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Comparing the effectiveness of Q-switched Ruby laser treatment with that of Q-switched Nd:YAG laser for oculodermal melanosis (Nevus of Ota)
Journal of Plastic, Reconstructive & Aesthetic Surgery (2011) 64, 339e345
Comparing the effectiveness of Q-switched Ruby laser treatment with that of Q-switched Nd:YAG laser for oculodermal melanosis (Nevus of Ota) Cheng-Jen Chang*, Ching-Song Kou Department of Plastic Surgery, Chang Gung Memorial Hospital, Chang Gung University, 199 Tung Hwa North Road, Taipei, Taiwan Received 12 November 2009; accepted 30 May 2010
KEYWORDS Q-switched Ruby laser; Q-switched Nd:YAG laser; Nevus of Ota; DermaSpectrometer
Summary Background and objective: The objective of this study was to compare the e f fi c a c y a n d s a f e t y o f Q - s w i t c h e d Ru b y l a s e r v e r s u s Q - s w i t c h e d n e o d y m i u m : yttriumealuminiumegarnet (Nd:YAG) laser for oculodermal melanosis (Nevus of Ota) birthmarks in a large group of patients. Study design/Materials and methods: A retrospective review was conducted of 94 patients with Nevus of Ota treated with a Q-switched Ruby laser and a Q-switched Nd:YAG laser over a 3-year period. The subjects’ ages ranged from 3 to 64 years; there were 70 females and 24 males, all of whom were of Asian descent. The number of treatments ranged from 1 to 8. Duration of treatment ranged from 6 months to 3 years and 10 months, with a mean of 14 months. Patients (n Z 47) received Q-switched Ruby laser treatment (694 nm) using light dosages of 7e10 J cm 2. Subsequent patients (n Z 47) received Q-switched Nd:YAG laser treatment (1064 nm) using light dosages of 7e10 J cm2. The primary efficacy measurement was the quantitative assessment of clearing and fading response using the DermaSpectrometer for the Q-switched Ruby laser group versus the Q-switched Nd:YAG laser group. Results: Based on a paired t-test, clinical and statistically significant differences in clearing and fading response were observed amongst the Q-switched Ruby laser-treated subjects as preferred to the appearance of Q-switched Nd:YAG laser-treated group (P < 0.05). In both groups, transient hyperpigmentation resolved in all subjects within 6 months. Permanent hyperpigmentation or scarring was not observed in either group. Conclusion: Use of a Q-switched Ruby laser resulted in better clearing and fading as compared with Q-switched Nd:YAG laser. ª 2010 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
* Corresponding author. Tel.: þ886 2 27135211x3502; fax: þ886 2 25140600. E-mail address: [email protected] (C.-J. Chang). 1748-6815/$ - see front matter ª 2010 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.bjps.2010.05.036
340 In 1939, Ota, reported as ‘nevus fusco-caeruleus ophthalmomaxillaris’, was an unusual syndrome consisting of a blue-black or grey-brown patchy pigmentation that most commonly occurs unilaterally or bilaterally in areas innervated by the trigeminal nerve.1 The lesions are present at birth in about 60% of patients and occur most commonly in Asian and dark-skinned patients.2 Histological findings, as seen in Mongolian spots, show that melanin pigment is contained in the dendritic dermal melanocytes. Macular blue staining of the ipsilateral sclera on the affected side is seen frequently. In this setting, melanocytic infiltration of the corneal, conjunctive and infraocular structures has been observed.3e7 Nevus of Ota should not be considered a cosmetic problem, per se, but a disease with potentially devastating psychological complications. Personality development is adversely influenced in all patients because of the reaction of others to a ‘marked person.’ Methodology for such patients has ranged from cosmetic and topical application to surgical procedures such as skin grafting. At present, various laser systems such as an Argon (488 nm and 514 nm), Q-switched Ruby (QSR) (694 nm), Q-switched Alexandrite (QSAlex) (755 nm) and Q-switched neodymium:yttriumealuminiumegarnet (QS Nd:YAG) (1064 nm) lasers have taken preference for clinical treatment of benign epidermal pigmented lesions of the skin.8e18 Such laser systems have also produced notable results when used in the clinical treatment of Nevus of Ota, as well as tattoos.19,20 However, hypertrophic scarring or changes in the normal skin pigmentation still pose as assumed complications that can arise from certain laser systems’ treatment. The purpose of this study was to compare the efficacy and safety of the two most commonly used depigmentation laser systems: the QSR laser and the QS Nd:YAG laser for the treatment of Nevus of Ota.
Materials and methods A review was conducted of 94 patients e all of whom share the same practictioner who led this study, Dr. Cheng-Jen Chang e with facial oculodermal melanosis (Nevus of Ota) birthmarks treated with a QSR laser and a QS Nd:YAG laser over a 3-year period (January 2005 to December 2007). The subjects’ ages ranged from 3 to 64 years; there were 70 females and 24 males, all of whom were Asian. The number of treatments ranged from 1 to 8. The duration of treatment ranged from 6 months to 3 years 10 months, with a mean of 14 months. All patients were observed for a minimum of 1 year following their treatment. Each patient was evaluated by chart review, including pre- and post-treatment photographs. Based on pretreatment photographs, each patient’s Nevus of Ota was assigned a severity grade using the Tanino classification system.21 These patients were separated into four different clinical types: (1) mild, (2) moderate, (3) intensive and (4) bilateral. Information regarding the following variables was extracted from charts: age, sex, Nevus of Ota severity grade prior to laser treatment, number of treatment(s), duration of treatment(s) and improvement following laser therapy. Adverse effects, with attention to scarring (persistent permanent textural changes) and dyspigmentation (transient or permanent, hypo- or hyperpigmentation) were defined, tabulated and reported.
C.-J. Chang, C.-S. Kou Treatments were performed using a QSR laser (l Z 694 nm; tp Z 25 ns, 1 Hz) (Derma-Laser, Hopkinton, MA, USA), and a QS Nd:YAG laser (l Z 1064 nm; tp Z 20e40 ns, 1e10 Hz) (Medlite, Livermore, CA, USA). Laser energy was delivered to the skin through an optical fibre and lens, which focussed the beam onto a 3-mm spot on the Nevus of Ota. Patients (n Z 47) received QSR laser treatment using light dosages of 7e10 J cm2 at 1 Hz. Subsequent patients (n Z 47) received QS Nd:YAG laser treatment using light dosages of 7e10 J cm2, at 5e10 Hz. For quantitative measurement of Nevus of Ota clearing and fading, an estimate of the dermal melanin fraction (melanin index) is required by using a DermaSpectrometer (Cortex Tech., Hadsund, Denmark). DermaSpectrometers have been used for obtaining quantitative treatment results of pigmented lesions for many years.22e24 Light emission is produced from diodes that emit light at two defined wavelengths of 568 nm (green) and 655 nm (red). Therefore, a DermaSpectrometer can be used to measure the absorbed and reflected light at the green and red wavelengths for the determination of oxyhaemoglobin and melanin levels. Calculations of the Nevus of Ota were taken before and after treatment(s) providing an acute way of analysing the values of the lesions and how they fluctuated throughout the observation period. The melanin index for pre-treated lesions, along with those of treated Nevus of Ota, was measured. The patients were observed after treatment(s), and those calculations were used in paired t sample tests to view the response of each group to their received treatment(s), and also to display a better correlation with how the Nevus of Ota differed from the initial pre-treated lesion calculations. The results were calculated and graded on the basis of a clearing and fading response score as follows: poore1 (0e25%), faire2 (26e50%), goode3 (51e75%) and excellente4 (76e100%). In addition, all pre- and post-treatment photographs were taken under standardised conditions for film, light source and exposure. Based on comparisons between preand post-treatment photographs, each patient’s Nevus of Ota was assessed. The pre- and post-treatment clearing and fading assessments were judged by three plastic surgeons knowledgeable and experienced in laser treatment, but not previously involved in the study. Each physician was given pre- and post-treatment photographs of each individual patient’s Nevus of Ota lesion to evaluate by paired comparison. The primary efficacy measure was the quantitative assessment of the clearing and fading response scores of the QSR laser-treated areas as compared, on a blinded basis, to the QS Nd:YAG laser-treated areas. Differences between the mean clearing and fading response scores for both of these groups were then determined and a chi-squared analysis was performed. Safety was evaluated for each treatment group by searching for any adverse effects, such as scarring or dyspigmentation. Scarring of the Nevus of Ota sites was defined as permanent-raised hypertrophic, depressed or atrophic laser-treated. Dyspigmentation was defined as a transient (resolving within 6 months post-treatment) or permanent change in skin colour on laser-treated Nevus of Ota sites as compared with adjacent normal skin.
Laser treatment of oculodermal melanosis Table 1
341
Treatment(s) outcome(s) of 94 patients with Nevus of Ota by Q-switched Ruby laser vs Q-switched Nd:YAG laser.
Outcome No. of Treatments
Poor (0e25%) QSRL
QS Nd:YAG QSRL
Fair (26e50%)
QS Nd:YAG QSRL
QS Nd:YAG QSRL
QS Nd:YAG QSRL
1 2 3 4 5 6 7 8 No. of patients percent
3 0 0 0 0 0 0 0 3 (3.2)
3 0 0 0 0 0 0 0 3 (3.2)
4 7 1 0 0 0 0 0 12 (11.7)
0 2 5 2 3 3 1 0 16 (17.0)
0 0 2 6 2 4 1 1 16 (17.0)
5 7 0 0 0 0 0 0 12 (12.7)
Good (51e75%)
0 1 7 3 0 0 0 0 11 (11.7)
Results
Excellent (76e100%)
0 0 2 8 3 5 1 2 21 (22.3)
Total (%)
8 8 9 11 3 5 1 2 47
QS Nd:YAG
(8.5) 7 (8.5) 9 (9.6) 8 (11.7) 8 (3.2) 5 (5.3) 7 (1.1) 2 (2.2) 1 (50.0) 47
(7.5) (9.6) (8.5) (8.5) (5.3) (7.5) (2.1) (1.1) (50.0)
Information regarding the variables of age, sex, severity score of Nevus of Ota prior to laser treatment(s), number of treatments and duration of treatment(s) was obtained for statistical analysis. The mean ages for the QSR laser and QS Nd:YAG laser groups were 27.5 and 28.3 years, respectively. The male-to-female ratios for the corresponding groups were 13:34 and 11:36, respectively. Nevus of Ota classification of severity grades were as follows: 23 patients for severity grade 1, 31 for severity grade 2, 34 for severity grade 3 and six for severity grade 4. The mean severity grades for the QS laser and QS Nd:YAG laser groups were 1.73 and 1.70, respectively; the mean number of laser treatments for the corresponding groups was 3.47 and 3.62, respectively (Table 1). Based on a multivariate analysis of variance (MANOVA; Chicago, IL, USA), there were no statistically significant differences between the two groups based on age, sex, Nevus of Ota severity grade prior to laser treatment(s) and number of treatments (P > 0.05). Of the 94 patients treated, 15 patients received only one treatment and 14 had two treatments with poor or fair fading response (Table 1). In the QSR laser group, 21 patients (44.7% of this group) had excellent results after treatment. Ten of these 21 patients (21.3%) required three or four treatments to achieve excellent results. The remaining 11 patients (23.4%) achieved such results after five to eight treatments. In the QS Nd:YAG laser group, 16 patients (34.0% of this group) had excellent results after treatment. Eight of these 21 patients (17.0%) required
three to four treatments to achieve excellent results. The other eight patients (17.0%) received excellent results following five to eight treatments. Such results among these two laser groups support the study’s implications for substantial Nevus of Ota fading by laser treatment. As the melanin index for normal skin ranges from 25.2e40.1 with a mean of 32.21 2.75, such an average was used for observation and analysis. In general, the mean melanin index of clearing and fading response scores of 46 patients between both groups showed excellent results, and thus provides a statistically significant difference in calculable analysis by means of a paired test with a P value of 0.01 (P < 0.05) (Table 2). For patients with severity grades 1 and 2 of Nevus of Ota, the quantitative assessment of QSR laser-treated patients as compared with QS Nd:YAG laser-treated patients with excellent melanin clearing and fading response scores were 36.95 1.35 and 35.79 1.70, respectively. However, with a P value of 0.471 (P > 0.05), analysis did not yield statistically significant results (Table 3). Quantitative assessment of QSR laser-treated patients as compared with QS Nd:YAG laser-treated patients with severity grade 3 and 4 Nevus of Ota produced excellent melanin clearing and fading response scores of 49.61 1.54 and 53.47 1.28, respectively. Based on their paired t-test analysis, the difference proved significant and favoured the QSR laser group as compared with the QS Nd:YAG laser group with a P value of 0.044 (P < 0.05) (Table 4). Conclusively for all patients, quantitative assessment of melanin clearing and fading response scores for each
Table 2 Mean Melanin d Index of patients Nevus of Ota clearing and fading response.
Table 3 Mean Melanin d Index of clearing and fading response of Nevus of Ota severity grade 1 & 2.
Excellent Good Fair Poor
No of Patients (94)
QSRL*
QS Nd:YAG*
46 19 23 6
36.9 1.53 46.6 2.07 54.2 1.63 63.1 1.44
40.7 1.74 49.8 2.39 55.7 1.76 66.5 1.83
* mean-index of normal skin Z 32.21 2.75. Note: ** P < 0.05.
Excellent Good Fair Poor
No of Patients (44)
QSRL*
QS Nd:YAG*
14 16 10 4
36.9 1.35 40.1 1.53 43.5 1.07 46.6 1.47
35.7 1.70 40.4. 1.46. 44.7. 1.11 48.5 1.75
* mean-index of normal skin Z 32.21 2.75. Note: ** P > 0.05.
342
C.-J. Chang, C.-S. Kou
Table 4 Mean Melanin d Index of clearing and fading response of Nevus of Ota severity grade 3 & 4.
Excellent Good Fair Poor
No of Patients (50)
QSRL*
QS Nd:YAG*
10 13 13 14
49.6 1.54 54.5 1.08 61.8 1.42 64.3 1.88
53.4 1.28 55.7 1.51 63.1 1.97 68.3 1.28
* mean-index of normal skin Z 32.21 2.75. Note: ** P < 0.05.
treated patient based on paired t-test analysis indicated superior enhancement and the most statistically significant improvement in the Nevus of Ota group receiving the QSR laser treatment (Figures 1 and 2) as compared with the QS Nd:YAG laser. Safety was evaluated for each Nevus of Ota group by searching for any early adverse effects such as scarring or dyspigmentation following treatment(s). Scarring was noted in 3.1% (n Z 3) of the patients. In the QSR laser group, a lesion on the nose of one patient, treated with 10 J cm2, revealed a small scar. In the QS Nd:YAG laser group, two patients developed one lesion (on the malar area and treated with 10 J cm2 at 10 Hz and on the periorbital rim treated with 9 J cm2 at 10 Hz). These two lesions developed in small areas of hypertrophic tissue approximately 0.7 cm in length and 0.3 cm wide following treatment. In those three cases, scars cleared up within 6 months without medical intervention. Permanent scarring was not observed in either group (Figure 3). Transient hyperpigmentation was noted in 6.4% (n Z 3) and 10.6% (n Z 5) of patients in the QSR laser group and QS Nd:YAG laser group, respectively. In both groups, transient hyperpigmentation was resolved without medical intervention in all patients within 6 months. Transient hypopigmentation was noted in 10.6% (n Z 5) and 14.9% (n Z 7)
of patients in the QSR Ruby laser group and QS Nd:YAG laser group, respectively. In both groups, transient hypopigmentation was resolved without medical intervention in each of the patients within 1 year. Patients who underwent subsequent treatment sessions to improve such early adverse effects suffered no complications. Based on their paired t-test analysis, the difference was not statistically significant between the QSR Ruby laser and the QS Nd: YAG laser with a P value of 0.065 (P > 0.05) (Table 5).
Discussion Most medical professionals today agree that melanocytes are of neuroectodermal origin. The dendritic melanocytes, found in a network along the epidermal basal lamina layer, originate from the embryonic neural crest (melanoblasts) and migrate into the epidermis during the 10th week of embryonic life. Most melanocytes diminish in number or melanogenic activity gradually during the foetal stages. Possible aetiologies of Nevus of Ota are: (1) failure of dermal melanocytes to disappear during foetal stage; (2) the arrested migration of melanocytes in the dermis; and (3) active melanin production by intradermal melanocytes.25 Melanin is formed in melanocytes and is contained in membrane-bound organelles known as melanosomes. Developmentally, melanosomes evolve from small Golgiderived vesicles containing tyrosinase; melanin deposition occurs where these vesicles contain tyrosinase. The calculated diameter for these melanin-containing structures is approximately 1.0 mm.26 The principal pathologic changes noted in Nevus of Ota are in the upper and middle dermis, which contains fusiform, dendritic or stellate, highly pigmented melanocytes in wide dispersion. At times, the melanocytes encircle the surrounding supporting connective-tissue sheaths of the adnexal structures. Nevertheless, the melanocytes generally lie with their long axes parallel to the skin surface. This may add weight to the assumption of an origin from which these dermal melanocytes,
Figure 1 Three-year-old Asian female with Nevus of Ota of the right cheek: A) prior to laser therapy; and B) two years after three treatments with Q-switched Ruby laser (694 nm) using an energy density of 9 J/cm2. Result was evaluated as an excellent cleaning and fading response.
Laser treatment of oculodermal melanosis
343
Figure 2 Sixteen-year-old Asian female with Nevus of Ota of the left cheek: A) prior to laser therapy; and B) three years after four treatments with Q-switched Ruby laser (694 nm) using an energy density of 9e10 J/cm2. Result was evaluated as an excellent cleaning and fading response.
Schwann cells or a neural element develop. The distribution of Nevus of Ota in the area of cutaneous nerves (trigeminal) presented in our patients indicated a neural relationship. It is interesting to note that the most common distribution seen was that of V2 (zygomatic branch).27e29 This does not necessarily imply that lesions with a V2 distribution are more common; however, it may be explained on the basis of anatomy and cosmesis, given that V2 is in the central face, that these patients may have
simply presented this outcome more frequently because of cosmetic concern or ophthalmic involvement. Although several other modalities such as dry ice, dermabrasion, electrodesiccation and skin grafting have been applied in the treatment for Nevus of Ota,13 nonspecific damage to adjacent structures occurs. In laser therapy, if a laser with a pulse duration shorter than the thermal relaxation time of the target structures (approximately 0.5e1 ms for melanosomes, and 7 ms for
Figure 3 Eighteen-year-old Asian male with Nevus of Ota of the right cheek. A) prior to laser therapy; B); and C) three years after five treatments with Q-switched Nd-YAG laser (1064 nm) using an energy density of 9e10 J/cm2. Result was evaluated as an excellent cleaning and fading response.
344
C.-J. Chang, C.-S. Kou
Table 5 Early adverse effects after laser treatment(s) for Nevus of Ota in 94 patients. No. of patients
Percent
QSRL QS Nd:YAG QSRL QS Nd:YAG Edema Erythema Ecchymosis Vesiculation Hypopigmentation Hyperpigmentation Scar
40 23 2 3 5 3 1
43 37 4 6 7 5 2
42.6 24.5 2.1 3.2 5.3 3.2 2.1
45.7 39.4 4.2 6.4 7.5 5.3 1.1
P > 0.05.
melanocytes) is used, selective thermal damage to only the targeted melanin-containing structure will be achieved. Thermal relaxation time is defined as the time required for the heat generated by the absorbed light energy within the target chromophore to cool to one-half the original value immediately after the laser pulse.26 Therefore, although the argon laser has been reported as an effective treatment for Nevus of Ota,8,20 the shortest available pulse duration is 0.01 s, which explains the nonspecific thermal damage produced by this device. In QSR laser therapy, high-intensity flash lamps are used to excite the ruby crystal (aluminium trioxide doped with chromium ions) to produce red photons at a wavelength of 694 nm with 20e40-ns pulse durations and extremely high peak powers (greater than 106 W cm2) at a maximum energy density of 10 J cm2. This laser pulse is suitably brief, and all the energy is invested in the target chromophore before much heat is lost by thermal diffusion out of the exposure field. Disruption of melanosomes at pulse widths less than the thermal relaxation time notably resulted from a shock wave for cavitations induced by thermal expansion. This result demonstrated that selective target damage can be expected due to the absorption of a specific wavelength with a pulse duration less than the thermal relaxation time.26,30e32 Thermal injury was observed to be intensified in the Nevus of Ota receiving QS Nd:YAG laser, which can be inferred to be due to the difference in wavelength intensity compared with that of the Q-switch Ruby laser. Overlapping laser spots during QSR laser treatment appeared to result in a more even fading of the lesion and did not leave the chequerboard or latticelike pattern seen when spaces were left between treated areas. The degree of overlap of laser pulses in our study was a matter of personal preference, without any data to support one approach over another. The definitive cause of the immediate change in skin colour following QSR laser irradiation, from darkly pigmented to ash white, is still unknown. Three hypotheses have been suggested: (1) an increase in optical scattering, and (2) a decrease in optical absorption or (3) both. A more probable explanation is that the empty spaces within ruptured melanosomes were the remnants of small vapour cavities induced in melanosomes by steam and pyrolytic products. Such vapour cavities would be of an appropriate size and optical character to scatter visible light strongly, and their gradual dissolution would explain the transient nature of the whitening.31,32
The clinical efficacy of QSR laser therapy has now been demonstrated in our facilities. In this study, excellent results were seen in 21 patients (44.68%) and good results in 11 patients (23.41%). In this series, all patients with an excellent assessment were due because of three or more treatments. Our results demonstrated that the number of treatments is related to the severity of the lesions. In contrast to other laser systems, no hypertrophic scarring, cutaneous depression, atrophy or skin changes occurred after use of the QSR laser. Test dosing to determine the lowest energy density that resulted in significant or complete fading of the lesion without these complications was one of the reasons for these results. Until the development of the QSR laser, children with Nevus of Ota had little hope of seeking remedial and/or lasting medical assistance from plastic surgeons. With this type of laser treatment, even children at their early adolescent years can be treated safely. Their chance of acquiring a dark lesion can thus be decreased. At present, there are no reports recommending the appropriate time and number of treatments for children. Our only child patient, who received QSR laser therapy, was 3 years old, and produced an excellent result after three treatments. This demonstrates that children can be treated successfully and thereby spared the psychological trauma of growing up with Nevus of Ota. The wavelength, pulse duration and energy densities inherent in the Q-switched Ruby laser and Q-switched Nd:YAG laser provide the desired laser parameters for melanin-selective photothermolysis. The significant degree of lesion clearing and fading, with no associated scarring or other nonspecific side effects, attests to the clinical advantage of having increased melanin pigmentladen cell selectivity. It is apparent that the Q-switched Ruby laser and the Q-switched Nd:YAG laser allow plastic surgeons an excellent clinical outcome for the treatment of Nevus of Ota while minimising potential adverse side effects. For achieving excellent results, the Q-switched Ruby laser was favoured due to the minimal number of treatments as compared with the Q-switched Nd:YAG laser. However, long-term follow-up and careful comparison with results obtained from these two treatment methods and other laser systems are necessary before final conclusions can be drawn.
Acknowledgements The authors gratefully acknowledge the support of J. Stuart Nelson MD, PhD, at the Beckman Laser Institute and Medical Clinic and Robert L.Newcomb, PhD, Director of the Center for Statistical Consulting, both at the University of California Irvine, who performed the statistical analyses.
Conflict of interest The authors state no conflict of interest.
References 1. Ota M. Nevus fuscocoerulens ophthalmo maxillaris. Tokio Med J 1939;63:1243e5.
Laser treatment of oculodermal melanosis 2. Hidallo A, kajima H, lkeda S, et al. Natural history of nevus of Ota. Arch Dermatol 1967;95:l87e95. 3. Font RL, Reyno1ds Jr AM, Zimmerman LE. Diffuse malignant melanoma of the iris in the nevus of Ota. Arch Ophthalmol 1967;77:513e8. 4. Halase A. Malignant melanoma in a case of bilateral nevus of Ota. Arch Ophthalmol 1970;84:l76. 5. Sang DN, Albert DM, Sober AJ, et al. Nevus of Ota with contralateral cerebral melanoma. Arch Ophthalmol 1977;95: 1820e4. 6. Gonder JR, Shields JA, Albert DM. Malignant melanoma of the choroid associated with oculodermal melanocytosis. Ophthalmology 1981;88:372e6. 7. Haim T, Meyer E, Kerner H, et al. Oculodermal melanocytosis (Nevus of Ota) and orbital malignant melanoma. Ann Ophthalmol 1982;l4:1132e6. 8. Goldberg DJ, Nychay SG. Q-switched ruby laser treatment of nevus of Ota. J Dermatol Surg Oncol 1992;l8:817e21. 9. Coldberg DJ. Benign pigmented lesions of the skin. Treatment with the Q-switched ruby laser. J Dermatol Surg Oncol 1993;l9: 376e9. 10. Tayor CK, Gange RW, Dover JS, et al. Treatment of tattoos by Q-switched ruby laser. A dose-response study. Arch Dermatol 1990;126:893e9. 11. Scheibner A, Kenny G, White W, et al. A superior method of tattoo removal using the Q-switched ruby laser. J Dermatol Surg Oncol 1990;16:1091e8. 12. Geronemus RG. Q-Switched ruby laser therapy of nevus of Ota. Arch Dermatol 1992;128:1618e22. 13. Taylor CR, Flotte TJ, Gange RW, et al. Treatment of nevus of Ota by Q-Switched ruby laser. J Am Acad Dermatol 1994;30:743e51. 14. Ogata H. Evaluation of the effect of Q-switched Ruby and Q-switched Nd-YAG laser irradiation on melanosomes in dermal melanocytosis. Keio J Med 1997;46:188e95. 15. Omprakash HM. Treatment of Nevus of OTA by Q-switched, frequency doubled, ND:YAG laser. Indian J Dermatol Venereol Leprol 2002;68:94e5. 16. Lam AY, Wong DS, Lam LK, et al. A retrospective study on the efficacy and complications of Q-switched Alexandrite laser in the treatment of acquired bilateral Nevus of Ota-like macules. Dermatol Surg 2001;27:937e41. 17. Chan HH, Leung RS, Ying SY, et al. A retrospective analysis of complications in the treatment of Nevus of Ota with the Q-switched Alexandrite and Q-switched Nd:YAG lasers. Dermatol Surg 2000;26:1000e6.
345 18. Chan HH, King WW, Chan ES, et al. In vivo trial comparing patients’ tolerance of Q-switched Alexandrite (QS Alex) and Q-switched neodymium:yttrium-aluminum-garnet (QS Nd:YAG) lasers in the treatment of Nevus of Ota. Lasers Surg Med 1999; 24:24e8. 19. Apfelberg DB, Maser MR, Lash H, et al. The argon laser for cutaneous lesions. J Am Med Assoc 1981;245:2073e5. 20. Apfelberg DB. Argon and Q-switched yttrium-aluminum-garnet laser treatment of nevus of Ota. Ann Plast Surg 1995;35:150e3. 21. Tanino H. Naevus fusco-caeruleus ophthalmomaxillaris (Ota). Jpn J Dermatol 1939;46:107e11. 22. Lualdi M, Colombo A, Carrara L, et al. Optical devices used for image analysis of pigmented skin lesions: a proposal for quality assurance protocol using tissue-like phantoms. Phys Med Biol 2006;51:429e40. 23. Rallan D, Bush NL, Bamber JC, et al. Quantitative discrimination of pigmented lesions using three-dimensional highresolution ultrasound reflex transmission imaging. J Invest Dermatol 2007;127:189e95. 24. Manousaki AG, Manios AG, Tsompanaki EI, et al. Use of color texture in determining the nature of melanocytic skin lesionsea qualitative and quantitative approach. Comput Biol Med 2006 Apr;36:419e27. 25. Kopf AW, Weidman AI. Nevus of Ota. Arch Dermatol 1962;85: 195e208. 26. Anderson RR, Parrish JA. Selective photothermolysis: precise microsurgery by selective absorption of pulsed radiation. Science 1983;220:524e7. 27. Chang CJ. Q-switch ruby laser for treatment of pigmented lesions. J Formosan Med Assoc Cont Med Edu 1993;3:1e3. 28. Chang CJ, Nelson JS. Q-Switched ruby laser treatment of mucocutaneous melanosis associated with Peutz-Jeghers syndrome. Ann Plast Surg 1996;36:394e7. 29. Chang CJ, Nelson JS, Achauer BM. Q-Switched ruby laser of oculodermal melanosis (Nevus of Ota). Plast Reconstr Surg 1996;98:784e90. 30. Hruza GJ, Dover JS, Flotte TJ, et al. Q-switched ruby laser irradiation of normal human skin. Histologic and ultrastructural findings. Arch Dermatol 1991;127:1799e805. 31. Polla LL, Margolis RJ, Dover JS, et al. Melanosomes are a primary target of Q-switched ruby laser irradiation in guinea pig skin. J Invest Dermatol 1987;89:281e6. 32. Dover JS, Margolis RJ, Polla LL. Pigmented guinea pig skin irradiated with Q-Switched ruby laser pulses. Arch Dermatol 1989;125:43e9.
Comparing the effectiveness of Q-switched Ruby laser treatment with that of Q-switched Nd:YAG laser for oculodermal melanosis (Nevus of Ota) Cheng-Jen Chang*, Ching-Song Kou Department of Plastic Surgery, Chang Gung Memorial Hospital, Chang Gung University, 199 Tung Hwa North Road, Taipei, Taiwan Received 12 November 2009; accepted 30 May 2010
KEYWORDS Q-switched Ruby laser; Q-switched Nd:YAG laser; Nevus of Ota; DermaSpectrometer
Summary Background and objective: The objective of this study was to compare the e f fi c a c y a n d s a f e t y o f Q - s w i t c h e d Ru b y l a s e r v e r s u s Q - s w i t c h e d n e o d y m i u m : yttriumealuminiumegarnet (Nd:YAG) laser for oculodermal melanosis (Nevus of Ota) birthmarks in a large group of patients. Study design/Materials and methods: A retrospective review was conducted of 94 patients with Nevus of Ota treated with a Q-switched Ruby laser and a Q-switched Nd:YAG laser over a 3-year period. The subjects’ ages ranged from 3 to 64 years; there were 70 females and 24 males, all of whom were of Asian descent. The number of treatments ranged from 1 to 8. Duration of treatment ranged from 6 months to 3 years and 10 months, with a mean of 14 months. Patients (n Z 47) received Q-switched Ruby laser treatment (694 nm) using light dosages of 7e10 J cm 2. Subsequent patients (n Z 47) received Q-switched Nd:YAG laser treatment (1064 nm) using light dosages of 7e10 J cm2. The primary efficacy measurement was the quantitative assessment of clearing and fading response using the DermaSpectrometer for the Q-switched Ruby laser group versus the Q-switched Nd:YAG laser group. Results: Based on a paired t-test, clinical and statistically significant differences in clearing and fading response were observed amongst the Q-switched Ruby laser-treated subjects as preferred to the appearance of Q-switched Nd:YAG laser-treated group (P < 0.05). In both groups, transient hyperpigmentation resolved in all subjects within 6 months. Permanent hyperpigmentation or scarring was not observed in either group. Conclusion: Use of a Q-switched Ruby laser resulted in better clearing and fading as compared with Q-switched Nd:YAG laser. ª 2010 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
* Corresponding author. Tel.: þ886 2 27135211x3502; fax: þ886 2 25140600. E-mail address: [email protected] (C.-J. Chang). 1748-6815/$ - see front matter ª 2010 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.bjps.2010.05.036
340 In 1939, Ota, reported as ‘nevus fusco-caeruleus ophthalmomaxillaris’, was an unusual syndrome consisting of a blue-black or grey-brown patchy pigmentation that most commonly occurs unilaterally or bilaterally in areas innervated by the trigeminal nerve.1 The lesions are present at birth in about 60% of patients and occur most commonly in Asian and dark-skinned patients.2 Histological findings, as seen in Mongolian spots, show that melanin pigment is contained in the dendritic dermal melanocytes. Macular blue staining of the ipsilateral sclera on the affected side is seen frequently. In this setting, melanocytic infiltration of the corneal, conjunctive and infraocular structures has been observed.3e7 Nevus of Ota should not be considered a cosmetic problem, per se, but a disease with potentially devastating psychological complications. Personality development is adversely influenced in all patients because of the reaction of others to a ‘marked person.’ Methodology for such patients has ranged from cosmetic and topical application to surgical procedures such as skin grafting. At present, various laser systems such as an Argon (488 nm and 514 nm), Q-switched Ruby (QSR) (694 nm), Q-switched Alexandrite (QSAlex) (755 nm) and Q-switched neodymium:yttriumealuminiumegarnet (QS Nd:YAG) (1064 nm) lasers have taken preference for clinical treatment of benign epidermal pigmented lesions of the skin.8e18 Such laser systems have also produced notable results when used in the clinical treatment of Nevus of Ota, as well as tattoos.19,20 However, hypertrophic scarring or changes in the normal skin pigmentation still pose as assumed complications that can arise from certain laser systems’ treatment. The purpose of this study was to compare the efficacy and safety of the two most commonly used depigmentation laser systems: the QSR laser and the QS Nd:YAG laser for the treatment of Nevus of Ota.
Materials and methods A review was conducted of 94 patients e all of whom share the same practictioner who led this study, Dr. Cheng-Jen Chang e with facial oculodermal melanosis (Nevus of Ota) birthmarks treated with a QSR laser and a QS Nd:YAG laser over a 3-year period (January 2005 to December 2007). The subjects’ ages ranged from 3 to 64 years; there were 70 females and 24 males, all of whom were Asian. The number of treatments ranged from 1 to 8. The duration of treatment ranged from 6 months to 3 years 10 months, with a mean of 14 months. All patients were observed for a minimum of 1 year following their treatment. Each patient was evaluated by chart review, including pre- and post-treatment photographs. Based on pretreatment photographs, each patient’s Nevus of Ota was assigned a severity grade using the Tanino classification system.21 These patients were separated into four different clinical types: (1) mild, (2) moderate, (3) intensive and (4) bilateral. Information regarding the following variables was extracted from charts: age, sex, Nevus of Ota severity grade prior to laser treatment, number of treatment(s), duration of treatment(s) and improvement following laser therapy. Adverse effects, with attention to scarring (persistent permanent textural changes) and dyspigmentation (transient or permanent, hypo- or hyperpigmentation) were defined, tabulated and reported.
C.-J. Chang, C.-S. Kou Treatments were performed using a QSR laser (l Z 694 nm; tp Z 25 ns, 1 Hz) (Derma-Laser, Hopkinton, MA, USA), and a QS Nd:YAG laser (l Z 1064 nm; tp Z 20e40 ns, 1e10 Hz) (Medlite, Livermore, CA, USA). Laser energy was delivered to the skin through an optical fibre and lens, which focussed the beam onto a 3-mm spot on the Nevus of Ota. Patients (n Z 47) received QSR laser treatment using light dosages of 7e10 J cm2 at 1 Hz. Subsequent patients (n Z 47) received QS Nd:YAG laser treatment using light dosages of 7e10 J cm2, at 5e10 Hz. For quantitative measurement of Nevus of Ota clearing and fading, an estimate of the dermal melanin fraction (melanin index) is required by using a DermaSpectrometer (Cortex Tech., Hadsund, Denmark). DermaSpectrometers have been used for obtaining quantitative treatment results of pigmented lesions for many years.22e24 Light emission is produced from diodes that emit light at two defined wavelengths of 568 nm (green) and 655 nm (red). Therefore, a DermaSpectrometer can be used to measure the absorbed and reflected light at the green and red wavelengths for the determination of oxyhaemoglobin and melanin levels. Calculations of the Nevus of Ota were taken before and after treatment(s) providing an acute way of analysing the values of the lesions and how they fluctuated throughout the observation period. The melanin index for pre-treated lesions, along with those of treated Nevus of Ota, was measured. The patients were observed after treatment(s), and those calculations were used in paired t sample tests to view the response of each group to their received treatment(s), and also to display a better correlation with how the Nevus of Ota differed from the initial pre-treated lesion calculations. The results were calculated and graded on the basis of a clearing and fading response score as follows: poore1 (0e25%), faire2 (26e50%), goode3 (51e75%) and excellente4 (76e100%). In addition, all pre- and post-treatment photographs were taken under standardised conditions for film, light source and exposure. Based on comparisons between preand post-treatment photographs, each patient’s Nevus of Ota was assessed. The pre- and post-treatment clearing and fading assessments were judged by three plastic surgeons knowledgeable and experienced in laser treatment, but not previously involved in the study. Each physician was given pre- and post-treatment photographs of each individual patient’s Nevus of Ota lesion to evaluate by paired comparison. The primary efficacy measure was the quantitative assessment of the clearing and fading response scores of the QSR laser-treated areas as compared, on a blinded basis, to the QS Nd:YAG laser-treated areas. Differences between the mean clearing and fading response scores for both of these groups were then determined and a chi-squared analysis was performed. Safety was evaluated for each treatment group by searching for any adverse effects, such as scarring or dyspigmentation. Scarring of the Nevus of Ota sites was defined as permanent-raised hypertrophic, depressed or atrophic laser-treated. Dyspigmentation was defined as a transient (resolving within 6 months post-treatment) or permanent change in skin colour on laser-treated Nevus of Ota sites as compared with adjacent normal skin.
Laser treatment of oculodermal melanosis Table 1
341
Treatment(s) outcome(s) of 94 patients with Nevus of Ota by Q-switched Ruby laser vs Q-switched Nd:YAG laser.
Outcome No. of Treatments
Poor (0e25%) QSRL
QS Nd:YAG QSRL
Fair (26e50%)
QS Nd:YAG QSRL
QS Nd:YAG QSRL
QS Nd:YAG QSRL
1 2 3 4 5 6 7 8 No. of patients percent
3 0 0 0 0 0 0 0 3 (3.2)
3 0 0 0 0 0 0 0 3 (3.2)
4 7 1 0 0 0 0 0 12 (11.7)
0 2 5 2 3 3 1 0 16 (17.0)
0 0 2 6 2 4 1 1 16 (17.0)
5 7 0 0 0 0 0 0 12 (12.7)
Good (51e75%)
0 1 7 3 0 0 0 0 11 (11.7)
Results
Excellent (76e100%)
0 0 2 8 3 5 1 2 21 (22.3)
Total (%)
8 8 9 11 3 5 1 2 47
QS Nd:YAG
(8.5) 7 (8.5) 9 (9.6) 8 (11.7) 8 (3.2) 5 (5.3) 7 (1.1) 2 (2.2) 1 (50.0) 47
(7.5) (9.6) (8.5) (8.5) (5.3) (7.5) (2.1) (1.1) (50.0)
Information regarding the variables of age, sex, severity score of Nevus of Ota prior to laser treatment(s), number of treatments and duration of treatment(s) was obtained for statistical analysis. The mean ages for the QSR laser and QS Nd:YAG laser groups were 27.5 and 28.3 years, respectively. The male-to-female ratios for the corresponding groups were 13:34 and 11:36, respectively. Nevus of Ota classification of severity grades were as follows: 23 patients for severity grade 1, 31 for severity grade 2, 34 for severity grade 3 and six for severity grade 4. The mean severity grades for the QS laser and QS Nd:YAG laser groups were 1.73 and 1.70, respectively; the mean number of laser treatments for the corresponding groups was 3.47 and 3.62, respectively (Table 1). Based on a multivariate analysis of variance (MANOVA; Chicago, IL, USA), there were no statistically significant differences between the two groups based on age, sex, Nevus of Ota severity grade prior to laser treatment(s) and number of treatments (P > 0.05). Of the 94 patients treated, 15 patients received only one treatment and 14 had two treatments with poor or fair fading response (Table 1). In the QSR laser group, 21 patients (44.7% of this group) had excellent results after treatment. Ten of these 21 patients (21.3%) required three or four treatments to achieve excellent results. The remaining 11 patients (23.4%) achieved such results after five to eight treatments. In the QS Nd:YAG laser group, 16 patients (34.0% of this group) had excellent results after treatment. Eight of these 21 patients (17.0%) required
three to four treatments to achieve excellent results. The other eight patients (17.0%) received excellent results following five to eight treatments. Such results among these two laser groups support the study’s implications for substantial Nevus of Ota fading by laser treatment. As the melanin index for normal skin ranges from 25.2e40.1 with a mean of 32.21 2.75, such an average was used for observation and analysis. In general, the mean melanin index of clearing and fading response scores of 46 patients between both groups showed excellent results, and thus provides a statistically significant difference in calculable analysis by means of a paired test with a P value of 0.01 (P < 0.05) (Table 2). For patients with severity grades 1 and 2 of Nevus of Ota, the quantitative assessment of QSR laser-treated patients as compared with QS Nd:YAG laser-treated patients with excellent melanin clearing and fading response scores were 36.95 1.35 and 35.79 1.70, respectively. However, with a P value of 0.471 (P > 0.05), analysis did not yield statistically significant results (Table 3). Quantitative assessment of QSR laser-treated patients as compared with QS Nd:YAG laser-treated patients with severity grade 3 and 4 Nevus of Ota produced excellent melanin clearing and fading response scores of 49.61 1.54 and 53.47 1.28, respectively. Based on their paired t-test analysis, the difference proved significant and favoured the QSR laser group as compared with the QS Nd:YAG laser group with a P value of 0.044 (P < 0.05) (Table 4). Conclusively for all patients, quantitative assessment of melanin clearing and fading response scores for each
Table 2 Mean Melanin d Index of patients Nevus of Ota clearing and fading response.
Table 3 Mean Melanin d Index of clearing and fading response of Nevus of Ota severity grade 1 & 2.
Excellent Good Fair Poor
No of Patients (94)
QSRL*
QS Nd:YAG*
46 19 23 6
36.9 1.53 46.6 2.07 54.2 1.63 63.1 1.44
40.7 1.74 49.8 2.39 55.7 1.76 66.5 1.83
* mean-index of normal skin Z 32.21 2.75. Note: ** P < 0.05.
Excellent Good Fair Poor
No of Patients (44)
QSRL*
QS Nd:YAG*
14 16 10 4
36.9 1.35 40.1 1.53 43.5 1.07 46.6 1.47
35.7 1.70 40.4. 1.46. 44.7. 1.11 48.5 1.75
* mean-index of normal skin Z 32.21 2.75. Note: ** P > 0.05.
342
C.-J. Chang, C.-S. Kou
Table 4 Mean Melanin d Index of clearing and fading response of Nevus of Ota severity grade 3 & 4.
Excellent Good Fair Poor
No of Patients (50)
QSRL*
QS Nd:YAG*
10 13 13 14
49.6 1.54 54.5 1.08 61.8 1.42 64.3 1.88
53.4 1.28 55.7 1.51 63.1 1.97 68.3 1.28
* mean-index of normal skin Z 32.21 2.75. Note: ** P < 0.05.
treated patient based on paired t-test analysis indicated superior enhancement and the most statistically significant improvement in the Nevus of Ota group receiving the QSR laser treatment (Figures 1 and 2) as compared with the QS Nd:YAG laser. Safety was evaluated for each Nevus of Ota group by searching for any early adverse effects such as scarring or dyspigmentation following treatment(s). Scarring was noted in 3.1% (n Z 3) of the patients. In the QSR laser group, a lesion on the nose of one patient, treated with 10 J cm2, revealed a small scar. In the QS Nd:YAG laser group, two patients developed one lesion (on the malar area and treated with 10 J cm2 at 10 Hz and on the periorbital rim treated with 9 J cm2 at 10 Hz). These two lesions developed in small areas of hypertrophic tissue approximately 0.7 cm in length and 0.3 cm wide following treatment. In those three cases, scars cleared up within 6 months without medical intervention. Permanent scarring was not observed in either group (Figure 3). Transient hyperpigmentation was noted in 6.4% (n Z 3) and 10.6% (n Z 5) of patients in the QSR laser group and QS Nd:YAG laser group, respectively. In both groups, transient hyperpigmentation was resolved without medical intervention in all patients within 6 months. Transient hypopigmentation was noted in 10.6% (n Z 5) and 14.9% (n Z 7)
of patients in the QSR Ruby laser group and QS Nd:YAG laser group, respectively. In both groups, transient hypopigmentation was resolved without medical intervention in each of the patients within 1 year. Patients who underwent subsequent treatment sessions to improve such early adverse effects suffered no complications. Based on their paired t-test analysis, the difference was not statistically significant between the QSR Ruby laser and the QS Nd: YAG laser with a P value of 0.065 (P > 0.05) (Table 5).
Discussion Most medical professionals today agree that melanocytes are of neuroectodermal origin. The dendritic melanocytes, found in a network along the epidermal basal lamina layer, originate from the embryonic neural crest (melanoblasts) and migrate into the epidermis during the 10th week of embryonic life. Most melanocytes diminish in number or melanogenic activity gradually during the foetal stages. Possible aetiologies of Nevus of Ota are: (1) failure of dermal melanocytes to disappear during foetal stage; (2) the arrested migration of melanocytes in the dermis; and (3) active melanin production by intradermal melanocytes.25 Melanin is formed in melanocytes and is contained in membrane-bound organelles known as melanosomes. Developmentally, melanosomes evolve from small Golgiderived vesicles containing tyrosinase; melanin deposition occurs where these vesicles contain tyrosinase. The calculated diameter for these melanin-containing structures is approximately 1.0 mm.26 The principal pathologic changes noted in Nevus of Ota are in the upper and middle dermis, which contains fusiform, dendritic or stellate, highly pigmented melanocytes in wide dispersion. At times, the melanocytes encircle the surrounding supporting connective-tissue sheaths of the adnexal structures. Nevertheless, the melanocytes generally lie with their long axes parallel to the skin surface. This may add weight to the assumption of an origin from which these dermal melanocytes,
Figure 1 Three-year-old Asian female with Nevus of Ota of the right cheek: A) prior to laser therapy; and B) two years after three treatments with Q-switched Ruby laser (694 nm) using an energy density of 9 J/cm2. Result was evaluated as an excellent cleaning and fading response.
Laser treatment of oculodermal melanosis
343
Figure 2 Sixteen-year-old Asian female with Nevus of Ota of the left cheek: A) prior to laser therapy; and B) three years after four treatments with Q-switched Ruby laser (694 nm) using an energy density of 9e10 J/cm2. Result was evaluated as an excellent cleaning and fading response.
Schwann cells or a neural element develop. The distribution of Nevus of Ota in the area of cutaneous nerves (trigeminal) presented in our patients indicated a neural relationship. It is interesting to note that the most common distribution seen was that of V2 (zygomatic branch).27e29 This does not necessarily imply that lesions with a V2 distribution are more common; however, it may be explained on the basis of anatomy and cosmesis, given that V2 is in the central face, that these patients may have
simply presented this outcome more frequently because of cosmetic concern or ophthalmic involvement. Although several other modalities such as dry ice, dermabrasion, electrodesiccation and skin grafting have been applied in the treatment for Nevus of Ota,13 nonspecific damage to adjacent structures occurs. In laser therapy, if a laser with a pulse duration shorter than the thermal relaxation time of the target structures (approximately 0.5e1 ms for melanosomes, and 7 ms for
Figure 3 Eighteen-year-old Asian male with Nevus of Ota of the right cheek. A) prior to laser therapy; B); and C) three years after five treatments with Q-switched Nd-YAG laser (1064 nm) using an energy density of 9e10 J/cm2. Result was evaluated as an excellent cleaning and fading response.
344
C.-J. Chang, C.-S. Kou
Table 5 Early adverse effects after laser treatment(s) for Nevus of Ota in 94 patients. No. of patients
Percent
QSRL QS Nd:YAG QSRL QS Nd:YAG Edema Erythema Ecchymosis Vesiculation Hypopigmentation Hyperpigmentation Scar
40 23 2 3 5 3 1
43 37 4 6 7 5 2
42.6 24.5 2.1 3.2 5.3 3.2 2.1
45.7 39.4 4.2 6.4 7.5 5.3 1.1
P > 0.05.
melanocytes) is used, selective thermal damage to only the targeted melanin-containing structure will be achieved. Thermal relaxation time is defined as the time required for the heat generated by the absorbed light energy within the target chromophore to cool to one-half the original value immediately after the laser pulse.26 Therefore, although the argon laser has been reported as an effective treatment for Nevus of Ota,8,20 the shortest available pulse duration is 0.01 s, which explains the nonspecific thermal damage produced by this device. In QSR laser therapy, high-intensity flash lamps are used to excite the ruby crystal (aluminium trioxide doped with chromium ions) to produce red photons at a wavelength of 694 nm with 20e40-ns pulse durations and extremely high peak powers (greater than 106 W cm2) at a maximum energy density of 10 J cm2. This laser pulse is suitably brief, and all the energy is invested in the target chromophore before much heat is lost by thermal diffusion out of the exposure field. Disruption of melanosomes at pulse widths less than the thermal relaxation time notably resulted from a shock wave for cavitations induced by thermal expansion. This result demonstrated that selective target damage can be expected due to the absorption of a specific wavelength with a pulse duration less than the thermal relaxation time.26,30e32 Thermal injury was observed to be intensified in the Nevus of Ota receiving QS Nd:YAG laser, which can be inferred to be due to the difference in wavelength intensity compared with that of the Q-switch Ruby laser. Overlapping laser spots during QSR laser treatment appeared to result in a more even fading of the lesion and did not leave the chequerboard or latticelike pattern seen when spaces were left between treated areas. The degree of overlap of laser pulses in our study was a matter of personal preference, without any data to support one approach over another. The definitive cause of the immediate change in skin colour following QSR laser irradiation, from darkly pigmented to ash white, is still unknown. Three hypotheses have been suggested: (1) an increase in optical scattering, and (2) a decrease in optical absorption or (3) both. A more probable explanation is that the empty spaces within ruptured melanosomes were the remnants of small vapour cavities induced in melanosomes by steam and pyrolytic products. Such vapour cavities would be of an appropriate size and optical character to scatter visible light strongly, and their gradual dissolution would explain the transient nature of the whitening.31,32
The clinical efficacy of QSR laser therapy has now been demonstrated in our facilities. In this study, excellent results were seen in 21 patients (44.68%) and good results in 11 patients (23.41%). In this series, all patients with an excellent assessment were due because of three or more treatments. Our results demonstrated that the number of treatments is related to the severity of the lesions. In contrast to other laser systems, no hypertrophic scarring, cutaneous depression, atrophy or skin changes occurred after use of the QSR laser. Test dosing to determine the lowest energy density that resulted in significant or complete fading of the lesion without these complications was one of the reasons for these results. Until the development of the QSR laser, children with Nevus of Ota had little hope of seeking remedial and/or lasting medical assistance from plastic surgeons. With this type of laser treatment, even children at their early adolescent years can be treated safely. Their chance of acquiring a dark lesion can thus be decreased. At present, there are no reports recommending the appropriate time and number of treatments for children. Our only child patient, who received QSR laser therapy, was 3 years old, and produced an excellent result after three treatments. This demonstrates that children can be treated successfully and thereby spared the psychological trauma of growing up with Nevus of Ota. The wavelength, pulse duration and energy densities inherent in the Q-switched Ruby laser and Q-switched Nd:YAG laser provide the desired laser parameters for melanin-selective photothermolysis. The significant degree of lesion clearing and fading, with no associated scarring or other nonspecific side effects, attests to the clinical advantage of having increased melanin pigmentladen cell selectivity. It is apparent that the Q-switched Ruby laser and the Q-switched Nd:YAG laser allow plastic surgeons an excellent clinical outcome for the treatment of Nevus of Ota while minimising potential adverse side effects. For achieving excellent results, the Q-switched Ruby laser was favoured due to the minimal number of treatments as compared with the Q-switched Nd:YAG laser. However, long-term follow-up and careful comparison with results obtained from these two treatment methods and other laser systems are necessary before final conclusions can be drawn.
Acknowledgements The authors gratefully acknowledge the support of J. Stuart Nelson MD, PhD, at the Beckman Laser Institute and Medical Clinic and Robert L.Newcomb, PhD, Director of the Center for Statistical Consulting, both at the University of California Irvine, who performed the statistical analyses.
Conflict of interest The authors state no conflict of interest.
References 1. Ota M. Nevus fuscocoerulens ophthalmo maxillaris. Tokio Med J 1939;63:1243e5.
Laser treatment of oculodermal melanosis 2. Hidallo A, kajima H, lkeda S, et al. Natural history of nevus of Ota. Arch Dermatol 1967;95:l87e95. 3. Font RL, Reyno1ds Jr AM, Zimmerman LE. Diffuse malignant melanoma of the iris in the nevus of Ota. Arch Ophthalmol 1967;77:513e8. 4. Halase A. Malignant melanoma in a case of bilateral nevus of Ota. Arch Ophthalmol 1970;84:l76. 5. Sang DN, Albert DM, Sober AJ, et al. Nevus of Ota with contralateral cerebral melanoma. Arch Ophthalmol 1977;95: 1820e4. 6. Gonder JR, Shields JA, Albert DM. Malignant melanoma of the choroid associated with oculodermal melanocytosis. Ophthalmology 1981;88:372e6. 7. Haim T, Meyer E, Kerner H, et al. Oculodermal melanocytosis (Nevus of Ota) and orbital malignant melanoma. Ann Ophthalmol 1982;l4:1132e6. 8. Goldberg DJ, Nychay SG. Q-switched ruby laser treatment of nevus of Ota. J Dermatol Surg Oncol 1992;l8:817e21. 9. Coldberg DJ. Benign pigmented lesions of the skin. Treatment with the Q-switched ruby laser. J Dermatol Surg Oncol 1993;l9: 376e9. 10. Tayor CK, Gange RW, Dover JS, et al. Treatment of tattoos by Q-switched ruby laser. A dose-response study. Arch Dermatol 1990;126:893e9. 11. Scheibner A, Kenny G, White W, et al. A superior method of tattoo removal using the Q-switched ruby laser. J Dermatol Surg Oncol 1990;16:1091e8. 12. Geronemus RG. Q-Switched ruby laser therapy of nevus of Ota. Arch Dermatol 1992;128:1618e22. 13. Taylor CR, Flotte TJ, Gange RW, et al. Treatment of nevus of Ota by Q-Switched ruby laser. J Am Acad Dermatol 1994;30:743e51. 14. Ogata H. Evaluation of the effect of Q-switched Ruby and Q-switched Nd-YAG laser irradiation on melanosomes in dermal melanocytosis. Keio J Med 1997;46:188e95. 15. Omprakash HM. Treatment of Nevus of OTA by Q-switched, frequency doubled, ND:YAG laser. Indian J Dermatol Venereol Leprol 2002;68:94e5. 16. Lam AY, Wong DS, Lam LK, et al. A retrospective study on the efficacy and complications of Q-switched Alexandrite laser in the treatment of acquired bilateral Nevus of Ota-like macules. Dermatol Surg 2001;27:937e41. 17. Chan HH, Leung RS, Ying SY, et al. A retrospective analysis of complications in the treatment of Nevus of Ota with the Q-switched Alexandrite and Q-switched Nd:YAG lasers. Dermatol Surg 2000;26:1000e6.
345 18. Chan HH, King WW, Chan ES, et al. In vivo trial comparing patients’ tolerance of Q-switched Alexandrite (QS Alex) and Q-switched neodymium:yttrium-aluminum-garnet (QS Nd:YAG) lasers in the treatment of Nevus of Ota. Lasers Surg Med 1999; 24:24e8. 19. Apfelberg DB, Maser MR, Lash H, et al. The argon laser for cutaneous lesions. J Am Med Assoc 1981;245:2073e5. 20. Apfelberg DB. Argon and Q-switched yttrium-aluminum-garnet laser treatment of nevus of Ota. Ann Plast Surg 1995;35:150e3. 21. Tanino H. Naevus fusco-caeruleus ophthalmomaxillaris (Ota). Jpn J Dermatol 1939;46:107e11. 22. Lualdi M, Colombo A, Carrara L, et al. Optical devices used for image analysis of pigmented skin lesions: a proposal for quality assurance protocol using tissue-like phantoms. Phys Med Biol 2006;51:429e40. 23. Rallan D, Bush NL, Bamber JC, et al. Quantitative discrimination of pigmented lesions using three-dimensional highresolution ultrasound reflex transmission imaging. J Invest Dermatol 2007;127:189e95. 24. Manousaki AG, Manios AG, Tsompanaki EI, et al. Use of color texture in determining the nature of melanocytic skin lesionsea qualitative and quantitative approach. Comput Biol Med 2006 Apr;36:419e27. 25. Kopf AW, Weidman AI. Nevus of Ota. Arch Dermatol 1962;85: 195e208. 26. Anderson RR, Parrish JA. Selective photothermolysis: precise microsurgery by selective absorption of pulsed radiation. Science 1983;220:524e7. 27. Chang CJ. Q-switch ruby laser for treatment of pigmented lesions. J Formosan Med Assoc Cont Med Edu 1993;3:1e3. 28. Chang CJ, Nelson JS. Q-Switched ruby laser treatment of mucocutaneous melanosis associated with Peutz-Jeghers syndrome. Ann Plast Surg 1996;36:394e7. 29. Chang CJ, Nelson JS, Achauer BM. Q-Switched ruby laser of oculodermal melanosis (Nevus of Ota). Plast Reconstr Surg 1996;98:784e90. 30. Hruza GJ, Dover JS, Flotte TJ, et al. Q-switched ruby laser irradiation of normal human skin. Histologic and ultrastructural findings. Arch Dermatol 1991;127:1799e805. 31. Polla LL, Margolis RJ, Dover JS, et al. Melanosomes are a primary target of Q-switched ruby laser irradiation in guinea pig skin. J Invest Dermatol 1987;89:281e6. 32. Dover JS, Margolis RJ, Polla LL. Pigmented guinea pig skin irradiated with Q-Switched ruby laser pulses. Arch Dermatol 1989;125:43e9.