Laser and Other Light Therapies for the Treatment of Acne Vulgaris: Systematic Review

F.L. Hamilton; J. Car; C. Lyons; M. Car; A. Layton; A. Majeed

The British Journal of Dermatology. 2009;160(6):1273-1285.

Abstract and Introduction

Abstract

Background: Acne is common and can lead to scarring of the skin, as well as to psychological distress and reduced self-esteem. Most topical or oral treatments for acne are inconvenient and have side-effects. Laser and other light therapies have been reported to be convenient, safe and effective in treating acne.
Objectives: To carry out a systematic review of randomized controlled trials of light and laser therapies for acne vulgaris.
Methods: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, PsycInfo, LILACS, ISI Science Citation Index and Dissertation Abstracts International for relevant published trials.
Results: We identified 25 trials (694 patients), 13 of light therapy and 12 of light therapy plus light-activated topical cream (photodynamic therapy, PDT). Overall, the results from trials of light alone were disappointing, but the trials of blue light, blue-red light and infrared radiation were more successful, particularly those using multiple treatments. Red-blue light was more effective than topical 5% benzoyl peroxide cream in the short term. Most trials of PDT showed some benefit, which was greater with multiple treatments, and better for noninflammatory acne lesions. However, the improvements in inflammatory acne lesions were not better than with topical 1% adapalene gel, and the side-effects of therapy were unacceptable to many participants.
Conclusions: Some forms of light therapy were of short-term benefit. Patients may find it easier to comply with these treatments, despite the initial discomfort, because of their short duration. However, very few trials compared light therapy with conventional acne treatments, were conducted in patients with severe acne or examined long-term benefits of treatment.

Introduction

Acne has a prevalence of 70-90% among teenagers^[1,2] and some people continue to have acne in adult life. It can lead to low self-esteem, loss of confidence and depression.^[3] It can even affect productivity and employability,^[4] and quality of life scales have assessed the impact of acne as similar to epilepsy or asthma.^[3] Scarring of the skin is also common and is difficult to treat.^[5]

Conventional treatments for acne tend to be inconvenient and associated with side-effects and this has prompted a search for more acceptable therapies. Acne often improves after exposure to sunlight, and this observation has led to the development of laser and other light therapies.^[6,7] These are thought to work either by killing Propionibacterium acnes directly or by selectively damaging sebaceous glands, depending on the wavelength of light used.

Propionibacterium acnes produces porphyrins which absorb light to form singlet oxygen radicals, which are highly reactive and kill the bacteria.^[8] Peak absorption occurs at 415 nm, in the middle of the blue light wavelengths.^[8,9] Green light is also absorbed by porphyrins and penetrates deeper into the skin.^[7] Red light is less effective at activating porphyrins but penetrates even more deeply into the skin, where it may have a direct effect on inflammatory mediators.^[10] Infrared lasers, radiofrequency devices and low-energy pulsed dye lasers are thought to improve acne by thermally damaging sebaceous glands directly.^[11,12]

Photodynamic therapy (PDT) uses light-activated creams which are absorbed into the pilosebaceous unit to amplify the response to light therapy. These agents include methyl aminolaevulinate (MAL),^[13,14] 5-aminolaevulinic acid (ALA)^[15,16] and indocyanine green.^[17] PDT tends to be more painful than light alone, and more likely to produce erythema, oedema, initial worsening of acne, crusting and epithelial exfoliation. The severity of side-effects depends partly on skin type,^[18] as melanocytes absorb light due to their pigment.

Optical therapies are generally not available through the National Health Service in the U.K., or from health insurance companies, so patients access them through private providers. Estimating the U.K. market for these procedures is difficult because there is no current requirement for external audit. The largest subsector of this category is optical therapy, but available figures combine all acne, hair removal and skin rejuvenation treatments. A recent Mintel report^[19] suggests that approximately 166 000 treatments were carried out in 2005, representing a market value of about £42 million, but this is likely to be an underestimate. Similarly, in the U.S.A. there are no accurate centrally available figures for light therapy, but the American Society for Aesthetic Plastic Surgery^[20] estimates that 576 509 'laser skin resurfacing' procedures were carried out in 2006 at a cost of around $610 million.

Clearly, patients are prepared to spend large sums of money on optical therapies for the treatment of acne. However, to date, the trials of light therapy have been small and the results conflicting. Given that people with moderate to severe inflammatory acne are vulnerable to commercial exploitation, it is important to review systematically the available evidence to determine to what extent laser and other light treatments improve acne.

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Table 1. Trials Investigating the Effect of Light Therapy Compared with Placebo as Control
Study (first author and year)	Participants	Intervention	Primary outcome measures	Results
Baugh (2005)^[28]	25 (4 M, 21 F) age 19-41 years (mean 27.8), diagnosed with mild to moderate inflammatory facial acne; Fitzpatrick skin types I-III	532 nm pulsed laser vs. sham in a split-face trial, both with skin cooling system; two exposures/week for 2 weeks. Assessed at 1 and 4 weeks post-treatment	1. Change in Michaelsson acne severity score	No significant difference in mean Michaelsson score between treated and control sides of the faces at 4 weeks. Majority of satisfaction scores for participants and assessor were 70-79% at 4 weeks
Baugh (2005)^[28]			2. Nonstandardized satisfaction scale (participant and assessor rated)
Bowes (2003)^[24]	11 (M/F proportion not given) with mild to moderate acne; skin types not given	532 nm pulsed laser vs. sham in a split-face trial, both with skin cooling system; two treatments weekly for 2 weeks; assessed at 1 week and 1 month after final treatment	Change in Michaelsson acne severity score	Acne scores on the light treatment side reduced by 33.9% and 35.9% at 1 week and 1 month, respectively, vs. no change and 11.8% increase on the control side
Elman (2003)^[30]	23 (11 M, 12 F), mean age 18.8 years (range not given) with papulopustular acne; skin types not documented	405-420 nm laser with skin cooling in a split-face trial, twice weekly for 4 weeks, assessed at each treatment and at 2, 4, and 8 weeks after treatment	Change in inflammatory lesion count	Significantly better median reduction in inflammatory lesion count on the treated side (53% at 8 weeks, P = 0.01 using McNemar test)
Jih (2006)^[25]	20 (10 M, 10 F) age 18-39 years (mean 23) with active inflammatory facial acne; Fitzpatrick skin types II-VI	1450 nm diode laser in a split-face trial using anaesthetic cream and 14 J cm^-2 in one group and 16 J cm^-2 in the second, with three treatments given at 3-4 week intervals, assessed at 1, 3, 6 and 12 months after final treatment	Change in inflammatory lesion count	Light therapy significantly reduced mean lesion count in both groups compared with control with reductions in inflammatory lesions after the third treatment of 75.1% for the lower intensity side and 70.6% for the higher intensity side, maintained at 12 months (P < 0.01) but no significant difference between the different light intensities
Na (2007)^[33]	30 (7 M, 23 F) age 19-33 years (mean 23.6) with mild to moderate acne; skin types not documented	635-670 nm portable red light device in a split-face trial, self-administered to the treatment side twice daily for 8 weeks; assessed at weeks 1, 2, 4 and 8 after treatment	Change in lesion count	59% reduction in noninflammatory lesions on the treatment side compared with 3% increase on control side (P < 0.05); 66% reduction in inflammatory lesions on the treatment side compared with 74% increase on control side (P < 0.05) at week 8
Orringer (2004)^[23]	40 (24 M, 16 F) age 13-31 years (mean 20.7) with clinically evident facial acne; skin types described: white (28), Asian (7), black (2), unknown (3)	585 nm pulsed dye laser in a split-face trial, single treatment and two treatment (2 weeks apart) groups, assessed at 2, 4, 6, 8, 10 and 12 weeks after final treatment	1. Change in inflammatory lesion count	Reduction in mean papule count was 39% on the treatment side vs. 25% on the control side; reduction for pustules was 0 on the treatment side vs. 31% on the control side. There was no significant difference between the treatment and control groups for either outcome measure
Orringer (2004)^[23]			2. Change in Leeds acne severity score
Orringer (2007)^[27]	46 (10 M, 36 F) mean age 23.9 years (range not reported) with clinically apparent active facial acne; Fitzpatrick skin types II-VI	1320 nm Nd:YAG laser in a split-face trial with cooling; three treatments at 3-week intervals; assessed 7 and 14 weeks after treatment	Change in modified Leeds score (global acne severity score)	27% reduction in open comedones on the treated side at week 7 (P = 0.04) compared with 12% increase on the control side. No significant difference in counts of other lesion types or overall acne severity
Papageorgiou (2000)^[10]	30 participants, mean age 24.8 years in blue-red light group; 25 participants, mean age 25.6 years in white light control group; randomized from the original 107 recruited (33 M, 74 F, age 14-50 years), all with mild to moderate acne; skin types not stated	415 nm plus 660 nm light vs. cool white light; treated daily for 12 weeks; assessed every 4 weeks for the 12-week treatment period	Change in inflamed and noninflamed lesion counts	Blue-red light was superior to white light at all time points (P = 0.001); inflammatory lesion counts reduced by 75% vs. 25%
Seaton (2003)^[11]	41 (15 M, 26 F), 31 age 23-32 years (mean 26) in the treatment group and 10 age 20-36 years (mean 31) in the control group, all with mild to moderate facial acne; Fitzpatrick skin types I-IV; described as white (23), Asian (6), African-Caribbean (2)	585 nm pulsed dye laser vs. sham laser, parallel groups trial, single treatment, assessed at 2, 4, 8 and 12 weeks after treatment	1. Change in lesion count	Significantly greater improvement in the intervention group; Leeds score reduced from 3.8 to 1.9 vs. 3.6 to 3.5 in control group (P = 0.007); 49% reduction in inflammatory lesions vs. 10% (P = 0.024)
Seaton (2003)^[11]			2. Change in Leeds acne severity score
Tzung (2004)^[35]	31 (28 completed: 10 M, 18 F age 15-32 years, mean 20.79) with mild to moderate acne; all Taiwanese; Fitzpatrick skin types III-IV	420 nm light in a split-face trial, twice weekly for four consecutive weeks, assessed after each treatment and at 1 month after final treatment	Change in Michaelsson acne severity score	Light therapy was significantly more effective than control at 8 weeks (52% improvement vs. 12%, P = 0.009)

Nd:YAG, neodymium:yttrium-aluminium-garnet.

Table 2. Trials Comparing the Effect of Light Therapy with Topical Treatment
Study (first author and year)	Participants	Intervention	Primary outcome measures	Results
Chang (2007)^[36]	30 women age 23-32 years (mean 25.7) with mild to moderate acne; all Korean; skin types not documented	IPL with 530-750 nm filter with cooling gel in a split-face trial, three sessions, 3 weeks apart, benzoyl peroxide gel used on both sides of the face. Assessed 3 weeks after final treatment	Change in Korean acne grading system	All patients experienced improvement in acne lesions on both sides of the face and there was no significant difference between the two sides
Gold (2005)^[9]	34 (25 completed the trial, 3 M and 22 F) age 13-55 years (mean 31.0) with mild to moderate acne; skin types described: Caucasian (16), African-American (7), American-Indian (1), Chinese (1); 13 participants in clindamycin group and 12 in blue light group	417 nm (blue light) twice weekly for 4 weeks vs. self-administered topical clindamycin 1% twice daily, parallel groups, assessed at 4 weeks after final treatment	1. Change in noninflammatory and inflammatory lesion count	Inflammatory lesion counts improved by 14% in the clindamycin group vs. 36% in the blue light group. Improvement and global scores reported as similar for both groups (figures not given in paper). No statistically significant difference between the groups
			2. Change in global severity score
			3. Overall improvement score
Papageorgiou (2000)^[10]	30 participants, mean age 24.8 years in blue-red light group and 25 participants, mean age 26.7 years in the benzoyl peroxide group, randomized from the original 107 recruited (33 M, 74 F, age 14-50 years) all with mild to moderate acne; skin types not stated	415 nm plus 660 nm light vs. 5% benzoyl peroxide, parallel groups, treated daily; assessed every 4 weeks for the 12-week treatment period	Change in inflamed and noninflamed lesion counts	Blue-red light was superior to benzoyl peroxide at week 8, 75% vs. 60% improvement (P = 0.02), and week 12 (P = 0.006)

IPL, intense pulsed light.

Table 3. Other Trials of Light Therapies
Study (first author and year)	Participants	Intervention	Primary outcome measures	Results
Papageorgiou (2000)^[10]	30 participants, mean age 24.8 years in blue-red light group; 27 participants, mean age 23.4 years in blue light group, randomized from the original 107 recruited (33 M, 74 F, age 14-50 years), all with mild to moderate acne; skin types not stated	Comparison of light of different wavelengths: 415 nm plus 660 nm light vs. blue light, treated daily for 12 weeks; assessed every 4 weeks for the 12-week treatment period	Change in inflamed and noninflamed lesion counts	Significant difference in inflamed lesion counts between blue-red light and blue light at week 4 (P = 0.02) and week 8 (P = 0.02) but not at week 12 (P = 0.10)
Wang (2006)^[31]	20 (7 M, 13 F) age 19-59 years (mean 34.3) with active inflammatory facial acne; Fitzpatrick skin types II-IV	1450 nm diode laser plus microdermabrasion in a split-face design with light treatment on the control side of the face with topical anaesthetic to whole face; four treatments, 3 weeks apart; assessed at 6 and 12 weeks after the final treatment	Change in lesion scores	Light treatment alone decreased the mean acne lesion count by 53.5% at 3 weeks, 52.8% by 6 weeks and 54.4% by 12 weeks (P < 0.02 compared with baseline counts). Microdermabrasion plus light treatment reduced the counts by 55.6% after 3 weeks, 53.5% by 6 weeks and 61.1% by 12 weeks (P < 0.05 compared with baseline counts). There was no statistically significant difference between the two treatments at any point

Table 4. Trials Comparing the Effect of Photodynamic Therapy (PDT) with Light Therapy Alone as Control
Study (first author and year)	Participants	Intervention	Primary outcome measures	Results
Genina (2004)^[17]	12 (5 M, 7 F) age 17-27 years (mean age not given) with light to severe acne on the face or back; skin types not stated	803 nm low-intensity diode laser ± ICG, single (8 participants) and multiple (4 participants) treatment groups, multiple treatment group had two treatments/week for 4 weeks, assessed 1 week and 1 month after treatment	Change in inflammatory lesion counts	23% improvement at 4 weeks for the single treatment group vs. 7% for control; 80% improvement at 4 weeks for the multiple treatment group vs. no improvement for control. More improvement was seen in participants with severe acne
Haedersdal (2008)^[32]	15 (5 M, 10 F) age 18-31 years (median 18), with at least 12 facial inflammatory acne lesions; Fitzpatrick skin type I-III	Split-face design with nonpurpuric LPDL 595 nm full-face treatment and MAL cream applied to randomized side of the face for 3 h before laser exposure, with dynamic cooling device; three treatments at 2-week intervals; assessed 4 and 12 weeks after final treatment	1. Change in lesion count	Significantly greater reduction in inflammatory lesions with MAL-LPDL vs. LPDL at weeks 4 (P = 0.03) and 12 (P = 0.004) with up to 80% reduction. Noninflammatory lesions reduced more on the MAL-LPDL side but did not achieve statistical significance. Patient satisfaction was slightly higher with the MAL-LPDL treatment but also did not achieve statistical significance
Haedersdal (2008)^[32]			2. Patient satisfaction score
Hongcharu (2000)^[16]	22 participants, age 18-44 years; 11 in single treatment group, mean age 30 years, 9 M, 2 F; 11 in multiple treatment group, mean age 27 years, 8 M, 3 F; all with mild to moderate acne of the back; Fitzpatrick skin types I-IV	Four areas on the back of each participant: 550-700 nm light source used. ALA-light; ALA alone; light alone; untreated control. Single and multiple treatment groups, assessed at 1, 2, 3, 10 and 20 weeks	1. Change in modified Michaelsson acne score	In both groups the ALA-PDT area showed improvement; single treatment from week 3 up to week 20 and multiple treatment from week 1 to week 20 (P < 0.05). Multiple ALA-PDT and multiple ALA treatment sites showed more improvement than single treatment (P < 0.001 and P = 0.007, respectively). Improvements for single and multiple treatments were in the range 50-75%
Hongcharu (2000)^[16]			2. Global clinical improvement
Hörfelt (2006)^[13]	30 (25 M, 5 F) age 15-28 years (mean 18) with moderate inflammatory facial acne (Leeds score 5-10); Fitzpatrick skin types I-III	653 nm light plus MAL vs. placebo cream and light in a split-face trial, two treatments, 2 weeks apart, assessed at 4 and 10 weeks after treatment	1. Change in lesion counts	MAL-PDT significantly more effective than light alone at weeks 4 (P = 0.0004) and 10 (P = 0.00049); overall > 50% improvement in acne with treatment compared with control
Hörfelt (2006)^[13]			2. Change in global severity
Pollock (2004)^[37]	10 (9 M, 1 F) age 16-40 years (mean 26.9) with mild to moderate acne of the back; skin types not stated	Four equal 30 cm² areas on the back: 635 nm light plus ALA vs. light alone; ALA alone; untreated control; treated weekly for 3 weeks, assessed at each treatment and 3 weeks after final treatment	1. Change in lesion count	Statistically significant reduction from baseline in inflammatory acne lesion counts from second treatment (P < 0.005) at the ALA-PDT site but not the other sites: reduction in acne was 69% at 21 days follow up
Pollock (2004)^[37]			2. Overall treatment response
Rojanamatin (2006)^[21]	14 (4 M, 10 F) age 16-27 years (mean age not reported) with active inflammatory facial acne; Fitzpatrick skin types III-V	550-700 nm light plus ALA vs. light alone in a split-face trial, three treatments at 3- or 4-week intervals, assessed at each treatment, 3 and 12 weeks after last treatment	1. Change in lesion count	Improvement on both sides; ALA-PDT side lesions decreased significantly after first treatment, maintained at 12 weeks (P < 0.01); light side only also improved from baseline after the second treatment, maintained at 12 weeks (P < 0.01); 87.7% reduction in mean acne lesion count at 12 weeks with ALA-PDT vs. 66.8% reduction at 12 weeks with light alone (P < 0.05). All patients reported improvement; 11/14 rated the improvement greater than 75%
Rojanamatin (2006)^[21]			2. Global clinical improvement assessed by patient
Tuchin (2003)^[26]	22 (11 M, 11 F) age 16-29 years (mean age not given) randomized to: six participants in preliminary control group; 12 in ICG plus low light intensity group; four in ICG plus medium light intensity. Participants had light to severe acne of the face or back; skin types not stated	Split-face or split-back design. Low intensity group (mild to moderate acne) received one to four treatments with 803 nm light, intensity depended on grade of acne; medium intensity group (moderate to severe acne) received eight or nine treatments twice weekly. The control group received one to three treatments with ICG alone or light alone. Participants were assessed every 2 weeks for 1 month after treatment	1. Change in Leeds acne score for all groups	No improvement for ICG alone or light alone, 'significant' improvement reported for the low intensity group compared with control, better with multiple treatments and for the more severe cases; 'significant' improvement for the medium intensity group compared with control, from 67% to 83% reduction in lesions, sustained at 1 month after treatment. Confusing description of interventions and outcomes for different groups. Data given only for the four participants in the medium intensity group and no statistical analysis of those data given in the paper
Tuchin (2003)^[26]			2. Change in number of active acne elements for multiple treatment group
Yeung (2007)^[29]	30 participants (M/F proportion not given) age 18-41 years (mean 25) with moderate facial acne; all Asian; Fitzpatrick skin types IV-V	All participants used topical adapalene 0.1% gel at night and were randomized to two split-face treatment groups: 530-750 nm light with contact cooling gel plus MAL vs. light only; and light with contact cooling gel vs. control; four treatments with intervals of 3 weeks, assessed after each treatment and at 4 and 12 weeks post-treatment	1. Change in lesion counts	Only the control group showed a statistically significant mean reduction (P = 0.01) in inflammatory acne lesion counts. Counts at 4 weeks and 12 weeks were 53% and 65% in the MAL-PDT group; 22% and 23% in the light only group; and 72% and 88% in the control group. A significant reduction in comedones in the MAL-PDT (P = 0.05) and light only (P = 0.01) groups at 12 weeks compared with the control group

ICG, indocyanine green; LPDL, long-pulsed dye laser; MAL, methyl aminolaevulinate; ALA, 5-aminolaevulinic acid.

Table 5. Other Trials of Photodynamic Therapy (PDT)
Study (first author and year)	Participants	Intervention	Primary outcome measures	Results
Hong (2005)^[15]	8 participants age 18-24 years (mean age and M/F proportion not given); all Korean; skin types not given	Comparison of PDT with placebo: 630 nm plus ALA on right side of face; other side untreated as control in a split-face trial; single treatment, assessed at 1, 3 and 6 months	1. Change in lesion count	Reduction in inflammatory lesion count at 1, 3 and 6 months was 27.6%, 37.9% and 41.9% for the treated side compared with 8%, 14.7% and 15.4% for the control side (P < 0.05). The treatment side showed a higher global clinical improvement score at all assessment periods compared with the control side (P < 0.05)
Hong (2005)^[15]			2. Clinical improvement score
Taub (2007)^[34]	22 recruited, 19 participated, mean ± SD age 26.5 ± 9.1 years, 7 M, 12 F, with moderate to severe acne and > 10 inflammatory acne lesions; Fitzpatrick skin types not given	Comparison of PDT with different light sources for activation: ALA activated by IPL (600-850 nm), or a combination of IPL (580-980 nm) and bipolar radiofrequency energies, or blue light (417 nm) in a parallel groups trial; three treatments at 2-week intervals; follow up at 1 and 3 months after final treatment	1. Change in lesion count and % change	Reductions in counts in all three groups, highest in the IPL activation group and lowest in the blue light group, but the difference was not statistically significant. Investigator assessed improvement was highest with IPL activation and lowest with blue light, which reached borderline statistical significance at 3 months (P = 0.0498)
			2. Change in acne grade
			3. Investigator and patient assessed improvements
Wiegell (2006)^[14]	15 participants > 18 years but age range not given, with > 12 inflammatory acne lesions; skin types not stated	Comparison of MAL and ALA creams: 620 nm light with split-face design; one full-face PDT treatment with MAL on one side and ALA on the other, assessed at 6 and 12 weeks after treatment	1. Change in lesion scores	A nonsignificant improvement in median lesion counts and Leeds scores from baseline on both sides. At 12 weeks 83% of participants had a slight to marked improvement on the MAL-light side of the face and 75% on the ALA-light side. The remainder had no change or a worsening of acne
Wiegell (2006)^[14]			2. Change in Leeds score
Wiegell (2006)^[22]	36 participants: 21 in treatment group age 23 ± 5 years (9 M, 10 F) and 15 in control group age 24 ± 5 years (3 M, 9 F), with > 12 inflammatory acne lesions; Fitzpatrick skin types II-V	Comparison of PDT with placebo: 630 nm plus MAL on one side of face vs. no treatment as a control in a parallel groups trial; two treatments, 2 weeks apart, assessed every 4 weeks for 12 weeks after treatment	1. Change in lesion count	A significant median reduction in inflammatory lesions in the treatment group at 8 and 12 weeks compared with controls (P = 0.023 and P = 0.0023): 68% vs. no change in the control group. No significant reduction in noninflammatory lesions in either group. No significant reduction in Leeds grade between the two groups. No significant difference between one and two treatments
Wiegell (2006)^[22]			2. Change in Leeds revised acne grading