Terminology
-
LASER: Laser is an acronym for “light amplification by stimulated emission of radiation.”
Stimulated emission was based on Einstein's quantum theory of radiation.[4] Laser light is monochromatic, coherent, unidirectional, and bright.
-
Intense pulsed light (IPL): Flash lamp usually emits wavelengths in the range from 380 to 1,200 nm and the shorter
and longer wavelengths can be eliminated by various cutoff filters (515–755 nm) and
water jacket, respectively.
-
Chromophore: Chromophores can be either endogenous or exogenous, meaning they can be either present
in the tissues or brought from outside, which absorbs particular wavelengths depending
on their absorption coefficient[5] ([Fig. 1]).
-
Selective photothermolysis (SPTL): In 1983, Anderson and Parrish[7] described the theory of SPTL, explaining a method of producing selective and localized
tissue damage while sparing the surrounding tissue. This revolutionized laser therapy.
-
Pulse duration: Thermal relaxation time (TRT) depends on the size of the target vessel and selection
of pulse duration is mainly guided by the TRT. As large objects take a long time to
get heated and to cool down, the larger the vessel, the longer the TRT. More difficulty
is encountered while lasing the smaller-diameter vessels. Small vessels need very
short pulse width, which makes the epidermis having a TRT of approximately 4 to 10
milliseconds more vulnerable. To overcome this, the short pulse is subdivided into
still shorter rations of subpulses that are delivered in rapid succession with a gap
of 10 to 40 milliseconds between them. This form of energy delivery is called multiple
synchronized pulsing.
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Multiple Synchronized Sequential Pulsing: Even though the epidermis is a strong competing chromophore, it can be spared as
long as the TRT of the target vessels is equal to or longer than that of the epidermis
([Fig. 2]; [Table 1]) Longer TRT means the target takes longer time to cool to 50% of the temperature
achieved. Multiple synchronized pulsing usually has two or three subpulses, with periods
of delay in between. By the first pulse, both the vessels and epidermis are heated
just within the threshold limit of the epidermis; therefore, the epidermis is not
damaged. After the first pulse, there is a delay, during which both epidermis and
target start cooling; However, as the target cools slowly at the end of the delay,
it still retains some heat, while the epidermis gets cooled down completely, aided
by the external cooling applied. During the second pulse and the delay thereafter,
the same sequence repeats, but now the target gets heated to a higher level as it
is starting from an elevated baseline. This pulsing is repeated till such time as
the temperature in the target at the end of the last pulse exceeds its threshold limit.[8]
Fig. 1 The absorption of various chromophores as a function of wavelength.[6] Nd:YAG, neodymium:yttrium aluminum garnet.
Fig. 2 Multiple synchronized sequential pulsing.[8]
Table 1
Approximate thermal relaxation time (TRT) for blood vessels of different diameters
and of epidermis
|
Lesion
|
Blood vessel
|
Epidermis
|
Pulse width
|
Energy Based Devices
|
|
Diameter (μm)
|
TRT (ms)
|
TRT (ms)
|
(ms)
|
EBDs
|
|
10
|
0.048
|
|
|
|
|
20
|
0.19
|
|
|
|
|
|
|
|
0.45
|
595 nm PDL
|
|
PWS
|
50
|
1.2
|
|
|
|
|
|
|
3.0
|
3.0
|
IPL
|
|
PWS
|
100
|
4.8
|
|
|
|
|
|
|
10.0
|
|
|
|
Hemangioma
|
200
|
19.0
|
|
4.5
|
1064 nm Nd:YAG
|
|
Hemangioma
|
300
|
42.6
|
|
|
1064 nm Nd:YAG
|
|
Hemangioma
|
400
|
|
|
5.7
|
1064 nm Nd:YAG
|
|
Venous Malformations
|
>400
|
|
|
8
|
1064 nm Nd:YAG
|
Abbreviations: IPL, intense pulsed light; PDL, pulsed dye laser; PWS, port wine stain.
Source: Adapted from Anderson and Parrish.[9]
Classification of Vascular Anomalies
In 1982, Mulliken and Glowacki[10] proposed a biologic classification system to describe two types of vascular anomalies:
hemangiomas and VMs. The most recent classification system adopted by the International
Society for the Study of Vascular Anomalies in 2014, and revised in 2018, defines
VMs in more detail, proposes more causal genes of vascular anomalies, and includes
more complex syndromes with other abnormalities.[11]
[12]
Role of Lasers in Vascular Lesions
Vascular lesions require proper diagnosis and a clear understanding of their biologic
behavior.[13] Cutaneous vascular lesions are one of the most common indications for laser treatment.
They are either persistent or growing because of intact vessel wall. Although their
chromophore is hemoglobin in its various forms, the ultimate target is the vessel
wall. Water content of blood and vessel wall also acts as an additional chromophore.
Cure in vascular lesions essentially lies in destroying the vessel wall permanently.[14]
Hemoglobin has an absorption coefficient curve with peaks at 418, 524, 577, and at
1,064 nm ([Fig. 1]). Even though the absorption coefficient is very high, wavelengths at 418 and 524 nm
are too short to penetrate to any useful depth in the dermis and their absorption
in the competing epidermal melanin is also very high; therefore, these wavelengths
cannot be used in vascular lesions. However, the spectrum between 580 and 595 nm is
useful clinically.[15] Histologic studies have shown findings that correspond to the clinically obvious
purpura seen after treatment with the pulsed dye laser (PDL). There are histologic
findings of agglutinated red blood cells, fibrin, and platelet thrombi within the
vessels of the papillary and superficial reticular dermis.[9] As would be expected, there is little or no damage to the surrounding tissue.[13] At fourth peak, which is the last peak of absorption coefficient of hemoglobin,
the 1,064-nm wavelength, being a longer wavelength, has the advantage of deeper penetration
and therefore is the wavelength of choice for deeper vascular lesions like thick or
nodular hemangiomas and venous malformations (VMs). Vascular lesions are unique in
the sense that their chromophore is moving, albeit slow in many of them, which raises
the issue of retention and effective application of heat to the vessel wall. Therefore,
only slow-flow lesions can retain the generated heat sufficiently long enough for
the vessel wall to get destroyed.
Vascular lesions are dynamic and changes are often visible during and immediately
after treatment. During treatment, the desired clinical effects are monitored, and
the treatment parameters are adjusted to achieve effective end point. This includes
observing for changes in the targeted vessel, such as blanching, graying, and simultaneously
observing the integrity and color of the epidermis. Clinically observed factors such
as blanching, whitening, purpura, erythema, edema, or severe pain should be closely
observed and continuously evaluated to guide optimal and safe treatment.
Hemangioma
The only limiting factor in laser treatment of deeper vascular lesions at present
is reaching the target and retaining the generated heat. Currently with the wavelength
of 1,064 nm, we can reach a maximum of 5 to 6 mm under the skin surface[16] ([Figs. 3]
[4]
[5]
[6]).
Fig. 3 (A) Hemangioma in a 5-month-old infant in rapid proliferative phase. (B) After five treatments with Nd:YAG (neodymium:yttrium aluminum garnet) 1064-nm laser.
The eye was protected by a special metal corneal shield.
Fig. 4 (A) Hemangioma in a proliferative phase. (B) After seven treatments with 1,064-nm Nd:YAG (neodymium:yttrium aluminum garnet)
laser at 130 J/cm2, 4.5-millisecond triple pulse, 30-millisecond delays between pulses.
Fig. 5 (A) A large proliferating hemangioma in a 6-month-old infant before starting laser treatment.
(B) Five years after the last treatment, hemangioma has subsided completely without
any residual “anetoderma,” that is crepelike skin observed after spontaneous resolution.
Fig. 6 (A) Mixed hemangioma occupying the upper lip, columella, and nostril sill. (B) Complete resolution after 10 treatments with 1,064-nm Nd:YAG (neodymium:yttrium
aluminum garnet) laser under short general anesthesia at 130 to 150 J/cm2, triple and then double pulse of 4.5 milliseconds with a delay of 30 milliseconds.
The last four treatments with 150 J/cm2, single pulse of 5.7 milliseconds, because, as the amount of chromophore reduces,
we need to increase the joules. (C) One and a half years after the last treatment. Please note the absence of scarring.
“Halo” of growth
When laser treatment of congenital or infantile hemangioma is started very early during
the neonatal period or during infancy in its proliferative phase, a peculiar phenomenon
is observed, which the author has named the “halo of growth.” With initial few laser
treatments, the already manifested hemangioma gets cleared, but a ring of capillaries
appears around it as this area was destined to be a hemangioma. This happens because
laser cannot act unless there is a chromophore. Prior intimation to the parents about
the possibility of this occurrence mitigates any misunderstanding ([Fig. 7]).
Fig. 7 (A) Halo of growth. Halo appeared 1 month after the first treatment at age 5.5 months.
(B) Halo getting cleared with the second laser treatment.
Things to Remember
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“Wait and watch” and “masterly inactivity” policies were advocated for hemangioma
when no definitive curative treatment existed.
-
Unpredictability of spontaneous involution of hemangiomas seems to favor earliest
intervention with a vascular-specific laser.
Capillary Malformations
Capillary malformations (CMs) are present at birth and persist throughout life. A
port wine stain (PWS) is one of the most common types of CM. Most CMs have a cosmetic
problem, but unlike the nevus simplex, a PWS does not fade in the early ages of childhood.
On the contrary, during puberty, the skin thickens and gradually becomes raised with
multiple nodular fibrovascular lesions due to underlying soft-tissue hypertrophy.
Because the dermal thickness increases with age allowing for less optimal targeting
of vessels, better response is achieved if the treatment is begun earlier during childhood.[17]
Port Wine Stain or Nevus Flammeus
Flash lamp PDL was the first example of a laser that was specifically constructed
to treat PWS.[18] Initially, this laser had a 577-nm wavelength to match the third peak of the absorption
curve of hemoglobin and 0.45-millisecond pulse duration, which was less than the TRT
of the smaller vessels (postcapillary venules) of PWS[7] ([Table 1]). Later on, it was replaced by yellow light at 585 and finally at 595 nm, having
still deeper penetration and giving better results ([Fig. 8]). TRT of the epidermis varies from 3 to 10 milliseconds. Capillaries of PWS are
very fine and range from 50 to 100 µm having a TRT of 1 to 5 milliseconds. Unless
the pulse is ultrashort, they cannot be heated till destruction. PDL has a 0.45-millisecond
pulse width, which is less than the TRT of the smaller vessels of PWS. Additionally,
the epidermis is protected with Dynamic Cooling Device (DCD).[19] Although PDL is considered the treatment of choice for most of the PWS, IPL sources
with a cutoff filter of 590 nm are also quite effective and are being routinely used
for a variety of superficial vascular lesions including PWS.
Fig. 8 Evolution of pulsed dye laser (PDL) wavelengths from 577 to 595, guided by their
effective penetration through the skin.
By extending the principle of SPTL and by making use of multiple synchronized sequential
pulsing, the laser surgeon is now able to selectively target a larger or a smaller
vessel in the same lesion having the same common chromophore, hemoglobin ([Fig. 9]).
Fig. 9 (A) Adult type port wine stain (PWS) before and on (B) 5 days after intense pulsed light (IPL) treatment with a 590-nm filter. Purpura
and superficial epidermal peeling are considered part of the treatment and they do
not leave any scars behind. (C) After 10 full and 3 touch-up treatments with 3.5-milliseond double pulse and 20-millisecond
delays.
Venous Malformations
VMs are developmental abnormalities of veins, present at birth and which do not subside
on their own like some hemangiomas. They are made up of thin-walled dilated channels
of variable size, which show progressive dilatation with age and persist till adulthood
([Fig. 10]). They are more frequent on the head and neck but may occur at any site and may
infiltrate any structure of the body including the skin, mucous membrane, bones, joints,
and even viscera.[20] For cutaneous and mucosal VMs, a 1,064-nm Nd:YAG (neodymium:yttrium aluminum garnet)
laser represents the most effective option as they are thick lesions. Since the absorption
coefficient of hemoglobin is low at 1,064 nm, use of high fluence is required. Contact
cooling and a large spot size is helpful in reducing scarring ([Figs. 11] and [12]). Their vessels are larger, very thin walled, and contain abundant deoxy hemoglobin;
therefore, even though they respond very well to Nd:YAG 1,064-nm laser, a rather low
energy has to be delivered to them as at times it can lead to scarring ([Fig. 13]).
Fig. 10 Venous malformation (A) before and (B) after four Nd:YAG (neodymium:yttrium aluminum garnet) 1,064-nm laser treatments.
Fig. 11 (A) Venous malformation persistent till age 23 years. (B) There was dramatic resolution in just one treatment with 1,064-nm Nd:YAG (neodymium:yttrium
aluminum garnet) laser at 110 J/cm2, triple pulse of 8 milliseconds and 30-millisecond delays between pulses, 20 shots.
Venous malformations respond early to laser treatment as compared with those arteriovenous
malformations (AVMs) with arterial dominance.
Fig. 12 (A) Venous malformation. (B) After the third treatment with 1,064-nm Nd:YAG (neodymium:yttrium aluminum garnet)
laser at 150 J/cm2, single pulse of 5.7 milliseconds. No scar was left.
Fig. 13 (A) History of trauma. A nonpulsatile lesion was present for the last 6 months. (B) After a single treatment with 1,064-nm Nd:YAG (neodymium:yttrium aluminum garnet)
laser, at 120 J/cm2, 4.5-millisecond triple pulse, with 30-millisecond delay between pulses. Seventy-five
shots of 4-mm spot size were an overtreatment, leading to scarring.
Arteriovenous Malformations
Arteriovenous malformations (AVMs) form when veins are connected to arteries without
an intervening capillary bed and are often mistaken for a hemangioma in children.
These are fast-flow VMs, in which the blood flows directly from a high-pressure system
to a low-pressure system.[21] The clinical management of pediatric AVMs requires a detailed examination and long-term
clinical observation. The most common treatments are surgical interventions and intravascular
embolotherapy/sclerotherapy, and a combination of both may sometimes be effective,
especially in children.[22] As compared with all other VMs, AVMs, being high-flow lesions, are unable to retain
the heat generated by laser. However, if an AVM can be converted into a low-flow lesion
by feeder ligation, then it can be treated with 1,064-nm Nd:YAG laser sessions. However,
feeder ligation may have to be repeated more than once as new feeders open up subsequently
([Figs. 14] and [15]).
Fig. 14 (A) Pulsatile arteriovenous malformation (AVM) of the frontoparietal scalp. (B) It was successfully treated in nine sessions of 1,064-nm Nd:YAG (neodymium:yttrium
aluminum garnet) laser interspersed with four sessions of feeder ligation. During
the last session of feeder ligation, few channels were also lased with 1,320-nm Nd:YAG
laser by intraluminal fiber placement under ultrasonography (USG) guidance. Her throbbing
headache completely subsided and a major vascular surgery was avoided. (C) Hair loss and depigmentation can be easily covered.
Fig. 15 (A) Pulsatile and enlarging arteriovenous malformation (AVM) in a 14-month-old boy.
(B) Pulsations stopped immediately after feeder ligation of both labial arteries and
the AVM size reduced. It was followed by nine treatments with 1,064-nm Nd:YAG (neodymium:yttrium
aluminum garnet) laser under short general anesthesia over the next 1.5 years.
Combined and Complex Combined Vascular Malformations
Due to hyperplasia of the lymphatic network, lymphatic malformations are slow-flow
vascular anomalies characterized by dilated lymphatic channels and cysts. Combined
malformations such as capillary-venous malformation (CVM), capillary-lymphatic malformation
(CLM), lymphaticovenous malformation (LVM), and complex combined malformation. Capillary-lymphaticovenous
malformations (CLVMs) have some vascular element that acts as a chromophore in addition
to water and absorbs laser. Because these are slow-flow lesions, the generated heat
gets time to be conducted to the vessel wall, leading to its destruction ([Fig. 16]).
Fig. 16 (A) Capillary lymphaticovenous malformation (CLVM) of the pinna. Oxy hemoglobin, deoxy
hemoglobin, and water were the chromophores. (B) After three treatments with 1,064-nm Nd:YAG (neodymium:yttrium aluminum garnet)
laser. (C) Late result after fourth treatment of only the lobule.
Role of Endovascular Lasers
The role of endovascular lasers in VMs is limited, wherein laser energy is directly
delivered to the vessel wall intraluminally carried through an optical fiber. Diodes
808, 1,470, 1,940, and Nd:YAG 1,320 nm are most suited as they can be carried through
the fine optical fiber. Deeply situated, large or extensive malformations, including
low-flow venous, lymphaticovenous, and AVMs can be partially controlled with this
modality performed under anesthesia under color Doppler guidance. After locating a
relatively straight segment of vessel, luminal access is gained with a 10-cm-long
18-gauge spinal needle, and a 600-µm or smaller, 400- or 200-µm, fiber is passed through
it and energy is delivered till its closure.
Adverse Effects and Complications
Excess fluence leads to epidermal erythema, superficial burn, or deep dermal burn
with incident scarring depending on the extent of injury. Edema is very common and
appears within a few minutes after laser treatment of vascular lesions. Application
of ice pack immediately after treatment and continuation till the burning sensation
subsides will help reduce it. It resolves within a few hours but one has to refrain
from prescribing nonsteroidal anti-inflammatory drugs (NSAIDs) to overcome it as the
aseptic inflammation is useful for closing the vessels. A word of caution is in order
here while treating vascular lesions in oral cavity and particularly on posterior
tongue or cheek, where severe edema can obstruct air passage in post treatment period.
One may administer only a few laser pulses during the first session to judge the edema
response and during subsequent sessions increase the number of pulses.
In case of lesions like PWS, ecchymosis and purpura followed by dry crusting are unavoidable.
Antiseptic creams should be used in the postlaser period. It usually peels off within
4 to 8 days. Moisturizer and sunscreen lotion or gel is to be continued throughout
the course of treatment.
In late complications, pigmentary changes either hypo- or, more frequently, hyperpigmentation
are due to repeated treatments on the same area and it may be visible after a few
sessions. Hyperpigmentation is undesirable as it competes during subsequent treatments.
Depigmenting creams and laser can be used to treat it.
In sequelae, scarring due to overtreatment is a hidden risk. In case of VMs, this
is attributable to thin-walled larger vessels filled with abundant chromophore, which
absorbs a lot of energy. Low fluence and minimum number of shots can mitigate this
complication.
Conclusion
The goal of management and treatment of VMs is to maintain functionality, control
associated symptoms, and preserve aesthetic integrity. Laser treatment plays a role
in achieving these goals in varying degrees. Complex VMs, although benign, cause deformation,
can impair function of vital structures, or even threaten the child's life. Such severe
life-threatening functional impairment mandates early intervention with nonlaser modalities.
Therefore, to ensure optimal treatment, a multifocal and a multidisciplinary team
approach is advocated with the patient's quality of life as the priority.[23] This includes observation, laser or radiofrequency ablation, sclerotherapy, embolotherapy,
surgical resection, and medical therapy.
