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TRANSCRIPT
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, FRCSC1,3,5,6-5
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.
4Departments of Molecular Genetics and Medical Biophysics, Faculty of Medicine,
University of Toronto, Toronto, Ontario, Canada. Department 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.
Authors’ contributions
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.
Critical review: Soliman, VandenHoven, MacKeen, Héon, Gallie
Overall responsibility: Soliman, VandenHoven, MacKeen, Héon, Gallie
Concept and design: Soliman, VandenHoven, MacKeen, Heon, Gallie
Data collection: Soliman, VandenHoven, MacKeen.
Figure construction: Soliman, VandenHoven.
Analysis and interpretation: Soliman, VandenHoven, MacKeen, Heon, Gallie.
Critical review: Soliman, VandenHoven, MacKeen, Heon, Gallie
Overall responsibility: Soliman, VandenHoven, MacKeen, Heon, Gallie
Financial Support: None
Conflict of Interest: No financial conflicting relationship exists for any author.
Running head: OCT guided retinoblastoma management
Word count: 21412 / 3000 words
Numbers of figures and tables: 98 figures and 3 tables; 1 supplementary table
Key Words: retinoblastoma, Optical coherence Tomography, OCT, Cancer,
Guide.
Meeting presentation: American Academy of Ophthalmology Annual Meeting
presentation (Chicago 2016, Monday 17th October 2016)
Abstract: (296185308/350 words)
Purpose: Assess the role of handheld Optical Ccoherence Tomography (OCT) role in
guiding management decisions during guiding diagnosis, treatment and follow-up of
eyes affected by 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 (SickKids) 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 (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 per eye (median =5,
range 1-15/eye, range 1-15). Younger Children Age at presentation and the presence
ofhose with positive a heritable RB1 mutation had significantly higher number
ofincreased the number of 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 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 the informative sessions, OCT guideddirected management treatment
decisions in 94% (293/312) of informative sessions (54%, (58%), diagnosis (16 %) and
follow-up (265%). , 15% guided treatment, 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.
AAO submitted abstract
Purpose: Assess Optical coherence Tomography (OCT)
role in management decisions guiding diagnosis,
treatment and follow-up of retinoblastoma.
Methods: Retrospective study of retinoblastoma
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: (3535/35 words; 226/460 characters)
We determined impact of handheld optical coherence tomography in retinoblastoma
management:
Precis:
94% of 339 OCT sessions contributed indication-related details in 63 affected eyes/ 44
patients;Retrospective 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 care;treatment, follow up and diagnosis in 9086% of
sessions and 15% influenced change in management.eyes.
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.
Optical Ccoherence Tomography (OCT) hasis well established asto playinging an
integralimportant role in ophthalmic patient assessment, improvingleading to improved diagnostic
accuracy and thus therapeutic decisions 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 usedperformed 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 studied had at 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). The extent cancer in each eye was retrospectively defined by the
2017 8th edition AJCC TNMH cancer staging.23
OCT Session and Systems
We defined aAn 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 improvedgood longitudinal
reproducibility.
DefinitionsTe and technical considerations and indications {24-27
OCT was performed with operator at 12 o’clock position of the supine patient. The Handheld
OCT scanner was pivoted approximately 1 cm above the cornea, the optimal working distance,
aiming the scanning beam through the pupillary center.26 Manually holding the OCT probe was
preferred as it provides the greatest flexibility and ease of angling the probe towards the areas of
interest. AdditionallyBy manually holding the scanner, the operator iswas 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 achievedoptimized 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;.26 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
researchWithinFor 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 provideds critical information about the quality of the scan and so the
OCT operator could respond in real-time the OCT operator can respond with positional
adjustments to improve subsequent scans. Additionally, When ClarificationTo clarify of
pathology localization wasis frequently required; , calipers were sometimescan bewere placed on
the OCT B-scan image to revealing the retinal position on the SVP image so that the precise area
of interest can be correlated to the specific retinal position. Calipers were also usedand 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 extensiveAlthough
algorithms might be applied to improve image quality via oversampling and averaging of
multiple scans,.27 In our practice, wwe routinely captured single line volume scans as they
achieved both rapid and high quality images with ample clinical 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.
Forinfants (≤ 6 months of ageTo assess the posterior pole) (Fig 2) to screen for a new pre-
clinical or “invisible” tumor in infants less than 6 months of age, we by obtaining screening
withused the widest volumetric scan settings available. In our center, weWe performed 9 mm x 9
mm scans with the( Envisu C2200 system) and 12 mm x 12 mm scans with( Envisu C2300
system) of fovea, optic nerve, temporal, superior and inferior quadrants. If a tumor is was
identified, the scan is was repeated with the scanner placement achieving tumor centration
centered within the OCT frame. (Fig .2, 33). (Figures 1-2)
Foveal assessment is indicated In For 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 handheldthe 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 probescanner is was angled
pointed towards the area of interest. Increased resolution for small If the lesions is small in size, it
can be ideal towas obtained by reducinge the the area of scan volume area to 8 x 8, or 6 x 6, to
maximizing thee 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
probescanner 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 being Directive if the information
provided from the OCT imaging helpedobtained guiding guided the management decisions
affecting either diagnosis, treatment or follow-up. Directive guidance that confirmed the pre-OCT
clinical decision can bewas considered Confirmatory, if it confirms the pre-OCT clinical decision
orand 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 (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 includingc) posterior pole screening in positive
germ line mutationschildren less that 6 months of age known to carry an RB1 mutant allele; 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 planned 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 aswhen 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),. 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 recieved 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?
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 cT2a23 or cT2b23 (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
or 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 or follow-
up 16/293 (7%) (Table 2). of 54%, 14% and 32% of influential sessions. Different OCT
influences are shown in table 3The most Influential OCT sessions were for scar and foveal
evaluation (Table 3).
OCT provided limited information in eyes with that were staged cT2 (TNMH 8th edition23)
(IIRC22 Group C, D) or with large tumors, due to absorption of optical signal by dense lesions and
lesion elevation beyond the scan capacity.26 Eyes staged cT123 (IIRC22 Groups A and B) were
easily scanned up to the mid periphery25 (Fig 5). OCT assessed well the location of tumor with
respect to retina: intra-retinal, pre-retinal, vitreal or subretinal (Fig 6). This supported accurate
TNMH23,24 or IIRC22 staging, for example, suspected tumor separate from the primary tumor was
shown by OCT to be subretinal tumor extension, not an independent new tumor (Fig 6C). This
influenced the diagnosis from multifocal tumor to seeding of a unifocal tumor. The verification of
tumor seeds by OCT16 also affected the choice of treatment modality (i.e., intra-vitreal
chemotherapy)28,29.
Discussion
The introduction of OCT in retinal imaging has been shown its effective ness in guidingto guide
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.5,6,9-12,14-16,18-20,25
At presentation, we showed that OCTs provide limited information of eyes where the with is
T225 (TNMH 8th edition23) equivalent toIIRC22 group C or higher or higher and of individual large
tumors are usually non-informative regarding large tumor. s, Thetumors. The optical signal is
absorbed through 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.26 Eyes with T125 tumors (IIRC22 groups A and B) are easily scanned even in the mid
periphery245 (Fig. 1,2,4). OCT helps assessing the level of the tumor whether intra-retinal, pre-
retinal, vitreal or subretinal (Fig. 6). This allows more accurate TNMH23,25 or IIRC22 grouping in
certain eyes where a suspected tumor mass away from the primary tumor is shown to by OCT to
be a subretinal mass versus and not a new separate tumor (Fig 6C). This changes the diagnosis
from a multifocal tumor (IIRC22 group B or C) to a seeding unifocal mass with IIRC22group D.
The verification of vitreous tumor seeds by OCT16 helps better grouping(what do you mean by
this??)helped accurate IIRC22 grouping and affects the choice of treatment modality (i.e.intra-
vitreal chemotherapy)28,29.
Detection of small and sometimes invisible tumors5,11 (Fig. Fig 2-3), has changedchanges the
visual outcome especially in familial retinoblastoma,. This leads to achieving eEarlier tumor
detection and control with less treatment burden (focal therapy only) and less retinal damage.24 In
familial casesFor children at risk of familial retinoblastoma under 3 months of age, detection of
the first invisible tumor by OCT can facilitated early, minimalized therapy.24 {Fe-Bornstein, 2002
#12863}29modify the follow up plan to include EUA instead of clinic visits.21
In unilateral retinoblastoma, OCT helpeds 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 retina and lesion. Sometimes,LackingWithout invivoin-vivo evidence of the nature of these
suspicious lesions, presumably many such lesions were may have been treated treated with focal
therapy, 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 and life-long surveillance for second cancers.21,30
Foveal pit detection (Fig. Fig 4) provides an important clueinformation 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 (ie, sequential
targeted laser therapy from away inwardsfrom the tumor side opposite the fovea, shown in
Figure 8). An intact flat fovea after treatment guides suggests benefit of the early start of
amblyopia therapy even in eyes with severe disease.31,32
It has been shown that OCT appearance can may 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 but may fail to distinguish tumor from
papilledemaOCT 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 thereby 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, with. absence of
correlation to a quantifiable outcome. I, since it was not practical to correlate OCT sessions with
outcomes such 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
related 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, and we took this into account in scoring the impact of the
OCT session.
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 (cT1b23, or IIRC22 Group B) (iswas
isodense within the retinal layers; the exact foveal location is was evident (yellow *) ; 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 (cT1b23 , 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 (cT1b23 b{Soliman, In
Press #18014}, 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) OCT on aA large er central
tumor (cT1b23 , or IIRC22 Group B) measuring 3.08 mm in height by on B-scan ultrasonography
was Confirmatoryey; 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 outer tumor boundary was ill defined.
Figure 2.: OCT screening of posterior quadrants (superior, temporal, inferior, and nasal). (A,
B) An invisible lesion was seen found (white **) in the inferior quadrant scan; (C) reimaging
centralized on the suspicious area (green 12mm x 12mm box) showeding an isodense small tumor
within the inner nuclear layer (Informative, Influential for diagnosis and treatment).
Figure 3.: First diagnosis of small tumors. (A - D) After detection on posterior pole screening,
small intra-retinal elevated isodense round tumors centralized on the inner nuclear layer
(cT1a23 {Soliman, In Press #18014} 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 (yellow **) was located in
horizontal (green line) and vertical (dotted 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
(yellow *) vs vitreous seed revealed an unsuspected nearby edge recurrence (arrow) (Informative,
Directive, Influential for diagnosis and treatment); . (C) tTwo months after both active tumors
were treated, clinical exam and OCT showed that the tumor tag (white *) extending into vitreous
had increased in size, while the edge recurrence (arrow) had completely disappeared was a flat
scar (Informative, Directive, Confirmatory); . (fFurther laser and cryotherapy resolved ablated the
tumor 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 with shadowing (arrows)
tumors in the retina; an isodense inner nuclear layer lesion (white **) 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 A large
white lesion (arrowwhead) inferior to large central tumor with inferior shallow retinal detachment
in unilateral retinoblastoma; was considered likely to be a separate primary tumordue to its
rounded appearance, so, it was considered as a separate primary tumor and the eye was staged
cT2a23 ( or IIRC22 Group C); OCT showed a this to be subretinal seeding within the shallow
retinal detachment, upgrading changing the initial staging to cT2b23 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 a cT2b23 ( or IIRC22 Group D) eye with two large tumors; the central tumor was
juxtafoveal; . (A) aAfter 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)
aAppearance 6 months after starting STLT;. (C) fovea was further away from the tumor edge
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 remaineds the same . (Informative/ Directive/
Confirmatory (Influential) for diagnosis, treatment, follow-up). Fovea marked by yellow *.
Figure 9 (A-C).: Evaluation of tumor scars. (A) OCT of aA clinically suspected recurrence in
scar (white arrow*head) showed on OCT an isodense elevation of indicating active tumor; , the
adjacent scar showed an unsuspected similar edge recurrence; both which waswere 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
two clinically suspicious white areas showed that the upper white area (white *) was a flat scar
(gliosis) and the lower white area (arrowwhite *) was an elevated lesiona tumor. (Informative/
Directive/ Influential (Confirmatory) for diagnosis and, 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 GroupClinical, Genetic and Tumor
characteristics..
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
Character Patients
Laterality
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
Treatment complication 0 0 0 0 0 0 1 4 1 3 0 0 1 2 0 0
Suscpicious lesion 0 0 0 0 0 0 0 0 1 3 11
4 0 0 0 0
Total (n)2
7 1001
91
001
411
002
71
003
91
00 71
006
31
001
61
00 43
Table 2: Stratification of different OCT assessments in diagnosis, treatment and follow up with indication for OCT imaging.. blah blah…..
Table 3.: Causes of different OCT assessment layers.
OCT
Assessment Causes N %
Non informative
Largetumor/elevatedlesion¶
1
9 70
Peripherallesion 4 15
Retinaldetachment 2 7
MediaOpacity 1 4
Awakechild 1 4
Total
2
7
10
0
Non Directive
Doubtfulindication
1
7 89
Academicinterest 2 11
Total
1
9
10
0
Directive
Influential
Diagnosis
ExcludeRB* 1 2
UpstageClinicalgrouping§ 2 4
Invisibletumors£ 1 2
Modifytreatmentplan# 2 4
RecurrenceversusGliosis¥ 1 2
Table 3. Causes of different OCT assessment layers.