Laser Therapy for Retinoblastoma in the Era of Optical Coherence Tomography

Authors:

Sameh Soliman, Stephanie Kletke, Kelsey Roelofs, Cynthia VandenHoven, Leslie Mckeen,

Brenda Gallie

Type of article: Review

Word limit:

Tables and Figures:

Keywords:

Abstract

Introduction: The past several decades have seen vast advancements in the treatments paradigm

for retinoblastoma., and the use of Focal laser therapy is certainly no exceptionconsistently a

cornerstone for disease control, but techniques have not been extensively described. T While the

first description of focal laser therapy for retinoblastoma dates towas over 6 decades ago, with

technologies and approaches several improvements in protocols have occurred over the past two

decades evolving with the intention to that have greatly improved our ability to achieve local

tumor control.

Areas covered: the literature search undertaken.????In this review the physical and optical

properties of lasers are briefly discussed, and the various mechanisms of action, delivery systems

and potential complications, optical coherence tomography (OCT) guided treatment decisions

and management of sub-clinical tumors are discussed. the literature search undertaken.????

Expert commentary:

Key issues

Introduction

Retinoblastoma is the most common intraocular malignancy that occurs secondary tois initiated

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

approximately 8000 new patientschildren are newly diagnosed present annually. Survival is very

high approachesing 100% if retinoblastoma presented is diagnosed while still intraocular, while

children with extraocular retinoblastoma carry have very poor survival.[1, 2] Treatment

strategiesy varyies according to presentation whether intraocular or extraocular but the main

conceptsfundamental primary goal of treating cancer is are life salvage, with as the primary goal

followed by vision salvage as a secondary goal. Eye Salvage of an eye per se without visual

potential should not be consideredmay be a dangerous goal, that can lead to unrecognized

recurrence of the cancer, extraocular extension except in certain situations where both eyes have

advanced intraocular disease or an only remaining eyeand loss of life.

The mainstay of therapy in for intraocular retinoblastoma is tumor size reduction via by

chemotherapy cycles (either systemic, intra-arterial or periocular chemotherapy) followed by

focal therapy in the form ofwith laser, or cryotherapy and intravitreal chemotherapy, according

to tumor location and size. Chemotherapy without focal consolidation is never sufficient alone to

control tumor retinoblastomawithout focal consolidation.[3, 4] Despite thatHowever, the role of

laser therapy in achieving controlling tumor controls is frequently commonly neglected

unmentioned while in presentation ofng outcomes of various treatment modalities such as intra-

arterial and intravitreal chemotherapy.[5, 6] Furthermore, techniques of laser therapy are poorly

rarely described in the published literature making it difficult to study or learn it withoutoutside

an apprenticeship guidancesituation.

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

disorders including retinoblastoma by allowing more detailed anatomical evaluation of the

retinal layers and tumor architecture. OCT allowed visualizesing subclinical new tumors and

tumor recurrences, . It differentiatesd tumor from gliosis during scar evaluation, and. It allowed

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

optic nerve. [4, 7]

In the current review, We now review the role of different lasers in management of

retinoblastoma and elaborate describe on OCT guided laser therapy to achieve precision in tumor

control and visual outcome.

Body

1. PHYSICS OF LASER:

Although Einstein initially 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] In fact, 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 to 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

cavityie’s 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, as this is whatwhich determines the

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

for all lasers equals the speed of light. Therefore, as the lasers 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 that 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 laser

machines have the option to control the shot pace or inter-shot interval, according to the

experience of treating ophthalmologist. In general, trainees are better to start by 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 one of the

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

emission is white light, consists ofa mixture of wavelengths between 400 and 1600 -nm and

results in full-thickness burns without selectively targeting ocular tissues. It has since beenis now

replaced by laser photocoagulation for retinoblastoma.

The commonest lasers used for focal therapy in retinoblastoma include are the 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 continuous wave Nd:YAG laser and the 810nm semiconductor infrared indirect or

trans-scleral diode laser. While all three lasers can be delivered with use of an indirect

ophthalmoscope, the 810nm diode laser can also be applied in a trans-scleral manner, which can

be particularly useful for anteriorly located tumors. and for treating tumors in the presence of

media opacities. Trans-scleral delivery also decreases the risk of cataract formation by limiting

laser transmittance through the pupil.[13] Of the three, the green 532 nm laser and 810 nm lasers

can treat tumor by photocoagulation. Both 810 nm and 1064 nm lasers can also treat by raising

tumor temperature (hyperthermia, commonly called transpupillary thermotherapy) 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 (BIO)

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).

3.1: Laser indirect ophthalmoscopy (LIO).

LIOIt was first described to treat retinoblastoma in 1992.[13] LBIO 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 utilized, the lower the image

magnification and the greater the field of view. The laser spot size on the retina varies because

the laser beam focuses at some distance from the indirect ophthalmoscope, and diverges on

either side of the focal point. It therefore depends on the power, relative positions of the headset

and BIO lenses, amount of light scattering by ocular media, as well as 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] The retinal spot size can be calculated by (ppower of the condensing

aspheric lens multiplied byx iImage plane spot size) divided by/ 60.[14] However, caution must

be exercised as LBIO is less stable than other delivery systems due to inherent instability of the

patient’s eye and the clinician’s head, particularly with simultaneous foot pedal depression.[14]

The positional requirements and relatively long treatment durations associated with LBIO laser

delivery contribute to higher prevalence of self-reported neck, hand, wrist and lower back pain

amongst ophthalmologists.[15]

3.2: Microscope-mounted delivery system.

This systemIt connects the laser with a slit-lamp or operating microscope. While the working

distance for LBIO is variable, the 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 of the periphery.[17] However,

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

oblique trajectory. LBIO is preferred for peripheral retinal laser treatments as the field of view is

greater than with microscope-mounted laser.

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

an aspheric lens in contact with the cornea and a convex lens at some fixed distance.[17, 18]

Compared to the Goldmann three-mirror which has the highest on-axis resolution, the Mainster

lens has improved field of view at the expense of poorer resolution.[16] Inverted image lenses

may produce smaller anterior than posterior segment laser beam diameters, thus 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]

3.3: Trans-scleral laser therapy. (STEPHANIE)

Diode laser photocoagulation may also be delivered via a trans-scleral approach using a

fiberoptic probe.[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 andand for treating tumors in the presence of media opacities. Trans-

scleral deliverydiode also decreases the risk of cataract formation by limiting laser transmittance

through the pupil.[21]

4. MECHANISMS OF LASER THERAPY:

4.1. 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]

Lasers in the visible electromagnetic spectrum, such as the 532 -nm frequency-doubled

Nd:YAG, are largely absorbed by hemoglobin and melanin, approximately half in the RPE and

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

coagulation and focal increase in necrotic cells. This leads to loss of retinal transparency and the

white laser response noted ophthalmoscopically. The 532 -nm laser also destroys the retinal

blood supply as the wavelength is near to the absorption peaks of oxyhemoglobin and

deoxyhemoglobin. However, this requires more energy due to the cooling effect of blood flow,

which has greater velocity than stationary tissues.[17] Confluent laser burns encircling

retinoblastoma tumors occlude large retinal blood vessels and other feeder vessels may require

supplementary treatment.[13] This explains why it is preferred not to start photocoagulation

before chemotherapy completion, in order to preserve the delivery of chemotherapy to the

tumorumor-delivery uninterrupted.

In larger tumors, encircling photocoagulation especially without chemotherapy, may sometimes

lead to failure of tumor control or earlier vitreous seeding secondary to obliteration of tumor

blood supply, with resultant tumor necrosis and loss of tumor compactness (Figure 1). In our

experience, combined tumor encircling and painting by lLaser is preferred over encircling laser

alone. (Figure 2)

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

the laser spot size with longer durations.[17] This may not be clinically apparent during

treatment and is one factor contributing to increased size of the laser scar post-operatively. When

a whitish response to the laser is noted, further penetration of the light energy to deeper

structures is prevented by light scattering.[24] Thus, repeated laser treatments on the same area

will only increase the lateral extent of the laser application, known as the “shielding effect”.

Laser photocoagulation ultimately leads to scarring, gliosis and variable RPE hyperplasia.

4.2. THERMOTHERAPY:

Thermotherapy has also been applied to retinal tumors to achieve localized tissue apoptosis. It

involves continuous laser application in the near-infrared spectrum (800-1064 nm), usually 810 -

nm diode, for longer durations (60 seconds) and with larger spot size and lower power than

photocoagulation.[17] This results in deeper tissue penetration (4 mm) since melanin absorption

decreases with increasing laser wavelength. The penetration depth of continuous wave 1064 nm

laser thus exceeds that for 810 nm diode and 532 nm lasers, which is important when

considering treatment of thicker tumors.[25] Resultant temperature rises are lower than for

classic photocoagulation (45 to 60 degrees Celsius).[26] The endpoint of TTT is faint whitening

or graying of the tumor and prominent laser changes may not be visible at the time of treatment.

[17, 26] This is dependent on fundus pigmentation and laser parameters.

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. [27-

29]Pretreatment with intravenous indocyanine green (ICG), a chromophore with an absorption

peak (805 nm) complementing the diode laser emission of 810 nm, results in photosensitization

and a dose-dependent decrease in the TTT fluence threshold and irradiance required for

treatment.[27] Enhancement with systemic ICG may lead to regression of tumors with

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

between ICG and TTT has not been full elucidated.

(FA and ICG enhanced TTT, STEPHANIE)

Complications of TTT reported following treatment of retinoblastoma include chorioretinal

scarring with focal scleral bowing.[23]

4.3 SEQUENTIAL LASER THERAPY:

Certain tumors especially large central juxtafoveal and perifoveal tumors might necessitate

combination of both photocoagulation and thermotherapy in successive or sequential treatments.

The tumor border and periphery are treated with 532 nm lLaser. 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 that compared laser mechanisms to set evidence to use any.[31]

5. COMPLICATIONS OF LASER THERAPY:

The most serious complications caused by laser therapy are often caused by use of excessive

energy, and as such, starting your treatment at a lower power and titrating to the desired effect

decreases the likelihood of complications. In cases where too small a spot size, too high a power

or too short a duration is used, an iatrogenic rupture of Bruchs’ membrane may occur. This might

act as precursor for choroidal neovascular membrane formation. Additionally, intense

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

rhegmatogenous retinal detachment. In retinoblastoma, this can result in vitreous seeding.[32]

OCT can help in visualizing and following these complications.

Although rare, biopsy-proven orbital recurrence of retinoblastoma has been reported following

successful treatment of a macular recurrence 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]

Additional complications can include focal iris atrophy, lenticular opacification, retinal traction,

retinal vascular obstruction and localized serous retinal detachment.[32, 34] Additionally, scars

from TTT (810 nm) have been shown to increase in size after treatment for

retinoblastomaretinoblastoma [35] and as such, one must be cautious in using this laser for

tumors located near the fovea and optic nerve. Other cComplications of TTT reported following

treatment of retinoblastoma include chorioretinal scarring with focal scleral bowing.[36]

Laser should be avoided over areas with retinal detachment whether high or shallow. OCT can

help diagnose subtle detachments. Laser over the optic nerve can compromise nerve fiber vitality

and should be avoided. The exact tumor relation to the optic nerve can be mapped by OCT and is

thus considered during treatment planning.

6. PUBLISHED EVIDENCE ON LASER IN RETINOBLASTOMA:

Meyer-Schwickerath reported the results first introduced the idea of xenon photocoagulation into

the management paradigm for retinoblastoma in 1955 and subsequently reported their results 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%.[46] 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)

7. OPTICAL COHERENCE TOMOGRAPHY (OCT) IN RETINOBLASTOMA:

OCT was introduced to retinoblastoma in the early 2000s. The first few reports focused on

describing how retinoblastoma appears and how to differentiate it from other simulating tumors.

[45, 46] Introduction of hand held OCT helped examining supine children under anesthetic

allowing imaging of more retinoblastoma tumors at different phases of their active treatment

from diagnosis to stability.[47, 48] This allowed visualization of a multitude of situations that

can affect and guide laser therapy as subclinical invisible tumors,[49, 50] subclinical tumor

recurrences either within a previous scar or edge recurrences,[7] topographic localization of

foveal center,[7, 51] differentiating whitish lesions such as gliosis and perivascular sheathing

from active retinoblastoma and possible optic nerve involvement.[52] OCT can demonstrate

tumor location within the retina whether superficial, deep or diffuse infiltrating retinoblastoma.

[7] OCT can visualize tumor seeds either vitreous or subretinal.[7, 53] It can also determine the

internal architecture of retinoblastoma whether solid or cavitary[54] that might affect the therapy

approach (Figure 2X). Despite very difficult, OCT can be used to examine the mid periphery but

highly dependent on the expertise of the photography specialist.[7]

OCT has crucially influenced our management decisions in retinoblastoma management. In a

recent research, the role of OCT in each examination under anesthetic (EUA) session for a child

with retinoblastoma was retrospectively classified into directive (direct diagnosis, treatment or

follow up) and academic sessions. Directive OCTs was found in 94% (293/312) OCT sessions.

Directive OCTs were further classified into confirmatory (if they confirm the pre-OCT clinical

decision) or influential (if they influence changing the pre-OCT clinical decision). It was found

that 17% of directive OCTs were influential highlighting the importance of OCT in the

armamentarium of evaluation during an EUA.

8.

[9.] THE FUTURE: OPTICAL COHERENCE TOMOGRAPHY GUIDED LASER:

68.1. INVISIBLE TUMORS:

Invisible tumors can be anticipated in children with positive RB1 variant either detected prenatal

or postnatal, positive parental family history of retinoblastoma or a child with other clinical

tumors (in H1 children). The ideal procedure to screen for invisible tumors is OCT mapping of

the posterior pole especially in the first 6 months of age. Once detected, the subclinical tumor

should be centralized in the OCT scan. Calipers and anatomic landmarks especially vessels and

its branching can be used to help locating the invisible tumor in the retinal image.

Photocoagulation with low laser power (100 mW) and short pulse duration (0.5 seconds) is

delivered, to gradually increase power until whitening is noted. Post laser OCT can verify

treatment where the tumor swells with increase reflectiveness and back shadowing. (Figure 3)

68.2. JUXTAFOVEAL TUMORS:

Tumors around the fovea are a treatment challenge to preserve the foveal center. Classical laser

treatment will eventually destroy the fovea as the resultant scar is usually greater than the tumor

size. OCT localizes the foveal center by obtaining two OCT macular cube scans (vertical and

horizontal) to precisely determine the foveal location, to avoid laser application to this critical

area. Photocoagulation is superior to TTT in posterior pole tumors 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.

68.3: RECURRENT AND RESIDUAL TUMORS:

OCT can detect subclinical tumor edge recurrences. OCT can differentiate between tumor

calcification and homogenous potential active tumor. Comparison between successive OCT

scans of the same area can detect subtle tumor recurrence. (Figure 4) This potentiate less

treatment burden regarding laser power, number of sessions and final outcome. Recurrences on

flat retina are usually treated with photocoagulation with 532 nm laser. However, recurrences

over calcified tumor require longer wavelength photocoagulation and even TTT.

Whitish treatment scars previously posed a clinical challenge to determine whether it is a tumor

residual, recurrence or a fibrosis. This was usually managed either by more laser treatment with

the possibility of more scarring and traction or observation with the potential danger of tumor

growth requiring more treatment burden. OCT helped visualizing the layers of this scars

differentiating between these conditions guiding the diagnosis and subsequent treatment choice.

OCT directed repeating laser treatment to specific areas with recurrence instead of the whole scar

thus reducing potential extensive scarring and retinal dragging.

68.4. PRE-EQUATORIAL TUMORS:

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

usually preferred in superior tumors to avoid potential cryotherapy associated uveal effusion and

exudative detachment. Flat pre-equatorial tumors are usually treated with 532 nm laser

photocoagulation for one or two sessions. More elevated tumors might require multiple laser

treatments as the tumor cannot be treated equally as the inward curve of the tumor cannot be

thoroughly painted with trans-pupillary laser. In subsequent sessions with more outward

flattening of the tumor, the inward curve can be better visualized and treated.

Despite challenging, peripheral OCT can assess tumor elevation, differentiate scarring from

residual tumors and identify peripheral potential tumor seeding (Figure 5). In certain tumors,

laser can be utilized as an initial belt like treatment surrounding the tumor as a preparatory step

prior to cryotherapy or plaque radiotherapy. Peripheral laser can be also used for potential

ischemic retina peripheral to an extensive tumor scar to prevent development of

neovascularization and probable subsequent vitreous hemorrhage. As a general rule, a smaller

spot size is required in peripheral lesions to prevent iris injury.

FUTURE PRESPECTIVE: (can be written in the 5 year view)

OCT and wide field imaging in one unit??

Conclusions

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

reduction. In spite of this fact, Laser was never properly studied in a randomized controlled

fashion to set evidence. Introduction of OCT improved tumor visualization and assessment

improving our laser strategies and minimizing complications.

Expert Commentary

??OCT and wide field imaging in one unit??

Five year view

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Table 1: Comparison between lasers in retinoblastoma.

Type of laser

Green

532nm

Diode

810nm

Continuous wave

1064nm

Frequency-doubled Nd-

YAG

Solid State

Semi-conductor Nd-YAG

Solid State

Common

delivery

method

Indirect Indirect or

transcleral

Indirect

Mechanism of

action

Retinal photocoagulation

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

penetration

Superficial: limited by the

resultant coagulation [32]

and by nature of shorter

wavelength. Estimated to

penetrate ~2 mm in non-

pigmented tumors such as

retinoblastoma.[10]

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. Penetration depth decreases in

necrotic tumors.[10]

Parameters Power: 0.3 – 0.8 W

Duration: 0.3-0.4 seconds

Power: 0.3-1.5 W

Duration: 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]

Lens Type

Image

Magnificatio

n

Laser Spot

Magnificatio

n

Static

Field of

View (°)

Dynamic

Field of

View (°)

Contact

or Non-

contact

Image

Characteristics

Goldmann

3-Mirror

Universal

0.93X 1.08X 36

74

(with 15°

tilt)

Contact

Virtual, erect

image located

near posterior

lens capsule

Ocular

Mainster

Wide Field

0.67X 1.50X 118 127 ContactReal, inverted

image in air

20 D BIO 3.13X 0.32X 46 60Non-

contact

Real, inverted,

laterally

reversed

Pan-retinal

2.2 BIO2.68X 0.37X 56 73

Non-

contact

Real, inverted,

laterally

reversed

28 D BIO 2.27X 0.44X 53 69Non-

contact

Real, inverted,

laterally

reversed

D= Diopter; BIO= Binocular indirect ophthalmoscopy