• #3. Development of Vascular Laser Ⅱ-1


    Continuing from the last chapter, the development of vascular lasers for treating nevus flammeus will be discussed this time. In order to understand why nevus flammeus has been brought up as a topic in the history, it is necessary to understand the disease itself. Nevus flammeus, or Port-wine stain, is a congenital disease not classified as a hemangioma, and is the most common type of capillary malformation. The term had been dismissed as a 19th century’s word in dermatology textbooks, but is now one of the most commonly found terms in articles with the development of vascular lasers.


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    Nevus Flammeus (Port-wine Stain)

    Being the most common type of capillary malformation, nevus flammeus appears in various sizes; it may develop on any area with geographical shape or along the dermatome. The lesion appears as light pink at first, turns to dark red throughout the adolescence, and to purple in the middle age. The surface becomes uneven; sometimes  nodules develop with aging. Histological finding is dilated ecstatic vessels composed of flat endothelial cells at the papillary dermis or the upper part of reticular dermis.


    Various treatments, including electrocautery, tattoo, dermabrasion and cryotherapy, had been attempted since long before, but they left scar and were not effective. Some textbooks even recommended a makeup to cover the lesion with a covermark. In my personal experience, nevus flammeus is not detectable in most newborn infants and a light pink spot starts to appear in 1-2 weeks after birth. The thickness of the blood vessel becomes thicker with age. Nevus flammeus is difficult to treat with a laser without general anesthesia or conscious sedation in 6 months to 1 year after birth. Therefore, the importance of treating exposed nevus flammeus with a proper laser upon detection after birth cannot be stressed enough. It would be hard for a clinician without an experience of treating infants to imagine the importance of transferring infants with early nevus flammeus detected at a Pediatrics or Obstetrics and Gynecology department to a hospital equipped with a suitable therapeutic facility.


    However, it is possible only when the clinician is aware of a hospital that is equipped with proper lasers and sometimes even the facility for general anesthesia (since it is difficult to equip both laser devices and general anesthesia facilities in the same operation room, even teaching hospitals are rarely prepared with such luxury). This is the matter of a child’s lifetime and I urge more attention to this matter from clinicians reading this article. Ultimately, nevus flammeus is the aggregation of dilated blood vessels, each vessel situated close to each other; therefore, the lesion is highly likely to end up with a scar if the blood vessels are not damaged selectively. Sporadic telangiectasia distributed here and there can be eliminated by a CO2 laser or eletrocautery. Thick blood vessels may require a laser therapy relatively less because they might be treated with a sclerotherapy. Probably this is why lasers that affect the blood vessels selectively have been first applied to nevus flammeus.


    Nevus flammeus could not be treated properly due to the issue of scarring; however, the treatment of nevus flammeus has took a new turn since starting to use argon lasers for the lesion. Argon laser would inflict damages to the surrounding tissues at a high rate, the issue of scarring is still remaining although this side effect has been remarkably reduced. However, 577nm pulsed dye laser, which had started to be used experimentally between the late 1970s and the early 1980s, had a physical property that could minimize the injury to the surrounding tissues, a development which could be considered as a whole new therapy. The development of dye lasers partially overlapped with the use of argon laser in time, often being presented as reversed order of dates for article publication. However, in this article, I would like to discuss the development of vascular lasers for nevus flammeus by introducing main papers. The order may not match with the sequence of publication, possibly because of some difference in the time of publication and the process of theoretical or practical therapeutic development.


    Finally, you should keep in mind, when reading the following studies, that nevus flammeus in infants or children was the main target when the concept of selective photothermolysis was first studied and published. Nevus flammeus in adults accompanies thicker blood vessels and changes of the surrounding tissues unlike that in children. If you are not aware of this difference, you may not be able to understand the treatment of nevus inflammeus or vascular lasers.


    1. Port-wine Stains, Nevus Flammeus

    The nature and evolution of port-wine stains: a computer-assisted study. Barsky SH, Rosen S, Geer DE, Noe JM. J Invest Dermatol. 1980 Mar;74(3):154~7.

    Nevus fllameus is characterized by increased number of blood vessels and ectasia. The number of blood vessels is the greatest immediately under the epidermis and gradually decreases toward the bottom. Mean depth is 0.46±0.17mm. The diameters of blood vessels become larger, and the color turns from pink to purple, with aging. Blood vessels have comparable characteristics at each depth until reaching 0.8mm – that is, blood vessels in each depth have unexpectedly uniform thickness.


    2. Nevus Flammeus Treatment Using Unselective Lasers, including Argon Laser and Copper Vapor Laser

    Hypertrophic scarring in argon Laser treatment of port-wine stains. Dixon JA, Huether S, Rotering R. Plast Reconstr Surg. 1984 May;73(5):771~9.

    Argon laser at 488nm and 514nm is not for selective absorption in the blood vessel nor is it suitable for the concept of selective photothermolysis due to the pulse duration longer than the thermal relaxation time of the blood vessels comprising a nevus flammeus. It had been introduced for clinical use, however, because it was more effective than other previous treatments. This laser could not avoid inflicting damage to normal tissues, contributing to high frequency of scarring, which was as high as 38% among patients younger than 12 years old and 21% in older patients in the Group 1. In the Group 2, 13.7% experienced scarring. The higher frequency of scarring in the children suggests the following: children, who have thinner blood vessel in the nevus flammeus, require a laser with relatively shorter pulse duration for selective damage, which was not the case in argon laser. This suggests, however, that argon laser would be worthwhile in adult hypertrophic type with thick blood vessels.  Yet, argon lasers are practically not used in hospitals anymore. Considering what would be the most appropriate laser for a certain patient among all kinds of lasers made by mankind, it is regrettable that argon laser has disappearred already.


    Histologic responses of port-wine stains treated by Argon, Carbon Dioxide, and tunable Dye Lasers. A preliminary report. Tan OT, Carney JM, Margolis R, Seki Y, Boll J, Anderson RR, Parrish JA. Arch Dermatol. 1986 Sep; 122(9):1016~22.

    It is predictable that tunable Dye Laser would cause less epidermal damage and fibrosis, and thereby less clinical side effects, compared to argon laser or CO2 laser based on the histological findings. This would appear simple now but please keep in mind that this study was performed when argon laser was commonly used, when scarring was considered as an inevitable result, not a side effect, before Dye Laser is commonly used.


    Histological responses of port-wine stains in brown skin after 578nm Copper Vapor Laser treatment. Chung JH, Koh WS, Youn JI. Lasers Surg Med. 1996;18(4):358~66.

    I personally performed the histology and staining in this study. It was a study that fell behind considering that it was published when Dye Laser was used already, which is why this study is introduced here before its actual time of publication. 578nm Copper Vapor Laser satisfies selective photothermolysis quite well for damaging blood vessels considering the wavelength, but 30-200ms pulse duration is not suitable for selective damaging of blood vessels of nevus flammeus. Nonetheless, the selective wavelength for HbO2 resulted in histological findings of selective blood vessel damage under some conditions, unlike argon laser. Higher fluence or longer pulse duration was associated with easy epidermal damage, however. Furthermore, the depth of blood vessel damage was only as low as 0.4mm because 577nm or 578nm does not provide enough penetration depth as well.


    3.The Beginning of the Concept of Selective Photothermolysis and Application for the Treatment of Nevus Flammeus; Introduction of Flash Lamp pumped tunable Pulsed Dye Laser

    Microvasculature can be selectively damaged using dye lasers: a basic theory and experimental evidence in human skin. Anderson RR, Parrish JA. Lasers Surg Med. 1981;1(3):263~76.

    This study proved selective microvessel damage by irradiating flashlamp pumped Dye Laser (0.3 microsecond) at 577nm, which is the absorption band of HbO2, to average Caucasians.  Argon laser required 20J/cm2(514 and 488 nm, approximately 100msec) and inflicted injury to areas other than blood vessels, but this was the first study to show that 577nm Pulsed Dye Laser could damage blood vessels selectively with approximately 2J/cm2. At this time, argon laser was being used, but this study might have been initiated to overcome the frequent scarring of argon laser. Since this was a study targeted on microvessels of in normal skin, the blood vessels were very superficial and thin (expected TRT approximately 1ms). The flashlamp pumped Dye Laser was easily applied to port-wine stains comprised of blood vessels with capillary malformation but relatively thinner than other hemangiomas or telangiectasia, which is why other studies from the same authors focused on the treatment of nevus flammeus. It is worth noting that the pulse duration was very short. This study is meaningful in that it marked the starting point of a long history of Dye Laser in the future, such as longer wavelength and longer pulse duration. Rox Anderson later published a study explaining the concept of selective photothermolysis in the Science based on Dye Laser used in this study.


    Selective photothermolysis: precise microsurgery by selective absorption of pulsed radiation. Anderson RR, Parrish JA. Science. 1983 Apr 29;220(4596):524~7.

    This study used the term ‘selective photothermolysis’ for the first time and used the same laser as that used in the above study (Candela Model SLL-1100, 577nm, 0.3 microsecond). The authors selected 577nm, which can penetrate most deeply among the absorption peaks of HbO2, which are 418, 542 and 577 nm. Thermal relaxation time for 20um blood vessel was hypothesized as 50 microseconds, and 0.3 microseconds was found to damage blood vessels without damaging the surrounding tissues or the epidermis. What’s worth noting in this study is that the thickness of the target blood vessel was as thin as 20um, and that purpura occurred. This thickness is similar to or slightly thinner than the blood vessels of nevus flammeus in newborn infants.


    - To be continued-


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