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,

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 and Expert commentary

Word limit: (/7000)

Tables and Figures: 6 figures and 2 tables.

Financial disclosure: None of the authors has any conflicting interests

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, few 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) detects microscopic retinoblastoma tumors and guides treatment,

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 adds precision to put laser in the forefront in achieving cure of

retinoblastoma.

Summary

This review discusses laser therapy for intraocular retinoblastoma and highlights the

role of optical coherence tomography in improving laser therapy to precision levels.

Keywords

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

medicine; primary tumor detection; early recurrence intervention.

1. 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 [3].

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 [4-6].

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 wavelength 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 [7, 8].

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 [5, 9].

2. 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 [10]. The

acronym LASER represents the underlying fundamental quantum-mechanical

principals involved: Light Amplification by Stimulated Emission of Radiation [11].

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 [11].

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 [12]. 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.

3. 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 [13, 14].

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.

The 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 [12]. Table 1

demonstrates the main differences between the different types of laser in

retinoblastoma.

4. 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 [15]. 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. Retinal spot size can be calculated by power of the condensing

aspheric lens multiplied by image plane spot size divided by 60 [16]. 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, neck,

hand, wrist and lower back pain among ophthalmologists [17].

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 [16]. Tilting the contact lens within 15

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

maximum 6.8% [18]. 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 [19, 20]. It contains mirrors at 59, 67 and 73 degrees

to aid in visualization and treatment of the periphery [19]. 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 [19, 20]. 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. 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 [18].

4.3 Trans-scleral laser therapy.

Infrared laser photocoagulation may also be delivered trans-sclerally using an optical

fiber [21, 22]. This technique was first described for the treatment of retinoblastoma in

1998 [23]. in the presence of media opacities. Trans-scleral diode also decreases the

risk of cataract formation by limiting laser transmittance through the lens [23].

5. Laser approaches 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° C temperature rise induces

protein denaturation and subsequent coagulation and necrosis, depending on the

duration and extent of thermal change [13]. Heat generation is influenced by the laser

parameters and optical properties of the absorbing tissue [19]. 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, (i.e. 532 nm frequency-

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

and half in the choroid [19]. 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 [19]. Confluent laser burns encircling retinoblastoma

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

blood supply [15], so photocoagulation is initiated only after systemic or intra-arterial

chemotherapy are completed.

Tumors less than 3 mm elevation (T1a/T1b) [25] may be controlled successfully

by laser without chemotherapy (Figure 1). Larger tumors (T1b/T2) [25] require

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 as plaque

radiotherapy. In larger tumors, encircling laser with consequent obliteration of the

blood supply may lead to loss of tumor cohesiveness and early vitreous seeding

(Figure 3).

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

extended beyond the laser spot size particularly with longer duration burns [19]. 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” [26]. Laser photocoagulation ultimately

leads to gliosis replacing the tumor with variable retinal pigment epithelial

hyperplasia.

Infrared semiconductor diode laser (810 nm) can be used for photocoagulation in

short duration (0.7 – 1.5 seconds). It can be delivered by indirect ophthalmoscopy or

trans-scleral laser delivery. 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 (figure 4). In vitro and in vivo studies

of trans-scleral thermotherapy for choroidal melanoma suggest tumor cell destruction

occurs at a threshold of 60° C, without permanent damage to scleral collagen or

increased risk of retinal tears [27, 28].

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 [19]. 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 [29]. Temperatures of TTT (45 to 60° C) are lower than for

photocoagulation [30]. The endpoint of TTT is faint whitening or graying of the

tumor and visible changes may not be visible at the time of treatment [19, 30].

In 1982, Lagendijk used trans-pupillary thermotherapy (TTT) in two cases of

recurrent retinoblastoma successfully [31]. 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

[32]. 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 [30].

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

fluency threshold and irradiance required for treatment [33]. 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 [34-36]. The

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

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 [37]. In fact, in a

series of 103 tumors treated with chemothermotherapy, Lumbroso et al. [38] reported

that tumor regression was seen in 96.1%. In this study, TTT was delivered shortly

after an intravenous injection of carboplatin.

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 [9]. Unfortunately, there is no

randomized clinical trial comparing lasers and technologies to establish evidence

[39].

6. 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 [40]. 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 [41]. 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.

Common less serious complications include focal iris atrophy, lenticular

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

detachment [40, 42]. Scars from TTT (810 nm) are recognized to increase in size with

time [43], so using TTT may be suboptimal for tumors located near the fovea and

optic nerve. Chorioretinal scarring with focal scleral bowing is reported following

TTT [44]. 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.

7. 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 [47, 48]. OCT visualization facilitates accurate laser

therapy, revealing for example, subclinical invisible tumors [49, 50], subclinical tumor

recurrences within a scar or edge recurrences [9], topographic localization of the

foveal center [9, 51], 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),

[9], visualize vitreous or subretinal tumor seeds,[9, 53], and determine solid or cavitary

internal architecture of retinoblastoma [54] that might affect therapeutic approach.

With skill and persistence, the hand-held OCT can be used in the mid periphery.[9].

OCT has become crucial in management decisions in retinoblastoma management

[9]. 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%) (changes the pre-OCT clinical decision), highlighting

the importance of OCT in optimal retinoblastoma management.

7.1. Invisible tumors

Invisible tumors (figure 5) 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 [55-57]. These children are

classified now by the 2017 Tumor Node Metastasis Heritability cancer staging for

retinoblastoma to be “H1” even if they do not yet have detectable cancer [5, 25].

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 [9].

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 [9]. Photocoagulation is more

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

migration.[43, 58] Recently, a laser crescent photocoagulation method was described

for perifoveal tumors [Submitted]. The anti-foveal tumor crescent is photocoagulated

using 532 nm laser to obliterate the tumor blood supply that causes central tumor

flattening to be treated in sequential sessions. Additionally, the peripheral anti-foveal

scarring causes a tangential pulling force. This technique was observed to have better

anatomical and visual outcome when the fovea is OCT-detectable at initial laser

session. Furthermore, OCT can detect subtle surrounding exudative retinal

detachment that stops laser treatment initiation.

7.3. Recurrent and residual tumors

OCT can differentiate between gliosis and homogenous potential active tumor

associated with scars [9]. Comparison of OCT of the same area between EUAs can

detect subtle differences (Figure 6), 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. 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 [59, 60]. 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 cannot be applied

perpendicular to the tumor with a trans-pupillary approach. In subsequent sessions

with flattening of the tumor, it 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. Laser can be

utilized to surround the tumor with a barrier to retinal detachment prior to

cryotherapy, plaque radiotherapy or pars plana vitrectomy [61]. 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

Laser therapy is a widely available, non-invasive, and relatively safe technique to destroy

residual tumor after chemoreduction (either systemic chemotherapy or IAC). It is a

necessity for posterior pole and superior tumors (especially if partially calcified) where

cryotherapy is not recommended or even contraindicated.

Despite all the recent improvements in retinoblastoma treatment, laser therapy

remains an under-reported cornerstone in tumor control after chemotherapy. Laser

therapy is one of the most frequently available modalities in low-income countries that

cannot afford expensive modalities such as IAC or plaque radiotherapy. The published

literature is deficient in details regarding methods and techniques of laser therapy making

it highly variable between centers, based on the experts’ experience. Variability in

technique and consequently the endpoint of therapy (flat scar versus stable fish flesh like

lesion) need dissemination of proper knowledge and implementation.

There is good opportunity for centers in low-income countries to utilize available

laser machines effectively for retinoblastoma. An effective way of teaching would be

videos in microscope mount laser delivery technique or pre- and post-laser wide-angle

fundus photos in indirect or trans-scleral laser delivery options. Another method would

be preoperative planning of the laser with experts via telemedicine that has proven

effective in decision-making. Laser workshops, conferences and collaborative or

twinning programs between Centers of Excellence may achieve effective utilization of

resources, to improve life, vision and eye salvage in retinoblastoma.

Hand-held OCT has improved our understanding of many aspects in retinoblastoma

diagnosis, treatment and follow-up. OCT is a powerful adjunct tool to laser, identifying

invisible tumors, distinguishing edge recurrences from scar with precise foveal

localization. Despite its cost, the hand-held OCT is important for a Center of Excellence

in retinoblastoma to achieve precision therapy for retinoblastoma. It is recommended to

improve OCT localization by sizing algorithms using calipers, blood vessels and

anatomic landmarks together with improved enhanced depth imaging to assess choroidal

structure for appreciation and differentiation of early tumor invasion versus scarring.

Five year view

Imaging technologies continue to rapidly improve. Soon wide-angle fundus imaging will

be combined with OCT in hand-held units appropriate for children under anaesthetic. In

five years, laser therapy will also be able to be delivered in one tool, guided directly by

fundus image and OCT cross-section to allow quick and accurate laser delivery.

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Figure Legends:

Table 1: Comparison between lasers in retinoblastoma.

Frequency-doubled Nd-YAG Semiconductor Diode Continuous wave Nd-YAG

Type of laser Green Infrared Far Infrared

Wave length 532 nm 810 nm 1064nm

Delivery Trans-pupillary Trans-pupillary or trans-scleral Trans-pupillary

Mechanism Photocoagulation Photocoagulation or Thermotherapy Thermotherapy

Penetration

Superficial (~2 mm in non-pigmented tumors) [12] limited

by resultant coagulation and shorter wavelength [40].

Deep (4.2 and 5.1mm respectively) primary anatomical site of action is in the choroid. Penetration decreases in necrotic

tumors [12].

ParametersPower: 0.3 – 0.8 W Power: 0.3-1.5 W Power: 1.4 – 3.0 W

Duration: 0.5-0.7 seconds Duration: 0.5-2.5 seconds Duration: 1 second

Clinical endpoint

Increase power by 0.1W increments until tumor/retinal

whitening visible [40]

Slight graying of retina without causing vascular spasm [30, 42]

Table 2. Types of contact and non-contact fundus lenses [15, 18, 19]

Lens TypeMagnification Field of View (°)

Image CharacteristicsImage Laser spot Static Dynamic

Contact Lenses

Goldmann 3-Mirror Universal 0.93X 1.08X 36 74 (15° tilt) Virtual, erect and near

posterior lens capsule

Ocular Mainster Wide Field 0.67X 1.50X 118 127 Real, inverted image in air

Non-Contact Lenses20 D BIO 3.13X 0.32X 46 60

Real, inverted, laterally reversed22 D BIO 2.68X 0.37X 56 73

28 D BIO 2.27X 0.44X 53 69D= Diopter; BIO= Binocular indirect ophthalmoscopy