Optical Coherence Tomography guided decisions in retinoblastoma management Sameh E. Soliman, MD, 1,2 Cynthia VandenHoven, 1 Leslie D. MacKeen, 1 Elise Héon, MD, FRCSC, 1,3,4 Brenda L. Gallie, MD, FRCSC 1,3,5,6 Authors affiliations 1 Department of Ophthalmology and Vision Sciences, Hospital for Sick Children, Toronto, Canada. 2 Department of Ophthalmology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt. 3 Department of Ophthalmology & Vision Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. 4 Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. 5 Division of Visual Sciences, Toronto Western Research Institute, Toronto, Ontario, Canada. 6 Departments of Molecular Genetics and Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. Corresponding author: Sameh E. Soliman, 555 University Avenue, room 7265, Toronto, ON, M5G 1X8. [email protected]
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Optical Coherence Tomography guided decisions in
retinoblastoma management
Sameh E. Soliman, MD,1,2 Cynthia VandenHoven,1 Leslie D. MacKeen,1 Elise Héon, MD,
FRCSC,1,3,4 Brenda L. Gallie, MD, FRCSC1,3,5,6
Authors affiliations
1Department of Ophthalmology and Vision Sciences, Hospital for Sick Children, Toronto,
Canada.
2Department of Ophthalmology, Faculty of Medicine, University of Alexandria,
Alexandria, Egypt.
3Department of Ophthalmology & Vision Sciences, Faculty of Medicine, University of
Toronto, Toronto, Ontario, Canada.
4Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, Ontario,
Canada.
5Division of Visual Sciences, Toronto Western Research Institute, Toronto, Ontario,
Canada.
6Departments of Molecular Genetics and Medical Biophysics, Faculty of Medicine,
University of Toronto, Toronto, Ontario, Canada.
Corresponding author:
Sameh E. Soliman, 555 University Avenue, room 7265, Toronto, ON, M5G 1X8.
Concept and design: Soliman, VandenHoven, MacKeen, Héon, Gallie
Data collection: Soliman, VandenHoven, MacKeen.
Figure construction: Soliman, VandenHoven.
Analysis and interpretation: Soliman, VandenHoven, MacKeen, Héon, Gallie.
Sameh Gaballah, 11/28/16,
1. Title PageThe title page should include the following information.a) Title: The title should be meaningful and brief (no longer than 135 characters); abbreviations should not be used. Please ensure the manuscript title on the cover page matches the title entered into the submission system.b) Authors: Provide first name, middle initial, last name, and no more than two advanced degrees. The journal does not print society affiliations. Also indicate each author's affiliation during the course of the study in footnotes on the title page using superscript numbers, not symbols (e.g., John Smith1). Specifically identify the corresponding author. Please carefully review the Authorship section of this guide, which addresses authorship criteria, Group/writing committee authorship, ghost authors, guest authors, corresponding authors, and related responsibilities. Verify numbers of authors when entering author names into the system.c) Meeting Presentation: If the material is under consideration for presentation or has been previously presented, supply the name, place, and date of the meeting. (e.g., the American Academy of Ophthalmology Annual Meeting, 20XX). This is especially important for AAO Meeting papers as the journal has the right of first refusal for these manuscripts.d) Financial Support: Identify all sources, public, and private. On the title page please state “Financial Support: None” or provide the agency name and city, company name and city, fellowship name, and grant number. If there is financial support, please provide also one of the two following statements, “The sponsor or funding organization had no role in the design or conduct of this research.” OR “The sponsor or funding organization participated in (list those that are appropriate, e.g., the design of the study, conducting the study, data collection, data management, data analysis, interpretation of the data, preparation, review or approval of) the manuscript.”e) Conflict of Interest: A blanket statement that “no conflicting relationship exists for any author” is requested on the title page, if appropriate. Otherwise, the corresponding author should summarize the disclosures sent by each author and upload the ICMJE COI form of each author.f) Running head: The running head, also known as the short title, which appears on the top of each right hand published page of the manuscript, should be a maximum of 60 characters.g) Address for reprints
Meeting presentation: American Academy of Ophthalmology Annual Meeting
presentation (Chicago 2016, Monday 17th October 2016)
Sameh Gaballah, 11/28/16,
Needs revisiting at final number
Sameh Gaballah, 11/28/16,
Word count
Abstract: (29185308/350 words)
Purpose: Assess the role of handheld Optical Ccoherence Tomography (OCT) role in
guiding management decisions during guiding diagnosis, treatment and follow-up of
retinoblastoma during active treatment period.
Design: Retrospective non-comparative single institution case series.
Participants: All children newly diagnosed with retinoblastoma children from January
2011 to December 2015 thatwho had an OCT imaging session during their active
treatment at The Hospital for Sick Children in Toronto, Canada. OCT sessions for fellow
eyes of unilateral retinoblastoma without any suspicious lesion and those performed
after 6more than six months after from the last treatment were excluded.
Methods: Data collected included: age at presentation,; sex, family history, RB1
mutation status, 8th edition TNMH Cancer staging and International Intraocular
Retinoblastoma Classification 1 (IIRC), and number of OCT sessions per eye. Details of
each session were reviewedscored for indication-related details (informative or not) and
assessed for being guidanceing (directive or not), diagnosis (staging changed, new
tumors found or excluded), treatment (modified, stopped or modality shifted), or follow-
up modified.
Main outcome measures: Frequency of OCT- guided management decisions, and
stratified by indication and type of guidance (confirmatory versus influential).
Results: Sixty-three eyes of 44 children had 339 OCT sessions (median =5, range 1-
15, sessions per /eye, range 1-15). Younger Children younger at presentation and those
with positivecarrying an RB1 mutation had significantly higher number ofmore OCT
sessions. Common Indications included evaluation of post-treatment scar (55%) or fovea
(16%), and posterior pole scanning for new tumors (11%). InformativeOf all sessions
were 92% (312/339) were informative; 19/27 non-informative sessions had and the main
Sameh Gaballah, 11/28/16,
Abstracts for Manuscripts and AAO Meeting Papers should not exceed 350 words and should be submitted on a separate page in the text. Deletion of any required section of the abstract must be justified in the “Author Comments” section of the online submission form. The following 7 sections must appear in the abstract; please select the most appropriate heading for each section (for example, chose either “Objective” or “Purpose” for the first section):1. Objective or Purpose: Concisely state the study goal.2. Design: Identify the study design using a phrase such as cross-sectional study, clinical trial, cohort study, etc. Study design types are summarized in the Study Design section of this guide. The CONSORT Worksheet is required for randomized controlled trials.3. Subjects, Participants, and/or Controls: Describe the persons or eyes studied and the controls if a separate control Group is included.4. Methods, Intervention, or Testing: Describe the principal treatment(s), procedure(s), test(s), or observation(s) performed.5. Main Outcome Measures: Define the main parameter(s) being measured (e.g., intraocular pressure, visual acuity, degree of inflammation, etc.)6. Results: Summarize the principal measurements (data) obtained.7. Conclusions: State the conclusion(s) derived from the data analysis.
cause was large, or elevated lesions; of these, in 70% of non-informative sessions
(19/27); 74% of which (14/19 ) were T2a or T2b (for IIRC{Murphree, 2005 #11984}IIRC
GroupGroup CD or D)C eyes at presentation. In 94% (293/312) of informative sessions,
OCT guideddirected management decisions in 94% (293/312) of informative sessionsfor
follow-up and diagnostic decisions respectively). Influential OCT guidance (OCT
datainfluenced and changed management fromed the pre-OCT clinical decisionplans)
was noted in 17% and 15% of directive and all OCT sessions respectively.
Conclusions: Clinical evaluation remains the gold standard for retinoblastoma
management. OCT improves accuracy of clinical evaluation gives valuable information
on tiny tumors, tumor scars and fovea improving precision in retinoblastoma
management.
Sameh Gaballah, 11/28/16,
PrécisAll manuscripts must include a précis of 35 words or less summarizing the main finding/outcome of the study. The précis should not duplicate the abstract conclusion. If the paper is published, the précis will appear under the title in the Table of Contents. The précis is submitted as a separate file and should not be included in the manuscript file. Please refrain from using abbreviations/acronyms in the précis.
children (2011-2015) that had OCT. Details of each
session were reviewed and scored for indication-related
details, guided diagnosis (staging changed, new tumors
found or excluded), treatment modified, stopped or
modality shifted, or follow-up modified.
Results: Forty children (59 eyes) had 300 OCT sessions
(median=5/eye). Common indications were evaluation of
post-treatment scar (67%) or fovea (19%), and new
tumor assessment (10%). Informative sessions were
93% (286/300). OCT guided management decisions in
90% (258/286, p<0.05) of informative sessions (67%,
20%, 13% guided treatment, follow-up and diagnostic
decisions respectively).
Conclusion: OCT gives valuable information on tiny
tumors, tumor scars and fovea improving precision in
retinoblastoma management.
Précis: (2935/35 words)
Precis:
In 63 eyes of 44 patients with retinoblastoma, of 339 optical coherence tomography
sessions, 94% contributed indication-related detailsRetrospective Review of 339 OCT
sessions, 86% performed for 59 63 eyes of 40 children with retinoblastoma from 2011 to
2015 during their active treatment phase showed that in 300 sessions evaluated (median
5/eye), the most common indication was post-treatment scar evaluation in 2/3 of
eyes,OCT provideding indication-related details in 9394% and significantly guided
caretreatment, follow up and diagnosis in 9086% of sessions, and 15% influenced
important change in managementeyes.
Background sentence:
OCT guides management decisions in macular and retinal diseases. Previous reports
showed OCT signs of retinoblastoma and simulating lesions, tiny tumors, fovea and optic
disc evaluation without studying OCT impact on active management.
Sameh Soliman, 11/28/16,
Provide a succinct statement explaining the background of why this study was undertaken or reported. You may use up to 250 characters or approximately 40 words (with spaces). Do not repeat the conclusion of the abstract or the précis.
Sameh Soliman, 11/28/16,
All paper/poster submissions must include a one-sentence précis (approximately 70 words or less and no more than 460 characters) summarizing the main finding/outcome of the study. The précis should not duplicate the abstract conclusion. The précis will be used by the Annual Meeting Program Committee in its selection of abstracts to be presented, but will NOT be published in the final program.
Optical Ccoherence Tomography (OCT) hasisis well established itself asto as playinging an
integralimportant role in ophthalmic patient assessment, improvingleading to improved diagnostic
accuracy and thus therapeutic decision making for a variety of ocular and retinal conditionshas
helped in better visualization of the retinal layers, optic disc, vitreoretinal interface and choroidal
anatomy. This improvesd the diagnostic and thus therapeutic decision makings in multiple
disorders as diabetic macular edema, macular hole and choroidal neovascular membranes.1-4
including ocular oncology. 5,6
Features of Retinoblastoma; the most common pediatric ocular malignancy; were better
appreciated Recently,in the recent years Hhandheld OCTwith the introduction of the handheld
OCT that which can be used used while the supine child is under anesthesia. during the active
management of their condition .7-10 has deepened out understanding of the features of
retinoblastoma, the most common pediatric ocular malignancy. 7-10
There are multiple published reports on the value of OCT in is shown valuable in
retinoblastoma in for detection of small invisible tumors,5,11-139- 12( Add Bremner as 9) foveal
evaluation,14,15 localization and microstructure of tumor seeds,16 and detection of optic nerve
infiltration.10,17 It is documented to help in assessment of tumor anatomy, scar edges and
simulating conditions5,18-20 (e.g. rRetinoma or aAstrocytoma). 5,18-20
Despite these various benefitsHowever, handheld OCT is still not commonly used except in
some highly rankedhighly specialized ocular oncology centers.7,21 In The current Canadian
Guidelines21 for retinoblastoma management we define the a center that has anusing handheld
OCT machine as a tertiary center and it is being updated to quaternary center in the updated
revised guidelines. Despite advances in imaging technologies, cClinical evaluation and decisions
is still the mainstay of retinoblastoma management in most situations. This raises the question of
whether OCT evaluation should be incorporated in the routine management of retinoblastoma or
that whether its use is not thatsignificantly influential on clinical decisions.
In this study, we evaluate the influence of hand held OCT in guiding the management
decisions in patientschildren with retinoblastoma children.
Methods
Study design
This study is a retrospective record review of all new children with retinoblastoma that who
presented to andwere managed in the Hhospital for Ssick Cchildren (SickKids), Toronto, Ontario,
Canada (SickKids) from January 2011 to December 2015. Ethics approval was obtained and the
study follows the guidelines of the Declaration of Helsinki.
Eligibility
The records of all children with rRetinoblastoma that who had receivedexamined with OCT
imaging during their management were reviewed. Fellow eyes of unilateral retinoblastoma
without any suspicious lesion and who had a single OCT session at presentation were excluded.
OCT sessions performed after 6 months from after the last treatment were excluded.
Data collection
The data collected included age at presentation, sex, family history, laterality, International
Iintraocular Rretinoblastoma Cclassification (IIRC)22 at presentation, genetics results, indication
for OCT, number of OCT sessions per /eye, and total active duration treatment (time from
diagnosis until last treatment).
OCT Session and Systems
An OCT session was defined as imaging a of single one eye for one or more indications, using
the OCT during an examination under anesthesia for one or more indications. During the course
of the study, two generations of handheld OCT systems were utilized: Bioptigen® Envisu C2200
andC2200 and Envisu C2300 (Bioptigen, Inc. a Leica Microsystems, Morrisville, NC USA). We
did not compare and contrast both the machines for resolution or depth. We did not receive
sponsorship or financial support to conduct this our research. At any point of time, we only had
one machine was available for both clinic and operating room. All OCT scans were captured by
one of two highly skilled mMedical imaging sSpecialists (authors CV and LM), following a
standardized methodology for improved longitudinal reproducibility.
DefinitionsTe and technical considerations and indications 23-26
OCT was performed with operator at 12 o’clock position of the supine patient. Handheld OCT
scanner was pivoted approximately 1 cm above the cornea, the optimal working distance, aiming
the scanning beam through the pupillary center.25 Manually holding the OCT probe was preferred
as it provides the greatest flexibility and ease of angling the probe towards the areas of interest.
Additionally, the operator is able to increase the probe to eye working distance in real time while
scanning over the apex of larger lesions. Image quality and scan brightness was achieved by a
combination of factors, including manual adjustment of the OCT spectrometer reference arm
settings in accordance to the patient’s axial length and optimizing the handheld probe focus for
the child’s refraction.25 and frequent application of 0.9% NaCl solution to prevents corneal
dryness.
The handheld OCT produces a variety of scan configurations of scans. For our researchWithin
this study cohort, we consistently routinely obtained volumetric scans that were composed of
non-unaveraged OCT volume scans consisting of( 1000 A-Ascans x 100 B-scans per volume)x 1
x 1. The accumulation of individual 100 B-scan produceds the associated C-scan fundus image
otherwise called the Sum Voxel Projection or (SVP). The OCT’s accompanying SVP image
provides critical information about the quality of the scan and in real-time the OCT operator can
respond with positional adjustments to improve subsequent scans. Additionally, When
clarification of pathology localization wasis frequently required; , calipers were sometimescan be
placed on the OCT B-scan image revealing the retinal position on the SVP image so that the
precise area of interest cancould be correlated to the specific retinal position. Calipers were also
used to measure tumor height in some instances . (Fig. Fig 1) . So while the Bscan OCT is of
significant value to interpreting tumour features, the SVP image is also as critical to ensure
accurate localization of lesions and interpretation of Bscan findings. It has been reported that
extensive algorithms might be applied to improve image quality via oversampling and averaging
of multiple scans.26 In our practice, we routinely captured single line volume scans as they
achieved both rapid and high quality images with ample detail to provide clinical information.
The SVP image that results when OCTs scans are averaged are unreadable. This affects the
ability to decipher the OCT tumor findings accurately.
For infants less than (≤ 6 months of age, we assessed the posterior pole) (Fig 2) to screen for a
new pre-clinical or “invisible” tumor by obtaining screening withusing the widest volumetric scan
settings available. In our center, weWe performed 9mm x 9mm scans with the( Envisu C2200
system) and 12mm x 12 mm scans with( Envisu C2300 system) of fovea, optic nerve, temporal,
superior and inferior quadrants. If a tumor is identified, the scan is repeated with the scanner
placement achieving tumor centration centered within the OCT frame. (Fig.3) (Figures 1-2)
Foveal assessment is indicated In the presence of foveal and or perifoveal tumors, to locate the
foveal center was located by obtaining a horizontal macular volumetric scan. As When needed,
this scan is followed by a vertically oriented foveal volume scan was performed whereby,with the
scanning angle is adjusted 90 degrees (within the software). The handheld scanner is held the
same physical configuration while t. The sum voxel fundus projectionSVP image is was
consequently rotated 90 degrees indicating the scan direction change. (Fig.ure Fig 34)
When For parafoveal scansning parafoveally, the handheld probe is angled towards the area of
interest. Increased resolution of the individual scans for small If the lesions is small in size, it can
be ideal towas obtained by reducinge the area of scan volume to 8 x 8 or 6 x 6, to maximize
number of A-scans per each line. of OCT B-scan, thus increasing the resolution of the individual
OCT scans. To assess the mid-periphery and beyond, a scleral depressor is was used to rotate the
eye toward the area of interest, while angling the handheld probe so that perpendicularity to the
retinal plane is achieved. (Fig.ure Fig 54)
Assessment layers
An OCT session will was be assessed as being first as being Informative if it provideds
sufficient data about the main indication for scanning; and then being as Directive if the
information provided from the OCT imaging helpedobtained guiding guided the management
decisions affecting either diagnosis, treatment or follow-up. Directive guidance can bewas
considered Confirmatory if it confirms the pre-OCT clinical decision or Influential if the
information providedit changed a pre-OCT clinical decision. Every OCT session during the active
treatment phase of each child will was be collected and assessed for all layers.
Decision guiding
Guidance is either in diagnosis, treatment or follow-up.
Guidance was provided for diagnosis, treatment or follow-up, summarized in Tables 2 and 3.
Diagnosis sessions Diagnostic cwere scored Confirmatory guidance was considered when
OCT OCT confirmeds; a) clinically suspicious tumor mass or in clinically suspicious area(s), b)
clinicalclinical eye IIRC22 grouping Group, or whenever c) the posterior pole screening was
screened in positive germ line mutationschildren known to carry an RB1 mutant allele who were
less that 6 months of age; and Influential when OCT excluded tumor in clinically suspicious
area(s), changed IIRC22 Group, or detected an invisible tumor during posterior pole screening.
up to six months of age. Diagnostic influential guidance was considered if OCT; a)
excluded tumor in clinically suspicious area(s), b) changed IIRC22 grouping or c) detected
an invisible tumor during posterior pole screening.
Treatment sessions were scored Confirmatory guidance was considered ifwhen OCT
confirmed a a) clinically suspicious new or recurrent tumor, or b) showed anatomic details (fovea,
scarring, seeds, traction…etc.) supporting the decided treatment plan;. Treatment and Influential
guidance waswhen considered if OCT a) showed revealed an unsuspected recurrent tumor within
a tumor scar, b) or showed anatomic details mandating changing or cessation of the treatment
modality or plan.
Follow-up sessions confirmatory guidance waswere considered Confirmatory if when the
OCT showed no change from the last scan in absence of active treatment;. Follow up influential
guidance was considered if and Influential when OCT showed anatomic details excluding
activity, leading to change of clinically decidedalteration in treatment plan.
Results:
Patient Demographics and numbers of OCTs
This We reviewed included 339 OCT sessions for 63 eyes of 44 children with retinoblastoma;
(26 were male, 59%). Eight children (10 eyes) are were still under active treatment from which
one child (one eye) was lost to follow up as they moved outside Canada. Demographic data are
summarized in table 1. The median number of OCT sessions per eye is was 5 sessions (range: 1-
15 sessions),. and were significantly higher for fFamilial eyes had a significantly higher median
session number of( 7) than versus 4 sessions to non-familial eyes(4) eyes (p=0.001, Mood’s
Median test). A significant negative correlation existed between the age at presentation and the
number of OCT sessions where Younger age children at presentation required significantly more
OCT sessions (r=-0.26, p=0.04). The most common indication for OCT was tumor scar
evaluation in 55% (186/339, 55%), of sessions followed by foveal assessment and posterior pole
screeningscreening (16% and 11% respectively) (. The indications for OCT imaging for each eye
are summarized in tTable 2). What are the types of the OCT machines for the duration 2011-
2016?
Gallie Brenda, 11/28/16,
Check changes in xlsStats repeated and same
Gallie Brenda, 11/28/16,
Who is this and why?This is Nyali Amparo. she travelled to USA
Gallie Brenda, 11/28/16,
Is this definedYes
OCT Impact Assessmenton Care
Informative versus Non-informative OCT
Informative OCT was found Informative in 92% of evaluated sessions (312/339) (Table 2).
Large or highly elevated lesions rendered OCT technically challenging and Uninformative iIn
19/27 sessions (8%), no valuable information was acquired. The main cause of non-informative
OCT was large or elevated lesion in 70% of sessions (19/27) (Table 3, Fig 1)2,5); approximately
74% of which (14/19 ) were was IIRC22 Group D or C at first tumorpresentation. In two2
eyes/children, there was loss of thOCT became e Uniformative informative status of the OCT
after multiple previously Informative OCTs OCTs, due to progression of the central tumor (in
one) aeye and tractional retinal detachment in another eye(one).
Directive versus Non-Directive OCT
Directive OCT was Directive found in 86% (293/339) of all OCT sessions and in 94%
(293/312) of Informative sessions (Table 2), guiding . OCT directed treatment (168/312, 54%),,
diagnosis (46/312, 15%), or follow up in 54% (168/312), 15% (46/312) and 25% (79/312, 25%)
of informative sessions respectively. In 19Nineteen OCT sessions were Non-
DirectiveUninformative, mainly because the OCT, the information given was not important in
directing management decisions. The main cause was performing non-not indicated performed to
assess a clinical decision OCT (17/19) or OCT performed for academic interest (2/19). (Table 3)
Confirmatory versus Influential OCT
Of Directive OCT sessions, Confirmatory OCT was found in 83% (243/293 (83%) were)
Confirmatory: of directive sessions and guidedfor treatment 141 (58%), diagnosis 39 (16%) and
follow-up 63 (up of 58%, 16% and 26%) of confirmatory sessions respectively (Table 2)..
Influential Of Directive OCT sessions, OCT was found in 17% (50/293 (17%) were Influential:
of directive sessions and guided for treatment 27/293 (11%), diagnosis 7/293 (3%) and follow- up
16/293 (7%) (Table 2). of 54%, 14% and 32% of influential sessions. Different OCT influences
Gallie Brenda, 11/28/16,
Check these details as Cynthia suggestsdone
are shown in table 3The most Influential OCT sessions were for scar evaluation and foveal
evaluation (Table 3).
Discussion
The introduction of OCT in retinal imaging has been shown its effective ness in guiding
management (diagnostic and therapeutic) decisions in multiple conditions, including as macular
holes,2, macular edema1 (diabetic and vascular) and age related macular degeneration.3,4 Multiple
reports were published showinghave shown the OCT differences between ocular tumors and how
useful OCT it can be useful to differentiate ocular tumors and simulating lesions.5,6,9-12,14-16,18-20,23
At presentation, we showed that OCTs provides limited information of in eyes where the with
retinoblastoma is T224 (TNMH 8th edition27) more advanced thanequivalent to IIRC22 groupGroup
C or higher or higher and ofwith individual large tumors are usually non-informative regarding
large tumor. s, Thetumors, due to absorption of . The optical signal is absorbed through by dense
lesions and the lesion elevation is beyond the imaging capacity.as the scan cannot include them in
its focus together with associated changes as calcification and detachment.25 Eyes with T124
tumors (IIRC22 groupGroups A and B) are easily scanned even inup to the mid periphery23 (Fig
5x) (Fig. 1,2,4). OCT helps assessingassesses well the location level of the tumor whether with
respect to retina: intra-retinal, pre-retinal, vitreal or subretinal (Fig. Fig 6). This allows more
accurate TNMH24,27 or IIRC22 groupstaginging in certain eyes where a suspected tumor mass away
from the primary tumor is shown to by OCT to be a subretinal mass extension of tumor versus
and not an independent new separate tumor (Fig 6C). This changes influences the diagnosis from
a multifocal tumor (IIRC22 group B or C) to a seeding of a unifocal mass tumorwith IIRC22group
D. The verification of vitreous tumor seeds by OCT16 helps better grouping(what do you mean by
this??)helped accurate IIRC22 grouping andalso affects the choice of treatment modality (iei.e.,
intra-vitreal chemotherapy)28,29.
Gallie Brenda, 11/28/16,
Can we show an OCT in the periphery? already done
Detection of small and sometimes invisible tumors5,11 (Fig. Fig 2-3) has changed the visual
outcome especially in familial retinoblastoma.24 This leads to earlier detection and control with
less treatment burden (focal therapy only) and less retinal damage. In familial casesFor children at
risk of familial retinoblastoma under 3 months of age, detection of the first invisible tumor by
OCT can facilitate early, minimalized therapy.30 {Fe-Bornstein, 2002 #12863}29modify the follow
up plan to include EUA instead of clinic visits.21
In unilateral retinoblastoma, OCT helps differentiateation of suspicious lesions from
retinoblastoma (Fig. Fig 7) in the fellow normal eye. Previously, this depended on clinical
examination opinion or B-scan ultrasonography, which does not show the inner architecture of
the a lesion. Sometimes,Lacking invivoin-vivo evidence of the nature of these suspicious lesions,
presumably manyoften such lesions were treated focally, potentially and falsely changing the
diagnosis of thislabeling the child into as bilateral , heritable retinoblastoma, imposing which has
a totally different follow-up, schedule with multiple unnecessary examinations under anesthesia.21
Foveal pit detection (Fig. Fig 4) provides an important clue about visual potential in with
perifoveal tumors.14 Its Foveal localization respective to the tumor location can affect choice of
treatment modality (chemoreduction chemotherapy versus primary focal therapy with Laser), its
which laser to use subtype (532 nm versus 810 nm laser) and technique (sequential targeted laser
therapy from away inwardsfrom the tumor side opposite the fovea, shown in Figure 8). An intact
flat fovea after treatment guides the early start of amblyopia therapy even in eyes with severe
disease.31,32
It has been shown that OCT can help raise suspicionus of optic nerve invasion in with
peripapillary tumors..10,17,33 In OCT, suspected optic nerve invasion can present similarly to that of
optic nerve edema. The OCT appearance of optic nerve swelling is not necessarily pathognomic
for optic nerve invasion, but should be considered and ruled out as being highly suspicious.
Scar evaluation was the most common indication for OCT in our seriesstudy. This helpsOCT
distinguishes gliosis and scar from precise diagnosis of tumor recurrence , (isodense areas with
medium reflectivity, Fig 9) especially useful with versus gliosis. It determines the exact extent of
recurrence especially in white choroidal scars, where visualization of recurrence is challenging to
appreciate,;33 which that canand affect alter the choice of treatment modality. We have observed
that active tumor recurrence at the edge of a scar presents as isodense areas with medium
reflectivity (Fig. 9). Additionally, the lesion will present with localized thickening within several
consecutive B-scans. Medium gray, isodense, with localized retinal thickening in relation to
surrounding structures are more suspicious than areas that may be highly reflective, flat and/or
sharply demarcated.11
The current study is limited by being a single center, retrospective study, and. absence of
correlation to a quantifiable outcome. I, since it was not practical to correlate OCT sessions with
outcomes as eye salvage, vision salvage, life salvage, which are affected by many other factors
like (tumor location, number and type, stage at presentation, complications of treatments,
treatment duration, etc.). rather than a single OCT session decision. The pPresence of a single
OCT machine limited the number of sessions in some eyes due to occasional unavailability due to
maintenance or concomitant use by others.
Timeothersother surgeons. Time constraints may have affected the number of OCTs per eye
due to limited OR time. Training and academic interest may have increased the number of the
OCT sessions performed for some eyes.
In conclusion, multiple studies have reported OCT signs of retinoblastoma at presentation,
seeds, scar, fovea and optic nerve evaluation. To our Knowledgeknowledge, this is the first study
with the largest number ofto evaluate thed OCT sessions impact on to determine whether the
OCT was valuable in guiding the management decisions of active retinoblastoma. In 86% of all
studied OCT sessions, OCT imaging directed was useful in the management decisions. In 17% of
these OCT sessions, the OCT provided evidence that influencedstrongystrongly influenced
changing the clinical decisions, showing that OCT enhanceingd precision of management.
Acknowledgement
There are no conflicts of interests or disclosures. BLG is the unpaid medical director of Impact
Genetics.
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Figure Legends
Figure 1. Central tumors. (A) A perifoveal tumor mass (T1b24 or IIRC22 Group B) (is
isodense within the retinal layers; the exact foveal location is evident (*) ; maximal tumor height
of 0.75 mm (Informative, Directive and influential in guiding laser treatment) was over-estimated
on B-scan ultrasonography. (B) A peripapillary tumor (T1b24 or IIRC22 Group B) not involving
the fovea measured 1.36 mm in height on B-scan ultrasonography; OCT provided no additional
data (Non-informative). (C) A juxtafoveal tumor (T1b24 or IIRC22 Group B) measured 1.65 mm in
height on B-scan ultrasonography; OCT showed intact overlying retinal layers and minimal
surrounding subretinal fluid (arrow head) (Informative, Directive and confirmatory for diagnosis)
. (D) A larger central tumor (T1b24 or IIRC22 Group B) measuring 3.08 mm in height by B-scan
ultrasonography confirmey; OCT was Non-informative regarding both tumor internal architecture
and overlying retinal layers. In (B-D) tumors, calipers could not be accurately utilized to measure
tumor thickness, as the internal tumor boundary was ill defined.
Figure 2: OCT screening of posterior quadrants (superior, temporal, inferior, and nasal).
(A, B) An invisible lesion was seen (*) in the inferior quadrant scan; (C) reimaging centralized
the suspicious area (green 12mm x 12mm box) showing an isodense small tumor within the inner
nuclear layer (Informative, Influential for Diagnosis and Treatment).
Figure 3: First diagnosis of small tumors. (A-D):. (A - D) After detection on posterior pole
screening, small intra-retinal elevated isodense round tumors centralized on the inner nuclear
layer (T1a24 or IIRC22 Group A) were confirmed when reimaged centralized in a 12mm x 12mm
box (Informative, Influential for Diagnosis and Treatment).
Figure 4: Perifoveal tumors. The exact location of the foveal center (*) was located in
horizontal (green line) and vertical (green dotted line) scans with the foveal pit at the intersection.
The foveal center was (A) on top of tumor, (B) partially involved or (C) adjacent to the tumor
mass (Informative, Influential for Diagnosis and Treatment).
Figure 5: Pre-equatorial lesions. The eyes were deviated in the required direction with
complimentary tilting of the OCT scanner; peripheral indentation with scleral depressor was
helpful. (A) OCT of a peripheral nasal elevated isodense lesion. (B) OCT to evaluate a tumor tag
(*) vs vitreous seed revealed an unsuspected nearby edge recurrence (arrowhead) (Informative,
Directive, Influential for Diagnosis and Treatment). (C) Two months after both active tumors
were treated clinical exam and OCT showed that the tumor tag extending into vitreous had
increased in size, while the edge recurrence had completely disappeared (Informative, Directive,
Confirmatory). (Further laser and cryotherapy resolved the tag.)
Figure 6: Suspected tumor seeds. (A) Multiple white small masses in the macular area of an
eye harboring a large nasal tumor were shown by OCT to be preretinal vitreous seeds
(Informative/ Directive/ Influential for Diagnosis and Treatment). (B) Multiple yellowish spots in
an eye with treated retinoblastoma, were shown on OCT to be retinal calcified tumors in the
retina; an isodense inner nuclear layer lesion (*) was considered an active new tumor, thereby
treated with laser (Informative/ Directive/ Influential for Diagnosis and Treatment). Multiple
vitrouus seeds cast shadowing on the OCT (arrowheads). (C) A large white lesion (arrowhead)
inferior to large central tumor with inferior shallow retinal detachment in unilateral
retinoblastoma; due to its rounded appearance, it was considered as a separate primary tumor and
the eye was staged T2a24 or IIRC22 Group C; OCT showed a subretinal seed within the shallow
retinal detachment, upgrading the staging to T2b24 or IIRC22 Group D eye changing treatment
(Informative/ Directive/ Influential for Diagnosis and Treatment).
Figure 7. Exclusion of retinoblastoma in second eyes of unilateral retinoblastoma. (A)
Coloboma (arrowhead), (B) peripapillary thickening, and (C) a kinked vessel (*) could have been
misdiagnosed or mistreated, but were verified by OCT to be not retinoblastoma (Informative/
Directive/ Confirmatory (Influential) for Diagnosis and Treatment).
Figure 8. Sequential targeted Laser therapy (STLT) in juxtafoveal retinoblastoma. The
child presented with T2b24 or IIRC22 Group D eye with two large tumors; the central tumor was
juxtafoveal. (A) After six cycles of systemic chemotherapy, the fovea was visible on OCT; STLT
was initiated using 532 nm laser starting from the edge farthest from the fovea sequentially
moving inwards (direction of the arrows) avoiding the tumor nearest to the fovea (*). (B)
Appearance 6 months after starting STLT. (C) Appearance 12 months after starting STLT; the
fovea is further away from the tumor edge that can be treated. (D) 18 months after starting STLT
OCT showed a flattened lesion with preserved foveal pit; 18 months after last treatment the tumor
remains the same. (Informative/ Directive/ Confirmatory (Influential) for Diagnosis, Treatment,
Follow-up)
Figure 9 (A-C): Evaluation of tumor scars. (A) A clinically suspected recurrence in scar
(arrowhead) showed on OCT an isodense elevation of indicating active tumor, which was treated
with laser. The adjacent unsuspected scar showed a similar edge recurrence and was also treated.
(B) OCT detected tumor activity (arrow) hidden within areas of calcification (star). (C) OCT of 2
clinically suspicious white areas showed that the upper white area (*) was a flat scar (gliosis) and
the lower white area (arrow) was an elevated lesion. (Informative/ Directive/ Influential
(Confirmatory) for Diagnosis, Follow-up).
Figure 3: Foveal assessment
Figure 4: Peripheral lesions
Figure 5: Optic nerve head assessment
Figure 6: Exclusion of RB.
Figure 7: Level of tumor
Figure 8: Sequential targeted laser therapy
Figure 9: Scar evaluation
Table legends
Table 1: Demographic characteristics of the studied groupGroup.
Character
Patient
s Eyes
Laterality
Bilateral 36 53
Unilateral 8 10
Total 44 63
Genetics
Germline
Familia
l 11 20
Sporadi
c 25 34
Total 36 54
Mosaic 2 3
NonGermline 6 6
Tumour
status
RB 44 58
Stable 36
Salvage
d 37
Enucleated 9
Active 8* 10
No
RB 0 5
*onechildislostfollowup,RB:Retinoblastoma
Table 2: layers of Assessment for the OCT sessions based on its indication