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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 lasers
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 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 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 far infrared 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 diodeinfrared lasers 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 ofcloser and farther from the focal point. It thereforeEffect depends on the power,
relative positions of the headset and BIO lenses, amount of light scattering by ocular media, as
well asand 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 delivers the laser with through 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 a 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)
DiodeInfra-red 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 THERAPYAPPRAOCHES FOR RETINOBLASTOMA:
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 cellsnecrosis. 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] Since the initial laser treatments cut off the tumor blood supply,
This explains why it is preferred not to start photocoagulation is initiated only before after
systemic or intra-arterial chemotherapy completionare completed, in order to preserve the
delivery of chemotherapy to the tumorumor-delivery uninterrupted.
Eyes with tumors less than 3 mm elevation may be successfully controlled by laser without
chemotherapy. Larger tumors require first chemotherapy, followed by first laser In larger tumors,
encircling photocoagulation to cut off blood supply and initiate tumor regression. On subsequent
treatments, four to six weeks apart, laser photocoagulation will be applied directly to the tumor
(Figure 2). Tumors that are too large for laser therapy only may not be controlled, and require
other modalities of treatmentespecially 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 particularly with with longer duration burns.[17] This may not be clinically
apparent during treatment and is one factorbut contributesing to increased a larger size of the
laser scar post-operatively. When the tumor becomes white with laser photocoagulation, fa
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 replaces the tumor with leads to scarring, gliosis and variable RPE
retinal pigment eplithelial hyperplasia.
4.2. TRANS-PUPILLARY THERMOTHERAPY:
Trans-pupillary thermotherapy (TTT) has also been applied to retinal tumors to achieve localized
tissue apoptosis. It involves continuous long duration (60 seconds) laser application treatment 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 TTT 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 forthe
810 nm diode and 532 nm lasers, which is important when considering treatment of thicker
tumors.[25] Resultant temperatures (45 to 60 o C) 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 visible laser changes may not be visible at the time of
treatment, dependent on fundus pigmentation and laser parameters.[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 of the effect with systemic ICG may lead to regression of tumors
withthat have shown a 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 COMBINING DIFFERENT LASERS:
Certain tumors especially large central juxtafoveal and perifoveal tumorsRetinoblastoma might
can be treated with a necessitate combination of both photocoagulation and thermotherapy in
successive one 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]
4.[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.
5.[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)
6.[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.
7.[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
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