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 Brenda L. Gallie, MD, FRCSC1,3-5
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.
5Division of Visual Sciences, Toronto Western Research Institute, 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
Financial Support: None
Conflict of Interest: No financial conflicting relationship exists for any author.
Running head: OCT guided retinoblastoma management
Word count: 2170 / 3000 words
Numbers of figures and tables: 9 figures and 3 tables; 1 supplementary table
Key Words: retinoblastoma, Optical coherence Tomography, OCT, Cancer,
Meeting presentation: American Academy of Ophthalmology Annual Meeting presentation
(Chicago 2016, Monday 17th October 2016)
Abstract: (296/350 words)
Purpose: Assess the role of handheld Optical Coherence Tomography (OCT) in guiding
management decisions during diagnosis, treatment and follow-up of eyes affected by
retinoblastoma.
Design: Retrospective non-comparative single institution case series.
Participants: All children newly diagnosed with retinoblastoma from January 2011 to
December 2015 who 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 more than six months after
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
scored for indication-related details (informative or not) and assessed for guidance (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, 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). Age at presentation and the presence of a heritable RB1 mutation significantly increased
the number of OCT sessions. Indications included evaluation of post-treatment scar (55%) or
fovea (16%), and posterior pole scanning for new tumors (11%). Of all sessions 92% (312/339)
were informative; 19/27 non-informative sessions had large, elevated lesions; of these, 14/19
were T2a or T2b (IIRC Group C or D) eyes. In 94% (293/312) of the informative sessions, OCT
directed treatment decisions (58%), diagnosis (16 %) and follow-up (26%). OCT influenced and
changed management from pre-OCT clinical plans in 15% of all OCT sessions.
Conclusions: OCT improves accuracy of clinical evaluation in retinoblastoma management.
Précis: (35/35 words; 226/460 characters)
We determined impact of handheld optical coherence tomography in retinoblastoma
management: 94% of 339 OCT sessions contributed indication-related details in 63 affected
eyes/ 44 patients; 86% significantly guided care; and 15% influenced change in management.
Optical Coherence Tomography (OCT) is well established to play an important role in ophthalmic patient
assessment, improving diagnostic accuracy and therapeutic decisions for a variety of ocular and retinal
conditions1-4 including ocular oncology.5,6 Handheld OCT performed while the supine child is under
anesthesia has deepened understanding of the features of retinoblastoma, the most common pediatric
ocular malignancy.7-10
OCT is shown valuable in retinoblastoma for detection of small invisible tumors,5,11-13 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
conditions (e.g. retinoma or astrocytoma).5,18-20
However, handheld OCT is still not commonly used except in highly specialized ocular oncology
centers.7,21 The current Canadian Guidelines21 for retinoblastoma management define a center using
handheld OCT as a tertiary center.
In this study, we evaluate the influence of handheld OCT in guiding the management decisions in
children with retinoblastoma.
Methods
Study design
This study is a retrospective review of children with retinoblastoma who were managed in the Hospital
for Sick Children (SickKids), Toronto, Ontario, Canada 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 examined with OCT imaging during management were
reviewed. Fellow eyes of unilateral retinoblastoma without any suspicious lesion studied at a single OCT
session at presentation were excluded. OCT sessions performed 6 months after the last treatment were
excluded.
Data collection
The data collected included age at presentation, sex, family history, laterality, International Intraocular
Retinoblastoma Classification (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 an OCT session as imaging of one eye for one or more indications, during an examination
under anesthesia. During the course of the study, two generations of handheld OCT systems were utilized:
Bioptigen® Envisu C2200 and Envisu C2300 (Bioptigen, Inc. Leica Microsystems, Morrisville, NC
USA). We did not compare the machines. We did not receive sponsorship or financial support to conduct
our research. At any point of time, one machine was available for both clinic and operating room. All
scans were captured by one of two highly skilled medical imaging specialists (authors CV and LM),
following a standardized methodology for good longitudinal reproducibility.
Technical considerations and indications
OCT was performed with operator at 12 o’clock position of the supine patient. The OCT scanner was
pivoted approximately 1 cm above the cornea, the optimal working distance, aiming the scanning beam
through the pupillary center.24 By manually holding the scanner, the operator was 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 optimized by a combination of factors: manual adjustment of the OCT
spectrometer reference arm settings in accordance to the patient’s axial length; optimizing the focus for
the child’s refraction;24 and frequent application of 0.9% NaCl solution to prevent corneal dryness.
The handheld OCT produces a variety of scan configurations. For this study cohort, we routinely
obtained volumetric scans composed of non-averaged OCT scans (1000 A-scans x 100 B-scans per
volume). The accumulation of individual 100 B-scan produced the associated C-scan fundus image
otherwise called the Sum Voxel Projection (SVP). The OCT’s accompanying SVP image provided
critical information about the quality of the scan and so the OCT operator could respond in real-time with
positional adjustments to improve subsequent scans. To clarify pathology localization calipers were
placed on the OCT B-scan image to reveal the retinal position on the SVP image and measure tumor
height (Fig 1). Although algorithms might be applied to improve image quality via oversampling and
averaging of multiple scans,25 we routinely captured single line volume scans as they achieved rapid and
high quality images with ample clinical detail. To assess the posterior pole (Fig 2) for pre-clinical or
“invisible” tumor in infants less than 6 months of age, we used the widest volumetric scan settings
available. We performed 9 mm x 9 mm scans (Envisu C2200 system) and 12 mm x 12 mm scans (Envisu
C2300 system) of fovea, optic nerve, temporal, superior and inferior quadrants. If a tumor was identified,
the scan was repeated with the tumor centered within the OCT frame (Fig 2, 3).
For foveal or perifoveal tumors, the foveal center was located by a horizontal macular volumetric scan.
When needed, a vertically oriented scan was performed with the scanner is held the same physical
configuration while the SVP image was rotated 90 degrees indicating the scan direction change (Fig 4).
For parafoveal scans, the scanner was pointed towards the area of interest. Increased resolution for
small lesions was obtained by reducing the scan volume area to 8 x 8, or 6 x 6, maximizing the number of
A-scans/line. To assess the mid-periphery and beyond, a scleral depressor was used to rotate the eye,
while angling the scanner perpendicular to the retinal plane (Fig 5).
Assessment
An OCT session was assessed Informative if it provided sufficient data about the main indication;
Directive if the information obtained guided management decisions affecting diagnosis, treatment or
follow-up. Directive guidance that confirmed the pre-OCT clinical decision was considered
Confirmatory, and Influential if it changed a pre-OCT clinical decision. Every OCT session during the
active treatment phase of each child was assessed. Guidance was provided for diagnosis, treatment or
follow-up (Tables 2 and 3).
Diagnosis sessions were scored Confirmatory when OCT confirmed a clinically suspicious tumor
mass or clinical eye IIRC22 Group, including children 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.
Treatment sessions were scored Confirmatory when OCT confirmed a clinically suspicious new or
recurrent tumor or showed anatomic details (fovea, scarring, seeds, traction, etc.) supporting the planned
treatment; and Influential when OCT revealed an unsuspected recurrent tumor within a tumor scar or
showed anatomic details mandating changing the treatment modality or plan.
Follow-up sessions were considered Confirmatory when the OCT showed no change from the last
scan in absence of active treatment; and Influential when OCT showed anatomic details excluding
activity, leading to alteration in treatment plan.
Results:
Patient Demographics and numbers of OCTs
We reviewed 339 OCT sessions for 63 eyes of 44 children with retinoblastoma; 26 were male. Eight
children (10 eyes) were under active treatment; one child (one eye) was lost to follow up when they
moved outside Canada. The median number of OCT sessions per eye was 5 (range: 1-15 sessions),
significantly higher for familial (7) than non-familial (4) eyes (p=0.001, Mood’s Median test). Younger
children at presentation received significantly more OCT sessions (r=-0.26, p=0.04). The most common
indication for OCT was tumor scar evaluation (186/339, 55%), followed by foveal assessment and
posterior pole screening (16% and 11% respectively) (Table 2).
OCT Impact on Care
Informative versus Non-informative
OCT was Informative in 92% of sessions (312/339) (Table 2). Large or highly elevated lesions
rendered OCT technically challenging and Uninformative in 19/27 sessions (Table 3, Fig 1); 14/19 were
cT2a23 or cT2b23 (IIRC22 Group D or C) at presentation. In two eyes/children, OCT became Uninformative
after multiple previously Informative OCTs, due to progression of central tumor (one) and tractional
retinal detachment (one).
Directive versus Non-Directive OCT
OCT was Directive in 86% (293/339) of all OCT sessions and 94% (293/312) of Informative sessions
(Table 2), guiding treatment (168/312, 54%), diagnosis (46/312, 15%), or follow up (79/312, 25%).
Nineteen OCT sessions were Non-Directive, mainly because the OCT was not performed to assess a
clinical decision (17/19) or performed for academic interest (2/19) (Table 3).
Confirmatory versus Influential OCT
Of Directive OCT sessions, 243/293 (83%) were Confirmatory: for treatment 141 (58%), diagnosis 39
(16%) or follow-up 63 (26%) (Table 2). Of Directive OCT sessions, 50/293 (17%) were Influential: for
treatment 27/293 (11%), diagnosis 7/293 (3%) or follow-up 16/293 (7%) (Table 2). The most Influential
OCT sessions were for scar and foveal evaluation (Table 3, Figs 1 to 9). We have previously published
one Influential OCT which showed tumor over optic nerve head.17
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.24 Eyes staged cT123 (IIRC22 Groups A and B) were easily scanned up
to the mid periphery26 (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 TNMH23,27 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
OCT in retinal imaging has been shown effective to guide management (diagnostic and therapeutic)
decisions in multiple conditions, including macular holes,2 macular edema1 (diabetic and vascular) and
age related macular degeneration.3,4 Multiple reports have shown how useful OCT can be to differentiate
ocular tumors and simulating lesions.5,6,9-12,14-16,18-20,26 Currently, hand-held OCT is used by mainly in
tertiary level ocular oncology centers and learning institutes due to its relative high cost and limited
published benefits.21 The current study highlights an important role of OCT in guiding management of
retinoblastoma in 85% of sessions by confirming (83%) or even changing (17%) pre-OCT clinical
decisions.
We show that OCT improved clinical diagnostic accuracy and clinical staging (Fig 6) for
retinoblastoma. In familial retinoblastoma, detection of tiny and sometimes invisible tumors5,11 by OCT
(Fig 2-3) facilitated tumor control by only focal therapy, achieving minimal retinal damage and better
final visual outcomes.27 In unilateral retinoblastoma, OCT helped differentiate suspicious lesions from
retinoblastoma (Fig 7) in the normal eye. Previously, this depended on clinical opinion or B-scan
ultrasonography, which does not show the inner architecture of retina and lesion. Without in-vivo
evidence of the nature of these suspicious lesions, such lesions may have been treated with focal therapy,
potentially falsely labeling the child as bilateral, heritable retinoblastoma, imposing multiple unnecessary
examinations under anesthesia and life-long surveillance for second cancers.21,30
OCT evaluated well important anatomic landmarks such as the fovea and the optic nerve disc, which
affected our treatment and follow up choices. Foveal pit detection (Fig 4) provided information about
anticipated visual potential with perifoveal tumors.14 Foveal localization respective to the tumor affected
choice of treatment modality (chemotherapy versus primary focal therapy), which laser to use (532 nm
versus 810 nm laser) and technique (ie, sequential targeted laser therapy from the tumor side opposite the
fovea, Fig 8). An intact fovea during or after treatment suggested benefit of early amblyopia therapy.31,32
In peripapillary tumors,10,17,33 OCT appearance may raise suspicion of optic nerve invasion but sometimes
failed to distinguish tumor from papilledema. OCT improved clinical judgment during tumor scar
evaluation, and distinguished gliosis and scar from tumor recurrence (Fig 9), especially useful with white
choroidal scars where visualization of recurrence is challenging,33 thereby altering choice of treatment
modality.
The current study is limited by being a single center, retrospective study, with absence of correlation
to a quantifiable outcome. 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 (tumor location, number
and type, stage at presentation, complications of treatments, treatment duration, etc.). The presence of a
single OCT machine limited the number of sessions in some eyes due to unavailability related to
maintenance or concomitant use by other surgeons. Training and academic interest may have increased
the number of OCT sessions performed for some eyes, and we took this into account in scoring the impact
of the OCT session.
Cost is an important consideration during technology assessment. We did not collect this data during
our study. We hypothesize that OCT imaging results in decreased the treatment costs in multiple
situations, such as earlier detection of tumors in familial cases reducing the need for systemic therapies.
In unilateral cases with suspicious lesion in the fellow eye, OCT reduced the number of required
examinations under anesthetic for follow-up. OCT detected earlier scar recurrences treated with focal
rather than costly systemic therapies. A cost-effectiveness study is suggested.
In conclusion, multiple studies have reported OCT signs of retinoblastoma at presentation. To our
knowledge, this is the first study to evaluate the impact of OCT on guiding management decisions of
active retinoblastoma. Hand-held OCT is recommended in the investigative armamentarium of any
tertiary ocular oncology center to provide precision of retinoblastoma management.
Acknowledgement
There are no conflicts of interests or disclosures. BLG is the unpaid medical director of Impact Genetics.
References
1. Panozzo G, Parolini B, Gusson E, et al. Diabetic macular edema: an OCT-based classification. Semin Ophthalmol. 2004;19(1-2):13-20.
2. Rubowitz A. Classification of macular holes. Ophthalmology. 2007;114(10):1956-1957; author reply 1957.
3. Quellec G, Lee K, Dolejsi M, Garvin MK, Abramoff MD, Sonka M. Three-dimensional analysis of retinal layer texture: identification of fluid-filled regions in SD-OCT of the macula. IEEE Trans Med Imaging. 2010;29(6):1321-1330.
4. Introini U, Casalino G, Querques G, Gimeno AT, Scotti F, Bandello F. Spectral-domain OCT in anti-VEGF treatment of myopic choroidal neovascularization. Eye (Lond). 2012;26(7):976-982.
5. Rootman DB, Gonzalez E, Mallipatna A, et al. Hand-held high-resolution spectral domain optical coherence tomography in retinoblastoma: clinical and morphologic considerations. Br J Ophthalmol. 2013;97(1):59-65.
6. Medina CA, Plesec T, Singh AD. Optical coherence tomography imaging of ocular and periocular tumours. Br J Ophthalmol. 2014;98 Suppl 2:ii40-46.
7. Gallie BL, Soliman S. Retinoblastoma. In: Lambert B, Lyons C, eds. Taylor and Hoyt's Paediatric Ophthalmology and Strabismus. Vol 5th Edition. Oxford, OX5 1GB, United Kingdom: Elsevier, Ltd.; In Press.
8. Dimaras H, Corson TW, Cobrinik D, et al. Retinoblastoma. Nature Reviews Disease Primers. 2015:15021.
9. Lee H, Proudlock FA, Gottlob I. Pediatric Optical Coherence Tomography in Clinical Practice-Recent Progress. Invest Ophthalmol Vis Sci. 2016;57(9):OCT69-79.
10. Mallipatna A, Vinekar A, Jayadev C, et al. The use of handheld spectral domain optical coherence tomography in pediatric ophthalmology practice: Our experience of 975 infants and children. Indian Journal Of Ophthalmology. 2015;63(7):586-593.
11. Berry JL, Cobrinik D, Kim JW. Detection and Intraretinal Localization of an 'Invisible' Retinoblastoma Using Optical Coherence Tomography. Ocul Oncol Pathol. 2016;2(3):148-152.
12. Saktanasate J, Vongkulsiri S, Khoo CT. Invisible Retinoblastoma. JAMA ophthalmology. 2015;133(7):e151123.
13. Bremner R. Retinoblastoma, an inside job. Cell. 2009;137(6):992-994.14. Samara WA, Pointdujour-Lim R, Say EA, Shields CL. Foveal microanatomy
documented by SD-OCT following treatment of advanced retinoblastoma. J AAPOS. 2015;19(4):368-372.
15. Hasanreisoglu M, Dolz-Marco R, Ferenczy SR, Shields JA, Shields CL. Spectral Domain Optical Coherence Tomography Reveals Hidden Fovea Beneath Extensive Vitreous Seeding From Retinoblastoma. Retina. 2015;35(7):1486-1487.
16. Munier FL. Classification and management of seeds in retinoblastoma. Ellsworth Lecture Ghent August 24th 2013. Ophthalmic Genet. 2014;35(4):193-207.
17. Yousef YA, Shroff M, Halliday W, Gallie BL, Heon E. Detection of optic nerve disease in retinoblastoma by use of spectral domain optical coherence tomography. J AAPOS. 2012;16(5):481-483.
18. Shields CL, Manalac J, Das C, Saktanasate J, Shields JA. Review of spectral domain-enhanced depth imaging optical coherence tomography of tumors of the retina and retinal pigment epithelium in children and adults. Indian Journal Of Ophthalmology. 2015;63(2):128-132.
19. Pierro L, De Francesco S, Hadjistilianou D, et al. Spectral-domain optical coherence tomography appearance of a posterior pole retinoma. J Pediatr Ophthalmol Strabismus. 2014;51(5):320.
20. Malhotra PP, Bhushan B, Mitra A, Sen A. Spectral-domain optical coherence tomography and fundus autofluorescence features in a case of typical retinocytoma. Eur J Ophthalmol. 2015;25(6):e123-126.
21. Canadian Retinoblastoma S. National Retinoblastoma Strategy Canadian Guidelines for Care: Strategie therapeutique du retinoblastome guide clinique canadien. Can J Ophthalmol. 2009;44 Suppl 2:S1-88.
22. Murphree AL. Intraocular retinoblastoma: the case for a new group classification. Ophthalmology clinics of North America. 2005;18:41-53.
23. Mallipatna A, Gallie BL, Chévez-Barrios P, et al. Retinoblastoma. In: Amin MB, Edge SB, Greene FL, eds. AJCC Cancer Staging Manual. Vol 8th Edition. New York, NY: Springer; 2017:819-831.
24. Maldonado RS, Izatt JA, Sarin N, et al. Optimizing hand-held spectral domain optical coherence tomography imaging for neonates, infants, and children. Invest Ophthalmol Vis Sci. 2010;51(5):2678-2685.
25. Scott AW, Farsiu S, Enyedi LB, Wallace DK, Toth CA. Imaging the infant retina with a hand-held spectral-domain optical coherence tomography device. Am J Ophthalmol. 2009;147(2):364-373 e362.
26. Choudhry N, Golding J, Manry MW, Rao RC. Ultra-Widefield Steering-Based Spectral-Domain Optical Coherence Tomography Imaging of the Retinal Periphery. Ophthalmology. 2016;123(6):1368-1374.
27. Soliman SE, Dimaras H, Khetan V, et al. Prenatal versus Postnatal Screening for Familial Retinoblastoma. Ophthalmology. 2016;123(12):2610-2617.
28. Munier FL, Gaillard MC, Balmer A, et al. Intravitreal chemotherapy for vitreous disease in retinoblastoma revisited: from prohibition to conditional indications. Br J Ophthalmol. 2012;96(8):1078-1083.
29. Munier FL, Soliman S, Moulin AP, Gaillard MC, Balmer A, Beck-Popovic M. Profiling safety of intravitreal injections for retinoblastoma using an anti-reflux procedure and sterilisation of the needle track. Br J Ophthalmol. 2012;96(8):1084-1087.
30. Villani A, Shore A, Wasserman JD, et al. Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study. The lancet oncology. 2016.
31. Watts P, Westal C, Colpa L, et al. Visual results in children treated for macular retinoblastoma. Eye. 2002;16(1):75-80.
32. Lengyel D, Klainguti G, Mojon DS. [Does amblyopia therapy make sense in eyes with severe organic defects?]. Klinische Monatsblatter fur Augenheilkunde. 2004;221(5):386-389.
33. Astudillo PP, Chan HS, Heon E, Gallie BL. Late-diagnosis retinoblastoma with germline mosaicism in an 8-year-old. J AAPOS. 2014;18(5):500-502.
Figure Legends
Figure 1. Central tumors. (A) A perifoveal tumor mass (cT1b23, IIRC22 Group B) was isodense within the
retinal layers; the exact foveal location 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, 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, IIRC22 Group B) measured 1.65 mm in height on B-scan ultrasonography;
OCT showed intact overlying retinal layers and minimal surrounding subretinal fluid (Informative,
Directive and Confirmatory for diagnosis). (D) OCT on a large central tumor (cT1b23, IIRC22 Group B)
measuring 3.08 mm in height on B-scan ultrasonography was Confirmatory; 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 outer tumor boundary was ill defined.
Figure 2. OCT screening of posterior quadrants (superior, temporal, inferior, and nasal). (A, B) An
invisible lesion was found (white *) in the inferior quadrant scan; (C) reimaging centralized on the
suspicious area (green 12mm x 12mm box) showed 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, IIRC22 Group A)
were confirmed (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 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 tumor (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) two 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)
was a flat scar (Informative, Directive, Confirmatory); further laser and cryotherapy 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 calcified with shadowing (arrows); an isodense inner nuclear
layer lesion (white *) was considered an active new tumor, thereby treated with laser (Informative/
Directive/ Influential for diagnosis and treatment). (C) A white lesion (arrow) inferior to large central
tumor with shallow retinal detachment in unilateral retinoblastoma was considered likely to be a separate
primary tumor, so the eye was staged cT2a23 (IIRC22 Group C); OCT showed this to be subretinal seeding
within shallow retinal detachment, changing initial staging to cT2b23 (IIRC22 Group D) changing
treatment (Informative/ Directive/ Influential for diagnosis and treatment).
Figure 8. Sequential targeted Laser therapy (STLT) in juxtafoveal retinoblastoma. The child presented
with a cT2b23 (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) fovea was
further away from the tumor edge 12 months after starting STLT; (D) 18 months after starting STLT OCT
showed a flattened lesion with preserved fovea; 18 months after last treatment the tumor remained the
same (Informative/ Directive/ Confirmatory (Influential) for diagnosis, treatment, follow-up). Fovea
marked by yellow *.
Figure 9. Evaluation of tumor scars. (A) OCT of a clinically suspected recurrence in scar (white *)
showed an isodense elevation of indicating active tumor; the adjacent scar showed an unsuspected similar
edge recurrence; both were treated with laser. (B) OCT detected tumor activity (arrow) hidden within
areas of calcification. (C) OCT of two clinically suspicious white areas showed that the upper white area
(white *) was scar (gliosis) and the lower area (white *) was a tumor. (Informative/ Directive/ Influential
(Confirmatory) for diagnosis and follow-up).
Table legends
Table 1. Clinical, Genetic and Tumor characteristics.
Table 2: Stratification of different OCT assessments in diagnosis, treatment and follow up with indication for OCT imaging.
Table 3. Causes of different OCT assessment layers.