QOA20004

8/10/2019 QOA20004

1/5

Skin Rejuvenation Regimens

A Profilometry and Histopathologic Study

John D. Rachel, MD; Jasmin J. Jamora, MD

Objective: To quantitatively examine the effects of skinrejuvenation regimens in treating photodamaged skin.

Methods:Fourteen patients with photodamaged skinwere considered for analysis. Skin rejuvenation regi-mens were as follows: (1)10 weeksof treatmentwith topi-cal0.05% tretinoin emollient cream, (2) 10 weeksof treat-ment with 0.05% tretinoin emollient cream and topical

ascorbic acid lotion, (3) 6 superficial trichloroacetic acidpeels, and (4) a combination of the topical treatmentsandsuperficial peels. Comparisons of the treatments wereanalyzed using profilometry and histologic findings.

Results:Profilometry analysis provided quantificationof the changes from each treatment group andamong thetreatment programs. Each group showed improvements

from baseline. Trichloroacetic acid peels combined withapplication of the topical products improved skin topog-raphy to a greater extent than the less aggressive regi-mens. Histologic changes correlated well with the skinreplica findings.

Conclusions: A 10-week skin rejuvenation regimen ob-jectively improved photodamaged facial skin. Significant

changes arenoted when combiningtopical treatmentswithsuperficial peels. Hence, use of a combination of trichlo-roacetic acid peels, 0.05% tretinoin emollient cream, andascorbic acid lotions is well tolerated and superior to ei-ther component aloneas part of a comprehensive skin careand sun protection program.

Arch Facial Plast Surg. 2003;5:145-149

P

HOTODAMAGED SKINis char-acterized by fine and coarsewrinkling, rough texture,sallow color, and uneven

pigmentation. These charac-teristics are associated with decreased mi-crocirculation, elastosis, epidermal atro-phy, cellular atypia, and preneoplasticdysplasia.1 Clinical skin changes presum-ably result fromfibroblast malfunctionsec-ondary to DNA and other cellular and pro-teindamage. The consequence is abnormalcollagen, elastin, and ground substancebreakdown and resynthesis and, thus,abnormal dermal structure repair andremodeling.2,3 In addition to actinic kera-tosis and skin cancer, these changes pre-dispose to decreased immune functionand

vitamin D synthesis and poor wound heal-ing. Long-term exposure to natural andsynthetic stimuli, including UV light,ozone, andtobaccosmoke, can lead to thedevelopment of photoaging.

The main pharmaceutical approach tothe prevention of photoaging lies in the as-siduous use of sunscreens. Many prod-ucts are available to reverse the damagingeffects of the sun and help rejuvenate theskin, including vitamin A, ascorbic acid

derivatives, and chemical peels. A fre-quently prescribed treatment regimen in-cludes combinations of these products.

Results of some studies4,5 haveshown

that the topical application of tretinoin, avitamin A derivative, is effective in revers-ing some changes in photoaging. Thesechanges include increasednumber andac-tivity of fibroblasts, reduced melanocyte ac-tivity, andrapidformation of a zone of sub-epidermal connective tissue with newcollagen and anchoring fibrils. This rever-sal results in reduction in fine wrinkling,roughness, and mottled hyperpigmenta-tion. Studies6-8 using skin replica analysisand histologic evaluation have confirmedthe tretinoin-associated improvements.

Oxidative damage to the skin is pro-

duced by reactive oxygen species such asfree radicals. Ascorbic acid is an antioxi-dant that neutralizes oxygen and free radi-cals and has a role in collagen stimulation.Cutaneous stores of ascorbic acid are de-pleted by UV light exposure.9 Oral inges-tion of the vitamin has been ineffective inachieving adequatelevels in the skin. Topi-cal application of ascorbic acid can in-creasethe cutaneouslevelsby more than20times the amount found in normal skin. A

ORIGINAL ARTICLE

From the Division ofDermatopathology, IndianaUniversity School of Medicine,Indianapolis (Dr Jamora).Dr Rachel is in private practicein Chicago, Ill.

(REPRINTED) ARCH FACIAL PLAST SURG/VOL 5, MAR/APR 2003 WWW.ARCHFACIAL.COM145

2003 American Medical Association. All rights reserved.

wnloaded From: https://jamanetwork.com/ on 10/19/2014

8/10/2019 QOA20004

2/5

stable form of L-ascorbate has allowed pharmacologic lev-els of ascorbic acid penetration targeted directly into theskin by topical application to affect the free radicals andstimulate collagen.10 Skin replica analysis and clinical as-sessments of ascorbic acidtreated skin have shown sig-nificant improvements in skin surface texture and tone.11

A third modality used in thearmamentarium for skinrejuvenationprograms is chemical peeling agents.Thepeelis intended to produce a controlled partial-thickness skin

injury, destroying varying amounts of epidermis and up-per portions of the dermis. Trichloroacetic acidpeels causewounding through protein precipitation.12,13 A wound-healing response after injury includes an increase in gly-cosaminoglycan content and qualitative changes in der-mal collagen. The overall clinical appearance of the skin ismore homogenous, with fewer rhytids and less pigmen-tary dyschromia. Chemical peeling agents can be classi-fied by the depth of penetration: superficial, medium, anddeep. This classification is based on studies showing thedepth of wound produced when the agents are applied incontrolled experimental situations. Many agents are avail-able for superficialchemical peels, includinga 10% to 25%solution of trichloroacetic acid. These agents are gener-

ally well tolerated, and the potential for systemic toxic ef-fects is minimal.14

The clinical changes resulting from application ofthese products have been studied individually in the past.Few studies comparing skin rejuvenation programs havebeen reported. This study aims to quantify the changesin skin surface topography in patients undergoing rou-tineskin caretreatment with combined topical0.05%treti-noin emollient cream, topical ascorbic acid, and super-ficial trichloroacetic acid peels.

METHODS

Fourteen patients were enrolled in this 10-week prospectivestudy carried out in a private facial plastic surgery practice and

ambulatory surgery center (Beeson Aesthetic Surgery Insti-tute, Indianapolis, Ind) fully accredited by the AccreditationAssociation for Ambulatory Health Care Inc. Twelve of the pa-tients were randomly assigned to 4 study groups. Group A re-ceived daily topical application of 0.05% tretinoin emollientcream (Renova; Ortho Dermatological, Skillman, NJ). GroupB applied 0.05% tretinoin emollient cream each evening andtopical ascorbic acid lotion (Cellex-C high-potency serum; Cel-lex-C International, Toronto, Ontario) each morning. GroupC received 6 weekly superficial trichloroacetic acid peels. Thefirst 3 peels were performed using a 10% solution and the last3 a 20% solution. Group D receiveda combination of the groupB and group C regimens. The peels started 2 weeks after ini-tiation of 0.05% tretinoin and ascorbic acid application. Thecreams were applieddaily to the entire facial area for 10 weeks

except on the days on which the peels were received. Two ad-ditional patients who agreed to undergo postauricular biop-sies at completion of the study were included in group D.

Patients were allowed to use a moisturizer anda mild soapad libitum andwere cautioned against sunexposure during thestudy. Patients were given verbal and written instructions forproper application anduse of all topical agents. Useof the samebrand and quantity of makeup used before the study was en-couraged in all patients. Patientswere instructed to refrain fromusing all topical skin products and cosmetics for 24 hoursbefore clinical assessments in which skin replicas were taken.Patients were to avoid the use of topical or systemic tretinoin,

alphahydroxy acids, kojic acid, hydroquinone, and corticoste-roidsfor at least 30 days beforestudy initiation and during treat-ment. No patients had a previous history of laser resurfacing,chemical peel, dermabrasions, or other cutaneous facial sur-gery for at least 1 year before study initiation. Discontinuationfrom the study occurred for the following reasons: a seriousadverse reaction occurred, patient noncompliance, or volun-tary withdrawal. Our institutional review board (Beeson Aes-thetic Surgery Institute) approved the project, and all partici-pants gave written informed consent before study initiation.

Profilometry and histologic analyses were performed withoutknowledge of patient identity or treatment assignments.

OPTICAL PROFILOMETRY

Optical profilometry measurements of silicone rubber caststakenfrom identical sites in the periorbital (crows feet) area wereobtained at baseline and at the end of the study for compari-son. Silicone skin surface replicas were taken from the perior-bital crows feet region at identical sites bilaterally by the sametechnician (J.D.R.) as described by Grove et al.6 The replicaswere then analyzed by optical profilometry using the Magi-scan System (Skin Study Center, Broomall, Pa).

The resultingskin surface image wasdigitally analyzed, andnumeric values were plotted to create profiles reflecting surface

featuresat these specific locations. Theseplots yieldvariables(Rz,Ra,and shadows) proportional to thedegree of wrinkling, rough-ness, and other surface irregularities. Rz divides the scan into 5sections and looks at the minimum-maximum within each seg-ment, calculating the average of these values. Ra involves gener-ating an average line through the center of the profile and deter-miningthe area above andbelow this line. Shadows representthearea of dark shadows seen with profilometric analysis.With thesevalues, illumination can be varied from different orientations.North-south (NS) measurements are obtained with the illumi-nation running perpendicular to the majorline axis,whereaseast-west (EW) measurements are made with parallel lighting.

HISTOLOGIC ANALYSIS

Histologic analysesof postauricular punch biopsy samples were

performed to further analyze the skin care regimens. Templatesmade of radiographic paper were fashioned to facilitate preciseapplication of the topical products and to serve as a referencefor biopsysite identification. Patients were given verbal andwrit-teninstructions for application of thetopical products in thepos-tauricular region. Product application followed the regimens ofthe 4 treatment groups.Postauricular site1 received0.05% treti-noin emollient cream alone, site 2 received 0.05% tretinoinemol-lient cream and ascorbic acid, site 3 receivedtrichloroacetic acidalone,and site 4 received thetrichloroacetic acid peels and0.05%tretinoin emollient cream and ascorbic acid. At completion ofthe study, a 4-mm round, stainless steel, trephine punch biopsywas used to obtaina sampleat each site. Thebiopsy tissue speci-men was fixed and examined by light microscopy. The derma-topathologist (J.J.J.) was masked to the origin of each biopsy

specimen. Thesections were preparedin the usualmanner withhematoxylin-eosin to observe cellular response and with vanGieson stain to observe elastic tissue response.

ANALYTICAL AND STATISTICAL METHODS

Patient data were analyzed by calculating the difference be-tween the baseline and week 10 measurements for each vari-able(RaNS,RaEW, RzNS, RzEW, shadow NS,and shadowEW).A negative result indicates improvement. At test was used toanalyze each variable and to analyze changes between groupsand was considered statistically significant at P.05. A corre-




8/10/2019 QOA20004

3/5

lation coefficient was calculated to determine comparabilityamong groups and between the right and left sides of each pa-tient at baseline.

RESULTS

Fourteen patients were included in the study, and eachcompleted the 10-week course of topical product appli-cation. No patients were excluded from analysis. All pa-tients were women aged 36 to 61 years (meanSD age,47.5 5.7 years). Four patients (29%) regularly used sunprecautions, and 6 (42%) reported a history of tobaccouse. Fitzpatrick skin type was II in 3 patients (21%), IIIin 8 (57%), and IV in 3 (21%). Glogau classification wasII in 2 patients (14%), III in 11 (78%), and IV in 1 (7%).The treatment groups were comparable at baseline withrespect to skin replica measurements and clinical char-acteristics, including overall severity of photodamage.Ad-verse effects were mild, resolved within the first week oftherapy, and included stinging, erythema, and dryness,which were easily treated with moisturization. In no casewas the study regimen altered.

Profilometric data were obtained from skin replicaanalysis at baseline and at the end of the study. Each pa-tient provided 2 sets of data. Table 1summarizes thecorrelationcoefficients in the population. Analysis showedthe treatment groups to be comparable at baseline andindicates strong reproducibility between sides.

Table 2summarizes the mean change from base-line for each variable in each group. Improvement in skintopography, measured as a mean decrease from baselineto week 10 in the Ra and Rz values, occurred in each ofthe4 treatmentgroups.Statistically significantchangesfrombaseline for all 4 groups were found for the RaNS, RzNS,andRzEW variables. TheRaEW value wassignificantlyim-provedfrombaselineingroups B and D.Shadow NSshowedsignificant changes in groups A and D. There were no sig-

nificant changes in the shadow EW variables.

Figure 1 illustrates the differences among the 4groups for each of the 6 variables. Treatment in group Apatients resulted in small (0 to 2) decreases in 3 vari-ables, mild (2 to 4) decreases in 2, and moderate (4to 6) decreases in 1. In group B, results indicate rela-tively small to moderate decreases across the variables,except for RzEW, which shows a large (6) meanchange. Groups C andD experiencedthe greatestchanges,with half of the variablesdemonstrating moderate to large

increases. The effects of trichloroacetic acid peels aloneandin combination with application of the 2 topical prod-ucts showed the greatest reductions from baseline in theNS and EW axis of the Rz variable.

The differences among patients in groups B, C, andD compared with group A showed statistically significantimprovements in the Rz variables. The EW axis was sig-nificantfor groupsB (P=.03),C(P=.05),andD(P.005),and the NS axis was significant for groups C (P=.03) andD (P=.001). Thedifferenceswere also largeforRaEW whencomparing groupsA and D (P=.001). TheRz variablesweresignificantly different as well when comparing groups Cand D with group B. The NS axis showed large differences(groups C, P=.01; groups D, P=.009) for both groups and

the EW axis showed significant changes for group D(P=.03). When comparing groups C and D, there were nosignificant differences in either the Ra or Rz variables. Al-though the mean changes for the shadow variables weresmall for all groups, some significant changes were noted.The NS variable was significantly different when compar-ing group B with group A and groups C and D with groupB (P=.04 for all). The EW variable was significantly dif-ferentonlywhen comparing groupD withgroupC (P=.05).

The histologic results, given as the average betweenthe2 patients except for theepidermal thickness measure-ments,showprogressive changesfromspecimens1 through4 in both patients. The stratum corneum was mostly bas-ket weave: +4on a scale from1 to 4 on specimen 1, which

became less evident on specimens 2 and 3 and was non-existentin specimen4. Compactorthokeratosis wasslightlypresent on specimen 1 (+1) butbecameprogressively moreevident on specimens 2 (+2), 3 (+3), and 4 (+4 ). Thesefindings indicate definite changes from basket-woven or-thokeratosis to compact orthokeratosis.

The granular cell layer was noted to be approxi-mately 1 cell thick in specimen 1, and this was noted toprogressively thicken, so that it was 2 cells thick by speci-men 3 and 4 cells thick by specimen 4. The thickness ofthe epidermis was measured from the granular cell layerto the bottom of the interpapillary epidermis and aver-

Table 1. Correlation Data for Profilometric Variables

Correlation Coefficient Patients, No. (%)

Between right and left sides

R0.90 9 (64)

R= 0.75-0.90 2 (14)

R0.75 3 (21)

Between groups at baseline

R0.98 14 (100)

Table 2. Image Analysis of Skin Surface Impressions: Change From Baseline*

Group RaNS RaEW RzNS RzEW Shadow NS Shadow EW

A 3.4 3.8 1.3 1.7 3.6 1.3 4.3 4.7 1.3 1.4 0.3 1.0

B 2.9 1.2 2.3 1.1 4.8 5.6 7.1 2.8 0.0 0.6 0.2 0.4

C 5.2 4.1 1.9 2.9 8.1 4.6 8.9 4.2 2.3 3.1 0.7 0.8

D 4.4 2.1 3.2 1.3 13.4 6.7 13.0 6.5 1.1 1.3 0.0 0.7

Abbreviations: See the Optical Profilometry subsection.*Data are given as mean SD.P.05.P.005.




8/10/2019 QOA20004

4/5

aged across the front of the specimen. On patient 1, it wasnoted to be 0.06 mm on specimen 1, 0.09 mm on speci-men 2, 0.10 mm on specimen 3, and 0.13 mm on speci-men 4. Measurementson thesecond patientwere0.08 mmon specimen 1, 0.09 mm on specimens 2 and 3, and 0.10mm on specimen 4. These results show an increased thick-ening of theepidermis on bothspecimens, progressing fromsites 1 through 4.Figure 2 illustrates these histologicchanges, comparing site 1 to site 4.

The elastic tissue, as demonstrated with the elastictissue stain, showed progressive increases from speci-

mens 1 to 4 (+2 in specimens 1 and 2, +3 in specimen 3,and +4 in specimen 4). There was also significant thick-ening in the papillary dermis (+2 at specimens 1, 2, and 3and +4 at specimen 4). There was an increase in thenum-ber of lymphocytes noted aroundthe capillaries from a fac-tor of approximately 25%. The average perivascular lym-phocytic infiltrate on specimen 1 was approximately 11mononuclear cells, which increased to 12 for specimen 2,13 for specimen 3, and 14 for specimen 4.

COMMENT

Combinations of therapeutic agents are often used in thetreatment of photodamaged and chronically aged skin toallow synergy of mechanisms with tolerability. New un-derstanding regarding the pathogenesis of aged skin hasallowed the development of topical medications de-signed to optimize skin appearance when used in con-junction with proper skin care and sun protection rou-tines. Little quantitativeinformation exists in the literatureabout the concomitant use of these products.

The use of skin replica analysis in conjunction withhistologic analysis provided an instrument to evaluate

thechanges in thephotodamagedskinduring the10-weekstudy. Studies6-8,15 have confirmedthe valueofoptical pro-filometry as an objective technique that could reproduc-ibly measure changes in skin topography with minimalvariability or potentialfor bias.Grove et al6 performedskinreplica analyses of photodamaged skin after therapy withtretinoin emollient cream, and improvements were foundin a dose-relatedfashion. Useof 0.05% tretinoin emollientcreamconsistentlygavegreaterreductionsinRaandRzvari-ables relative to vehicle. Data also showedgreater changesin Ra and Rz with EW measurements than with NS mea-surements, supporting the clinical datashowing a greatereffect on superficial fine lines than on coarse wrinkles.Thedeeper crows feet have considerable impact ontheNS

measurements, whereas the contribution of fine lines oncrowsfeetisrelativelygreaterwiththeEWmeasurements. 16

The present study supports 0.05% tretinoin emol-lient cream as an effectivetopical treatment for improvingphotodamagedskin. Significant changes frombaselinewerefound in Ra and Rz variables, with the greatest changes inthe EW axis. The addition of ascorbic acid and treatmentwithtrichloroacetic acidpeels alone resulted in similar find-ings, with significantchanges in Ra andRz variables,againwith the greatest changes in the EW axis. This is consis-tent withfindingsfrom previousstudies11,17,18 demonstrat-ing improvement in fine wrinkling with the use of topicalascorbicacidand superficial trichloroacetic acidpeels. Trai-kovich11 used optical profilometry and clinical analysis to

determine the efficacy of topical ascorbic acid in treatingmild to moderate photodamage. Clinical investigator as-sessment was consistent with findings from skin replicaanalysisshowinggreaterimprovement in finewrinkling anda smoothening of the skin surface.

Group D profilometry results demonstrated signifi-cant changes from baseline (P.005) across the NS andEW measurements of Ra andRz variables. Data were simi-lar for both measurements, indicating further improve-ment with the combination therapy. Examination of pro-filometric data between groups supports these findings.

0

4

2

6

8

10

12

14A B C D

Group

MeanChangeFromB

aseline

RaNS

RaEW

RzNS

RzEW

Shadow NS

Shadow EW

Figure 1.Image analysis results. See the Optical Profilometry subsectionfor descriptions of the variables.

A

B

Figure 2.Histologic comparison between site 1 (A) and site 4 (B)(hematoxylin-eosin, original magnification40).




8/10/2019 QOA20004

5/5

RzEW was significantly different in groups B, C(P.05),andD(P.01) with use of 0.05% tretinoin alone.When trichloroacetic acid peels were performed (groupsC and D), RzNS was also improved. These findings mayinitially indicate an additive effect of the peels to the skincare regimen. This effect is supported in comparison of2 peel groupsand thepatientswho applied tretinoin emol-lient cream and ascorbic acid, resulting in significantchanges in the Rz variables. The additive effect remains

questionable, however, when reviewing the group C andD comparisons. There were no significant differences inthe Rz or Ra variables, although trends were noted in theRzNS (P.06) and RzEW (P.06) variables.

Histologically, several mechanisms have been pro-posed to account for the beneficial effects of skin reju-venation products.4,19,20 A reorganization in dermal struc-tural elements, collagen and elastin, and an increase indermal volume have been found to restore skin struc-ture and function. Researchers21,22 have previously re-ported that an increase in glycosaminoglycan contentwould obligate an influx of water into the dermis, in-creasing the volume and thus decreasing wrinkling.

The most notable early histologic findings23 in pa-

tients treated with tretinoin included increases in epider-malthickness,decreasedmelanocytehypertrophy,andcom-pactionofthe basket-weave pattern of thestratum corneum.Histologic results from this study represent early changesand show progressive changes from groups A to D. Al-thoughthese histologic findingsaresubtle, they were con-sistent with those of previous studies. In our series, thetri-chloroacetic acid peel groups experienced the histologicchanges earlier than groups A or B. Slides from groups Cand D showed increased perivascular lymphocytesaroundthecapillaries, indicating a deeper andexaggerated wound-ing response relative to groups A and B. Treatment in thetrichloroacetic acid groups compared with groups A andB would allow induction ofan inflammatory reactiondeeper

in thetissue. This hasbeen shown to createcumulative ben-efits through activation of the mediators of inflammation,inducing the production of collagen and ground sub-stance (glycosaminoglycans) in the dermis.14

These findings areencouraging, butlimitations of thisstudy include sample size andlength of treatment. Lengthof treatment in studies of similar products varies greatly,providing data in the literature for the short- and long-term effects of these products on the skin. Another limi-tation is that biopsy samples were from skin that does notundergo similar chronic sun exposure as the face. This isof little consequence because the results are comparableto those of the other groups, and nontreated skin is not in-cluded as a biopsy site. Application of the topical prod-

ucts in thepostauricular regionwascarefullyreviewedwitheach patient, and templates were provided for consistencyofplacementandlocalization ofbiopsysites.Product place-ment and timing of application was arranged to minimizeagent crossover. However, one cannot completely controlor measure patient compliance in these matters.

In conclusion, all test products modified some of thevariables selected in the present study. The changes couldall be interpreted as improvements for the skin condi-tions. Significant differences in efficacy were yielded be-tween product combinations. In general, the use of 0.05%

tretinoinemollient creamalone resulted in the weakest ben-eficial effect among the product groups. Trends were notedtoward greater improvement with the addition of ascorbicacid lotion. Useof trichloroaceticacid peelsresultedin thegreatest changes in the study variables. The combinationof trichloroacetic acid peels with the tretinoin emollientcream and ascorbic acid lotion achieved results as good asthe best of its components, and application was toleratedwell. Therefore, for the treatment of photoaging, the com-

bination of these products is well tolerated and superiorto either component as part of a comprehensive skin careand sun protection program.

Accepted for publication October 2, 2002.This paper was selected for the American Academy of

Facial Plastic and Reconstructive Surgery JohnOrlando RoeAward and was presented at the American Academy of Cos-metic Surgery 18th Annual Scientific Meeting, Ft Lauder-dale, Fla, February 1, 2002.

Corresponding author andreprints: JohnD. Rachel, MD,680 N Lake Shore Dr, Suite 1201, Chicago, IL 60611.

REFERENCES

1. Ortonne JP,MarksR. Photodamaged Skin. London, England: MartinDunitz Ltd;1999:11-28.

2. Cunningham WM. Aging and photoaging. In: Baran R, Maibach HI, eds.Text-bookof Cosmetic Dermatology.2nded. London, England: MartinDunitz Ltd; 1998:455-468.

3. MatarassoS. Indications for skinresurfacing.In: Coleman WP,LawrenceN, eds.Skin Resurfacing.Baltimore, Md: Williams & Wilkins; 1998:45-56.

4. Noble S, Wagstaff AJ. Tretinoin: a review of its pharmacological properties andclinicalefficacy inthe topicaltreatmentof photodamaged skin. DrugsAging. 1995;6:479-496.

5. Bhawn J. Short- and long-term histologic effects of topical tretinoin on pho-todamaged skin.Int J Dermatol.1998;37:286-292.

6. Grove GL, Grove MJ, Leyden JJ, et al. Skin replica analysis of photodamagedskinafter therapy withtretinoinemollient cream. J AmAcad Dermatol.1991;25:231-237.

7. Olsen EA, Katz HI, Levine N, et al. Tretinoin emollient cream for photodamagedskin.J Am Acad Dermatol. 1997;37:217-226.

8. Creidi P, Vienne MP, Ochonisky S, et al. Profilometric evaluation of photodam-

age after topical retinaldehyde and retinoic acid treatment. J Am Acad Dermatol.1998;39:960-965.

9. Darr D, Pinnell SR. Reactive oxygen species and antioxidant protection in pho-todermatology. In: Lowe NJL, Shaath NAS, Pathak MAP, eds. Sunscreens.2nded. New York, NY: Marcel Dekker Inc; 1996.

10. ColvenRM,PinnellSR.TopicalvitaminC inaging. ClinDermatol. 1996;14:227-234.11. Traikovich SS.Use of topical ascorbicacid and its effects on photodamaged skin

topography.Arch Otolaryngol Head Neck Surg.1999;125:1091-1098.12. Brodland DG, Cullimore KC, Roenigk RK. Depths of chemoexfoliation induced

by various concentrations andapplication of trichloroacetic acidin a porcine model.J Dermatol Surg Oncol.1989;15:967-971.

13. Lawrence N, Coleman WP. Superficialchemical peeling.In: Coleman WP,LawrenceN, eds.Skin Resurfacing.Baltimore, Md: Williams & Wilkins; 1998:45-56.

14. Basic concepts in skin peeling. In: Rubin MG.Manual of Chemical Peels: Super-ficial and Medium Depths.Philadelphia, Pa: JB Lippincott Co; 1995:44-59.

15. Grove GL, Grove MJ, Leyden JJ. Optical profilometry: an objective method forquantification of facial wrinkles. J Am Acad Dermatol. 1989;21:631-637.

16. Leyden JJ, Grove GL, Grove MJ, et al. Treatment of photodamaged facial skinwith topical tretinoin. J Am Acad Dermatol. 1989;21:638-644.

17. Coleman WP, Brody HJ. Advances in chemical peeling.Dermatol Clin.1997;15:19-26.18. Stuzin JM, Baker TJ, Gordon HL. Treatment of photoaging: facial chemical peel-

ing (phenol and trichloroacetic acid) and dermabrasion.Clin Plast Surg. 1993;20:9-25.

19. Moy LS, Peace S, Moy RL. Comparison of the effect of various chemical peelingagents in a mini-pig model. Dermatol Surg.1996;22:429-432.

20. Butler PE,Gonzalez S, Randolph MA.Quantitative andqualitative effectsof chemi-cal peeling on photo-aged skin. Plast Reconstr Surg.2001;107:222-228.

21. Behin F, Feuerstein SS, Marovitz WF. Comparative histological study of mini pigskin after chemical peel and dermabrasion. Arch Otolaryngol.1977;103:271-277.

22. Vagotis FL,BrundageSR.Histologic studyof dermabrasionandchemicalpeelin ani-malmodel afterpretreatmentwith Retin-A. Aesthetic PlastSurg. 1995;19:243-246.

23. Weiss JS, Ellis CN, Headington JT, et al. Topical tretinoin improves photoagedskin: a double-blind vehicle-controlled study. JAMA.1988;259:527-532.



Documents

QOA20004