IPL Literature Review

Review of optical devices and their potential to be used to

treat both medical and cosmetic conditions, including skin

rejuvenation, tendinopathy and chronic wounds.

This review was conducted as part of a summer placement with the regenerative medicine group at the Institute of Life Sciences of

Swansea University.

Rhys Alun Luckwell

2012[Type the company address]

Rhys Luckwell July 2012

Rhys Luckwell

Review of optical devices and their potential to be used to treat both medical and cosmetic conditions, including skin rejuvenation, tendinopathy and chronic

wounds.

This review was conducted as part of a summer placement with the regenerative medicine group at the Institute of Life Sciences of Swansea University.

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Contents

1) Abstract........................................................................................................3

2) Introduction....................................................................................................4

2.1) Connective tissue and associated extracellular matrix............................4

2.2) Physiology of the skin..............................................................................5

2.3) Physiology of tendons..............................................................................6

2.4) Wounds....................................................................................................7

3) Optical Devices............................................................................................10

3.1) Brief history of lasers and IPL.................................................................10

3.2) The reaction mechanism of photons......................................................10

3.3 Light-tissue interactions..........................................................................12

3.4) IPL devices.............................................................................................12

3.5) IPL Vs Lasers..........................................................................................12

4) Literature review.........................................................................................14

4.1) Skin rejuvenation................................................................................14

4.2) Tendinopathy.........................................................................................19

4.3) Chronic wounds......................................................................................23

5) Conclusion....................................................................................................27

6) References...................................................................................................28

1) Abstract

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This literature review was conducted into how optical devices can be used in both

medicine and cosmetics. There is vast amount of literature and research on the effects of

optical devices and to cover it all in finite detail is not within the scope of this review.

Therefore, this review will focus on the effect of lasers,light emitting diodes (LED) and

concentrate mainly on intense pulsed light systems (IPL) devices on how they can

improve skin rejuvenation, chronic wounds and tendinopathy.

By looking at how such devices work on a cellular level and the effect they have In Vitro,

In Vivo and in clinical trials the potential benefits that optical devices can have will be

summarised. Such benefits include reducing the healing time of chronic wounds and

injured tendons, and allowing repair to restore the tissue to its former native biochemical

and biomechanical composition. In doing so, optical devices can help reduce the cost of

treatment allowing hospitals to save on expensive resources used to treat these cases

and limit the number of hospital beds being used at any given time

This review will also look at the benefits on IPL over traditional laser treatment. With IPL

devices being more mobile, cheaper and requiring less maintenance than lasers they

provide an attractive alternative to physicians and cosmetic retailers.

This review concludes that the use of optical devices in medicine and cosmetics has

tremendous potential and that IPL in particular has a big future role to play in the

treatment of skin rejuvenation, chronic wounds and tendinopathy.

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2) Introduction

2.1) Connective tissue and associated extracellular matrix

Connective tissue is one of the four types of tissue of the body. Examples of connective

tissue include skin, bone, tendons, ligaments, adipose tissue and blood. For connective

tissue to carry out its structural role it must be supported by the extracellular matrix

(ECM). The ECM therefore is essential in providing a framework for tissue movement and

for the transmission of mechanical forces (Silver et al., 2003). However, the idea of the

ECM providing only ‘scaffolding’ for the tissue has been put to rest and it is now agreed

that the ECM is an important mediator of cellular events. It is thought that cell migration,

proliferation, survival, migration and differentiation are a result of ECM remodelling which

occurs through MMPs and their inhibitors. This process is coordinated by hormones and

growth factors (Nieto and Lutolf , 2011).

The ECM is composed of collagens, elastins, glycoproteins, proteoglycans and GAGs. It’s

the specific composition of these materials that give different connective tissues their

specific biochemical properties. These components are secreted by fibroblast cells.

Fibroblasts are spindle shaped cells that sit in the ECM that they have secreted and are

required for connective tissue homeostasis as well as being essential in the repair of

tissue. The most common protein found in ECM is collagen. Its fibrillar collagen (type I,

II,III and V) that provides the structural framework. These types of collagen can bare

great tensile forces. Another important collagen is FACIT collagen. FACIT collagen is

involved in transferring these tensile loads through connecting fibril collagen to other

parts of the ECM (Silver at al.,2003). The composition of ECM is in a dynamic equilibrium

of catabolism and anabolism. This equilibrium can change with age, thus affecting the

structure and strength of ECM. With age there is a decrease in proteoglycan content

(Suchuckett and Malemad, 1989), decrease in collagen type III (Mays et al.,1988),

fragmentation of elastin in skin and cardiac tissue and an unravelling of collagen in the

skin (Lavker et al., 1987).

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Figure 1) Scanning electron microscope image of a fibroblast interacting with the ECM that it has

secreted. The type I collagen can be clearly seen as a meshwork of intertwining fibres (Image

taken from Ree and Grinnell, 2008)

As mentioned, fibroblasts are essential in the repair of injured tissue. After an injury

fibroblasts undergo a phenotypic change that results in them being increasingly mobile

allowing them to migrate to the site of injury quicker (Raffetto et al., 2001). Factors such

as, U.V light, aging and diseased cells can disrupt the relationship between fibroblasts

and ECM environment in which they sit. This disruption can lead to the prolonged healing

of chronic wounds, wrinkles (Vedrenne et al., 2012) and a reduction in the diameter of

collagen fibrils in tendons which can cause a reduction in the mechanical strength of

tendons (Dressler et al., 2005).

The next part of this review will go look at the biochemical and physiological make up of

skin and tendons and provide and insight into the acute and chronic wound healing

processes.

2.2) Physiology of the skin

Firstly I will review the structure of skin and how it is related to its specific functions. I will also look at how the structure-function relationship is affected by factors such as age, smoking and U.V light.

2.2.1) Structure and Function of skin

Skin has many functions. It provides protection, sensation, thermoregulation, metabolic

and immune functions. Skin is composed of 2 main layers, the epidermis and the dermis.

Below the dermis a layer of subcutaneous tissue (hyperdemis). Each layer is separated

by a basal membrane (Wysoki et al.,1999) (Prost-Squarcioni et al., 2008). The epidermis

is a protective layer made up of keratinised squamous tissue. This layer contains

keratinocytes, melanocytes, Langerhans cells and dendritic cells. The dermis is

composed of fibrous connective tissue which provides strength and elasticity through

collagen and elastin. Both fibrillar collagens (e.g. type I,III and V) and FACIT collagens

(e.g. type XI,IX) are found here (Prost-Squarcioni et al., 2008 ) . The dermis contains

fibroblasts, macrophages, mast cells, hair follicles and sweat glands. It also contains

blood vessels and nerves (Nigam and Night , 2008).

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Figure 2) Image showing the structure of human skin. The distinct structural layers of

the epidermis, dermis and subcutaneous layer can be clearly seen (Taken from Shier et

al., 1999).

2.2.2) Natural, Photoaging and smoking induced changes to skin

With age the anatomical and biochemical structure of skin can change. The skin can

loosen and develop the appearance of wrinkles. These can arise naturally from the

prolonged effect of gravity, the loss and uneven distribution of subcutaneous fat and the

repeated use of facial muscles. Biochemical changes include a decrease in the amount of

collagen present in the skin. This can be as much as a 1% decrease per year once

entered adulthood (Rigel et al.,2004). Other biochemical changes include fibroblasts

shrivelling and becoming less responsive to growth factors, atrophy in collagen bundles,

an increase in MMPs and a decrease in blood vessels in the dermis. Such biochemical

changes can also be induced by exposure to U.V radiation (photoaging). Exposure of the

skin to U.V radiation causes an increase in reactive oxygen species (ROS) which through

signalling cascades can activate enzymes e.g. MMPs that are capable of breaking down

the collagen and other ECM proteins (Nigam and Night , 2008). Smoking can also induce

premature skin ageing and early wrinkling. It is that believed smoking does this through

the toxins acting directly on the epidermis and indirectly on the dermis through the blood

stream. The major target of the toxins is believed to be the elastin in the ECM (Kennedy

et al., 2003) (Just et al., 2007).

2.3) Physiology of tendons

Tendons are fibrous connective tissue with a primary role of connecting muscle to bone.

Here they help transmit forces, change direction of pull and withstand compression and

sheer forces. Tendons are full of ECM that is secreted by specialised fibroblasts called

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tenocytes which lie in the ECM between the collagen fibres. The main components of the

ECM are collagen type I, elastin and proteoglycans (Benjamin et al.,2008). Type I

collagen and elastin make up 65-80% and 2% of the dry mass of a collagen fibre

respectively. Tendons are composed of a precise hierarchical arrangement of type I

collagen. Collagen fibrils are arranged together into a collagen fiber. Collagen fibers are

arranged together to form a primary fiber bundle (subfascicle). Primary fiber bundles are

grouped together to form a secondary fiber bundle (fascicle). Secondary fiber bundles

are arranged to form a tertiary fiber bundle, which are then arranged together to form

the tendon. The primary, secondary and tertiary fiber bundles are surrounded by the

endotendon. The endotendon is loose connective tissue that contains blood vessels and

nerves. These blood vessels and nerves provide the nutrients, oxygen and innervation

that the collagen fibers require. The tendon is surrounded by the epitendon, which is the

site of entry for the blood vessels and nerves (Kannus, 2000).

Figure 3) Image showing the hierarchal structure of a tendon (Adapted Kasteilic et al.,

1978)

With respect to tendons, this review will focus on Achilles tendinopathy as the Achilles

tendon is the largest tendon in the human body (Benjamin et al.,2008) and is one of the

most commonly injured tendons taking weeks/months to heal. Tendinopathy is a

common case that can result from sports injury or when the tendon is subject to

unusually high loads (Cook et al.,2002). The Achilles tendon has a long repair time due to

it having a low blood supply, with the midpoint of the tendon being hypovascular and this

is the site most prone to injury (Doral et al., 2010). During this repair time, the tendon is

normally immobilised, thus preventing further change to the biochemistry of the tendon

(Oliveira et al., 2009). Other traditional treatments are also usually conservative, such as

eccentric training or electrotherapeutic modalities as part of physiotherapy programme

(Miners and Bougie, 2011). There are two forms of tendinopathy; inflammatory and

degenerative. The degenerative form is known as tendinosis. The inflammation is known

as tendinitis. Tendinitis can develop before any symptoms show. Symptoms of Achilles

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Epitendon


tendinopathy typically occur at middle or insertion point of the tendon (Sussmilch-leitch

et al.,2012).

2.4) Wounds

The next part of the review will look at the process of acute wound healing and what leads to chronic wounds.

2.4.1) Acute Wound healing

A wound, as defined by Enoch and Price (2004) is a ‘break in the epithelial integrity of

the skin’ and heals normally through a dynamic cascade of events requiring coordination

of different cellular process. The cellular process involved in wound healing include;

mesenchymal cell differentiation, mitogenesis, angiogenesis, re- epithelialization,

collagen synthesis and alignment (Methieu et al.,2006).

There are four stages of acute wound healing; haemostasis, Inflammatory phase,

proliferation and remodelling (Enoch and Leaper, 2005).

2.4.1.1) HaemostasisHaemostasis is a dynamic process of when after injury blood vessels contract and the

coagulation cascade is initiated. This helps to minimize blood loss. Platelets adhere to the

exposed endothelial and aggregate to form the haemostatic plug (Ridel et al., 2007). This

haemostatic clot contains fibrin, fibronectin, von willebrand factor and provides the

primary meshwork for platelets aggregation. Platelets contain 3 types of secretory

granules; alpha granules, dense bodies and lysosomes (King and Reed, 2002). Alpha

granules and dense bodies in particular contain contents important in haemostasis. The

alpha granules contain growth factors such as IGF-1, EGF and TGF-β. These growth

factors initiate wound healing by activating fibroblasts, endothelial cells and

macrophages. Dense Bodies contain serotonin which increases the vascular permeability

of the vessels (Enoch and Price, 2004).

2.4.1.2) Inflammatory PhaseInflammation occurs with the activation of the complement cascade. The complement

proteins such as C5a attract neutrophils, macrophages and lymphocytes to the wound

(Campos et al.,2008). These phagocytes stick to the endothelial cells by a process of

margination and eventually move through the vessel wall by a process of diapedesis,

(Smith, 1993). Neutrophils engulf and destroy foreign bacteria through releasing reactive

oxygen species (ROS) thus helping to prevent wound infection (Guo and Dipetro, 2010).

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Monocytes are attracted to the wound by chemoattractants such as complement

proteins, platelet factor V and TGF-B. On entering the wound monocytes become

macrophages and release cytokines and growth factors into the wound, playing a key

role in wound healing. These cytokines and growth factors attract fibroblasts,

keratinocytes and endothelial cells to then wound site where these cells stimulate tissue

repair (Mosser and Edwards et al., 2008). Decrease in macrophages numbers can lead

to poor wound healing as a result from slower rates of fibroblast proliferation and poor

angiogenesis.

2.4.1.3) ProliferationCharacterised by epithelial migration and proliferation and re-epithelialzation. Fibroblasts

migrate into the wound (as mentioned in response to such growth factors as TGF-B) and

begin to proliferate and make new ECM through secreting fibronectin, HA, collagen type I

and III and proteoglycans (PGs). Collagens play a structural role through providing

strength and integrity to the repair tissue (Guo and DiPetro, 2010).

2.4.1.4)Remodelling PhaseAs the new ECM continues to develop the fibronectin and the HA are slowly broken down

and the diameter of the collagen fibres increase, increasing the tensile strength of the

recovering wound.

During remodelling the collagen is in equilibrium of being broken down and synthesised.

Collagen is broken down by MMPs which are secreted by macrophages and fibroblasts.

As the remodelling process continues the numbers of MMPs decrease and the number of

TIMPs increase, thus promoting a net gain of ECM. This equilibrium is controlled by TGF-B

(Enoch and Price, 2004).

Collagen reorganisation is achieved by wound contraction. The contractile tissue

underneath the wound contracts bringing the wound margins together this is thought to

be controlled by myofibroblasts (Campos et al.,2008).

Macrophages and fibroblasts begin to decrease in number as a result of apoptosis which

is stimulated potentially due to a decrease in cytokines. Finally angiogenesis stops

resulting in an acellular and avascular scar (Enoch and Price, 2004).

2.4.2) Chronic Wound Healing

Chronic wounds occur as a result of malfunctions in this acute healing process described

above. A wound is defined as chronic if it has not managed to heal within 4 – 6 weeks

after injury and does not show signs of doing so (Banikol and Potzschke, 2012).

According to Banikol and Potzschke chronic wounds arise from many factors (poor

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oxygenation, diabetes, nutrition). These factors can alter the cells metabolism, causing

the cell to become fixed in any of the 4 healing phases (Guo and Dipetro, 2010) this

disrupting the level of growth factors, cytokines and protease activity which play such a

crucial role in wound repair (Enoch and Price , 2004). The levels of MMP and serine

proteases such as neutrophil elastase have been found to increase in chronic wounds

compared to normal healing wounds (Yager et al., 1996). At the same time the level of

their specific inhibitors decreases which results in an increased degradation of the ECM

proteins. It’s the ECM proteins (Fibronectin, vitronectin and tenasin) that are responsible

for creating the ECM for collagen to be laid upon (Enoch and Price, 2004).

To summarise, disease cells associated with chronic wounds have distinctly different

biochemical and cellular features to acute wound;

i) Keratinocytes migrate less

ii) Change of fibroblast and keratinocyte phenotype

iii) Decrease in the amount of growth factors secreted

iv) Decreased response of fibroblasts to growth factors

v) Increase in MMP secretion by fibroblasts.

3) Optical Devices

3.1) Brief history of lasers and IPL

The first laser developed was the monochromatic light ruby laser which was developed in

1961 by Maiman (Raulin and Karsai 2011). This laser was a result of research through the

1950 that was based on Einstein’s principal of stimulating radiation (Greiges 2011). The

ruby laser was first used in dermatology in 1963 when Dr Leon Goldman used a ruby

laser to treat vascular lesions (Stier et al., 2008). In 1976 polychromatic light was used

by Muhlbauer to treat vascular lesions. This eventually led to IPL being launched for use

as a medical devices in 1994(Schoenwolf et al.,2011).

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3.2) The reaction mechanism of photons

Optical devices can induce a biological effect by various reaction mechanisms. These

reactions include photochemical, photothermal (most commonly used in dermatology)

photoablation, plasma induced ablation and photomechanical. These different reactions

are achieved by changing the pulse duration and energy densities of the irradiance

(Weber et al., 2011). Here I will look at the most common three:

3.2.1) Photothermal

This reaction, through the principal of selective thermolyisis is often considered as the

principal reaction associated with IPL treatment. (Schoenewolf et al., 2011). Although

this is the reaction associated with use of IPL for hair removal and skin rejuvenation, the

other reactions are used in other IPL treatment.

Heat is produced in the targeted tissue as a result of photons being absorbed by

chromophores. This rise in temperature in the tissues results in damage to the living

tissue (Raulin and Karsai, 2011). The basis of photothermal reaction is photothermolysis.

Described by Anderson and Parish in 1983 where only the targeted tissue is destroyed

through heating (Raulin, 2003)(Anderson and Parish, 1983).

3.2.2) Photomechanical

This mechanism involves short periods of high intensity irradiance. The high energy

results in the breaking of intramolecular bonds. It’s a photomechanical reaction that is

used to remove tattoos (Thomson,1991) Jacques, 1992).

3.2.3) Photochemical

There are two photochemical interactions described by Raulin and Karsai (2011);

biostimulation and photodynamic therapy (PDT). Biostimulation works on the basis that

when a chromophore absorbs a photon the energy of the photon causes a change in the

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signalling pathways of the cell and thus changing the metabolism of the cell. The change

in metabolism can result in change of gene expression (Zungu et al., 2006).

Mitochondria are common targets. The effect of stimulating chromophores in

mitochondria can cause an increase in cellular respiration (Whelan et al., 2001). This

can result in:

i) Increased production of ROS

ii) Increased ATP synthesis

iii) Changes in the permeability of cell membranes

iv) Nitric oxide release

These effects can cause an increasing cell proliferation and ECM synthesis (Raulin and

Karsai, 2011).

Low-level laser therapy (LLLT) is an example of laser therapy that works by the

photochemical biostimulation mechanism. It works through this mechanism as the low

power emitted from LLLT is not significant to cause damage to the tissue through rising

the temperature.

The photodynamic mechanism involves 3 parts; i) light for activation ii) sensitizer iii)

molecular oxygen.

The sensitizers accumulate in the target tissue and then become exited on absorption of

photons. The energy from the exited sensitizer is then transferred to molecular oxygen.

This exiting the molecular oxygen, causing it to become a free radical, and destroying

the cell. Photodynamic therapy is used in tumour treatment and imaging as the

sensitizers are fluorescent (Raulin and Karsai, 2011).

3.3 Light-tissue interactions

Before these reactions can take place the photons must interact with the tissue and

become absorbed. Not all the photons will be instantly absorbed. Around 4-10% of

photons that are emitted onto tissue are reflected (Raulin and Karsai,2011). This

reflection is dependent on the angle of incidence, when the angle of incidence is 90

degrees the reflection is lowest. The other photons enter the tissue. Once in the tissue

the photons can become absorbed by chromophores or can become scattered changing

their direction. This scattering can be caused by structures within the tissue e.g. muscle

12


fibres. The extent of scattering is dependent on the wavelength of light, the spot size and

tissue particle size. Photons of the lager light wavelengths will penetrate deeper into the

tissue without being absorbed (Allemann and Kaufman, 2011).

3.4) IPL devices

IPL’s are flash lamps that emit pulsed polychromatic high intensity light (Babillis et al.,

2010) between wavelengths of 500-1,200 (Haedersdal et al., 2008). IPL devices have

great potential as there is great scope to alter the pulse duration, pulse frequency and

the fluence. Thus giving them the ability to be carefully manipulated to suit different skin

types and conditions. Due to the broad range of light emitted it is possible to activate

many chromophores with a single irradiance. Different target chromophores have

different maximum wavelength absorptions, e.g. Haemoglobin absorbs at 580 nm where

melanin absorbs between 400-750 nm. Therefore by selecting the correct parameters

IPL can selectively target the target tissue through specific reaction mechanisms (Raulin

et al.,2003).

The fact that the parameters of IPL devices are so flexible it demands expertise to ensure

the right parameters are selected so side effects can be avoided kept to the minimum.

Poor and careless use of IPL can cause hyperpigmentation (Babilas et al., 2010).

What is Hyperpigmentation and other side effects? Erythema?

3.5) IPL Vs Lasers

IPL technology is similar to lasers in the respect that energy from the laser/IPL device is

transferred to chromophores in the skin (Schoenewolf et al., 2011). The use of lasers,

although effective, does come with their limitations. Lasers have restrictions on the

range wavelength and beam of light emitted. The fact that lasers emit a narrow beam of

light limits the size of the target area that can be treated. LED and IPL devices emit

larger arrays of light allowing the treatment area to be larger. The other limitation with

lasers comes from the heat produced which can damage surrounding tissue and the

intensity of the beam can damage eyes (Whelan et al., 2001). Lasers are also less

mobile and need greater maintenance than IPL and LED devices (Fushimi et al., 2012).

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4) Literature review

4.1) Skin rejuvenation

With regards to skin rejuvenation, treatment of chronic wound and tendinopathy the area

with greatest research on the effectiveness of IPL is skin rejuvenation. I will therefore

begin by reviewing the effectiveness of IPL in this field.

Paper Type of study

Population/Skin types/sex/Age

Optical device

Treatment course

Fluence (J/cm2)

Cut of filter (nm)

Results

Sasaya et al. (2011

Clinical trial on effect of IPL on hand solar letigenes

Japanese/female/ 40-74 (Ave.60.2)

Lumenis One

Treated 3-5 times at intervals of one month

10-12 515 ·62 % of patients showed 50 % improvement·23 % of patients showed a 75% improvement·0% of patients showed hyperpigmentation

Mohanan et al., 2012

Clinical trial on effect of IPL on acne

Indian/male and female/18-40

IFLi200 A maximum of 5 treatments at 3 weeks intervals

10/12 ·87.5% of patients were deemed to have had a ‘good’ response(51-75 % reduction).

Campolmi et al., 2011.

Clinical trial on vascular and pigmented lesions

European/Fitzpatrick skin types I-IV/male and female/ 28-75

Xe-pulsed Lamp(Minisilk FT)

4-6 treatments each at 3 week intervals.

16-23 Specific for each different skin type and type of lesion (see report)

·80% of lesions showed an ‘marked’ improvement.·87.5% of patients with Fitzpatrick type I skin showed a ‘marked’ improvement , compared to only 69.6 % of the Fitzpatrick type III patients.·97.7 % of patients were either satisfied or very satisfied.

Haung et al.,(2011)

In vitro -Effect of IPL on the secretion of MMP-1, TGF-β and on the MAPK signalling pathway in human skin fibroblasts

Human skin fibroblasts

·Levels of MMP-1 only increases at fluence of 10 J/cm2 .·Levels of TGF-β increases by exposure to fluences of 72J/cm.·IPL has an ‘bidirectional influence’ on MMP-1 and TGF-β levels.

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Wong et al.,(2008)

In vitro-Effect of IPL on human dermal fibroblast

Cultured from adult dermal fibroblast of 30-50 years of age

PhotoDerm VL/pL

Treated once and monitored for up to 72 hours after treatment. Levels of MMP-2 and -14 monitored by western blotting and RT-PCR

20,50 and 75

570 ·A dose dependant inhibition of both MMP-2 and -14 by IPL.· MMP -2 levels decreased by 40% compared to the control when exposed to a fluence of 75 J/cm2

This inhibition was maintained for up to 72 hours

Table 1) Table summarising the papers reviewed on various aspects of IPL skin rejuvenation.

4.1.1 IPL treatment of solar lentigines

Sasaya et al. (2011) looks at the effectiveness of IPL at treating solar lentigines on the

back of the hands. Solar lentigines are hyper pigmented lesions that result from over

exposure to U.V light. They can be common in the middle aged and elderly. Although

there is no treatment needed for solar lentigines, they can cause patients distress due to

cosmetic reasons (Farris, 2004). IPL has previously been shown to be an effective

method of treatment of facial solar lentigines for example Kawada et al. (2002) showed

that 48 % of the patients with facial lentigines treated with IPL showed >50%

improvement and Mayers et al. (2005) also showed that IPL could be used to treat a

variety of both vascular and solar damage problems of the skin. With 80% of the patients

treated were classed as having an ‘excellent’ reaction to treatment.

In the study by Sasaya et al. (2011), 31 Japanese females were treated with a Lumines

One IPL device. The device was a noncoherent , filtered broadband pulsed lamp emitting

light of a wavelength between 500-1200 nm. A cut off filter of 515 nm was used due to

this being the wavelength of greatest absorption by melanin. Melanin is found to

accumulate in the epidermal basal layers of solar lentigines, making melanin the target

chromophore.

Each patient received 3-5 treatments at 4-5 week intervals. The treatment consisted of a

fluence of 10-12 J/cm2 that was delivered at pulses of 4.0ms.

The results of the treatment suggest that IPL can be used as a potential method for

treatment of solar lentigines of the back of the hands. 52% of patients were rated by

physicians to have shown a moderate or marked improvement. Only 6% of the patients

showed no change and 0 patients showed side effects. With 94% of the patients

expressing some levels of satisfaction it indicates that IPL can be used as a tolerable and

attractive method of treating solar lentigines to the back of the hand.

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4.1.2 IPL treatment of Acne

Acne is a chronic inflammatory disease which is mostly commonly found on sites such as

the face, shoulders and back. It is common for it to affect not only adolescents but also

young adults. It is caused by the abnormal breakdown of the follicular epithelium. This

results in the obstruction of the pilosebaceous canal which leads to the formation of

comedones (Bjerring and Christianse, 2011). The treatments of acne can be for both

medical and cosmetic purposes. Some cases require the treatment for serious

psychological issues compared to some patients who would like to have it treated merely

for vanity.

Mohanan and colleagues (2012) have investigated the effects of IPL on the Indian

population. There is vast amount of research on the effect of IPL on acne suffers of the

Western world but not on the Indian population. The Indian population may react

differently to IPL treatment due to the higher melanin content of the skin (Mohanan et

al., 2012) .

Mohanan and colleagues (2012) ran a 17 months study were they investigate the benefit

of IPL on Indians aged 18 – 40 that suffered from mild to moderate acne. Prior to

treatment with IPL the patients were asked for a period of 2 weeks to cleanse their skin

and to apply sun cream. They were also asked to stop any other on-going treatments e.g

antibiotic courses.

For the effect of IPL to be measured the total number of comedones, papules and

pustules were counted and photographs taken before each treatment of IPL.

The IPL device used was the IFL i200. The device emitted multiple pulses of light at an

average frequency of 0.25Hz at a fluence of 10-12 J/cm2.

All 8 patients that finished the trail were of Fitzpatrick skin type 3 or 4 and aged below

25. All showed a reduction in lesion count. The overall reduction ranged from 44% - 73%,

with 7 out of the 8 deemed to have showed a ‘good’ response. Greater reduction was

seen in the count of papules and pustules than comedones, but not a significant amount,

nor was there significant correlation between the different skin types.

The study showed minimal and impermanent side effects, therefore indicating that IPL

could prove effective at treating Indian acne sufferers, provided they also undertake

protection from the sun through sun creams (Mohanan et al., 2012).

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4.1.3 IPL treatment on vascular and solar lesions

In a study by Campolmi et al. (2011) 85 patients with Fitzpatrick skin type’s I-IV between

the ages of 28 – 75 were treated with IPL and followed up for a period of 2 years. During

this time they received 4-6 treatments of IPL at 3 week intervals. The IPL device used

was Xe Pulsed Lamp. The pulse time was 3 – 8 ms with a double pulse, the pulse delay

was 10 ms. The fluence used was between 16 – 23 J/cm2 . Different cut off filters were

used for different lesions, this allowing different wavelengths to be emitted so different

lesions of different skin types could be specifically targeted. For vascular lesions a cut off

filter of 500 nm was used for skin types I and II, 520 nm was used for Fitzpatrick skin

types III and IV. Whereas for the pigmented lesions a cut off filter of 550 nm was used for

skin types I-III and 600 nm for IV.

The results of the study showed that all 85 patients showed improvements to their skin.

With 72 out of the 89 lesions that were strung across the 85 patients being deemed as

having a ‘marked’ improvement. The study found that 4 IPL treatments is needed for

improving the quality of pigmented lesions were as 6 IPL treatments were required for

vascular lesion. The results of the study by Campolmi et al.(2011) show that there is

difference in the efficiency of IPL with different skin types. 87.5 % of the Fitzpatrick skin

type I showed an marked improvement, whereas only 69.6 % of Fitzpatrick skin type III

shows a marked improvement. There was no significant correlation between the

efficiency of IPL with age. Best results were found when acting on Fitzpatrick skin

phototypes I-II with a wavelength of 500 – 520 nm and a pulse time of 8 ms.

Age % of age group that showed a ‘marked’

improvement

20-39 81.8

40-59 80.5

60-79 80.7

Table 2) Table showing the % of patients that showed a ‘marked’ improvement grouped

on age. No significant correlation was found.

The majority of the patients (55/85) showed no side effects and 97.7 said they were

either satisfied or very satisfied. Again this indicated that IPL is a safe and attractive

method for rejuvenating skin.

17


4.1.4 In Vitro analysis of IPL on levels of MMP-1 and TGF-β and the MAPK signalling cascade of human skin fibroblasts

Research by Huang et al. (2011) looked into the molecular biology behind the skin

rejuvenating actions of IPL. One way that IPL is thought to work is by effecting different

cytokines. It’s this specific action that causes the final out come to the targeted skin.

Haung et al. (2011) investigated the effect that IPL had on the levels of MMP-1 and TGF-

β1 that were secreted by human fibroblast cells. Haung and colleagues also looked at the

effect IPL had on the MAPK signalling cascade. Their results showed:

i) The level of MMP-1 secreted increased only when IPL was applied at a fluence

of 10 J/cm2 .

ii) TGF-β1 secretion was inhibited when IPL was applied at a fluence of below 36

J/cm2 .

iii) Levels of TGF-β1 increased when IPL was applied at a fluence of 72 J/cm2.

iv) MAPK signalling proteins decrease/become inhibited by IPL. This having a range

of effects;

- ) When ERK become inhibited MMP-1 secretion decreased but had no

significant effect on TGF-β1.

- ) Inhibition of JNK resulted in the increase of MMP-1 and decrease of TGF-β1

- ) P38 inhibition did not have a significant effect on MMP-1 levels but did

cause an increase in TGF-β1 secretion.

Huang et al. (2011) therefore suggests that it is this ‘bidirectional influence’ that IPL has

on MMP-1 and TGF-β1 that can cause skin rejuvenation. This coincides with other

research as it is known that TGF-β1 can induce angiogenesis, stimulate the production of

collagen I and III through activating fibroblasts, and cause the granulation of tissue

(Roberts et al., 1986).

4.1.5 In Vitro analysis of how IPL effects levels of MMP-2 and MMP-14 secreted by human dermal fibroblasts

A study by Wong et al. (2008) discusses the underlying effects that IPL has on biological

tissue by looking at how IPL affects human dermal fibroblasts. Wong and colleagues

cultured primary human dermal fibroblasts from a selection of adult skin dermis explants

that were between the ages of 30 -50 years old. Wong et al. were particularly interested

18


to see at how IPL effected the expression of MMPs and TIMPs, essential mediators that

maintain the firmness of skin.

The IPL device used was PhotoDerm VL/pL system. A cut off filter of 570 nm was used at

triple pulses of 7 ms at pulse intervals of 70 ms. Fluency’s of 20, 50 and 75 J/cm2 were

used. After irradiation the tissue was placed in DMEM/10% FBS and left for 74 hours. On

removal the fibroblast in lattices were taken for RNA isolation.

MMP-2 activity was analysed by gelatin Zymography and the protein levels of MMP-2

were examined by western blotting and RT-PCR. MMP-2 and -14 was found to be inhibited

by IPL treatment. This inhibition was dose dependant.

Fluence (J/cm2) Decline in MMP-2 mRNA compared to the

control group (%)

25 11

50 18

75 40

Table 3) Table showing how the inhibition of MMP-2 was dose dependant. With increasing

fluency’s there was a greater decrease in MMP-2 mRNA.

Fluence (J/cm2) Decline in MMP-14 mRNA compared to the

control group (%)

25 14

50 23

75 41

Table 4) Table showing how the inhibition of MMP-14 was dose dependant. With

increasing fluencies there was a greater decrease in MMP-14 mRNA.

The results from the study by Wong et al. (2008) show that treatment by IPL can down

regulate MMP-2 and -14 thus helping to reduce the catabolic effects of these MMPs,

which could result in an overall net increase in ECM. This suggesting that IPL rejuvenates

skin not only by stimulating an increase in the production ECM proteins like shown by

Haung et al (2011), but also by reducing the amount of ECM that gets broken down by

inhibiting MMPs. This helps to counter act the increase in MMPs that can occur from

exposure of skin to UVR (Wertz et al., 2004).

4.2) Tendinopathy

Another area where optical devices have been shown to be useful is in the treatment of

tendinopathy. As discussed previously in the review (see section 2.3) injury to tendons

19


can easily occur and repairing it can be a lengthy progress. The use of IPL in

tendinopathy repair has not been as extensively researched as it has been in skin

rejuvenation there was therefore limited literature available. This section will therefore

also look at the effectiveness of other optical devices i.e. lasers and LED at treating

tendinopathy.

Paper Type of study

Population/Subject

Optical device Treatment details

Fluence (J/cm2)

Results

Tsai et al.2012

In Vitro Tenocytes from rat Achilles tendon

LLLT at 660 nm (Konftec,Megalus-AM-800)

(See method) 1.01.52.0

·Dose dependant tenocyte migration in LLLT groups·Dose dependant increase in dynamin-2 expression in LLLT groups·Suppression of tenocyte migration in LLLT groups treated with dynasore.

Hutchinson et al., 2012

In Vivo Human Achilles tendon

IPL - iPulse (Cyden,Wales)

Irradiation was given at 2-6 cm above calcaneus (See method)

13.5 ·It was concluded that an IPL device emitting a fluence of 13 J/cm2 is significant to produce enough energy for photons to reach the depth of an human Achilles tendon.· Wavelengths between 645-843 were transmitted the best.

Tumility et al.,2012

Clinical Human Achilles tendon

LLLT at 810 nm (Thor DD therapy unit)

Laser treatment was given 3 times a week for 4 weeks.Exercise program consisted of heavy load eccentric movements twice a day every day of the week for a period of 12 weeks

3.0 By using VISA-A and NPRS questionnaires no statistical difference was found between the LLLT + exercise group and the Placebo + exercise group.

Stergirulas et al.,2008

Clinical Human Achilles tendon

LLLT at 820 nm (Biotherapy 2000)

Laser treatment was given twice a week between weeks 1-4 and once a week between weeks 5-8.Exercise program consisted of eccentric exercise 4 times a week for 8 weeks.

5.4 The LLLT + E.E group at week for showed similar results to the placebo + E.E group at week 12Suggesting that LLLT can decrease the repair time of tendinopathy

Bjordal et Clinical Human lateral LLLT – Various See paper for See paper LLLT at wavelength of

20


al., 2008 review elbow tendon treatments between wavelengths of 632 to 1094

individual methods

904 nm when applied directly to the lateral elbow tendon provided short term pain relief and increased mobility of joint. Dose dependant.

Table 5) Table summarising the papers reviewing the effect of optical devices to treat

tendinopathy

4.2.1 Use of Low-level laser therapy (LLLT) to treat tendinopathy

Low-level laser therapy (LLLT) can be used to treat such Achilles tendinopathy (Tsai et

al., 2012). LLLT has been shown to stimulate an increase in proliferation of fibroblasts

and therefore collagen synthesis, thus helping tendon repair (Almeida-Lopes et al., 1998)

(Pindfildi et al., 2005) (Salute et al., 2005). It is suggested that LLLT also improves

injuries to Achilles tendons by improving the organisation of collagen fibril deposition,

preventing oxidative stress and reducing fibrosis (Casalechi et al., 2009). The mechanism

behind this is suggested to be photochemical (see section 3.2.3) (Lane, 2006). LLLT has

also been shown to increase tenocyte proliferation and collagen I in pig tendons (Chen et

al., 2009).

Figure 4) Image showing common site of injury (red spot) and treatment areas (yellow arrows) of Achilles tendinopathy (Taken from Tumilty et al.,2012)

4.2.1.1 Effect of LLLT of tenocyte migration and dynamin-2 expression

For tendons to heal they require the co-ordination of 3 phases (similar to the 4 of wound

healing); inflammation, regeneration and remodelling and maturation (Leadbeater,

1992). During the regenerative phase the tenocytes migrate to the wounded site where

they begin synthesising new ECM. This tenocyte migration is therefore essential to the

repair of an injured tendon (Tsai et al., 2012).

A study by Tsai et al. (2012) investigated the effect of LLLT on the migration of tenocytes

and how the expression of dynamin-2 was effected. Tenocytes of the Achilles tendon of

rats were exposed to low level laser of a wavelength of 660 nm at fluences of 1.0, 1.5

21


and 2.0 J/cm2. The in vitro study found that there was greater tenocyte migration in the

groups with laser treatment than in the control group. This tenocyte migration was dose

dependant. The group treated with fluences of 1 J/cm2 saw 18% greater migration than

the control. The group treated with fluences of 1.5 J/cm2 saw 33% more migration and the

group treated with fluences of 2 J/cm2 resulted in 56.5% more migration. Real-time PCR

analysis of the study also showed that treatment with low level laser increases the

expression of dynamin-2. With a 14% and 35% increase in groups treated by 1.5 J/cm2

and 2.0 J/cm2 compared to the control group.

Dynamin-2 is a GTPase involved in cell migration through its role in expanding the

membrane lip through actin polymerisation (Kruchten, 2006). Therefore by up regulating

dynamin it enables tenocytes to migrate to the site of injury. The study also showed that

when the tendon samples were treated with dynasore, a non-competitive inhibitor of

dynamin (Macia et al., 2006), the migration of tenocytes that was induced by LLLT was

inhibited. This further shows that dynamin plays a role in cell migration. Therefore it

suggests that optical devices such as LLLT can be useful in the treatment of

tendinopathy by inducing gene expression of dynamin through stimulating the required

signalling pathway.

4.2.1.2 Effectiveness of LLLT at treating Achilles tendinopathy when combined with traditional eccentric exercise

Research by Tamility et al. (2012) looks at the possible benefits to Achilles tendinopathy

when combining LLLT with a traditional eccentric exercise programme. 40 patients

entered the trail and were divided into 2 groups, 20 LLLT and 20 placebo. The LLLT group

were subject to laser treatment and an eccentric exercise program whereas the placebo

group were subject to a placebo laser and the eccentric exercise programme. The laser

treatment consisted of 3 treatments a week for the first 4 weeks at a fluence of 3J/cm2.

The laser used was Thor DD laser therapy unit at a wavelength of 810nm. The exercise

protocol involved heavy load eccentric movements twice a day every day of the week for

the first 12 weeks of the trail with the first 4 weeks being supervised by a

physiotherapist. Through using a VISA-A and NPRS questionnaires the pain of the

patients was recorded at week 0, 4, 12 and 52. Out of the 33 patients (17 LLLT group, 16

placebo group) that finished the 52 week assessment there was found to be no

significant difference between them. This trial therefore suggests that there is no benefit

of combing LLLT with traditional Achilles tendinopathy treatment methods.

4.2.1.3 Effectiveness of LLLT combined with eccentric exercise at treating chronic Achilles tendinopathy in humans

22


A similar study to above was carried out by Stergiralas et al.(2008). Again this study

examines the potential of improving on traditional eccentric exercise therapy, which can

take a while to show progressive results, by combing it with LLLT. 52 patients were

randomly divided into 2 groups; LLLT + eccentric exercise or placebo + eccentric

exercise. Patients were included in the trail if they had been suffering from Achilles

tendinopathy for 6 months or more and had pain between 2-6 cm proximal to insertion

on the os calcaneus. The LLLT consisted of 12 treatments, with 2 treatments a week for

the weeks 1- 4 weeks then 1 treatment a week between weeks 5-8. The laser device

used was an infrared laser at a wavelength of 820 nm (Biotherapy 2000). The eccentric

exercise program involved 4 sessions a week for the 8 weeks. Weeks 9-12 were free of

treatment and used for follow up purposes.

The results of the study showed that at week 4 the LLLT group showed similar results to

the placebo group at week 12. This suggested that LLLT can be used alongside eccentric

exercise programmes to improve recovery of Achilles tendinopathy and potentially be

used instead of Nonsteroidal Antiflamatory drugs (NSAID) which can cause adverse side

effects such as gastrointestinal ulcers or cardiovascular problems (Marcos et al.2011).

4.4.1.4 Effectiveness of LLLT at treating lateral elbow tendinopathy

Another common tendon disorder that can result from sport injury or from day to day life

is lateral elbow tendinopathy (LET) also known as tennis elbow. Traditional treatments for

LET are similar to those discussed above for treatment of Achilles tendinopathy. Such as

steroid injections, NSAIDs and eccentric exercise (Bjordal et al.,2008)

A study by Bjordal et al., (2008) looks at the use of LLLT to treat LET. The study showed

that by emitting light of wavelength of 904 nm directly to the lateral elbow tendon it

could provide short term pain relief and greater mobility.

4.2. 2 Efficiency of IPL treatment on human Achilles tendinopathy

As discussed IPL has been proven to work on skin to reduce the appearance of vascular

lesions e.g. Rosacea and Pigmented lesions e.g. solar lentigines (section 4.1.3). One

problem with IPL however is that it is not yet known how the efficiency of IPL treatment is

effected as the depth of the target tissue increases (Hutchinson et al.,2012). If IPL can be

shown to reach such structures as Achilles tendons it could be used to treat

tendinopathy.

A study by Hutchinson et al. (2012) aimed to find if IPL transmission would reach a

human Achilles tendon when emitted on the surface of the skin. If their study showed

that IPL could be used to transmit light through tissue to that depth it’s possible that IPL

23


has potential in the treatment of Achilles tendinopathy. The study also set out to find the

amount of light that would be attenuated within the tendon.

Hutchinson and colleagues (2012) used 3 human Achilles tendons that were irradiated 2-

6 cm above the insertion into the calcaneus. The IPL device used was an model iPulse

(Cyden Ltd, Wales, UK). A single pulse of 25ms was used between wavelengths of 530-

1110 nm. The fluence used was 13 J/cm2. To analyse the transmission of light radiation a

standard SLR digital camera, spectrometer and an external energy meter were used. All

three devices found the IPL device to have emitted light radiation through the 3 samples.

4 – 8.1% of the fluence was found to have been transmitted through the sample by the

energy meter. The spectrometer showed that the longer wavelengths of light of between

645-843 nm were transmitted through the tissue the best. The percentage of light

radiation that was attenuated with the tendon was between 10.7-17.32 %.

Hutchison et al. (2012) concludes that the study suggests that an IPL device emitting a

fluence of 13 J/cm2 onto the surface of the skin produces significant light radiation that is

capable of penetrating to the depth of a human Achilles tendon. Therefore IPL could

provide beneficial to sufferers of Achilles Tendinopathy.

4.3) Chronic wounds

The last field that shall be reviewed is how optical devices can help in the repair of

chronic wounds. Chronic wounds are a strain on the worlds health care system. It is

estimated that chronic wounds cost the U.S health system between $6-$15 billion dollars

every year (Markova et al.,2012) and that 0.3% of the general population suffers from

chronic ulcers.. The most common ulcers are venous leg ulcers and diabetic foot ulcers

(Markova et al.,2012) (Costin et al.,2012). Chronic venous leg ulcers account for 70 –

90% of lower limb ulcers and may never heal (Kalkurni et al., 2007). Treatment of chronic

ulcers was described as inadequate by McMullin (2001) and over the last 10 years there

been no improvements in their treatment (Jones, 2009). Currently the best way to treat

chronic ulcers is through compression bandage which acts by decreasing venous

hypertension and improves blood flow through veins (O’Meara, 2009). It is therefore

these chronic wounds that will be the focus of this section.

Paper Type of Study

Case/Subject Optical device used

Fluence Results

Kaviani et al.,2011

Clinical Chronic Diabetic Foot Ulcers

LLLT at 685 nm

10 J/cm2 ·By week 4 the LLLT group had showed a significant reduction in the size of ulcers (Not found in the placebo group)·After 20 weeks , 61% of the LLLT group had fully recovered compared to only 30% of the placebo group

Jude et al.,2002

In Vivo Chronic Diabetic Foot Ulcers

- - Western blotting showed that fibroblasts of diabetic foot ulcers secreted less TGF-β1 and no increase in TGF-β receptors. This could be the principal reasons behind such chronic wounds

24


Fishimi et al.,2012

In VivoIn Vitro

·Excision across the dorsal of mice·Human dermal fibroblasts

Red, Blue and Green LED

Specific for each LED wavelength and subject (See method)

·Mice exposed to red and green LED showed total wound re-epithelisation 2 days before those control mice and those exposed to blue LED.·The In Vitro study showed that fibroblasts exposed to green LED secreted a increased amount of cytokines.·In Vitro study also showed that keratinocyte migration increased when exposed to red and green LED.

Landau et al., 2011

Clinical Diabetic Ulcers and Venous Ulcers

LLLT and LED between wavelengths of 400-800 nm

Specific to the optical device used and the ulcer treated(See method)

·90% of wounds of the treatment group closed with an average 89 % reduction in size· Only 33% of the placebo group ulcers closed with an average 54% reduction in size

Minatel et al.,2009

Clinical Diabetic Ulcers

LED 3.0 ·At day 90, 58.3% of treatment group ulcers had healed fully and 75% of them had healed by 90 -100%.·At day 90 only one placebo group ulcer had fully healed.

Table 7) Table summarising the findings of the papers reviewed with regards to chronic

wounds.

4.3.1 Role of TGF-β in chronic ulcersTGF-β plays an important role in the wound healing process. TGF-β co-ordinates the

inflammation, angiogenesis, re-epithelialization and the regeneration of connective tissue

ECM (Pastet et al., 2010). It has been shown that fibroblasts, which are essential cells

in the remodelling of connective tissue, can become unresponsive to growth factors such

as TGF-β in cases of chronic ulcers (Barrientos et al., 2008). In normal wound healing

TGF-β controls the wound healing process by binding to TGF-β receptors this causing

heterodimerization between TGF-βRI and TGF-βRII. This results in TGF-BII

phosphorylating the signalling proteins Smad 2 or Smad 3. Smad 2 or 3 then bind with

Smad 4. This newly formed complex moves to the nucleus where binds to the Smad

binding promoter elements where it can regulate the expression of genes needed for

wound healing (Schiller at al., 2004) (Nicolas et al., 2004).

During normal wound repair, there is an increase in secretion of TGF-B1 by keratinocytes,

platelets, fibroblast and macrophages after trauma (Faler at al., 2006) allowing the

signalling cascade described above to take place at a greater rate.

A study by Jude et al. (2002) investigated how the levels of TGF-β1, 2, 3 and TGF-β

receptors I and II in cells of diabetic foot ulcers compared to normal cells. By using

western blotting to determine the protein levels of TGF-β Jude et al. found that fibroblasts

associated with diabetic ulcers secreted reduced levels of TGF-β1 compared to normal

cells nor is there the increase in TGF-βRII which is associated with normal healing cells. In

theory by stimulating TGF-β release the wound healing process of such chronic wounds

could be improved and thus reducing the healing time.

25


4.3.2 Treatment of Chronic Ulcers with optical devices

Chronic wounds can be treated through laser treatment. As Laser and LED treatment are

non-invasive treatments they are of particular use in patients who are at increased risk of

infection from surgical treatment, for example diabetic sufferers whose poor immunity

puts them at the risk of opportunistic infections (Kalani et al., 2003).

4.3.2.1 LLLT for chronic diabetic foot ulcers

A study by Kaviani et al. (2011) looked into the benefit of low level laser therapy on

chronic diabetic foot ulcers. In this study, 23 patients were followed for 20 weeks. With

13 being treated with LLLT and 10 with a placebo treatment. The LLLT given was at a

wavelength of 685 nm at a fluence of 10 J/cm2. The study found that after week 4 there

had been a significant reduction in the size of the ulcers in the LLLT patients. This was

not found in the placebo group. After the 20 week follow up period, 8 out of the 13

patients who had been treated with LLLT had fully recovered compared to only 3 out of

the 10 in the placebo group. This suggested that LLLT could decrease the healing time of

chronic diabetic ulcers.

4.3.2.2 LED and LLLT for treatment of chronic diabetic ulcers and venous ulcers

A study by Landau et al. (2011) conducted research on a small group of both diabetic

and venous ulcer patients. The study investigates the effect of wavelengths between

400-800 nm had on these wounds. The participant were divided into either placebo or

treatment groups. The treatment group consisted of 10 patients with a total of 19 ulcers.

The placebo group consisted of 6 patients with a total of 6 ulcers. The laser treatment

involved treatment of 180mw/cm twice a day.

The results of the study showed that 90% of the treatment group ulcers closed with an

89% reduction in size, whereas only 33% of the placebo group ulcers closed with a 54%

reduction in size. Although these results come from a small pool of patients they

significantly show that treatment with low level lasers can improve chronic ulcers

26


4.3.2.2 LED treatment of chronic wounds

The other optical device which has been shown to improve the rate of chronic wound

healing is LED. Fushimi et al. (2012) investigated the effects of LED on both In vivo and In

vitro by analysing wound repair in 8 week old male mice and in human dermal fibroblast

respectively.

The In vivo study involved each mouse having an 8mm excision made across its dorsal

side and were divided into 4 groups; control (no LED exposure), red LED (638 nm, 0.3

J/cm2), blue LED (456 nm, 0.3 J/cm2) and green LED (518 nm, 0.3 J/cm2). The 3 LED

groups were exposed to 20 minutes of irradiation every other day from a distance of 10

cm. The wound size was measured before each irradiation period. By day 11 the groups

exposed to the red and green LED showed complete epitheliazation of the wound. The

blue LED and control group showed total epitheliazation on day 13. Therefore form the

study it can be suggested that exposure to red or green LED can decrease the healing

time of wounds. In In vitro studies also used 4 groups; red LED (638 nm,0.6 J/cm2 ), blue

LED (456 nm, 0.3 J/cm2 ), green LED (518 nm,0.2 J/cm2 ). By measuring the mRNA and

protein levels by using RT-PCR and an ELISA assay respectively and also keratinocyte

migration, by using a migration assay the results showed that exposure to green LED

caused an increase in cytokine(HGF,KGF, Leptin ,IL-8 and VEGF) secretion by fibroblast

cells. The results from the study also showed that migration of keratinocyte also

increased on exposure to both red and green LED. The study by Fushimi et al. (2012)

therefore suggests that green LED can improve wound healing by increasing

keratinocyte migration and by increasing the levels of cytokines secreted by fibroblasts.

The secretion of cytokines and keratinocyte migration to wound site are essential aspects

to the repair of wounds, as discussed previously.

4.3.2.3 Effectiveness of LED on chronic diabetic ulcers

A study by Minatel et al. (2009) carried out research on the effect of LED on chronic

diabetic leg ulcers that have failed to respond to other treatments. The study comprised

of a treatment and placebo group with 14 patients in both. The patients in the treatment

group were subject to two treatment of LED a week at a fluence of 3 J/cm2 for 90 weeks.

The ulcers were analysed at days 15, 30, 45, 60, 75 and 90. The results suggested that

LED treatment could improve the healing of diabetic ulcers. At day 90 58% of the

27


treatment group ulcers had fully healed and 75% had recovered by between 90-100%.

Compared to the placebo group, which at day 90, only one ulcer showed complete

healing and no other ulcer from that group healed by 90% +.

There has been plenty of research and literature supporting the beneficial effect of lasers

and LED therapy on chronic wounds, such as diabetic and chronic venous ulcers.

However, these methods of treatment do have their negatives. Lasers and LED as well as

being expensive are fixed at one wavelength. Although there is no doubt over the

potential strength of a laser some research groups question whether the output from a

LLLT or LED is really strong enough to stimulate an effect in the tissue (Posten et al.,

2005). A potential optical device that could also benefit the treatment of chronic wound

are IPL devices. As reviewed IPL has been proven to help rejuvenate the skin and possess

potential in wound healing.

28


5) Conclusion

Optical devices, such as IPL have great promise in a number of medical and cosmetic

applications. It had been shown that through different biochemical reactions that photons

emitted from optical devices can rejuvenate skin, improve the healing of chronic wound

and help in treatment of tendinopathy. It has been shown that the molecular basis

behind these actions is through stimulating fibroblast proliferation, increasing the

synthesis and organised attachment of collagen, greater production of other ECM

components (proteoglycans, glycoproteins, elastin) increase in growth factor and

cytokine production (KGF, HGF, VGEF, TGF-B),stimulate angiogenesis, epithelialization of

wounds, decrease numbers of MMPs and induce the stimulation of macrophage and

neutrophils.

Although there is not as extensive research on the beneficial effects of IPL on wound

healing and tendinopathy as there is on its use in skin rejuvenation and for hair removal

it is fair to say that there is enough potential benefits and theory on why IPL could be

used to help improve these problems to warrant further research. For example,

decreasing the healing time of chronic wounds has many benefits such as reducing the

use of compression bandages thus saving costs and can also free up hospital beds

reducing the burden on health care resources. IPL also possess practical benefits over

lasers and LED, such as price, greater flexibility in terms of selection of parameters and

are more mobile.

To conclude, optical devices have many uses in both medicine and cosmetics. Further

research into the use of IPL to treat chronic wounds and tendinopathy is needed as there

is potential for IPL treatment to reduce costs and resources needed to treat these

diseases.

29


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