This needs to be carefully formatted for the book criteria: Reference location and style? Headings and fonts and paragraph spacings? Precision Laser Therapy for Retinoblastoma Authors: Sameh Soliman 1-2 , Stephanie Kletke 1 , Kelsey Roelofs 3 , Cynthia VandenHoven 1 , Leslie Mckeen 1 , Brenda Gallie 1 . Authors’ affiliations: 1 Department of Ophthalmology and Visual Sciences, Hospital for Sick children, Toronto, Ontario, Canada. 2 Department of Ophthalmology, Faculty of Medicine, University of Alexandria, Egypt. 3 Department of Ophthalmology, Alberta children hospital, University of Calgary, Alberta, Canada Corresponding author:
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This needs to be carefully formatted for the book criteria:
Authors’ names and affiliation: Including address, academic qualifications and job titles of all authors, as well as telephone number and email address of the author for correspondence on a separate cover sheet as the peer reviewers will be blinded to the authors’ identity. Please note that only the address of the first author of the article will appear on Medline/PubMed, not necessarily the corresponding author.
Word limit:
Tables and Figures:
Abstract
Introduction–Laser therapy is a cornerstone for control of intraocular
retinoblastoma, after chemotherapy has brought the disease under initial control.
Since first described over 6 decades ago, laser technologies and approaches have
evolved. to improve tumor control. Despite its important role, lfew publications
describe techniques, types of lasers, and modes of delivery for retinoblastoma.
Areas covered–The physical and optical properties of lasers, mechanisms of
action, delivery systems, complications, are described. Hand-held optical coherence
tomography (OCT) guides treatment and detection of microscopic retinoblastoma
tumors, achieving precision primary therapy and elimination of recurrences.
Expert commentary–In all the excitement of new therapies to cure intraocular
retinoblastoma, laser treatment always compliments but is rarely mentioned. Hand-
held OCT now puts adds precision to put laser in the forefront in achieving cure of
retinoblastoma.
Keywords
Sameh Soliman, 01/07/18,
Keywords: A brief list of keywords, in alphabetical order, is required to assist indexers in cross-referencing. The keywords will encompass the therapeutic area, mechanism(s) of action, key compounds and so on.
Gallie Brenda, 01/07/18,
ABSTRACTIntroduction: Diabetic retinopathy (DR) is a common complication of diabetes and a leading cause of blindness in working age population. Fluorescein angiography is still the gold standard in the evaluation of retinal vascular perfusion and diagnosis of macular ischemia. However, it is a costly, time-consuming procedure and it requires intravenous injection of contrast agent, exposing patients to potential side effects. Optical coherence tomography angiography (OCTA) is a novel, non-invasive imaging technique that provides dyeless visualization of blood flow in different retinal layers.Areas covered: An extensive review of the literature was performed to detail technical principles of OCTA and to discuss the current concepts on its application in diabetic patients.Expert commentary: In patients with DR, OCTA shows early features in unprecedented detail: enlargement of the FAZ, areas of capillary non-perfusion, and some microvascular abnormalities can be seen with much better clarity than with fluorescein angiography. OCTA is also able to detect several features that are currently accepted as prognostic indicators in patients with DME. The most relevant are the presence of diabetic macular ischemia and pronounced microvascular abnormalities. It has been shown that these alterations may influence the response to anti-VEGF therapy.KEYWORDS: OCT, optical coherence tomography, OCTA, optical coherence tomography angiography, DME, diabetic macular edema, superficial capillary plexus, deep capillary plexus, macular ischemia, prognostic indicator
Sameh Soliman, 01/07/18,
Structured abstract (maximum 200 words): The aim of the abstract is to draw in the interested reader and provide an accurate reflection of the content of the paper. We therefore request the following structure is followed for full-length review articles:Introduction: Authors are required to describe the significance of the topic under discussion.Areas covered: Authors are required to describe the research discussed and the literature search undertaken.Expert commentary: The author’s expert view on the current status of the field under discussion.References must not be included in the abstract.
Sameh Soliman, 01/07/18,
Figures and Tables: Up to 5 figures and 5 tables are permitted.
Sameh Soliman, 01/07/18,
The word limit for Reviews is 7,000 words (not including figures, tables or references).
medicine; primary tumor detection; early recurrence intervention.Introduction
Retinoblastoma is the most common intraocular malignancy, initiated by mutations
in both copies of the retinoblastoma gene (RB1 gene) [1]. Worldwide, 8000 children
are newly diagnosed annually. Survival approaches 100% if retinoblastoma is
diagnosed and treated while still intraocular, but when retinoblastoma is extraocular,
children have poor survival [1, 2]. The fundamental primary goal of treating cancer is
life salvage, and for retinoblastoma vision salvage is a secondary goal. Salvage of an
eye without visual potential may be dangerous since unrecognized recurrence of the
cancer, can leads to extraocular extension and loss of life.
Despite the recent advances and new treatment modalities, the primary therapy for
intraocular retinoblastoma remains tumor size reduction by chemotherapy (systemic,
intra-arterial or periocular) followed by focal therapy with laser, cryotherapy, plaque
radiotherapy and/or intravitreal chemotherapy, according to tumor location and size.
Chemotherapy without focal consolidation is rarely sufficient to control
retinoblastoma [3, 4]
Laser is appropriate as primary therapy only for small tumors. Techniques of laser
therapy are rarely described making it difficult to study or learn outside an
apprenticeship situation. Choice of laser wave length is variable according to
experience and availability. Furthermore, the role of laser in achieving primary or
recurrent tumor control is unmentioned or even neglected in reporting or comparing
outcomes of recent treatments as intra-arterial chemotherapy (IAC) or Intravitreal
Sameh Soliman, 01/07/18,
Body of the article:Introduction: Incorporating basic background information on the area under review.Body: Body of the review paper covering the subject under review, using numbered subsections.Conclusion: The conclusion for all articles should contain a brief summary of the data presented in the article. Please note that this section is meant to be distinct from, and appear before the ‘Expert opinion’ section.
chemotherapy (IViC) giving the reader the false impression of insignificant role of
Laser [5, 6].
Optical coherence tomography (OCT) has revolutionized our perspective of variable
retinal disorders including retinoblastoma by allowing detailed anatomical evaluation
of the retinal layers and tumor architecture. OCT visualizes subclinical new tumors
and tumor recurrences, differentiates tumor from gliosis during scar evaluation, and
improves perception of important anatomic landmarks for vision such as the fovea
and optic nerve [4, 7].
1. Physics of laser
Einstein postulated the concept behind the stimulated emission process upon which
lasers are based in 1917, but it was not until 1960 that T.H. Maiman performed the
first experimental demonstration of a ruby (Cr3+AL2O3) solid state laser [8]. The
acronym LASER represents the underlying fundamental quantum-mechanical
principals involved: Light Amplification by Stimulated Emission of Radiation [9].
All lasers require a pump, an active medium and an optical resonance cavity. Energy
is introduced into the system by the pump, which excites electrons to move from a
lower to higher energy orbit. As these electrons return to their ground state, they emit
photons, all of which will be of the same wavelength resulting in light that is
monochromatic (one color), coherent (in-phase) and collimated (light waves
aligned). Mirrors at either end of the resonance cavity reflect photons traveling
parallel to the cavity axis, which then stimulate more electrons, resulting in
amplification of photon emission. Eventually photons exit the laser cavity through
the partially reflective mirror into the laser delivery system.[9]
Lasers are typically categorized by their active medium, which determines the laser
beam wavelength. For all lasers, the wavelength multiplied by the frequency of
oscillation equals the speed of light. Therefore, as the laser wavelength increases its
frequency decreases proportionally and vice versa. Additionally, Planck’s law
(E=h) states that the energy (E) of a photon is a product of Planck’s constant
(h=6.626 x 10-34 m2kg/s) multiplied by the frequency (). As such, lasers with low
wavelengths (and high frequency) impart high energy, and those with high
wavelengths (and low frequency) are less powerful. Broad categories of lasers
include solid state, gas, excimer, dye and semiconductor.
The power of a laser is expressed in watts (W), which is the amount of energy in
joules (J) per unit time (J/sec). Power density takes into account both the power (W)
and the area over which it is distributed (W/cm2). It is important to note that if spot
size is halved, the power density is quadrupled, and if the amount of energy (J)
remains constant, decreasing the duration will increase the power (W) delivered.
Longer pulse duration increases the risk that heat waves will extend beyond the
optical laser spot, thus damaging surrounding normal tissue.[10] All lasers have the
option to control the shot pace or inter-shot interval, according to the experience of
treating ophthalmologist. In general, trainees start with single shots or a longer inter-
shot interval.
Gallie Brenda, 01/07/18,
What is the correct format for refs?? Check carefully if the ref number comes before or after the .
2. Types of lasers for retinoblastoma
Xenon arc photocoagulation, first described by Meyer-Schwickerath in 1956, was the
earliest photocoagulation method adopted for treatment of retinoblastoma.[11, 12]
Xenon emission is white light, a mixture of wavelengths between 400 and 1600 nm
and results in full-thickness burns without selectively targeting ocular tissues. It is
now replaced by laser photocoagulation for retinoblastoma.
The commonest lasers used for focal therapy in retinoblastoma are green (532 nm)
frequency doubled neodymium Nd:YAG (yttrium-aluminum-garnet) by indirect
ophthalmoscope, 810 nm semiconductor infrared indirect or trans-scleral diode laser,
and the 1064 nm far infrared continuous wave Nd:YAG laser. While all three lasers
can be delivered with use of an indirect ophthalmoscope, the infrared lasers can also
be applied in a trans-scleral manner, particularly useful for anteriorly located tumors.
Green 532 nm and 810 nm lasers can treat tumor by photocoagulation. The 810 nm
and 1064 nm lasers can also treat by raising tumor temperature (hyperthermia,
commonly called trans-pupillary thermotherapy or TTT) in a sub-threshold
manner[10]. Table 1 demonstrates the main differences between the different types
of laser in retinoblastoma.
3. Laser delivery
Retinal laser treatments can be delivered by either binocular indirect ophthalmoscopy
using non-contact, hand-held lenses (20 D, pan-retinal 2.2 D or 28 D) or by
microscope-mounted laser with contact lenses (Goldmann Universal Three-Mirror,
Ocular Mainster Wide Field) and a coupling agent (Table 2).
Gallie Brenda, 01/07/18,
What else was there? None I know of…..
4.1. Laser indirect ophthalmoscopy (LIO).
LIO was first described to treat retinoblastoma in 1992.[13] LIO combined with
manipulation of eye position with a scleral depressor is the ideal laser delivery
technique for children under general anesthesia. The higher the power of the
condensing lens, the lower the image magnification and the greater the field of view.
The laser spot size on the retina is minimized (with most power) at the focal point, a
specific distance from the indirect ophthalmoscope, and diverges closer and farther
from the focal point. Effect depends on power, relative positions of the headset and
lenses, light scattering by ocular media, and the patient’s refractive error. For
instance, a 20 D lens causes a 900 µm image plane spot to be reduced to 300 µm in
an emmetropic eye.[14] Retinal spot size can be calculated by power of the
condensing aspheric lens multiplied by image plane spot size divided by 60.[14]
However, LIO requires careful optimization and coordination of the inherent
instability of the patient’s eye, the clinician’s head, and simultaneous foot pedal
depression, [15]
4.2. Microscope-mounted delivery system.
Laser may also be delivered through a slit-lamp or operating microscope: the
working distance from the microscope to the patient’s eye is fixed. Therefore, retinal
laser spot size is only dictated by the patient’s refractive error, contact lens and pre-
selected laser spot diameter on the microscope.[14] Tilting the contact lens within 15
degrees does not cause significant distortion of the laser spot, as irradiance differs by
maximum 6.8%.[16] The universal Goldmann three-mirror (Power -67 D) has a flat
anterior surface that cancels the optical power of the anterior cornea, therefore
Gallie Brenda, 01/07/18,
explain this?
Gallie Brenda, 01/07/18,
???
decreasing peripheral aberrations.[17, 18] It contains mirrors at 59, 67 and 73
degrees to aid in visualization and treatment of the periphery.[17] However,
photocoagulation efficiency is reduced in the far periphery, as the laser follows an
off-axis, oblique trajectory. LIO is preferred for peripheral retinal laser treatments as
the field of view is greater than with a microscope-mount.
Also commonly used is the Mainster wide-field (Power +61 D) contact lens,
containing an aspheric lens in contact with the cornea and a convex lens at a fixed
distance.[17, 18] The Mainster lens has improved field of view at the expense of
poorer resolution, while the Goldmann three-mirror which has the highest on-axis
resolution.[16] Inverted image lenses may produce smaller anterior than posterior
segment laser beam diameters, leading to higher irradiance in the anterior segment.
Injury to the cornea and lens have been reported during retinal photocoagulation with
inverted image lenses, particularly in the presence of high power settings and ocular
media opacities.[16]
4.3 Trans-scleral laser therapy.
Infra-red laser photocoagulation may also be delivered trans-sclerally using an
optical fiber.[19, 20] This technique was first described for the treatment of
retinoblastoma in 1998.[21] Direct visualization of a red laser aiming beam through
the wall of the globe confirms the treatment area, with the main outcome being
whitening of the tumor and surrounding retina. In vitro and in vivo studies of trans-
scleral thermotherapy for choroidal melanoma suggest tumor cell destruction occurs
at a threshold of 60 degrees Celsius, without permanent damage to scleral collagen or
increased risk of retinal tears.[22, 23] Given the precise nature of delivery and
Gallie Brenda, 01/07/18,
Are there any current paper on this for retinoblastoma?We used to occasionally do this but not in many years.
effective scleral transmission, trans-scleral diode is useful for treatment of anteriorly
located retinoblastoma tumors and in the presence of media opacities. Trans-scleral
diode also decreases the risk of cataract formation by limiting laser transmittance
through the lens.[21]
4. Laser appraoches for retinoblastoma:
5.1. Photocoagulation
Photocoagulation is the process by which laser light energy is absorbed by a target
tissue and converted into thermal energy. A 10-20 degree Celsius temperature rise
induces protein denaturation and subsequent coagulation and necrosis, depending on
the duration and extent of thermal change.[11] Heat generation is influenced by the
laser parameters and optical properties of the absorbing tissue.[17] Absorption
characteristics are dictated by tissue-specific chromophores, such as melanin in the
retinal pigment epithelium (RPE) and choroidal melanocytes, hemoglobin in blood
vessels, xanthophyll in the inner and outer plexiform layers, lipofuscin and
photoreceptor pigments.[24]
Laser light in the visible electromagnetic spectrum, (ie 532 nm frequency-doubled
Nd:YAG), is largely absorbed by hemoglobin and melanin, half in the RPE and half
in the choroid.[17] Heat is conducted to the neurosensory retina, causing inner retinal
coagulation and focal necrosis, noted ophthalmoscopically as loss of retinal
transparency and a white laser burn. The 532 nm laser is near the absorption peaks of
oxyhemoglobin and deoxyhemoglobin so is taken up by retinal blood vessels, which
is countered by the cooling effect of blood flow, which has greater velocity than
stationary tissues.[17] Confluent laser burns encircling retinoblastoma tumors may
occlude capillaries and large retinal blood vessels, cutting off the tumor blood
supply,[13] so photocoagulation is initiated only after systemic or intra-arterial
chemotherapy are completed.
Tumors less than 3 mm elevation may be successfully controlled by laser without
chemotherapy. Larger tumors require first chemotherapy to initiate tumor regression,
followed by laser encircling photocoagulation to cut off blood supply and on
subsequent treatments, 4–6 weeks apart, laser photocoagulation is applied directly to
the tumor (Figure 2). Tumors that are too large for laser therapy require other
modalities of treatment (Figure 1).
“Thermal blooming” is the process by which the photocoagulation zone may
extended beyond the laser spot size particularly with longer duration burns.[17] This
may not be clinically apparent during treatment but contributes to a larger laser scar.
When the tumor becomes white with laser photocoagulation, further penetration of
the light energy to deeper structures is prevented by light scattering.[24] Thus,
repeated laser on the same area will only increase the lateral extent of the laser
application, known as the “shielding effect”. Laser photocoagulation ultimately leads
to gliosis replacing the tumor with variable retinal pigment eplithelial hyperplasia.
5.2. Trans-pupillary thermotherapy
Trans-pupillary thermotherapy (TTT) involves long duration (60 seconds) laser in the
near-infrared spectrum (usually 810 nm diode) with larger spot size and lower power
than photocoagulation.[17] TTT results in deeper tissue penetration (4 mm) since
melanin absorption decreases with increasing laser wavelength. Continuous wave
Gallie Brenda, 01/07/18,
check the ref style: if superscript will be after the punctuation, if number in brackets will ve before the punctuation
Gallie Brenda, 01/07/18,
Reference????
Sameh Soliman, 01/07/18,
Combined approach
Sameh Gaballah, 01/07/18,
FIGURE 1 include tumors with encircling photocoagulation. Leslie.
Sameh Soliman, 01/07/18,
Combined approach
1064 nm laser penetrates deeper that the 810 nm diode, important in treatment of
thicker tumors.[25] Temperatures of TTT (45 to 60 oC) are lower than for
photocoagulation.[26] The endpoint of TTT is faint whitening or graying of the
tumor and visible changes may not be visible at the time of treatment.[17, 26]
Standard TTT may be insufficient to treat large, thick tumors or lesions associated
with significant chorioretinal atrophy. Furthermore, while TTT requires inherent
lesion pigmentation to achieve an adequate response, retinoblastoma is
characteristically non-pigmented. Pretreatment with intravenous indocyanine green
(ICG), a chromophore with absorption peak 805 nm complementing the diode 810
nm laser, results in photosensitization and a dose-dependent decrease in the TTT
fluence threshold and irradiance required for treatment.[27] Enhancement of the laser
effect by systemic ICG may lead to regression of tumors that have shown a
suboptimal response to systemic chemotherapy and standard TTT.[28-30] The
optimal timing between ICG injection and TTT has not been determined.
5.3 Therapy combining different lasers
Retinoblastoma can be treated with a combination of photocoagulation and
thermotherapy in one or sequential treatments. The tumor border and periphery are
treated with 532 nm laser. A longer wavelength laser is used to treat the elevated
center either in the same or sequential session.[7] Unfortunately, there is no
randomized clinical trial comparing lasers and technologies to establish evidence.
[31]
5. Complications of laser therapy
Sameh Soliman, 01/07/18,
ADD our sequential and the Pakistani paper here
Gallie Brenda, 01/07/18,
more papers on the dragging of retina and shifting of scara?
The most serious complications of laser therapy are usually caused by use of
excessive energy. Therefore treatments start at lower power to titrate to the desired
effect to decrease likelihood of complications. Too small a spot size, too high a
power or too short can induce an iatrogenic rupture of Bruchs’ membrane, which
might be a precursor for choroidal neovascular membrane formation. Intense
photocoagulation may result in full thickness retinal holes which may progress to
rhegmatogenous retinal detachment, or may induce vitreous seeding of
retinoblastoma.[32] OCT is useful to visualize and analyze complications.
Biopsy-proven orbital recurrence of retinoblastoma has been reported following
repeated treatment of a macular recurrence of retinoblastoma with aggressive argon
and diode laser.[33] In this case, MRI demonstrated a large intraconal mass
contiguous with the sclera, and B-scan ultrasound confirmed scleral thinning at the
recurrence site. The orbital recurrence was felt to result from tumor seeding of the
orbit at a site of focal scleral thinning within an atrophic chorioretinal scar, following
multiple intense laser treatments.[33]
Common less serious complications include focal iris atrophy, lenticular
opacification, retinal traction, retinal vascular obstruction and localized serous retinal
detachment.[32, 34] Scars from TTT (810 nm) are recognized to increase in size with
time [35] so may be in using this laser for tumors l suboptimal for tumors located
near the fovea and optic nerve. Chorioretinal scarring with focal scleral bowing is
reported following TTT.[36] Laser is ineffective in areas with any retinal
detachment. OCT is useful to delineate subtle detachments. Laser over the optic
Sameh Soliman, 01/07/18,
Brenda, do you want to include a figure regarding SMW?
nerve can compromise nerve fibers. The exact tumor relation to the optic nerve can
be mapped by OCT to guide accurate laser treatment near critical structures.
PUBLISHED EVIDENCE ON LASER IN RETINOBLASTOMA:
Meyer-Schwickerath reported the results of xenon photocoagulation for
retinoblastoma in 1955 and subsequently in 1964. [37] Although laser therapy for
retinoblastoma has been used for several decades[37, 38] it wasn’t until the 1980’s
and 1990’s that the role for focal laser therapy in the management of retinoblastoma
became widely popularized.[39] In 1982 Lagendijk used trans-pupillary
thermotherapy (TTT) in two cases of recurrent retinoblastoma successfully.[40]
Subsequently, a relatively large study by Lumbroso et al reported their outcomes in
239 children using TTT delivered with a diode laser through an operating microscope
and found that when this was combined with chemotherapy excellent local tumor
control and eye preservation was achieved.[41] Other groups similarly concluded
that while chemoreduction alone may not be adequate at achieving complete tumor
control, chemoreduction in combination with adjuvant treatment (including laser
photocoagulation, thermotherapy, cryotherapy and radiation) resulted in good retinal
tumor control, even in eyes with advanced disease.[42]
As the use of laser therapy in the management of retinoblastoma gained traction,
several clinicians investigated this potentially synergistic role between thermotherapy
and chemotherapy. This treatment algorithm was termed chemothermotherapy and
was based on the hypothesis that the delivery of heat facilitates the cellular uptake of
certain chemotherapeutic agents.[43] In fact, in a series of 103 tumors treated with
chemothermotherapy, Lumbroso et al[44] reported that tumor regression was seen in
Gallie Brenda, 01/07/18,
WHY IS THIS A SPECIAL SECTION?? I THINK IT SHOULD ALL BE INTEGRATED INTO THE PREVIOUS SECTIONS.
96.1%. In this study, TTT was delivered shortly after an intravenous injection of
carboplatin.
Predictors for success of focal laser photocoagulation and thermotherapy have also
been identified. Abramson et al. concluded that tumors <1.5 disc diameters in base
diameter can be successfully treated with TTT alone, with nearly two thirds (64%) of
tumors only requiring one session.[26] Alternative laser techniques have also been
described, including the use of the 532-nm laser which has been shown to effectively
treat small (<2mm in height, <4 disc diameter) tumors. [32] Depending on the tumor
location, the clinician may prefer one laser type over the other. For instance, while
TTT using the 810-nm diode laser is effective, the scar that is created can increase in
size after treatment [35] and therefore when applying laser near vital macular
structures some prefer laser photocoagulation (532-nm laser). Similarly, trans-scleral
diode laser may be the preferred modality for small anteriorly located
retinoblastomas.[21] Although a variety of potential complications as discussed
above have been noted, the majority of these can be avoided by using the minimal
effective laser power.[32] It is important to note however that despite the use of laser
focal therapy being a mainstay in the treatment of retinoblastoma, there have been no
randomized controlled trials evaluating the effect of systemic chemotherapy with
versus without laser therapy for post-equatorial retinoblastoma [31].
NEW PAPERS ON LASER AND VISUAL OUTCOME: (KELSEY)
6. Laser guided by optical coherence tomography (OCT)
Gallie Brenda, 01/07/18,
PUT ALL THIS INTO THE RELEVANT PLACES ABOVE
Sameh Soliman, 01/07/18,
Fabian, Am J Ophthalmol. 2017 Jul;179:137-144.
First reports of OCT focused on the appearance of retinoblastoma and differentiation
from simulating lesions [45, 46]. The hand held OCT expanded the use to supine
children under anesthetic to image retinoblastoma tumors from diagnosis through
treatments, to eventual stability.{Scott, 2009 #13722;Maldonado, 2010 #13713}
OCT visualization facilitates accurate laser therapy, revealing for example,
White treatment scars previously posed a challenge to distinguish residual or
recurrennt tumor and gliosis. With OCT, laser can be delivered with precision to
specific areas of recurrence instead of the whole scar, reducing risk of excessive
scarring and retinal dragging. When OCT images suggest stability, observation can
be undertaken without danger of tumor growth requiring increased treatment burden.
7.4. Pre-equatorial tumors
Pre-equatorial tumors can be treated by either photocoagulation or cryotherapy.
Laser therapy is preferred in superior tumors to avoid uveal effusion and exudative
detachment associated with cryotherapy. Shallow tumors may be treated with 532 nm
laser photocoagulation for one or two sessions. Elevated pre-equatorial tumors might
Gallie Brenda, 01/07/18,
SAMEH CAN YOU SIMPLIFY AS YOU NOW CHOSE FOR YOUR PAPER?
require multiple treatments as the laser beam is not able to apply perpendicular to the
tumor with a trans-pupillary approach. In subsequent sessions with flattening of the
tumor, the tumor can be better visualized and treated.
With expertise, peripheral OCT can assess tumor elevation, differentiate scarring
from residual tumors and identify peripheral potential tumor seeding (Figure 5).
Laser can be utilized to surround the tumor with a barrier to retinal detachment prior
to cryotherapy, plaque radiotherapy or pars plana vitrectomy.{Zhao, 2017 #20057}
Laser can be also used to ablate ischemic or potentially ischemic retina isolated by
extensive scar to protect against neovascularization and subsequent vitreous
hemorrhage.
Conclusions
Laser therapy is integral in retinoblastoma tumor control after initial reduction in size
by chemotherapy. However, laser was not been studied in any clinical trial. Improved
tumor visualization and assessment by OCT opens the door to precision laser
treatments of smaller tumors and recurrence, potentially improving cancer outcomes,
reducing invasive procedures, and reducing complications.
Sameh Soliman, 01/07/18,
Sameh to write
Sameh Soliman, 01/07/18,
Discuss with Brenda. ?? AD
Expert Commentary
I would include something related to the future of OCT guided laser.
BG will do next.
Five year view
Imaging technology are continuing to rapidly improve. Soon wide-angle fundus
imaging will be combined with OCT in hand-held units appropriate for children
under anaesthetic. Perhaps in five years, laser therapy will also be able to be
delivered in on tool, guided directly by both fundus image and OCT cross-section to
allow quick and accurate laser delivery.
Sameh Soliman, 01/07/18,
Five-year viewAuthors are challenged to include a speculative viewpoint on how the field will have evolved five years from the point at which the review was written.
Sameh Soliman, 01/07/18,
Expert Commentary: 500-1000 words (included in overall word count).To distinguish the articles published in the Expert Review series, authors must provide an additional section entitled ‘Expert Commentary’. This section affords authors the opportunity to provide their interpretation of the data presented in the article and discuss the developments that are likely to be important in the future, and the avenues of research likely to become exciting as further studies yield more detailed results. The intention is to go beyond a conclusion and should not simply summarise the paper. Authors should answer the following:What are the key weaknesses in clinical management so far?What potential does further research hold? What is the ultimate goal in this field?What research or knowledge is needed to achieve this goal and what is the biggest challenge in this goal being achieved?Is there any particular area of the research you are finding of interest at present?Please note that ‘opinions’ are encouraged in the Expert commentary section, and, as such, referees are asked to keep this in mind when peer reviewing the manuscript.
References
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2. Kivela, T., The epidemiological challenge of the most frequent eye cancer: retinoblastoma, an issue of birth and death. Br J Ophthalmol, 2009. 93(9): p. 1129-31.
3. Gallie, B.L. and S. Soliman, Retinoblastoma, in Taylor and Hoyt's Paediatric Ophthalmology and Strabismus, B. Lambert and C. Lyons, Editors. 2017, Elsevier, Ltd.: Oxford, OX5 1GB, United Kingdom. p. 424-442.
4. Soliman, S.E., et al., Genetics and Molecular Diagnostics in Retinoblastoma--An Update. Asia Pac J Ophthalmol (Phila), 2017. 6(2): p. 197-207.
5. Yousef, Y.A., et al., Intra-arterial Chemotherapy for Retinoblastoma: A Systematic Review. JAMA Ophthalmol, 2016.
6. Scelfo, C., et al., An international survey of classification and treatment choices for group D retinoblastoma. Int J Ophthalmol, 2017. 10(6): p. 961-967.
7. Soliman, S.E., et al., Optical Coherence Tomography-Guided Decisions in Retinoblastoma Management. Ophthalmology, 2017.
8. Maiman, T.H., Stimulated Optical Radiation in Ruby. Nature, 1960. 187(4736): p. 493-494.
9. Eichhorn, M., Laser physics : from principles to practical work in the lab. 1st edition. ed. Graduate texts in physics. 2014, New York: Springer. pages cm.
10. Niederer, P. and F. Fankhauser, Theoretical and practical aspects relating to the photothermal therapy of tumors of the retina and choroid: A review. Technol Health Care, 2016. 24(5): p. 607-26.
11. Krauss, J.M. and C.A. Puliafito, Lasers in ophthalmology. Lasers Surg Med, 1995. 17(2): p. 102-59.
12. Abramson, D.H., The focal treatment of retinoblastoma with emphasis on xenon arc photocoagulation. Acta Ophthalmol Suppl, 1989. 194: p. 3-63.
13. Augsburger, J.J. and C.B. Faulkner, Indirect ophthalmoscope argon laser treatment of retinoblastoma. Ophthalmic Surg, 1992. 23(9): p. 591-3.
14. Friberg, T.R., Principles of photocoagulation using binocular indirect ophthalmoscope laser delivery systems. Int Ophthalmol Clin, 1990. 30(2): p. 89-94.
15. Kitzmann, A.S., et al., A survey study of musculoskeletal disorders among eye care physicians compared with family medicine physicians. Ophthalmology, 2012. 119(2): p. 213-20.
16. Mainster, M.A., et al., Ophthalmoscopic contact lenses for transpupillary thermotherapy. Semin Ophthalmol, 2001. 16(2): p. 60-5.
Sameh Soliman, 01/07/18,
References: A maximum of 100 references is suggested. Ensure that all key work relevant to the topic under discussion is cited in the text and listed in the bibliography. Reference to unpublished data should be kept to a minimum and authors must obtain a signed letter of permission from cited persons to use unpublished results or personal communications in the manuscript.Annotated bibliography: Important references should be highlighted with a one/two star system and brief annotations should be given (see the journal’s Instructions for Authors page for examples and for a more detailed description of our referencing style).
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Table 1: Comparison between lasers in retinoblastoma.
Type of
laser
Green
532nm
Diode
810nm
Continu
ous
wave
1064nm
Frequency-
doubled Nd-
YAG
Solid State
Semi-
conduct
or
Nd-
YAG
Solid
State
Common
delivery
method
Indirect Indirect
or
transcle
ral
Indirect
Mechani
sm of
action
Retinal
photocoagulatio
n results in
tumor apoptosis
Acts in a subthreshold manner
to raising choroidal
temperature. Causing minimal
thermal damage to the RPE
and overlying retina
Depth of
penetrati
on
Superficial:
limited by the
resultant
coagulation [32]
and by nature of
Deep: primary anatomical site
of action is in the choroid.
Diode and Nd:YAG lasers are
estimated to penetrate 4.2 and
5.1mm respectively.
shorter
wavelength.
Estimated to
penetrate ~2
mm in non-
pigmented
tumors such as
retinoblastoma.
[10]
Penetration depth decreases in
necrotic tumors.[10]
Paramete
rs
Power: 0.3 – 0.8
W
Duration: 0.3-
0.4 seconds
Power:
0.3-1.5
W
Duratio
n: 0.5 –
1.5
seconds
Power:
1.4 – 3.0
W
Duration
: 1
second
Clinical
endpoint
Increase power
by 0.1W
increments until
tumor/retinal
whitening
visible[32]
Slight graying of retina without
causing vascular spasm [26,
34]
Table 2. Types of contact and non-contact fundus lenses [13, 16, 17]