch Dermatol, 1999; 135:679–683.

17.

Angermeier

. Treatment of facial vascular lesions with intense pulsed light. J Cutan Laser Ther, 1999; 1:95–100.

18.

Mark

, Sparacio

, Voigt

, Marenus

, Sarnoff

. Objective and quantitative improvement of rosacea-associated erythema after intense pulsed light treatment. Dermatol Surg, 2003; 29:600–604.

19.

Raulin

, Werner

, Hartschuh

, Schönermark

. Effective treatment of hypertrichosis with pulsed light: a report of two cases. Ann Plast Surg, 1997; 39:169–173.

20.

Gold

, Bell

, Foster

, Street

. Long-term epilation using the EpiLight broad band, intense pulsed light hair removal system. Dermatol Surg, 1997; 23:909–913.

21.

Bitter

. Noninvasive rejuvenation of photodamaged skin using serial, full-face intense pulsed light treatments. Dermatol Surg, 2000; 26:835–843.

22.

Weiss

, Weiss

, Marwaha

, Harrington

. Hair removal with a non-coherent filtered flashlamp intense pulsed light source. Lasers Surg Med, 1999; 24:128–132.

23.

Bjerring

, Cramers

, Egekvist

, Christiansen

, Troilius

. Hair reduction using a new intense pulsed light irradiator and a normal mode ruby laser. J Cutan Laser Ther, 2000; 2:63–71.

24.

Lor

, Lennartz

, Ruedlinger

. Patient satisfaction study of unwanted facial and body hair: 5 years experience with intense pulsed light. J Cosmet Laser Ther, 2002; 4:73–79.

25.

Johnson

, Dovale

. Intense pulsed light treatment of hirsutism: case reports of skin phototypes V and VI. J Cutan Laser Ther, 1999; 1:233–237.

26.

Radmanesh

, Mostaghimi

, Yousefi

, et al. Leukotrichia developed following application of intense pulsed light for hair removal. Dermatol Surg, 2002; 28:572–574.

27.

Gold

, Foster

, Bell

. Nevus spilus successfully treated with an intense pulsed light source. Dermatol Surg, 1999; 25:254–255.

28.

Bjerring

, Christiansen

. Intense pulsed light source for treatment of small melanocytic nevi and solar lentigines. J Cutan Laser Ther, 2001; 2:177–181.

29.

Kawada

, Shiraishi

, Asai

, et al. Clinical improvement of solar lentigines and ephelides with an intense pulsed light source. Dermatol Surg, 2002; 28:504–508.

30.

Kawada

, Asai

, Kameyama

, et al. Videomicroscopic and histopathological investigation of intense pulsed light therapy for solar lentigines. J Dermatol Sci, 2002; 29:91–96.

31.

Remington

, Remington

. Treatment of facial lentigines in Peutz-Jeghers syndrome with an intense pulsed light source. Dermatol Surg, 2002; 28:1079–1081.

32.

Moreno Arias

, Ferrando

. Intense pulsed light for melanocytic lesions. Dermatol Surg, 2001; 27:397–400.

33.

Cuerda-Galindo

, Díaz-Gil

, Palomar-Gallego

, Linares-Garcíavaldecasas

. Increased fibroblast proliferation and activity after applying intense pulsed light 800–1200 nm. Ann Anat, 2015; 198:66–72.

34.

Goldberg

, Cutler

. Nonablative treatment of rhytids with intense pulsed light. Lasers Surg Med, 2000; 26:196–200.

35.

Goldberg

, Samady

. Intense pulsed light and Nd:YAG laser non-ablative treatment of facial rhytids. Lasers Surg Med, 2001; 28:141–144.

36.

Kumaresan

, Srinivas

. Efficacy of IPL in treatment of acne vulgaris: comparison of single- and burst-pulse mode in IPL. Indian J Dermatol, 2010 Oct–Dec; 55:370–372.

37.

Weiss

, Weiss

, Beasley

. Rejuvenation of photoaged skin: 5 years results with intense pulsed light of the face, neck, and chest. Dermatol Surg, 2002; 28:1115–1119.

38.

Weiss

, Goldman

, Weiss

. Treatment of poikiloderma of Civatte with an intense pulsed light source. Dermatol Surg, 2000; 26:823–828.

39.

Goldman

, Weiss

. Treatment of poikiloderma of Civatte on the neck with an intense pulsed light source. Plast Reconstruct Surg, 2001; 107:1376–1381.

40.

Adatto

. Photorejuvenation of the forearms by treating hyperpigmented lesions with intense pulsed light source: a case report. J Cosmet Laser Ther, 2009; 5:117–119.

41.

, Chan

, Ying

, Chan

, Burd

, King

. Prospective study on the treatment of postburn hyperpigmentation by intense pulsed light. Lasers Surg Med, 2003; 32:42–45.

42.

Kontoes

, Vlachos

. Intense pulsed light is effective in treating pigmentary and vascular complications of CO(2) laser resurfacing. Aesthet Surg J, 2002; 22:489–491.

43.

Moreno-Arias

, Ferrando

. Noncoherent-intense-pulsed light for the treatment of relapsing hairy intradermal melanocytic nevus after shave excision. Lasers Surg Med, 2001; 29:142–144.

44.

Miyake

, Miyake

, Kauffman

. Skin temperature measurements during intense pulsed light emission. Dermatol Surg, 2001; 27:549–554.

45.

Friedmann

, Goldman

, Fabi

, Guiha

. The effect of multiple sequential light sources to activate aminolevulinic acid in the treatment of actinic keratoses: a retrospective study. J Clin Aesthet Dermatol, 2014; 7:20–25.

46.

Kassir

, Kolluru

, Kassir

. Intense pulsed light for the treatment of rosacea and telangiectasias. J Cosmet Laser Ther, 2011; 13:216–222.

47.

Lim

, Lee

, Won

, et al. The efficacy of intense pulsed light for treating erythematotelangiectatic rosacea is related to severity and age. Ann Dermatol, 2014; 26:491–495.

48.

Tsunoda

, Takahashi

, Ogino

, et al. Treatment of facial telangiectasia with a small spot of intense pulsed light: a case series of three patients. J Dermatol, 2014; 41:638–641.

49.

Nymann

, Hedelund

, Haedersdal

. Long-pulsed dye laser vs. intense pulsed light for the treatment of facial telangiectasias: a randomized controlled trial. J Eur Acad Dermatol Venereol, 2010; 24:143–146.

50.

Faurschou

, Togsverd-Bo

, Zachariae

, Haedersdal

. Pulsed dye laser vs. intense pulsed light for port-wine stains: a randomized side-by-side trial with blinded response evaluation. Br J Dermatol, 2009; 160:359–364.

51.

Babilas

, Schreml

, Hohenleutner

, Szeimies

, Landthaler

. Split-face comparison of intense pulsed light with short- and long-pulsed dye lasers for the treatment of port-wine stains. Lasers Surg Med, 2010; 42:720–727.

52.

, Lin

, Wu

, Zhou

, Gold

. Clinical analysis of port wine stains treated by intense pulsed light. J Cosmet Laser Ther, 2010; 12:2–6.

53.

Wang

, Wu

, Zhu

, et al. Treatment of neck port-wine stain with intense pulsed light in Chinese population. J Cosmet Laser Ther, 2013; 15:85–90.

54.

, Gold

, Sun

, Tang

, Wang

, Sheng

. Treatment of infantile hemangioma with optimal pulse technology. J Cosmet Laser Ther, 2010; 12:145–150.

55.

Caucanas

, Paquet

, Henry

, Piérard-Franchimont

, Reginster

M-A

, Piérard

. Intense pulsed-light therapy for proliferative haemangiomas of infancy. Case Pep Dermatol Med, 2011; 2011:253607.

56.

Wang

C-C

, Yuh-Mou

, Chih-Hsiung

, Chih-Kang

. A comparison of Q-switched alexandrite laser and intense pulsed light for the treatment of freckles and lentigines in Asian persons: a randomized, physician-blinded, split-face comparative trial. J Am Acad Dermatol, 2006; 54:804–810.

57.

Park

, Tsao

. Combined use of intense pulsed light and Q-switched ruby laser for complex dyspigmentation among asian patients. Lasers Surg Med, 2008; 40:128–133.

58.

Rusciani

, Motta

, Fino

, Menichini

. Treatment of poikiloderma of Civatte using intense pulsed light source: 7 years of experience. Dermatol Surg, 2008; 34:61–72.

59.

Kawasaki

, Kawana

. Efficacy and safety of a topical carbon suspension photoenhancer adjunctive to intense pulsed light treatment for pigmented lesions in Japanese patients: a pilot study. Laser Ther, 2014; 23:13–19.

60.

Shokeir

, El Bedewi

, Sayed

, El Khalafawy

. Efficacy of pulsed dye laser versus intense pulsed light in the treatment of striae distensae. Dermatol Surg, 2014; 40:632–640.

61.

Aldhalimi

, Abo Nasyria

. A comparative study of the effectiveness of intense pulsed light wavelengths (650 nm vs 590 nm) in the treatment of striae distensae. J Cosmet Laser Ther, 2013; 15:120–125.

62.

Lisa

, Sabrina

, Goldman

. Treatment of melasma and the use of intense pulsed light: a review. J Drugs Dermatol, 2012; 11:1316–1320.

63.

Figueiredo Souza

, Trancoso Souza

. Single-session intense pulsed light combined with stable fixed-dose triple combination topical therapy for the treatment of refractory melasma. Dermatol Ther, 2012; 25:477–480.

64.

Cunha

, Pinto

, Mattos

, Cabrini

, Tolosa

. New insight in the treatment of refractory melasma: laser Q-switched Nd:YAG non-ablative fractionated followed by intense pulsed light. Dermatol Ther, 2015; 28:296–299.

65.

Yun

, Moon

, Lee

, Choi

, Chang

. Combination treatment of low-fluence 1,064-nm Q-switched Nd:YAG laser with novel intense pulse light in Korean melasma patients: a prospective, randomized, controlled trial. Dermatol Surg, 2014; 40:842–850.

66.

Yun

, Lee

, Han

, et al. A prospective, split-face, randomized study of the efficacy and safety of a novel fractionated intense pulsed light treatment for melasma in Asians. J Cosmet Laser Ther, 2015; 17:1–25.

67.

Chung

, Choi

, Lee

, Cho

, Lee

. Pulse in pulse intense pulsed light for melasma treatment: a pilot study. Dermatol Surg, 2014; 40:162–168.

68.

Sardana

, Garg

. Lasers are not effective for melasma in darkly pigmented skin. J Cuten Aesthet Surg, 2014 Jan; 7:57–60.

69.

Mcgill

, Hutchison

, McKenzie

, Mcsherry

, Mackay

. A randomised, split-face comparison of facial hair removal with the alexandrite laser and intense pulsed light system. Lasers Surg Med, 2007; 39:767–772.

70.

Rezvanian

, Adibi

, Siavash

, Kachuei

, Shojaee-Moradie

, Asilian

. Increased insulin sensitivity by metformin enhances intense-pulsed-light-assisted hair removal in patients with polycystic ovary syndrome. Dermatology, 2009; 218:231–236.

71.

Cameron

, Ibbotson

, Dawe

, Ferguson

, Moseley

. Within-patient right-left blinded comparison of diode (810 nm) laser therapy and intense pulsed light therapy for hair removal. Lasers Med Sci, 2008; 23:393–397.

72.

Klein

, Steinert

, Baeumler

, Landthaler

, Babilas

. Photoepilation with a diode laser vs. intense pulsed light: a randomized, intrapatient left-to-right trial. Br J Dermatol, 2013; 168:1287–1293.

73.

Jian

, Xiu-Jun

, Meng-Hua

. Split-leg comparison of low fluence diode laser and high fluence intense pulsed light in permanent hair reduction in skin types III to IV. Australas J Dermatol, 2012; 53:186–189.

74.

Ormiga

, Ishida

, Boechat

, Ramos-E-Silva

. Comparison of the effect of diode laser versus intense pulsed light in axillary hair removal. Dermatol Surg, 2014; 40:1061–1069.

75.

Emerson

, Town

. Hair removal with a novel, low fluence, home-use intense pulsed light device. J Cosmet Laser Ther, 2009; 11:98–105.

76.

Hedelund

, Due

, Bjerring

, Wulf

, Haedersdal

. Skin rejuvenation using intense pulsed light: a randomized controlled split-face trial with blinded response evaluation. Arch Dermatol, 2006; 142:985–990.

77.

El-Domyati

, El-Ammawi

, Moawad

, Medhat

, Mahoney

, Uitto

. Intense pulsed light photorejuvenation: a histological and immunohistochemical evaluation. J Drugs Dermatol, 2011; 10:1246–1252.

78.

Yang

, Xiang

, Gold

. 5-Aminolevulinic acid-based photodynamic intense pulsed light therapy shows better effects in the treatment of skin photoaging in asian skin: a prospective, single-blinded, controlled trial. J Clin Aesthet Dermatol, 2010; 3:40–43.

79.

Dover

, Bhatia

, Brigitte

, Arndt

. Topical 5-aminolevulinic acid combined with intense pulsed light in the treatment of photoaging. Arch Dermatol, 2005; 141:1247–1252.

80.

Freedman

. Topical antioxidant application augments the effects of intense pulsed light therapy. J Cosmet Dermatol, 2009; 8:254–259.

81.

Taub

. A comparison of intense pulsed light, combination radiofrequency and intense pulsed light, and blue light in photodynamic therapy for acne vulgaris. J Drugs Dermatol, 2007; 6:1010–1016.

82.

Choi

, Suh

, Yoon

, Min

, Lee

, Suh

. Intense pulsed light vs. pulsed-dye laser in the treatment of facial acne: a randomized split-face trial. J Eur Acad Dermatol Venereol, 2009; 24:773–780.

83.

Lee

, Lim

, Shin

, Suh

, Lee

, Kim

. An open-label, split-face trial evaluating efficacy and safty of photopneumatic therapy for the treatment of acne. Ann Dermatol, 2009; 13:99–110.

84.

Omi

. Photopneumatic technology in acne treatment and skin rejuvenation: histological assessment. Laser Ther, 2012; 21:113–123.

85.

Erol

, Gurlek

, Agaoglu

, Topcuoglu

, Oz

. Treatment of hypertrophic scars and keloids using intense pulsed light (IPL). Aesthetic Plast Surg, 2008; 32:902–909.

86.

Sarkar

, Dewangan

, Bain

, et al. Effect of intense pulsed light on immature burn scars: a clinical study. Indian J Plast Surg, 2014; 47:381–385.

87.

Shamsi Meymandi

, Rezazadeh

, Ekhlasi

. Studying intense pulsed light method along with corticosteroid injection in treating keloid scars. Iran Red Crescent Med J, 2014; 16:e12464.

88.

Kim

, Park

, Yoon

, Cho

. Efficacy of IPL device combined with intralesional corticosteroid injection for the treatment of keloids and hypertrophic scars with regards to the recovery of skin barrier function: a pilot study. J Dermatolog Treat, 2015:481–484.

89.

Hultman

, Friedstat

, Edkins

. Efficacy of intense pulsed light for the treatment of burn scar dyschromias: a pilot study to assess patient satisfaction, safety, and willingness to pay. Ann Plast Surg, 2015; 74(Suppl 4):S204–S208.

90.

Toyos

, Mcgill

, Briscoe

. Intense pulsed light treatment for dry eye disease due to meibomian gland dysfunction; a 3-year retrospective study. Photomed Laser Surg, 2015; 33:41–46.

91.

Craig

, Yen-Heng

, Turnbull

. Prospective trial of intense pulsed light for the treatment of meibomian gland dysfunction. Invest Ophthalmol Vis Sci, 2015; 56:1965–1970.

92.

Shirakawa

, Ozawa

, Tateishi

, Fujii

, Sakahara

, Ishii

. Intense pulsed light therapy for aberrant Mongolian spots. Osaka City Med J, 2012; 58:59–65.

93.

Tawfik

. Novel treatment of nail psoriasis using the intense pulsed light: a one-year follow-up study. Dermatol Surg, 2014; 40:763–768.

94.

Murad

, Dover

, Arndt

. Treatment of facial telangiectasia with variable-pulse high-fluence pulsed-dye laser: comparison of efficacy with fluences immediately above and below the purpura threshold. Dermatol Surg, 2003; 29:681–685.

95.

Iyer

, Carranza

, Kolodney

, Macgregor

, Chipps

, Soriano

. Evaluation of procollagen I deposition after intense pulsed light treatments at varying parameters in a porcine model. J Cosmet Laser Ther, 2007; 9:75–78.

96.

Wang

, Liu

, Yuan

, Du

. Effect of intense pulsed light on transforming growth factor-beta1 mRNA expression in rat skin [in Chinese]. Nan Fang Yi Ke Da Xue Xue Bao, 2009; 29:92–93, 96.

97.

Florence

, Céline

, Thierry

, et al. Repeated exposure of human skin fibroblasts to UVB at subcytotoxic level triggers premature senescence through the TGF-beta1 signaling pathway. J Cell Sci, 2005; 118:743–758.

98.

Dan

, Yan

, Di

, Yang

, Chen

, Xue

. Impact of intense pulse light irradiation on BALB/c mouse skin-in vivo study on collagens, matrix metalloproteinases and vascular endothelial growth factor. Lasers Med Sci, 2009; 24:101–108.

99.

Ohnishi

, Tajima

, Akiyama

, Ishibashi

, Kobayashi

, Horii

. Expression of elastin-related proteins and matrix metalloproteinases in actinic elastosis of sun-damaged skin. Arch Dermatol Res, 2000; 292:27–31.

100.

Cuerda-Galindo

, Díaz-Gil

, Palomar-Gallego

, Linares-Garcíavaldecasas

. Intense pulsed light induces synthesis of dermal extracellular proteins in vitro. Lasers Med Sci, 2015; 30:1–9.

101.

Wong

, Shyu

, Tsai

, Hsu

, Lee

, Pang

. Intense pulsed light modulates the expressions of MMP-2, MMP-14 and TIMP-2 in skin dermal fibroblasts cultured within contracted collagen lattices. J Dermatol Sci, 2008; 51:70–73.

102.

Okamoto

, Akaike

, Maeda

. Activation mechanism of matrix metalloproteinases. Biol Chem, 1997; 378:151–160.

103.

Shin

, Lee

, Oh

, Kim do

, Kim

, Jung

, Lee

. Altered vimentin protein expression in human dermal microvascular endothelial cells after ultraviolet or intense pulsed light treatment. Lasers Surg Med, 2014; 46:431–438.

104.

Lask

, Friedman

, Elman

, Fournier

, Shavit

, Slatkine

. Pneumatic skin flattening (PSF): a novel technology for marked pain reduction in hair removal with high energy density lasers and IPLs. J Cosmet Laser Ther, 2006; 8:76–81.

105.

Mohammad

, Mohsen

, Arash

, Naderi

. Burning, paradoxical hypertrichosis, leukotrichia and folliculitis are four major complications of intense pulsed light hair removal therapy. J Dermatol Treat, 2008; 19:360–363.

106.

Negishi

, Kushikata

, Tezuka

, Takeuchi

, Miyamoto

, Wakamatsu

. Study of the incidence and nature of very subtle epidermal melasma in relation to intense pulsed light treatment. Commentary. Dermatol Surg, 2004; 30:881–886.

107.

Haedersdal

. Potential risks of non-physicians' use of lasers and intense pulsed light in dermatology [in Danish]. Ugeskr Laeger, 2005; 167:4095–4097.

108.

Beyer

1, Wulf

, Stender

, Haedersdal

. Treatment by non-physicians of skin diseases—including potentially malignant diseases with lasers and intense pulsed light [in Danish]. Ugeskr Laeger, 2006; 168:3899–3902.

109.

Hammes

, Karsai

, Metelmann

, et al. Treatment errors resulting from use of lasers and IPL by medical laypersons: results of a nationwide survey. J Dtsch Dermatol Ges, 2013; 11:149–156.

110.

El-Domyati

1, El-Ammawi

, Medhat

, Moawad

, Mahoney

, Uitto

. Expression of p53 protein after nonablative rejuvenation: the other side of the coin. Dermatol Surg, 2013; 39:934–943.

111.

Hedelund

, Lerche

, Wulf

, Haedersdal

. Carcinogenesis related to intense pulsed light and UV exposure: an experimental animal study. Lasers Med Sci, 2006; 21:198–201.

112.

Chan

, Yang

, Leung

, Wei

, Lai

. An animal study of the effects on p16 and PCNA expression of repeated treatment with high-energy laser and intense pulsed light exposure. Lasers Surg Med, 2007; 39:8–13.

113.

Nevien

, Maha

. Topical liposomal Rose Bengal for photodynamic white hair removal: randomized, controlled, double-blind study. J Drugs Dermatol, 2014; 13:436–442.

114.

Jay

, Borek

. Treatment of a venous-lake angioma with intense pulsed light. Lancet, 1998; 351:112.

115.

Levy

. Intense pulsed light treatment for chronic facial erythema of systemic lupus erythematosus: a case report. J Cutan Laser Ther, 2000; 2:195–198.

116.

Cheng-Sheng

, Li-Cheng

, Hong-Shang

, Yue-Zon

. Treatment of a tufted angioma with intense pulsed light. J Dermatol Treat, 2007; 18:109–111.

117.

Poenitz

, Koenen

, Utikal

, Goerdt

. Angioma serpiginosum following the lines of Blaschko—an effective treatment with the IPL technology [in German]. J Dtsch Dermatol Ges, 2006; 4:650–653.

118.

Morais

, Santos

, Baudrier

, Mota

, Oliveira

, Azevedo

. Angiokeratomas of Fabry successfully treated with intense pulsed light. J Cosmet Laser Ther, 2008; 10:218–222.

119.

, Bae

, Kim

, Kwon

, Lee

. Effective treatment of facial redness caused by atopic dermatitis using intense pulsed light systems. Dermatol Surg, 2010; 36:475–482.

120.

Lee

, Rho

, Kim

. A case of faun tail naevus treated by intense pulsed light. Ann Dermatol, 2009; 21:147–149.

121.

Sasaya

, Kawada

, Wada

, Hirao

, Oiso

. Clinical effectiveness of intense pulsed light therapy for solar lentigines of the hands. Dermatol Ther, 2011; 24:584–586.

122.

Cymbalista

, Prado de Oliveira

. Treatment of idiopathic cutaneous hyperchromia of the orbital region (ICHOR) with intense pulsed light. Dermatol Surg, 2006; 32:773–784.

123.

Fink

, Harold

, Andrew

, Robert

. Use of intense pulsed light and a retinyl-based cream as a potential treatment for cellulite: a pilot study. J Cosmet Dermatol, 2006; 5:254–262.

124.

Paradela

, del Pozo

, Martínez

, et al. Pyogenic granuloma: satellitosis after carbon dioxide laser vaporization resolved with an intense pulsed light system. Dermatol Surg, 2007; 33:104–108.

125.

Kalil

, Salenave

, Cignachi

. Hand warts successfully treated with topical 5-aminolevulinic acid and intense pulsed light. Eur J Dermatol, 2008; 18:207–208.

126.

Santos-Juanes

, Mas-Vidal

, Coto-Segura

, Sánchez del Río

, Galache Osuna

. Pigmented actinic lichen planus successfully treated with intense pulsed light. Br J Dermatol, 2010; 163:662–663.

127.

Rosende

, Pozo

, Andrés

, Varela

. Intense pulsed light therapy for lupus pernio [in Spanish]. Actas Dermosifiliogr, 2012; 103:71–73.

128.

Comstedt

, Svensson

, Troilus

. Improvement of microstomia in scleroderma after intense pulsed light: a case series of four patients. J Cosmet Laser Ther, 2012 Apr; 14:102–106.

129.

Ichikawa

, Furue

. Successful treatment of scrotal angiokeratomas (Fordyce type) with small-spot narrow-band intense pulsed light. Dermatol Surg, 2013 Oct; 39:1547–1548.

130.

Gupta

, Huilgol

. Successful treatment of Dowling-Degos disease using intense pulsed light. Australas J Dermatol, 2014; 56:e63–e65.

131.

Fioramonti

, Fino

, Ponzo

, Ruggieri

, Onesti

. Intense pulsed light in the treatment of telangiectasias: case report of Behcet's disease with superficial vascular involvement. J Cosmet Laser Ther, 2014; 16:124–128.

132.

Sojin

, Jong Rak

, Taehyung

. Pigment deposition of cosmetic contact lenses on the cornea after intense pulsed-light treatment. Korean J Ophthalmol, 2010; 24:367–370.

133.

Crabb

, Weng

, Taranath

, Huilgol

. Intense pulsed light therapy (IPL) induced iritis following treatment for a medial canthal capillary malformation. Australas J Dermatol, 2014; 55:289–291.

134.

Maria Leticia

, Silva

ACR

, Maeda

DEM

, Fernanda

. Papular hyperplasia of the follicular infundibulum after intense pulsed light treatment for photoaging. Dermatol Surg, 2009; 35:2046–2049.

135.

Shin

, Roh

, Lee

. Vitiligo following intense pulsed light treatment. J Dermatol, 2010; 37:674–676.

136.

Tourlaki

, Boneschi

, Tosi

, Pigatto

, Brambilla

. Granulomatous tattoo reaction induced by intense pulse light treatment. Photodermatol Photoimmunol Photomed, 2010; 26:275–276.