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Precision Laser Therapy for Retinoblastoma

Authors:

Sameh Soliman1-2, Stephanie Kletke1, Kelsey Roelofs3, Cynthia VandenHoven1,

Leslie Mckeen1, Brenda Gallie1.

Authors’ affiliations:

1Department of Ophthalmology and Visual Sciences, Hospital for Sick children,

Toronto, Ontario, Canada.

2Department of Ophthalmology, Faculty of Medicine, University of Alexandria,

Egypt.

3Department of Ophthalmology, Alberta children hospital, University of Calgary,

Alberta, Canada

Corresponding author:

Dr. Brenda Gallie at the Department of Ophthalmology and Vision Sciences, the

Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada,

or at brenda@gallie.ca

Type of article: Review

Word limit:

Tables and Figures:

Abstract

Introduction–Laser therapy is a cornerstone for control of intraocular

retinoblastoma, after chemotherapy has brought the disease under initial control.

Since first described over 6 decades ago, laser technologies and approaches have

evolved. to improve tumor control. Despite its important role, lfew publications

describe techniques, types of lasers, and modes of delivery for retinoblastoma.

Areas covered–The physical and optical properties of lasers, mechanisms of

action, delivery systems, complications, are described. Hand-held optical coherence

tomography (OCT) guides treatment and detection of microscopic retinoblastoma

tumors, achieving precision primary therapy and elimination of recurrences.

Expert commentary–In all the excitement of new therapies to cure intraocular

retinoblastoma, laser treatment always compliments but is rarely mentioned. Hand-

held OCT now puts adds precision to put laser in the forefront in achieving cure of

retinoblastoma.

Keywords

Retinoblastoma; laser therapy; hand-held optical coherence tomograph; precision

medicine; primary tumor detection; early recurrence intervention.Introduction

Retinoblastoma is the most common intraocular malignancy, initiated by mutations

in both copies of the retinoblastoma gene (RB1 gene) [1]. Worldwide, 8000 children

are newly diagnosed annually. Survival approaches 100% if retinoblastoma is

diagnosed and treated while still intraocular, but when retinoblastoma is extraocular,

children have poor survival [1, 2]. The fundamental primary goal of treating cancer is

life salvage, and for retinoblastoma vision salvage is a secondary goal. Salvage of an

eye without visual potential may be dangerous since unrecognized recurrence of the

cancer, can leads to extraocular extension and loss of life.

Despite the recent advances and new treatment modalities, the primary therapy for

intraocular retinoblastoma remains tumor size reduction by chemotherapy (systemic,

intra-arterial or periocular) followed by focal therapy with laser, cryotherapy, plaque

radiotherapy and/or intravitreal chemotherapy, according to tumor location and size.

Chemotherapy without focal consolidation is rarely sufficient to control

retinoblastoma [3, 4]

Laser is appropriate as primary therapy only for small tumors. Techniques of laser

therapy are rarely described making it difficult to study or learn outside an

apprenticeship situation. Choice of laser wave length is variable according to

experience and availability. Furthermore, the role of laser in achieving primary or

recurrent tumor control is unmentioned or even neglected in reporting or comparing

outcomes of recent treatments as intra-arterial chemotherapy (IAC) or Intravitreal

chemotherapy (IViC) giving the reader the false impression of insignificant role of

Laser [5, 6].

Optical coherence tomography (OCT) has revolutionized our perspective of variable

retinal disorders including retinoblastoma by allowing detailed anatomical evaluation

of the retinal layers and tumor architecture. OCT visualizes subclinical new tumors

and tumor recurrences, differentiates tumor from gliosis during scar evaluation, and

improves perception of important anatomic landmarks for vision such as the fovea

and optic nerve [4, 7].

1. Physics of laser

Einstein postulated the concept behind the stimulated emission process upon which

lasers are based in 1917, but it was not until 1960 that T.H. Maiman performed the

first experimental demonstration of a ruby (Cr3+AL2O3) solid state laser [8]. The

acronym LASER represents the underlying fundamental quantum-mechanical

principals involved: Light Amplification by Stimulated Emission of Radiation [9].

All lasers require a pump, an active medium and an optical resonance cavity. Energy

is introduced into the system by the pump, which excites electrons to move from a

lower to higher energy orbit. As these electrons return to their ground state, they emit

photons, all of which will be of the same wavelength resulting in light that is

monochromatic (one color), coherent (in-phase) and collimated (light waves

aligned). Mirrors at either end of the resonance cavity reflect photons traveling

parallel to the cavity axis, which then stimulate more electrons, resulting in

amplification of photon emission. Eventually photons exit the laser cavity through

the partially reflective mirror into the laser delivery system.[9]

Lasers are typically categorized by their active medium, which determines the laser

beam wavelength. For all lasers, the wavelength multiplied by the frequency of

oscillation equals the speed of light. Therefore, as the laser wavelength increases its

frequency decreases proportionally and vice versa. Additionally, Planck’s law

(E=h) states that the energy (E) of a photon is a product of Planck’s constant

(h=6.626 x 10-34 m2kg/s) multiplied by the frequency (). As such, lasers with low

wavelengths (and high frequency) impart high energy, and those with high

wavelengths (and low frequency) are less powerful. Broad categories of lasers

include solid state, gas, excimer, dye and semiconductor.

The power of a laser is expressed in watts (W), which is the amount of energy in

joules (J) per unit time (J/sec). Power density takes into account both the power (W)

and the area over which it is distributed (W/cm2). It is important to note that if spot

size is halved, the power density is quadrupled, and if the amount of energy (J)

remains constant, decreasing the duration will increase the power (W) delivered.

Longer pulse duration increases the risk that heat waves will extend beyond the

optical laser spot, thus damaging surrounding normal tissue.[10] All lasers have the

option to control the shot pace or inter-shot interval, according to the experience of

treating ophthalmologist. In general, trainees start with single shots or a longer inter-

shot interval.

2. Types of lasers for retinoblastoma

Xenon arc photocoagulation, first described by Meyer-Schwickerath in 1956, was the

earliest photocoagulation method adopted for treatment of retinoblastoma.[11, 12]

Xenon emission is white light, a mixture of wavelengths between 400 and 1600 nm

and results in full-thickness burns without selectively targeting ocular tissues. It is

now replaced by laser photocoagulation for retinoblastoma.

The commonest lasers used for focal therapy in retinoblastoma are green (532 nm)

frequency doubled neodymium Nd:YAG (yttrium-aluminum-garnet) by indirect

ophthalmoscope, 810 nm semiconductor infrared indirect or trans-scleral diode laser,

and the 1064 nm far infrared continuous wave Nd:YAG laser. While all three lasers

can be delivered with use of an indirect ophthalmoscope, the infrared lasers can also

be applied in a trans-scleral manner, particularly useful for anteriorly located tumors.

Green 532 nm and 810 nm lasers can treat tumor by photocoagulation. The 810 nm

and 1064 nm lasers can also treat by raising tumor temperature (hyperthermia,

commonly called trans-pupillary thermotherapy or TTT) in a sub-threshold

manner[10]. Table 1 demonstrates the main differences between the different types

of laser in retinoblastoma.

3. Laser delivery

Retinal laser treatments can be delivered by either binocular indirect ophthalmoscopy

using non-contact, hand-held lenses (20 D, pan-retinal 2.2 D or 28 D) or by

microscope-mounted laser with contact lenses (Goldmann Universal Three-Mirror,

Ocular Mainster Wide Field) and a coupling agent (Table 2).

4.1. Laser indirect ophthalmoscopy (LIO).

LIO was first described to treat retinoblastoma in 1992.[13] LIO combined with

manipulation of eye position with a scleral depressor is the ideal laser delivery

technique for children under general anesthesia. The higher the power of the

condensing lens, the lower the image magnification and the greater the field of view.

The laser spot size on the retina is minimized (with most power) at the focal point, a

specific distance from the indirect ophthalmoscope, and diverges closer and farther

from the focal point. Effect depends on power, relative positions of the headset and

lenses, light scattering by ocular media, and the patient’s refractive error. For

instance, a 20 D lens causes a 900 µm image plane spot to be reduced to 300 µm in

an emmetropic eye.[14] Retinal spot size can be calculated by power of the

condensing aspheric lens multiplied by image plane spot size divided by 60.[14]

However, LIO requires careful optimization and coordination of the inherent

instability of the patient’s eye, the clinician’s head, and simultaneous foot pedal

depression, [15]

4.2. Microscope-mounted delivery system.

Laser may also be delivered through a slit-lamp or operating microscope: the

working distance from the microscope to the patient’s eye is fixed. Therefore, retinal

laser spot size is only dictated by the patient’s refractive error, contact lens and pre-

selected laser spot diameter on the microscope.[14] Tilting the contact lens within 15

degrees does not cause significant distortion of the laser spot, as irradiance differs by

maximum 6.8%.[16] The universal Goldmann three-mirror (Power -67 D) has a flat

anterior surface that cancels the optical power of the anterior cornea, therefore

decreasing peripheral aberrations.[17, 18] It contains mirrors at 59, 67 and 73

degrees to aid in visualization and treatment of the periphery.[17] However,

photocoagulation efficiency is reduced in the far periphery, as the laser follows an

off-axis, oblique trajectory. LIO is preferred for peripheral retinal laser treatments as

the field of view is greater than with a microscope-mount.

Also commonly used is the Mainster wide-field (Power +61 D) contact lens,

containing an aspheric lens in contact with the cornea and a convex lens at a fixed

distance.[17, 18] The Mainster lens has improved field of view at the expense of

poorer resolution, while the Goldmann three-mirror which has the highest on-axis

resolution.[16] Inverted image lenses may produce smaller anterior than posterior

segment laser beam diameters, leading to higher irradiance in the anterior segment.

Injury to the cornea and lens have been reported during retinal photocoagulation with

inverted image lenses, particularly in the presence of high power settings and ocular

media opacities.[16]

4.3 Trans-scleral laser therapy.

Infra-red laser photocoagulation may also be delivered trans-sclerally using an

optical fiber.[19, 20] This technique was first described for the treatment of

retinoblastoma in 1998.[21] Direct visualization of a red laser aiming beam through

the wall of the globe confirms the treatment area, with the main outcome being

whitening of the tumor and surrounding retina. In vitro and in vivo studies of trans-

scleral thermotherapy for choroidal melanoma suggest tumor cell destruction occurs

at a threshold of 60 degrees Celsius, without permanent damage to scleral collagen or

increased risk of retinal tears.[22, 23] Given the precise nature of delivery and

effective scleral transmission, trans-scleral diode is useful for treatment of anteriorly

located retinoblastoma tumors and in the presence of media opacities. Trans-scleral

diode also decreases the risk of cataract formation by limiting laser transmittance

through the lens.[21]

4. Laser appraoches for retinoblastoma:

5.1. Photocoagulation

Photocoagulation is the process by which laser light energy is absorbed by a target

tissue and converted into thermal energy. A 10-20 degree Celsius temperature rise

induces protein denaturation and subsequent coagulation and necrosis, depending on

the duration and extent of thermal change.[11] Heat generation is influenced by the

laser parameters and optical properties of the absorbing tissue.[17] Absorption

characteristics are dictated by tissue-specific chromophores, such as melanin in the

retinal pigment epithelium (RPE) and choroidal melanocytes, hemoglobin in blood

vessels, xanthophyll in the inner and outer plexiform layers, lipofuscin and

photoreceptor pigments.[24]

Laser light in the visible electromagnetic spectrum, (ie 532 nm frequency-doubled

Nd:YAG), is largely absorbed by hemoglobin and melanin, half in the RPE and half

in the choroid.[17] Heat is conducted to the neurosensory retina, causing inner retinal

coagulation and focal necrosis, noted ophthalmoscopically as loss of retinal

transparency and a white laser burn. The 532 nm laser is near the absorption peaks of

oxyhemoglobin and deoxyhemoglobin so is taken up by retinal blood vessels, which

is countered by the cooling effect of blood flow, which has greater velocity than

stationary tissues.[17] Confluent laser burns encircling retinoblastoma tumors may

occlude capillaries and large retinal blood vessels, cutting off the tumor blood

supply,[13] so photocoagulation is initiated only after systemic or intra-arterial

chemotherapy are completed.

Tumors less than 3 mm elevation may be successfully controlled by laser without

chemotherapy. Larger tumors require first chemotherapy to initiate tumor regression,

followed by laser encircling photocoagulation to cut off blood supply and on

subsequent treatments, 4–6 weeks apart, laser photocoagulation is applied directly to

the tumor (Figure 2). Tumors that are too large for laser therapy require other

modalities of treatment (Figure 1).

“Thermal blooming” is the process by which the photocoagulation zone may

extended beyond the laser spot size particularly with longer duration burns.[17] This

may not be clinically apparent during treatment but contributes to a larger laser scar.

When the tumor becomes white with laser photocoagulation, further penetration of

the light energy to deeper structures is prevented by light scattering.[24] Thus,

repeated laser on the same area will only increase the lateral extent of the laser

application, known as the “shielding effect”. Laser photocoagulation ultimately leads

to gliosis replacing the tumor with variable retinal pigment eplithelial hyperplasia.

5.2. Trans-pupillary thermotherapy

Trans-pupillary thermotherapy (TTT) involves long duration (60 seconds) laser in the

near-infrared spectrum (usually 810 nm diode) with larger spot size and lower power

than photocoagulation.[17] TTT results in deeper tissue penetration (4 mm) since

melanin absorption decreases with increasing laser wavelength. Continuous wave

1064 nm laser penetrates deeper that the 810 nm diode, important in treatment of

thicker tumors.[25] Temperatures of TTT (45 to 60 oC) are lower than for

photocoagulation.[26] The endpoint of TTT is faint whitening or graying of the

tumor and visible changes may not be visible at the time of treatment.[17, 26]

Standard TTT may be insufficient to treat large, thick tumors or lesions associated

with significant chorioretinal atrophy. Furthermore, while TTT requires inherent

lesion pigmentation to achieve an adequate response, retinoblastoma is

characteristically non-pigmented. Pretreatment with intravenous indocyanine green

(ICG), a chromophore with absorption peak 805 nm complementing the diode 810

nm laser, results in photosensitization and a dose-dependent decrease in the TTT

fluence threshold and irradiance required for treatment.[27] Enhancement of the laser

effect by systemic ICG may lead to regression of tumors that have shown a

suboptimal response to systemic chemotherapy and standard TTT.[28-30] The

optimal timing between ICG injection and TTT has not been determined.

5.3 Therapy combining different lasers

Retinoblastoma can be treated with a combination of photocoagulation and

thermotherapy in one or sequential treatments. The tumor border and periphery are

treated with 532 nm laser. A longer wavelength laser is used to treat the elevated

center either in the same or sequential session.[7] Unfortunately, there is no

randomized clinical trial comparing lasers and technologies to establish evidence.

[31]

5. Complications of laser therapy

The most serious complications of laser therapy are usually caused by use of

excessive energy. Therefore treatments start at lower power to titrate to the desired

effect to decrease likelihood of complications. Too small a spot size, too high a

power or too short can induce an iatrogenic rupture of Bruchs’ membrane, which

might be a precursor for choroidal neovascular membrane formation. Intense

photocoagulation may result in full thickness retinal holes which may progress to

rhegmatogenous retinal detachment, or may induce vitreous seeding of

retinoblastoma.[32] OCT is useful to visualize and analyze complications.

Biopsy-proven orbital recurrence of retinoblastoma has been reported following

repeated treatment of a macular recurrence of retinoblastoma with aggressive argon

and diode laser.[33] In this case, MRI demonstrated a large intraconal mass

contiguous with the sclera, and B-scan ultrasound confirmed scleral thinning at the

recurrence site. The orbital recurrence was felt to result from tumor seeding of the

orbit at a site of focal scleral thinning within an atrophic chorioretinal scar, following

multiple intense laser treatments.[33]

Common less serious complications include focal iris atrophy, lenticular

opacification, retinal traction, retinal vascular obstruction and localized serous retinal

detachment.[32, 34] Scars from TTT (810 nm) are recognized to increase in size with

time [35] so may be in using this laser for tumors l suboptimal for tumors located

near the fovea and optic nerve. Chorioretinal scarring with focal scleral bowing is

reported following TTT.[36] Laser is ineffective in areas with any retinal

detachment. OCT is useful to delineate subtle detachments. Laser over the optic

nerve can compromise nerve fibers. The exact tumor relation to the optic nerve can

be mapped by OCT to guide accurate laser treatment near critical structures.

PUBLISHED EVIDENCE ON LASER IN RETINOBLASTOMA:

Meyer-Schwickerath reported the results of xenon photocoagulation for

retinoblastoma in 1955 and subsequently in 1964. [37] Although laser therapy for

retinoblastoma has been used for several decades[37, 38] it wasn’t until the 1980’s

and 1990’s that the role for focal laser therapy in the management of retinoblastoma

became widely popularized.[39] In 1982 Lagendijk used trans-pupillary

thermotherapy (TTT) in two cases of recurrent retinoblastoma successfully.[40]

Subsequently, a relatively large study by Lumbroso et al reported their outcomes in

239 children using TTT delivered with a diode laser through an operating microscope

and found that when this was combined with chemotherapy excellent local tumor

control and eye preservation was achieved.[41] Other groups similarly concluded

that while chemoreduction alone may not be adequate at achieving complete tumor

control, chemoreduction in combination with adjuvant treatment (including laser

photocoagulation, thermotherapy, cryotherapy and radiation) resulted in good retinal

tumor control, even in eyes with advanced disease.[42]

As the use of laser therapy in the management of retinoblastoma gained traction,

several clinicians investigated this potentially synergistic role between thermotherapy

and chemotherapy. This treatment algorithm was termed chemothermotherapy and

was based on the hypothesis that the delivery of heat facilitates the cellular uptake of

certain chemotherapeutic agents.[43] In fact, in a series of 103 tumors treated with

chemothermotherapy, Lumbroso et al[44] reported that tumor regression was seen in

96.1%. In this study, TTT was delivered shortly after an intravenous injection of

carboplatin.

Predictors for success of focal laser photocoagulation and thermotherapy have also

been identified. Abramson et al. concluded that tumors <1.5 disc diameters in base

diameter can be successfully treated with TTT alone, with nearly two thirds (64%) of

tumors only requiring one session.[26] Alternative laser techniques have also been

described, including the use of the 532-nm laser which has been shown to effectively

treat small (<2mm in height, <4 disc diameter) tumors. [32] Depending on the tumor

location, the clinician may prefer one laser type over the other. For instance, while

TTT using the 810-nm diode laser is effective, the scar that is created can increase in

size after treatment [35] and therefore when applying laser near vital macular

structures some prefer laser photocoagulation (532-nm laser). Similarly, trans-scleral

diode laser may be the preferred modality for small anteriorly located

retinoblastomas.[21] Although a variety of potential complications as discussed

above have been noted, the majority of these can be avoided by using the minimal

effective laser power.[32] It is important to note however that despite the use of laser

focal therapy being a mainstay in the treatment of retinoblastoma, there have been no

randomized controlled trials evaluating the effect of systemic chemotherapy with

versus without laser therapy for post-equatorial retinoblastoma [31].

NEW PAPERS ON LASER AND VISUAL OUTCOME: (KELSEY)

6. Laser guided by optical coherence tomography (OCT)

First reports of OCT focused on the appearance of retinoblastoma and differentiation

from simulating lesions [45, 46]. The hand held OCT expanded the use to supine

children under anesthetic to image retinoblastoma tumors from diagnosis through

treatments, to eventual stability.{Scott, 2009 #13722;Maldonado, 2010 #13713}

OCT visualization facilitates accurate laser therapy, revealing for example,

subclinical invisible tumors,{Rootman, 2013 #10244;Berry, 2016 #13759}

subclinical tumor recurrences within a scar or edge recurrences,{Soliman, 2017

#15422} topographic localization of the foveal center,{Hasanreisoglu, 2015

#13211;Soliman, 2017 #15422} and differentiating benign white lesions (gliosis,

perivascular sheathing of active retinoblastoma and possible optic nerve

involvement).[52] OCT can demonstrate intraretinal tumor location (superficial, deep

or diffuse infiltrating),[7] visualize vitreous or subretinal tumor seeds,[7, 53] and

determine solid or cavitary internal architecture of retinoblastoma[54] that might

affect therapeutic approach (Figure X). With skill and persistence, the handheld OCT

can be used in the mid periphery.[7]

OCT has become crucial in management decisions in retinoblastoma management.

{Soliman, 2017 #17193} The role of OCT in each examination under anesthetic

(EUA) for a child with retinoblastoma was retrospectively determined to be directive

(direct diagnosis, treatment or follow up) in 94% (293/312) of OCT sessions, or

academic. Directive OCTs were further classified as confirmatory (confirm the pre-

OCT clinical decision) or influential (17%) (change the pre-OCT clinical decision),

highlighting the importance of OCT in optimal retinoblastoma management.

7.1. Invisible tumors

Invisible tumors are anticipated in children carrying a pathogenic variant of the RB1

tumor suppressor gene detected either prenatal or postnatal, because they have a

positive parental family history of retinoblastoma. These children are classified now

by the 2017 Tumor Node Metastasis Heritablity cancer staging for retinoblastoma to

be “H1” even if they do not yet have detectable cancer. Screening for invisible

tumors by OCT of the posterior pole of each eye in the first 6–9 months of age can

reveal tiny spheres of altered density in the inner nuclear layer of the retina. Once

detected, the subclinical tumor can be centralized in the OCT scan and combination

of calipers and anatomic landmarks (branching vessels, etc) help to locate the

invisible tumor in the retina for ablation by 532 nm laser. Photocoagulation with low

laser power (100 mW) and short pulse duration (0.5 seconds) is delivered, gradually

increasing power until whitening is noted. Post laser OCT can verify that the laser

burn(s) were in the correct location, including the tiny tumor (Figure 3).

7.2. Juxtafoveal tumors

Tumors near the fovea are a challenge to treat with focal therapy and preserve the

foveola. OCT with two OCT macular cube scans (vertical and horizontal) determines

the foveal location to avoid laser to this critical area. Photocoagulation is more

precise than TTT for this sensitive precise work, to preserve vision and avoid scar

migration. Recently an OCT guided sequential laser crescent photocoagulation

method was described for juxtafoveal tumors avoiding the fovea. The antifoveal

tumor crescent is photocoagulated using 532 nm laser to obliterate the blood supply

to the tumor. This will flatten the tumor center that will be treated in sequential

sessions. Additionally, the peripheral scarring causes a tangential anti-foveal force

pulling tumor away from the fovea. (Figure 3) This technique was described to have

better anatomical and visual outcome in juxtafoveal tumors where the fovea is OCT

detectable at initial laser session. Furthermore, OCT can detect subtle surrounding

exudative retinal detachment that might stop us from initiating laser treatment.

7.3. Recurrent and residual tumors

OCT can differentiate between gliosis and homogenous potential active tumor

associated with scars. Comparison of OCT of the same area between EUAs can

detect subtle differences (Figure 4), facilitating early, less intensive treatments (laser

power, number of sessions) and improved outcomes. Recurrences on flat retina are

usually treated with photocoagulation with 532 nm laser. However, recurrences over

calcified tumor require longer wavelength photocoagulation.

White treatment scars previously posed a challenge to distinguish residual or

recurrennt tumor and gliosis. With OCT, laser can be delivered with precision to

specific areas of recurrence instead of the whole scar, reducing risk of excessive

scarring and retinal dragging. When OCT images suggest stability, observation can

be undertaken without danger of tumor growth requiring increased treatment burden.

7.4. Pre-equatorial tumors

Pre-equatorial tumors can be treated by either photocoagulation or cryotherapy.

Laser therapy is preferred in superior tumors to avoid uveal effusion and exudative

detachment associated with cryotherapy. Shallow tumors may be treated with 532 nm

laser photocoagulation for one or two sessions. Elevated pre-equatorial tumors might

require multiple treatments as the laser beam is not able to apply perpendicular to the

tumor with a trans-pupillary approach. In subsequent sessions with flattening of the

tumor, the tumor can be better visualized and treated.

With expertise, peripheral OCT can assess tumor elevation, differentiate scarring

from residual tumors and identify peripheral potential tumor seeding (Figure 5).

Laser can be utilized to surround the tumor with a barrier to retinal detachment prior

to cryotherapy, plaque radiotherapy or pars plana vitrectomy.{Zhao, 2017 #20057}

Laser can be also used to ablate ischemic or potentially ischemic retina isolated by

extensive scar to protect against neovascularization and subsequent vitreous

hemorrhage.

Conclusions

Laser therapy is integral in retinoblastoma tumor control after initial reduction in size

by chemotherapy. However, laser was not been studied in any clinical trial. Improved

tumor visualization and assessment by OCT opens the door to precision laser

treatments of smaller tumors and recurrence, potentially improving cancer outcomes,

reducing invasive procedures, and reducing complications.

Expert Commentary

I would include something related to the future of OCT guided laser.

BG will do next.

Five year view

Imaging technology are continuing to rapidly improve. Soon wide-angle fundus

imaging will be combined with OCT in hand-held units appropriate for children

under anaesthetic. Perhaps in five years, laser therapy will also be able to be

delivered in on tool, guided directly by both fundus image and OCT cross-section to

allow quick and accurate laser delivery.

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Table 1: Comparison between lasers in retinoblastoma.

Type of

laser

Green

532nm

Diode

810nm

Continu

ous

wave

1064nm

Frequency-

doubled Nd-

YAG

Solid State

Semi-

conduct

or

Nd-

YAG

Solid

State

Common

delivery

method

Indirect Indirect

or

transcle

ral

Indirect

Mechani

sm of

action

Retinal

photocoagulatio

n results in

tumor apoptosis

Acts in a subthreshold manner

to raising choroidal

temperature. Causing minimal

thermal damage to the RPE

and overlying retina

Depth of

penetrati

on

Superficial:

limited by the

resultant

coagulation [32]

and by nature of

Deep: primary anatomical site

of action is in the choroid.

Diode and Nd:YAG lasers are

estimated to penetrate 4.2 and

5.1mm respectively.

shorter

wavelength.

Estimated to

penetrate ~2

mm in non-

pigmented

tumors such as

retinoblastoma.

[10]

Penetration depth decreases in

necrotic tumors.[10]

Paramete

rs

Power: 0.3 – 0.8

W

Duration: 0.3-

0.4 seconds

Power:

0.3-1.5

W

Duratio

n: 0.5 –

1.5

seconds

Power:

1.4 – 3.0

W

Duration

: 1

second

Clinical

endpoint

Increase power

by 0.1W

increments until

tumor/retinal

whitening

visible[32]

Slight graying of retina without

causing vascular spasm [26,

34]

Table 2. Types of contact and non-contact fundus lenses [13, 16, 17]

L

e

n

s

T

y

p

e

I

m

a

g

e

M

a

g

n

if

ic

at

i

o

n

L

a

s

e

r

S

p

o

t

M

a

g

n

if

ic

at

i

o

n

Sta

tic

Fie

ld

of

Vi

ew

(°)

D

y

n

a

m

i

c

F

i

e

l

d

o

f

V

i

e

w

C

on

ta

ct

or

N

on

-

co

nt

ac

t

Im

ag

e

Ch

ara

cte

ris

tic

s

(

°

)

G

o

l

d

m

a

n

n

3

-

M

i

r

r

o

r

U

n

0.

9

3

X

1.

0

8

X

36 7

4

(

w

i

t

h

1

5

°

t

i

l

t

)

C

on

ta

ct

Vi

rtu

al,

ere

ct

im

ag

e

loc

ate

d

ne

ar

po

ste

rio

r

len

s

ca

i

v

e

r

s

a

l

ps

ule

O

c

u

l

a

r

M

a

i

n

s

t

e

r

0.

6

7

X

1.

5

0

X

11

8

1

2

7

C

on

ta

ct

Re

al,

in

ve

rte

d

im

ag

e

in

air

W

i

d

e

F

i

e

l

d

2

0

D

B

I

O

3.

1

3

X

0.

3

2

X

466

0

N

on

-

co

nt

ac

t

Re

al,

in

ve

rte

d,

lat

era

lly

re

ve

rse

d

P

a

n

-

r

e

t

i

n

a

l

2

.

2

B

I

O

2.

6

8

X

0.

3

7

X

567

3

N

on

-

co

nt

ac

t

Re

al,

in

ve

rte

d,

lat

era

lly

re

ve

rse

d

2

8

D

2.

2

7

X

0.

4

4

X

53 6

9

N

on

-

co

Re

al,

in

ve

B

I

O

nt

ac

t

rte

d,

lat

era

lly

re

ve

rse

d

D= Diopter; BIO= Binocular indirect ophthalmoscopy