Are All Infrared Lasers Equally Effective in Skin Rejuvenation Tina S. Alster, MD, and Jason R. Lupton, MD

In an attempt to limit the prolonged postoperative healing associated with ablative laser skin resurfac- ing and in response to growing public interest in less invasive treatment modalifies, nonablative laser and light source technology was developed. Over the past few years, several clinical and histolagic research studies have been conducted to deter- mine the relative efficacy of these nonablafive sys- tems. These systems stimulate dermal collagen re- modeling using wavelengths and concomitant tissue cooling that limit injury to the epidermis, thereby minimizing or eliminating postoperative se- quelae. While nonablative lasers do not supersede already established ablative laser technologies, they supplement the treatment armamentarium, making a wider range of treatment options available and enhancing the ability to correlate the needs of individual patients more closely with the specific advantages offered by a particular modality. Copyright 2002, Elsevier Science (USA). All rights reserved.

N ONABLATIVE CUTANEOUS LASER resur- facing has emerged over the past 5 years as

an increasingly popular method of noninvasive facial rejuvenation. Rapid development of this technology has produced several lasers and light sources capable of improving fine facial rhytides and shallow atrophic facial scars with minimal postoperative recovery or risk of untoward effects. Although ablative carbon dioxide (CO 2) and er- bium:yttrium-aluminum garnet (Er:YAG) lasers can effect excellent clinical improvement of pho- todamaged and scarred facial skin, their use is often associated with prolonged postoperative healing and a myriad of potential long-term side effects and complications, i s In exchange for fewer associated risks and shorter recovery times, patients are now willing to accept the more rood-

From the Washington Institute of Dermatologic Laser Surgery, Washington, DC.

Address reprint requests to Tina S. Alster, MD, Director, Wash- ington Institute of Dermatologic Laser Surgery, 2311 M St, NW, Suite 200, Washington, DC 20037.

Copyright 2002, Elsevier Science (USA). All rights reserved. 1085-5629/02/2104-0005535.00/0 doi: l O. 1053/sder.2002.36766

est clinical improvement of treatment with non- ablative lasers and light sources.

Most available' nonablative systems emit light within the infrared portion of the electromagnetic spectrum (1000-1500 nm). Tissue water absorp- tion at these wavelengths permits deeper dermal penetration of light energy with only 50% beam attenuation at depths of 300 to 1500/.tin. A selec- tive dermal wound is thus created through the use of tissue water as the primary chromophore. In addition, stimulation of inflammatory mediators occurs by the thermal gradient produced.

Because nonablative "subsurface" remodeling involves creation of a dermal wound without in- tegumental injury, all of these laser systems con- tain unique means by which to ensure epidermal preservation during treatment. These methods typically include contact cooling handpieces or dynamic cryogen devices capable of delivering variable duration spray spurts either before, dur- ing, and/or after laser irradiation for maximal pro- tection. Because laser beam penetration and der- mal wounding must be targeted to the relatively superficial portion of the dermis, contact cooling devices that theoretically lead to excessive dermal cooling may affect the level or degree of energy deposition in the skin. As such, there remains no general consensus concerning which method of cooling is most efficacious during treatment.

In general, treatment of facial rhytides and scars with nonablative infrared range laser systems does not produce results comparable to those of abla- tive CO2 and erbium lasers; however, these non- ablative devices do provide mild to modest im- provements in dermal pathology without creation of an external wound-- the chief advantage of this form of treatment. This article reviews the infra- red range nonablative laser systems currently available, their basic features, and the results of studies to date regarding their efficacy for the treatment of facial rhytides and atrophic scars.

1064 nm Q-SWITCHED Nd:YAG LASER

The 1064 nm Q-switched neodymium:YAG (Nd:YAG) laser was the first laser system studied

274 Seminars in Cutaneous Medicine and Surgery, Vol 21, No 4 (Decembe 0, 2002: pp 274-279

INFRARED LASERS

for subsurface remodeling. Although absorption of energy by tissue water is relatively weak at the 1064 nm wavelength, it was possible to achieve dermal penetrative depths that could potentially induce neocollagenesis. The nanosecond range pulse duration of the Q-switched Nd:YAG laser was also determined to limit significant thermal diffusion to surrounding structures, thereby mak- ing it suitable for nonablative rejuvenation.

In 1997, Goldberg and Whitworth 9 published their experience by using a 1064 nm Nd:YAG laser for facial rhytide reduction. Eleven patients with Fitzpatrick skin phototypes I-II and class I or II periorbital or perioral rhytides underwent treat- ment on one side of the face with a Q-switched Nd:YAG laser at a fluence of 5.5 J/cm 2 (3-mm spot size) and CO 2 laser ablation on the contralateral side for comparison purposes. Pinpoint bleeding was used as the clinical endpoint of treatment on the Nd:YAG laser-treated side. Not unexpectedly, all of the CO2-1aser irradiated sites showed signif- icant rhytide improvement at end-study. On the Nd:YAG laser-treated side, however, only 3 pa- tients showed improvement. These three patients had also developed prolonged post-treatment erythema (lasting up to 1 month)--suggest ing that the amount of dermal wounding (and even- tual collagen remodeling) was directly related to the degree of cutaneous injury.

A subsequent study using the Q-switched Nd: YAG laser for rhytide reduction in 61 patients (242 sites) was conducted using a topical carbon solution for improved optical penetration of the 1064 nm light. ~~ Patients underwent 3 consecu- tive monthly treatment sessions with the Nd:YAG laser at a fluence of 2.5 J/cm 2 (7 m m spot), pulse duration of 6 ns-20 ns, and repetition rate of 1 to 10 Hz. Facial rhytides were evaluated up to 8 months after treatment with specific attention to improvements in skin texture, elasticity, and rhyt- ide reduction. At least slight improvement was seen in 97% of class I rhytides and 86% of the class II rhytides. Side effects of treatment were mild and limited, including transient erythema, purpura (5 patients), and postinflammatory hyperpigmenta- tion (1 patient). This study thus showed that the 1064 nm Nd:YAG laser could be used with a top- ical carbon suspension to effect improved wrinkle reduction without epidermal disruption or signif- icant adverse sequelae.

275

1320 nm N d : Y A G LASER

A 1320 nm Nd:YAG laser (CoolTouch; ICN Pharmaceuticals, Costa Mesa, CA) was the first commercially available system marketed solely for the purpose of nonablative laser skin resurfacing. The 1320 nm wavelength is associated with a high scattering coefficient that allows for dispersion of laser irradiation throughout the dermis. The latest model (CoolTouch II} is capable of delivering en- ergy densities up to 24J/cm 2 with a pulse duration of 350/xs through a 10-mm spot size handpiece. The 1320 nm Nd:YAG laser handpiece contains 3 portals: the laser beam itself, a thermal feedback sensor that registers skin surface temperature, and a dynamic cryogen spray apparatus used for epi- dermal cooling. When skin surface temperatures are maintained at 40 to 45 ~ C, dermal tempera- tures reach 60 to 65 ~ C during laser irradiation, thereby effecting collagen contraction and neocol- lagenesis. To prevent unwanted sequelae (eg, blis- tering) from excessive heat production, it is im- perative that epidermal temperatures be kept lower than 50 ~ C. A series of 3 or more treatment sessions are scheduled at regular time intervals (typically once a month) for maximum reduction of rhytides or softening of atrophic scars (Fig 1). Side effects of treatment are generally mild and include transient erythema and edema.

Menaker et a111 reported effective rhytide re- duction in an early study with a prototype 1320 nm Nd:YAG laser. Ten patients with periocular rhytides received 3 consecutive laser treatments at biweekly time intervals. Three 300/xs pulses were delivered at 100 Hz and fluence of 32J/cm 2 with a 5 mm spot size handpiece. Epidermal protection was achieved with application of a 20 ms cooling spray after a 10 ms preset delay (no thermal feed- back sensor was used). Patients were evaluated at 1 and 3 months post-treatment. Although 4 of the 10 patients showed clinical improvement in rhyt- ide severity by end-study, these findings were not statistically significant. Similarly, the slight ho- mogenization of collagen noted on histology at 1 and 3 months after treatment was not statistically significant and inconsistent with the clinical find- ings.

In another study, Kelly et a112 treated 35 pa- tients with mild, moderate, and severe rhytides with a 1320 nm Nd:YAG laser. Three treatments were delivered at 2-week intervals with fluences ranging 28-36 J/cm 2 with a 5-mm spot size. Cryo-

276 ALSTER AND LUPTON

Fig 1. (A) Periocular rhytides before Rx. (B) SIP third 1320 nm Nd:YAG laser treatment,

Fig 2. (A) Transverse neck lines before treatment. (B) One month SIP third 1450 nm diode Rx.

Fig 3. (A) Atrophic acne scars before treatment, (B) S/P third 1450 nm diode laser treatment.

Fig 4. (A) Perioral rhytides before treatment. (B) S/P 3 1540 nm Er:glass laser sessions.

INFRARED LASERS

gen spray cooling was applied in 20 to 40 ms spurts with 10 ms delays. Patients were evaluated at 12 and 24 weeks after treatment with statisti- cally significant improvement noted in all clinical grades after 12 weeks. Only the most severe rhyt- ides; however, showed persistent improvement 24 weeks after treatment. Transient tissue edema was surmised to be responsible for the initial improve- ments observed in the milder rhytide categories.

Goldberg s3 devised 2 similar studies to examine the effectiveness of the 1320 nm Nd:YAG laser for the treatment of facial rhytides. In the first study, 10 patients with skin types I-II and class I-II rhyt- ides in the periorbital, perioral, and cheek areas were treated. 13 Four treatments were adminis- tered over a 16-week period by using fluences of 28-38 J/cm 2 with a 30% overlap and a 5-mm spot size. One or 2 laser passes were applied to achieve the treatment endpoint of mild erythema. Skin surface temperatures were limited to 40~ to 48~ by using the aforementioned dynamic cooling spray to provide epidermal protection, and effect- ing dermal temperatures ranging 60~176 Six months after treatment, 2 patients showed no clinical improvement, 6 showed "some" improve- ment, and 2 showed "substantial" improvement. This study emphasized several key points in non- ablative laser resurfacing. First, some form of ther- mal feedback sensor should be used intraopera- tively in order for appropriate treatment fluences to be selected based on the individual patient's cutaneous temperature, thereby maximizing der- mal temperatures that effectively lead to collagen reformation. Second, longer follow-up periods are usually required to fully appreciate the effect of serial treatment sessions on dermal collagen stim- ulation. In Goldberg's second s tudy, 14 10 patients underwent full-face treatments with the 1320 nm Nd:YAG laser at 3- to 4-week intervals. As with the first study, treatment results were u n e v e n - - 4 patients showed no improvement, 4 showed some improvement, and 2 showed substantial improve- ment in facial rhytides and overall skin tone.

Trelles et al s5 also studied the 1320 nm Nd:YAG laser for treatment of facial rhytides in 10 women. Full-face treatment was administered to 3 pa- tients, 2 patients had periorbital treatment and 5 patients received perioral treatment. Laser flu- ences of 30 to 35J/cm 2 were delivered in triple 300 /,s pulses at a repetition rate of 100 Hz. Dynamic cryogen spray cooling was used with a 30 ms spurt and a 40 ms delay between cryogen spurt and laser

277

irradiation. A thermal sensor was also used to maintain peak surface temperatures in the range of 42~176 to avoid excessive tissue heating. Treatments were administered twice a week over a 4-week period for a total of 8 sessions. Only 2 of 10 patients expressed satisfaction with their final result despite clinician evaluations showing sig- nificant improvement in 5 of 10 patients and fair improvements in another three. In addition, there was no correlation between histologic changes and the degree of subjective clinical improvement as judged by the patients.

A more recent study by Fatemi et aP 6 showed that the 1320 nm Nd:YAG laser (CoolTouch I) produced mild subclinical epidermal injury that could potentially lead tO enhanced skin texture and new papillary collagen synthesis by stimula- tion of cytokines and other inflammatory media- tors. Thus, the long-term histologic improvement seen in photodamaged skin may not be based solely on direct laser heating of collagen, but by further enhancement of other stimulatory factors.

1450 nrn DIODE

The 1450 nm mid-infrared wavelength diode laser targets dermal water and penetrates the skin to a depth of about 500/xm. This low-power laser system achieves peak powers in the 10 to 15 W range with relatively long pulse durations of 150 to 250 ms. Because of these long exposure times, epidermal cooling must be delivered in sequence during the application of laser energy to avoid excessive heat buildup within the superficial lay- ers of the skin.

Goldberg et a117 reported on the effects of 1450 nm diode laser irradiation in 20 patients with class I-II rhytides. Two to 4 treatment sessions were delivered with 6 months follow-up evaluation. Pa- tients were treated with laser and cryogen spray cooling on 1 side of the face and cryogen spray cooling alone on the contralateral side. On the laser-treated facial halves, 7 did not show any im- provement, 10 showed mild improvement, and 3 had moderate improvement. None of the sites treated with cryogen alone showed any improve- ment after 6 months. Side effects of treatment were mild and included transient erythema, edematous papules, and 1 case of postinflamma- tory hyperpigmentation persisting for 6 months. The authors concluded that the 1450 nm diode laser was effective for treatment of mild to moder- ately severe facial rhytides with minimal morbid-

278

ity. Their study further showed that nonablative laser treatment alone was responsible for the clin- ical improvements and that the nonspecific injury induced by cryogen spray cooling could not effect the changes seen.

Three additional studies with the 1450 nm di- ode laser have recently been reported by Alster et al.lS-2~ Twenty patients with periorbital and peri- oral rhytides were included in a controlled study in which long-pulsed 1450 nm diode laser irradi- ation was randomly applied to one periorbital region or half of the perioral region (using the contralateral periorbital and perioral half as non- treated controls). Clinical and histologic evalua- tion showed improvement in all laser-treated ar- eas with the highest clinical scores in periorbital regions.iS In another controlled study of 20 pa- tients with transverse neck lines, pulsed 1450 nm diode laser (Smoothbeam; Candela Laser Corp, Wayland, MA) irradiation was shown to effect significant improvement in their appearance and texture, as measured by blinded clinical assess- ments and through 3-dimensional in vivo micro- topography (PRIMOS Imaging System; GFM, Germany). 19 Mean fluences of 11.6 J/cm 2 were used with a 6 m m spot and interval cooling set- tings of 10 ms precool, 20 ms intracool, and 20 ms postcool (Fig 2).

This same group showed superior effectiveness of the 1450 nm diode laser compared to the 1320 nm Nd:YAG laser for treatment of atrophic scars. 2~ A series of 20 patients with atrophic facial sears were randomly assigned to receive 1450 nm diode laser treatment on 1 side of the face and 1320 nm Nd:YAG laser on the contralateral side. Fluences of 9 to 14 J/cm 2 (average 11.8 J/cm 2) with nonoverlapping 6 mm spots were delivered in a single pass with the diode laser (Fig 3).

The Nd:YAG laser was operated at fluences ranging 11 to 17J/cm 2 (average 13.9J/cm2), using a 10-ram spot size. Skin surface temperature was maintained at 38~176 by using varying degrees of pre- and postcooling during the delivery of 2 consecutive Nd:YAG laser passes. In vivo micro- topography measurements, clinical ratings, and histologic evaluations all showed significant im- provement of the laser-treated scars, with the long-pulsed 1450 nm diode system showing sig- nificantly greater effect than the 1320 nm Nd:YAG system 6 months after the third monthly treat- ment.

ALSTER AND LUPTON

1540 n m ERBIUM:GLASS

The 1540 nm erbium-doped phosphate glass laser is another mid-infrared range laser that has also been used for amelioration of fine facial rhyt- ides and atrophic facial scars. Similar to other in- frared laser systems, the erbium glass laser targets intracellular water and penetrates tissue to a depth of 0.4 to 2 mm. The 1540 nm wavelength also has the least amount of melanin absorption compared with the 1320 nm and 1450 nm laser systems--a potential advantage of this system when treating tanned or darker-skinned patients. Mordon et a121 studied the 1540 nm erbium glass laser on hairless rat abdominal skin with pulse train irradiation (1.1 J, 3 Hz, 30 pulses) and varying cooling tem- peratures (+5~ 0~ -5~ Biopsies were ob- tained 1, 3, and 7 days after treatment and showed fibroblast proliferation and new collagen synthe- sis as early as the third day. The authors con- cluded that this laser system held promise for treating facial rhytides because of its high water absorption and reduced scattering effect allowing light energy deposition to remain in the upper dermis where the bulk of solar elastosis resides.

Ross et a122 used the 1540 nm erbium glass laser with a sapphire cooling handpiece to treat the preauricular skin of 9 patients. A 5 mm collimated beam was used to deliver fluences of 400 to 1200 mJ. Epidermal necrosis and scar formation were noted at the highest pulse energies. Dermal fibro- plasia was evident after 2 months in sites without epidermal necrosis, but was too deep in the tissue to effect clinical rhytide reduction. Several key points were illustrated by this study; namely, that denatured collagen located deep in the dermis (>600/xm) is associated with granuloma forma- tion and that the peaks of heating and cooling with nonablative laser resurfacing are, by neces- sity, in very close proximity because heat needs to be confined to a zone 100 to 400/xm beneath the skin surface to provide for maximum wrinkle re- duction.

More recently, Lupton et a123 reported their use of a 1540 nm erbium glass laser (Fig 4) (Aramis; Quantel Medical, Clermond-Fernad, France) to treat 24 patients with fine periorbital and perioral rhytides. Patients underwent a series of 3 treat- ments on a monthly basis with a 4-ram spot size, 10 J/cm 2 fluence, 3.5 ins pulse duration, and 2 Hz repetition rate. Epidermal protection was achieved with concomitant application of a con-

INFRARED LASERS 279

tact sapph i re lens c o o l e d to 5~ His to log ic spec-

imens s h o w e d inc rea sed d e r m a l f ibroplasia by

e n d - s t u d y (6 m o n t h s ) . Average cl inical scores

were i m p r o v e d 1 and 6 m o n t h s after the th i rd

t r e a t m e n t sess ion w i t h s l ight ly be t te r resul ts

no t ed in the per io rb i t a l regions.

Side effects of t r e a t m e n t were mi ld and in-

c luded t rans ien t e r y t h e m a and edema. Thus , the

cl inical and h i s to log ic resul ts r e p o r t e d in this

s tudy were c o m p a r a b l e to those seen in o the r s im-

i larly des igned s tudies u s ing the 1320 n m Nd:YAG

and 1450 n m d iode laser systems.

CONCLUSION

Nonab la t ive c u t a n e o u s laser resur fac ing w i t h a

var ie ty of inf rared range laser sys tems (eg, 1320

n m Nd:YAG, 1450 n m diode , 1540 n m e rb ium:

glass) has b e c o m e a p o p u l a r t r ea tmen t a l t e rna t ive

for m i l d facial rhy t ides and scars, w i th s igni f icant

c l inical and h i s to log ic i m p r o v e m e n t seen after a

series of t r ea tments in m o s t pat ients . T r e a t m e n t s

are typical ly de l ive red at m o n t h l y t ime in te rva ls

w i t h final c l inical resul ts t ak ing several m o n t h s

after laser i r rad ia t ion to be real ized. A l t h o u g h

t r e a t m e n t effects w i t h these nonab la t ive sys tems

are no t yet on par w i t h those of ablat ive c a r b o n

d iox ide or e rb ium:YAG lasers, t hey do i m p r o v e

overa l l sk in texture , tone, and e l a s t i c i t y - - s u b j e c -

t ive f indings of ten dffficult to r ep resen t in p h o t o -

graphs. N o n e of the n o n a b l a t i v e laser sys tems has

ye t e m e r g e d as b e i n g c lear ly s u p e r i o r - - e a c h

effects s imi lar degrees of i m p r o v e m e n t in der-

mal pa tho logy after m u l t i p l e sess ions at s tan-

da rd t r e a t m e n t pa ramete rs . W i t h c o n t i n u e d

re sea rch efforts focused on nonab la t ive laser

sk in resurfac ing, it is p robab le that fur ther ref ine-

m e n t s and advances in this t e c h n o l o g y wil l m o r e

closely a p p r o x i m a t e the effects of ablat ive laser

t r e a t m e n t w i t h o u t its assoc ia ted compl i ca t i ons

and risks.

REFERENCES

1. Alster TS: Cutaneous resurfacing with CO 2 and erbium: YAG lasers: Preoperative, intraoperative, and postoperative considerations. Plast Reconstr Surg 103:619-632, 1999

2. Ratner D, Tse Y, Marchell N, et al: Cutaneous laser resur- facing. J Am Acad Dermatol 41:365-389, 1999

3. Alster TS, Lupton JR: Lasers in dermatology: An over- view of types and indications. Am J Clin Dermatol 2:291-303, 2001

4. Alster TS, Lupton JR: An overview of cutaneous laser resurfacing. Clin Plast Surg 28:37-52, 2001

5. Alster TS, LnptonJR: Complications of laser skin resur- facing. Facial Plast Surg Clin N Am 8:163-172, 2002

6. Bernstein LJ, Kauvar ANB, Grossman MC, et al: The short- and long-term side effects of carbon dioxide laser resur- facing. Dermatol Surg 23:519-525, t997

7. Nanni CA, Alster TS: Complications of carbon dioxide laser resurfacing. Dermatol Surg 24:315-320, 1998

8. Alster TS, Lupton JR: Prevention and treatment of side effects and complications of cutaneous laser resurfacing. PIast Reconstr Surg 109:308-316, 2002

9. Goldberg DJ, Whitworth J: Laser skin resurfacing with the Q-switched Nd:YAG laser. Dermatol Snrg 23:903-906, dis- cussion 906-907; 1997

10. Goldberg DJ, Metzler C: Skin resurfacing utilizing a low-fluence Nd:YAG laser. J Cutan Laser Ther 1:23-27, 1999

11. Menaker GM, Wrone DA, Williams RM, et al: Treat- ment of facial rhytids with a nonablative laser: A clinical and histologic study. Dermatol Surg 25:440-444, 1999

12. Kelly KM, Nelson S, Lask GP, et al: Cryogen spray cooling in combination with nonablative laser treatment of facial rhytides. Arch Dermatol 135:691-694, 1999

13. Goldberg DJ: Nonablative subsurface remodeling: Clin- ical and histologic evaluation of a 1320 nm Nd:YAG laser. J Cutan Laser Ther 1:153-157, 1999

t4. Goldberg DJ: Full-face nonablative dermal remodeling with a 1320 nm Nd:YAG laser. Dermatol Surg 26:915-918, 2000

15. Trelles MA, Allones I, Luna R: Facial rejuvenation with a nonablative 1320 nm Nd:YAG laser. A preliminary clinical and histologic evaluation. Dermatol Surg 27:111-116, 2001

16. Fatemt A, Weiss MA, Weiss RA: Short-term histologic effects of nonablative resurfacing: Resuhs with a dynamically cooled millisecond-domain 1320 nm Nd:YAG laser. Dermatol Surg 28:172-176, 2002

17. Goldberg DJ, Rogachefsky AS, Silapunt S: Nonablative laser treatment of facial rhytides: A comparison of 1450 nm diode laser treatment with dynamic cooling as opposed to treatment with dynamic cooling alone. Lasers Surg Med 30:79- 81, 2002

18. Tanzi EL, Williams CM, Alster TS: Treatment of facial rhytides with a nonablative 1450 nm diode laser: A controlled clinical and histologic study. Dermatol Surg 2002 (in press)

19. Alster TS, Tanzi EL: Treatment of transverse neck lines with a 1450 nm diode laser. Lasers Surg Med 14:33, 2002 (suppl)

20. Tanzi EL, Alster TS: Comparison of a 1450 nm diode laser and a 1320 nm Nd:YAG laser in the treatment of atrophic facial scars. Lasers Surg Med suppl 14:33, 2002

21. Mordon S, Capon A, Creusy C, et al: In vivo experimen- tal evaluation of nonablative skin remodeling using a 1.54/~m laser with surface cooling. Lasers Surg Med 27:1-9, 2000

22. Ross EV, Sajben FP, Hsia J, et al: Nonablative skin re- modeling: selective dermal heating with a mid-infrared laser and contact cooling combination. Lasers Surg Med 26:186- 195, 2000

23. Lupton JR, Williams CM, Alster TS: Nonablative laser skin resnrfacing using a 1540 nm erbium glass laser: A clinical and histologic analysis. Dermatol Surg 28:833-835, 2002