Optical Coherence Tomography guided decisions in

retinoblastoma management

Sameh E. Soliman, MD,1,2 Cynthia VandenhovenVandenHoven,1 Leslie

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.

samehelsayedsoliman@yahoo.com

Authors’ contributions

Concept and design: Soliman, VandenHhoven, MacKeen, Heon, Gallie

Data collection: Soliman, VandenHhoven, MacKkeen.

Figures construction: Soliman, VandenHhoven.

Analysis and interpretation: Soliman, VandenHhoven, MacKkeen, Heon, Gallie.

Critical review: Soliman, VandenHhoven, MacKekeen, Heon, Gallie

Overall responsibility: Soliman, VandenHhoven, MacKkeen, Heon, Gallie

Financial Support: None

Conflict of Interest: No financial conflicting relationship exists for any author. BLG is an

unpaid medical director for Impact Genetics Inc.

Running head: OCT guided management in retinoblastoma management

Word count: / 3000 words

Numbers of figures and tables: 8 figures and 3 tables; 1 supplementary table

Key Words: retinoblastoma, Optical coherence Tomography, OCT, Cancer, Guide.

Meeting presentation: American Academy of Ophthalmology meetingAAO

presentation (Chicago 2016)

Abstract: (299/350 words)

Purpose: Assess Optical coherence Tomography (OCT) role in management

decisions guiding diagnosis, treatment and follow-up of retinoblastoma during

active treatment period.

Design: Retrospective non-comparative single institution case series.

Participants: All newly diagnosed retinoblastoma children from January 2011 to

December 2015 that had an OCT imaging session during their active treatment

at SickKids hospital in Toronto. OCT sessions for fellow eyes of unilateral

retinoblastoma without any suspicious lesion and those performed after 6 months

from the last treatment were excluded.

Methods: Data collected included age at presentation; sex, family history, RB1

mutation status, International intraocular retinoblastoma classification (IIRC),

number of OCT sessions per eye. Details of each session were reviewed for

indication-related details (informative or not) and assessed for being guiding

(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: Forty-four children (63 eyes) had 339 OCT sessions (median=5/eye,

range 1-15). Younger children at presentation and hose with positive RB1

mutation had significant higher number of OCT sessions. Common indications

included evaluation of post-treatment scar (55%) or fovea (16%), and posterior

pole scanning (11%). Informative sessions were 92% (312/339) and the main

cause was large or elevated lesion in 70% of non-informative sessions (19/27);

74% of which (14/19) were for IIRC group D or C eyes at presentation. OCT

guided management decisions in 94% (293/312) of informative sessions (54%,

25%, 15% guided treatment, follow-up and diagnostic decisions respectively).

Influential OCT guidance (OCT data changed the pre-OCT clinical decision) was

noted in 17% and 15% of directive and all OCT sessions respectively.

Conclusions: OCT 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: (35/35 words)

Precis:

Retrospective Review of 339 OCT sessions 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 treatment, follow up

and diagnosis in 9086% of sessionseyes.

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) has 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

Features of Retinoblastoma; the most common pediatric ocular malignancy; were better

appreciated in the recent years with the introduction of the handheld OCT that which can be used

while the supine child is under anesthesia during the active management of their

condition .condition. 5-8 There are multiple published reports on the value of OCT in

Retinoblastoma in detection of small invisible tumors,9-129- 12( Add Bremner as 9) foveal

evaluation,13,14 localization and microstructure of tumor seeds15 and detection of optic nerve

infiltration.8,16 It is documented to help in assessment of tumor anatomy, scar edges and

simulating conditions11,17-19 (e.g. Retinoma or Astrocytoma).

Despite these various benefits, handheld OCT is still not commonly used except in some highly

ranked ocular oncology centers.5,20 In the current Canadian Guidelines20 for retinoblastoma

management we define the center that has an 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 presented

to and managed in the Hhospital for Ssick Cchildren, 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 Retinoblastoma that who had received OCT imaging during their

management were reviewed. Fellow eyes of unilateral retinoblastoma without any suspicious

lesion and had a single OCT session at presentation were excluded. OCT sessions performed

after 6 months from the last treatment were excluded.

Data collection

The data collected included age at presentation, sex, family history, laterality, International

Iintraocular Rretinoblastoma Cclassification (IIRC)21 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 single eye using the OCT during an examination under

anesthesia for one or more indications. During 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 machines

for resolution or depth. We did not receive sponsorship or financial support to conduct this

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 two highly skilled mMedical Imaging

sSpecialists (authors CV and LM), following a standardized methodology for improved

longitudinal reproducibility.

DefinitionsTe and technical considerations and indications 22-25

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 produces the associated C-scan fundus image

otherwise called the Sum Voxel Projection or SVP. Calipers were sometimes placed on the OCT

B-scan image revealing the retinal position on the SVP image so that the area of interest can be

correlated to the specific retinal position. Calipers were also used to measure tumor height in

some instances. (Fig. 1) This allows for thorough assessment across a large retinal area without

large gaps between OCT Bscans. While it has been reported that applying extensive algorithms to

improve image quality via oversampling and averaging of multiple scans25 25 , in our practice, The

majority of scans produced were unaveraged single line volume scans which producedproduced

both rapid and, high quality images with ample detail to provide the clinical information to guide

diagnostic decision making. In our practice, the production of averaged OCT images to achieve

higher quality images was rarely yielded increased diagnostic information.

The While highly averaged scans produce little extra clinicial information, the production of

volume scans was highly relevant in that the accumulation of individual 100 Bscan produces the

associated Cscan fundus image otherwise called the Sum Voxel Projection or SVP 25. The SVP

image is critical for identification and localization of OCT findings to retinal anatomy and

pathology 25. Calipers can be placed on the OCT bscan image revealing the retinal position on the

SVP image so that the area of interest can be correlated to the specific retinal position for focal

treatment purposes. Additionally, the SVP image provides information about the quality of the

scan and in real-time the OCT operator can assess this imagrespond withe to make hand-held

scanner positional adjustments to improve subsequent scans.

Posterior pole scanning assessment (Fig. 2) is indicated in infants (≤ 6 months of age) to screen

for a new pre-clinical or “invisible” tumor by obtaining screening with 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 scanner

placement achieving tumor centration within the OCT frame. (Fig.3) (Figures 1-2)

Foveal assessment is indicated in foveal and perifoveal tumors to locate the foveal center by

obtaining a horizontal macular volumetric scan. As needed, this scan is followed by a vertically

oriented foveal volume scan whereby, 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 consequently rotated 90 degrees indicating the scan direction

change. (Fig.ure 34)

When scanning parafoveally, the handheld probe is angled towards the area of interest. If the

lesion is small in size, it can be ideal to reduce the area of scan volume to 8x8 or 6x6 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 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 54)

Assessment layers

OCT will be assessed first as being informative if it provides sufficient data about the main

indication for scanning; and being directive if the information provided from the OCT imaging

helped guiding guide the management decision affecting either diagnosis, treatment or follow-up.

Directive guidance can be confirmatory if it confirms the pre-OCT clinical decision or

influential if the information provided changed a pre-OCT clinical decision. Every OCT session

during the active treatment phase will be collected and assessed for all layers.

Decision guiding

Guidance is either in diagnosis, treatment or follow-up.

Diagnostic confirmatory guidance was considered when OCT confirms; a) tumor mass

in clinically suspicious area(s), b) clinical IIRC21 grouping or c) posterior pole screening

in positive germ line mutations up to six months of age. Diagnostic influential guidance

was considered if OCT; a) excluded tumor in clinically suspicious area(s), b) changed

IIRC21 grouping or c) detected an invisible tumor during posterior pole screening.

Treatment confirmatory guidance was considered if OCT confirmed a) clinically

suspicious new or recurrent tumor, or b) showed anatomic details (fovea, scarring, seeds,

traction…etc.) supporting the decided treatment plan. Treatment Influential guidance

was considered if OCT a) showed an unsuspected recurrent tumor within a tumor scar, b)

showed anatomic details mandating changing or cessation of the treatment modality or

plan.

Follow-up confirmatory guidance was considered if the OCT showed no change from

the last scan in absence of active treatment. Follow up influential guidance was

considered if OCT showed anatomic details excluding activity leading to change of

clinically decided treatment.

Results:

Patient Demographics

This review included 339 OCT sessions for 63 eyes of 44 children with Retinoblastoma (26 were

male, 59%). Eight children (10 eyes) are still under active treatment from which one child (one

eye) was lost to follow up. Demographic data are summarized in table 1. The median number of

OCT sessions per eye is 5 sessions (range: 1-15 sessions). Familial eyes had a significantly higher

median session number of 7 versus 4 sessions to non-familial 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 at presentation required more OCT sessions (r=-0.26, p=0.04).

The most common indication was tumor scar evaluation in 55% (186/339) 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 table 2. What are the types of the

OCT machines for the duration 2011-2016?

OCT Assessment

Informative versus Non-informative OCT

Informative OCT was found in 92% of evaluated sessions (312/339). In 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) was IIRC D or C at first tumorpresentation. In 2 eyes, there was loss of the

informative status of the OCT after multiple previous informative OCTs due to progression of

the central tumor in one eye and tractional retinal detachment in another eye.

Directive Versus Non-Directive OCT

Directive OCT was found in 86% (293/339) of all OCT sessions and in 94% (293/312) of

informative sessions. OCT directed treatment, diagnosis or follow up in 54% (168/312), 15%

(46/312) and 25% (79/312) of informative sessions respectively. In 19 sessions, the

information given was not important in directing management decisions. The main cause was

performing non-indicated OCT (17/19) or OCT performed for academic interest (2/19). (Table

3)

Confirmatory versus Influential OCT

Confirmatory OCT was found in 83% (243/293) of directive sessions and guided treatment,

diagnosis and follow up of 58%, 16% and 26% of confirmatory sessions respectively.

Influential OCT was found in 17% (50/293) of directive sessions and guided treatment,

diagnosis and follow up of 54%, 14% and 32% of influential sessions. Different OCT

influences are shown in table 3.

Discussion

The introduction of OCT in retinal imaging has shown its effectiveness in guiding management

(diagnostic and therapeutic) decisions in multiple conditions as macular holes2, macular edema1

(diabetic and vascular) and age related macular degeneration.3,4 Multiple reports were published

showing the OCT differences between ocular tumors and how it can be useful to differentiate

simulating lesions.7-11,13-15,17-19,22,26

Ideally, OCT is performed prior to other contact imaging that may inadvertently impair the

corneal clarity providing clear view of fundus. Operator sits at 12 o’clock position of the supine

patient with the OCT monitor placed so that an optimal view of the patient and screen can be

achieved. Handheld OCT scanner is pivoted approximately 1 cm above the cornea, the optimal

working distance, aiming the scanning beam through the pupillary center.24 While it is possible to

utilize an armature to aid in the stabilization of the handheld probe, it can also be manually held

with finger and thumb placed between the probe tip and the patient’s brow and cheek bone 25 .

This allows for consistent maintenance of the typical working distance between longitudinal

sessions and allows for a stable imaging positioning. Handheld OCT scanner is pivoted

approximately 1 cm above the cornea aiming the scanning beam through the pupillary center.

Manually holding the OCT probe is the preferred method of the authors as it provides the greatest

flexibility and ease of use to angle the probe towards the areas of interest. Additionally by

handholding the probe, the operator is able to increase the probe to eye working distance in real

time while scanning over the apex of larger lesions.

Handheld OCT scanner is pivoted approximately 1 cm above the cornea aiming the scanning

beam through the pupillary center. Frequent application of 0.9% NaCl solution prevents corneal

dryness. Image quality and scan brightness is achieved by a combination of factors, including

manual aAdjustment 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. working

distance to the axial length according to the child age help better image quality.24 and fFrequent

application of 0.9% NaCl solution prevents corneal dryness.

The production of averaged OCT scans allowed for thorough assessment across a large retinal

area without large gaps between OCT B-scans. In our practice, single line volume scans produced

both rapid and high quality images with ample detail to provide information. It has been reported

that extensive algorithms might be applied to improve image quality via oversampling and

averaging of multiple scans.25 In our practice, the production of averaged OCT images to achieve

higher quality images rarely yielded increased information. Additionally, the SVP image provides

information about the quality of the scan and in real-time the OCT operator can respond with

positional adjustments to improve subsequent scans.

At presentation, we showed that OCTs provide limited information of eyes with IIRC21 group C

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.24 Eyes with IIRC21 groups A and B are easily scanned

even in the mid periphery22 (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 IIRC21 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 (IIRC21 group B or C) to a seeding unifocal mass with IIRC23 group D.

The verification of vitreous tumor seeds by OCT15 helps better grouping(what do you mean by

this??)helped accurate IIRC21 grouping and affects the choice of treatment modality (intra-vitreal

chemotherapy)27,28.

Detection of small and sometimes invisible tumors9,11 (Fig. 2-3) has changed the visual outcome

especially in familial retinoblastoma.23 This leads to earlier detection and control with less

treatment burden (focal therapy only) and less retinal damage. In familial cases under 3 months of

age, detection of the first tumor can modify the follow up plan to include EUA instead of clinic

visits.20,23

In unilateral retinoblastoma, OCT helps differentiation of suspicious lesions from retinoblastoma

(Fig. 7) in the fellow eye. Previously, this depended on clinical examination or B-scan

ultrasonography, which does not show the inner architecture of the lesion. Sometimes,Lacking

invivoin-vivo evidence of the nature of these suspicious lesions, presumably many such lesions

were treated and falsely changing the diagnosis of this child into bilateral retinoblastoma, which

has a totally different follow-up, schedule with multiple unnecessary examinations under

anesthesia.20

Foveal pit detection (Fig. 4) provides an important clue about visual potential in perifoveal

tumors.13 Its localization respective to the tumor location can affect choice of treatment modality

(chemoreduction versus primary focal therapy with Laser), its subtype (532 nm versus 810 nm

laser) and technique (sequential targeted laser therapy from away inwards shown in Figure 8). A

flat fovea after treatment guides the early start of amblyopia therapy even in eyes with severe

disease.29

It has been shown that OCT can help raise suspicious of optic nerve invasion in peripapillary

tumors.8,16,30 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 series. This helps precise

diagnosis of tumor recurrence versus gliosis. It determines the exact extent of recurrence

especially in white choroidal scars, where visualization of recurrence is challenging to

appreciate;30 which that can affect 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. Absence of correlation

to a quantifiable outcome, since it was not practical to correlate 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 rather than a

single OCT session decision. Presence 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.

Timeothers. 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 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 of evaluated OCT sessions to determine whether the OCT was valuable in guiding

the management decisions of active retinoblastoma. In 86% of studied OCT sessions, OCT

imaging directed the management decision. In 17% of these sessions, OCT provided evidence

that influenced changing the clinical decision, showing that OCT enhanced 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 (A-D): OCT assessment of central tumors. (A) A perifoveal tumor mass

(IIRC21 group B) is seen in the colored fundus image appearing as an isodense tumor

within the retinal layers and the exact location of the foveal pit can be appreciated

(*). A caliper was used to measure the maximal tumor height of 0.75 mm which was

not appreciated on B-scan ultrasonography. (B) A peripapillary tumor mass (IIRC21

group B) not involving the foveal center is seen in the colored fundus image and

measuring 1.36 mm in height on B-scan ultrasonography. OCT provide minimal

information (non-informative) regarding the tumor internal architecture. (C) A

juxtafoveal tumor mass (IIRC21 group B) is seen in the colored fundus image and

measuring 1.65 mm in height on B-scan ultrasonography with OCT showing intact

overlying retinal layers and minimal fluid collection on its sides (arrow head). (D) A

larger central tumor mass (IIRC21 group B) measuring 3.08 mm in height by B-scan

ultrasonography and non-informative OCT regarding both tumor internal

architecture and overlying retinal layers. In (B-D) tumors, calipers cannot be

accurately utilized to measure tumor thickness, as the internal tumor boundary is ill

defined.

Figure 2: Posterior pole assessment. OCT imaging along the four quadrants

(superior (S), temporal (T), inferior (I) and nasal (N)). An invisible suspicious lesion

was seen (*) in the inferior quadrant and reimaged with suspicious area centralized

in the green (12mm x 12mm) box showing an isodense small tumor within the

retinal layers to be treated by focal laser therapy under OCT guidance.

Figure 3 (A-D): OCT appearance of small tumors. After posterior pole assessment,

the lesion is centralized in a 12mm x 12mm box and reimaged. A-D scans show

different eyes that presented with a small tumor (IIRC21 group A). All tumors appear

as an elevated isodense rounded lesion within the retinal layers with intact retinal

pigment epithelium (RPE) line.

Figure 4 (A-C): Foveal assessment. In perifoveal tumors, the exact location of the

foveal center (*) is located by having 2 scans (one horizontal and one vertical), the

fovea is identified by the two intersecting approximately perpendicular scans

containing the foveal pit. This foveal center can be overlying tumor (A), partially

involved (B) or non-involved by the tumor mass.

Figure 5 (A-C): OCT imaging in pre-equatorial lesions. OCT can verify elevated

tumor masses in the pre-equatorial region by deviating the globe in the required

direction with complimentary tilting of the OCT scanner. A peripheral indentation

using scleral depressor may be helpful. (A) A peripheral nasal tumor can be OCT

scanned showing an elevated isodense lesion. (B) A suspicious tumor tag (*) was

OCT scanned to show a nearby edge recurrence (arrowhead) that was not clinically

suspected (influential treatment guidance) while the tag can be seen. (C) After 2

months the vitreous tumor tag can be clinically noted to be increasing in size. The

OCT confirmed growth by increasing tag size from previous scan with complete

disappearance of the edge recurrence.

Figure 6: OCT appearance of suspected tumor seeds. (A) Multiple white small

masses can be seen in the macular area of an eye harboring a large nasal tumor,

proven by OCT to be preretinal vitreous seeds. (B) Multiple yellowish white masses

in an eye with treated retinoblastoma, proven by OCT to be retinal calcified lesions

with an isodense lesion (*) that might be active and need treatment. (C) A large

white lesion (arrowhead) inferior to large central tumor in an eye of a unilateral

retinoblastoma with inferior shallow retinal detachment. Clinically and due to its

rounded appearance, it was initially considered as a separate tumor and the eye was

grouped as IIRC21 group C. OCT showed that the mass is a subretinal seed within the

shallow retinal detachment. That upgraded the grouping to IIRC21 group D eye with

different treatment chemotherapy protocol (Influential diagnostic guidance).

Figure 7. Exclusion of Retinoblastoma by OCT in fellow eyes of unilateral

retinoblastoma. Fellow eyes might have a suspicious lesion as (A) a coloboma

(arrowhead), (B) peripapillary thickenng and (C) a kinked vessel (*) that may be

misdiagnosed or mistreated as a retinoblastoma and can be verified by OCT imaging

to be not retinoblastoma.

Figure 8 (A-D): Sequential targeted Laser therapy (STLT) in juxtafoveal

retinoblastoma. The child presented with IIRC21 group D eye with two large

tumors. The central tumor was juxtafoveal. (A) Appearance after six cycles of

systemic chemotherapy. The fovea can be appreciated by OCT. the decision of STLT

using 532 nm Laser starting from the farthest edge from the fovea and converging

inwards (direction of the arrows) avoiding the tumor nearest to the fovea (*). (B)

Appearance after 6 months from starting STLT. (C) Appearance after 12 months

from starting STLT and the fovea is now away from the tumor edge that can be

treated. (D) 18 months after starting STLT showing a flattened inactive lesion with

preserved foveal pit. The child show the same appearance as D now after 18 months

from last treatment session.

Figure 9 (A-C): OCT evaluation of tumor scars. (A) OCT evaluation of a clinically

suspected edge recurrence (arrowhead) showed an isodense elevation of moderate

reflectively showing active tumor. Another adjacent unsuspected scar showed a

similar appearance (Influential treatment guidance). (B) OCT can identify areas of

suspected activity (arrow) from areas of calcification (star). (C) OCT of 2 clinically

suspicious white area showed that the upper white area (*) is a flat scar (gliosis)

and the lower white area (arrow) to be an elevated lesion.

Figure1: New tumors (??post. pole screening)

Figure 2: Central tumors

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 group.

Character Patients Eyes

LateralityBilateral 36 53

Unilateral 8 10Total 44 63

GeneticsGermline

Familial 11 20Sporadic 25 34

Total 36 54Mosaic 2 3

Non Germline 6 6

Tumour statusRB 44 58

Stable 36Salvaged 37Enucleated 9

Active 8* 10No RB 0 5

* one child is lost follow up, RB: Retinoblastoma

Table 2: layers of Assessment for the OCT sessions based on its indication

IndicationNon-

Informative

Informative

TotalNon-

Directive

Directive

Treatment Diagnosis Follow up TotalConfirm Influence Confirm Influence Confirm Influence Confirm Influence

N % N % N % N % N % N % N % N % N % N % N %Scar evaluation 12 44 0 0 99 70 17 63 0 0 1 14 43 68 14 88 142 58 32 64 186 55Posterior pole screening 1 4 11 58 0 0 0 0 19 49 1 14 6 10 0 0 25 10 1 2 38 11Foveal assessment 2 7 6 32 26 18 8 30 2 5 1 14 8 13 1 6 36 15 10 20 54 16ONH assessment 5 19 1 5 8 6 0 0 2 5 0 0 5 8 1 6 15 6 1 2 22 6New tumor evaluation 2 7 0 0 3 2 0 0 12 31 0 0 0 0 0 0 15 6 0 0 17 5Main tumor evaluation 5 19 1 5 4 3 1 4 1 3 1 14 0 0 0 0 5 2 2 4 13 4Others

Seed assessment 0 0 0 0 1 1 0 0 1 3 2 29 0 0 0 0 2 1 2 4 4 1Treatment complication 0 0 0 0 0 0 1 4 1 3 0 0 1 2 0 0 2 1 1 2 3 1

Suscpicious lesion 0 0 0 0 0 0 0 0 1 3 1 14 0 0 0 0 1 0 1 2 2 1

Total (n) 27 100 19 100 141 100 27 100 39 100 7 100 63100 16 100 243

100 50 100 339 100

Table 3: Causes of different OCT assessment layers.

OCT Assessment Causes N %

Non informative

Large tumor/elevated lesion¶ 19 70Peripheral lesion 4 15

Retinal detachment 2 7Media Opacity 1 4

Awake child 1 4Total 27 100

Non DirectiveDoubtful indication 17 89Academic interest 2 11

Total 19 100

Directive Influential

DiagnosisExclude RB* 1 2

Upstage Clinical grouping § 2 4Invisible tumors £ 1 2

Modify treatment plan # 2 4Recurrence versus Gliosis ¥ 1 2

Follow upNo treatment required 16 32

TreatmentModify treatment plan 16 32

Stop CT 2 4Give CT (IAC/IVC) 3 6Specialized FT # 11 22

Retreatment (Recurrence) 8 16Enucleate 3 6

Total 50 100CT: Chemotherapy; FT: Focal therapy; IAC: Intra-arterial chemotherapy; IVC: Intra-venous chemotherapy¶Figure12; *Figure 76; § Figure 67; £ Figure 2-31 ; ¥ Figure 9; ♯Figure 8