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Utilities of optical coherence tomography in retinoblastoma
*Corresponding author: Niragh Sikdar, Department of Opthalmology, Medical College and Hospital, Kolkata, West Bengal, India. niraghsikdar@gmail.com
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Received: ,
Accepted: ,
How to cite this article: Sikdar N, Sardar M, Mengistie CT, Negussie MA. Utilities of optical coherence tomography in retinoblastoma. doi: 10.25259/IJMS_36_2025
Abstract
Optical coherence tomography (OCT), a non-invasive imaging tool, significantly enhances retinoblastoma’s diagnosis, management, and follow-up, the most common pediatric intraocular malignancy. Retinoblastoma is often diagnosed in advanced stages when the tumor occupies substantial intraocular space, presenting with leukocoria, strabismus, proptosis, or ocular inflammation – conditions that can compromise globe preservation and patient survival. For decades, indirect ophthalmoscopy and retinal photography have been standard practice in retinoblastoma management. However, these methods have limitations in detecting submillimeter tumors and determining tumor activity for targeted treatment. OCT has proven valuable in detecting subtle tumor features, enabling earlier intervention, improving prognosis, enhancing eyeball preservation rates, and maintaining vision.
Keywords
Non-invasive imaging
Ophthalmology
Optical coherence tomography
Retinoblastoma
Tumor
INTRODUCTION
Optical coherence tomography (OCT) is a non-invasive imaging technology that utilizes reflected laser light interference to generate cross-sectional images of the posterior retina. While ocular oncologists have traditionally relied on indirect ophthalmoscopy and retinal photography to manage retinoblastoma, these methods often fail to detect small active tumors requiring additional treatment.[1]
OCT provides critical information that can influence clinical decision-making in retinoblastoma cases. A recent study by Soliman et al. demonstrated that OCT confirmed pre-OCT clinical decisions in 83% of cases while redirecting clinical management in 17% of cases, highlighting its impact on treatment strategies.[2] Furthermore, OCT enables detailed evaluation of important anatomical landmarks such as the fovea and optic nerve, influencing treatment selection and follow-up protocols while providing insights into potential visual outcomes following treatment.
Advancements in retinoblastoma diagnosis and treatment have led to 5-year survival rates exceeding 95% in developed countries, ranking among the highest for pediatric cancers.[1] This remarkable progress underscores the importance of early detection and precise management, areas where OCT has made significant contributions.
SEARCH STRATEGY
A comprehensive database search of PubMed, Embase, and Cochrane Library using keywords such as “retinoblastoma,” “OCT,” “early detection,” and “treatment” yielded 102 records. After deduplication, 48 unique records remained. Title and abstract screening, conducted independently by two reviewers, excluded 22 records based on predefined inclusion and exclusion criteria. Full-text assessment of the remaining records led to the final inclusion of 26 studies in the systematic review [Figure 1].
- Preferred reporting items for systematic reviews and meta-analyses chart.
DIAGNOSIS
OCT has revolutionized the diagnostic landscape for retinoblastoma in several key ways:
Differentiation from other retinal lesions
OCT helps exclude retinoblastoma in the unaffected eye of unilateral cases by correctly identifying non-malignant conditions that may mimic retinoblastoma, such as colobomas, peripapillary thickening, and vessel kinking.[2]
Detection of small tumors
One of OCT’s most significant advantages is its ability to visualize submillimeter retinoblastomas that remain invisible on indirect ophthalmoscopy, particularly those smaller than 100 μm in basal dimension.[3] By enabling frame-by-frame OCT analysis, clinicians can identify small homogeneous lesions representing either new tumors or subclinical recurrences before chemoreduction. This capability facilitates earlier diagnosis and targeted laser treatment, resulting in improved visual and anatomical outcomes through minimized damage to retinal layers.[4]
CHARACTERISTIC OCT SIGNS
OCT scans have identified two pathognomonic signs of submillimeter retinoblastoma:
“Fishtail” sign
Detected in 95% (19/20) of tumors, this sign appears as tumor expansion within the hyporeflective inner nuclear layer (INL) at the tumor margins, resembling a fish’s tail.[5] This sign is particularly valuable for detecting tiny retinoblastomas confined to a single retinal layer and has been observed in tumors as small as 151 μm.[6]
“Shark fin” sign
Present in 75% (15/20) of tumors, this sign results from folding of the outer nuclear layer (ONL) and outer plexiform layer (OPL) at lateral tumor margins, creating a pointed tip in the OPL and wave-like displacement of the hyporeflective ONL.[5] All tumors displaying the “shark fin” sign also exhibit the “fishtail” sign.
Intratumoral microcalcification
Visualized in 70% (14/20) of tumors, providing another distinguishing feature.[5]
DETERMINATION OF TUMOR ORIGIN
Analysis of OCT features at tumor epicenters and margins has revealed that 95% (19/20) of submillimeter retinoblastomas originate from the INL, with only 5% (1/20) showing equivocal origin.[5] The “fishtail” and “shark fin” signs strongly suggest INL origin, corroborated by histopathological studies of small retinoblastoma tumors.[7]
TUMOR LOCALIZATION
OCT accurately determines tumor location relative to retinal structures (intraretinal, preretinal, subretinal, or vitreal), enabling more precise tumor staging. This capability helps differentiate between the subretinal extension of a primary tumor and new tumor formation, preventing misclassification as multifocal disease. In addition, detection of vitreous seeds may indicate the need for intravitreal chemotherapy.[8]
DIFFERENTIAL DIAGNOSIS
OCT facilitates differentiation between small retinoblastomas and other suspicious lesions:
Small retinal hemangioblastomas
Originating from the INL or ganglion cell layer with posterior bowing of the OPL, these lack calcification and the “shark fin” sign present in retinoblastomas.[9]
Benign retinal astrocytic hamartomas
These may display calcifications on OCT but originate from the retinal nerve fiber layer and often have a distinctive “moth-eaten” appearance.[10]
Combined hamartoma of the retina and RPE
Characterized by dense preretinal fibrosis or epiretinal membrane resulting in a saw-tooth appearance or complete retinal folding, contrasting with retinoblastoma which shows no vitreoretinal traction.[11]
Congenital simple hamartoma of the RPE
A rare pigmented tumor with abrupt margins, typically in the perifoveal region, displaying deep shadowing with crisp margins on OCT.[10]
The ability to distinguish between these entities, previously dependent on ultrasound and clinical expertise, has improved with hand-held OCT. This advancement has prevented unnecessary treatment and misclassification of children as having bilateral or hereditary retinoblastoma, eliminating needless examinations under anesthesia and lifelong screening for second cancers.[4]
ADDITIONAL DIAGNOSTIC BENEFITS
Spectral-domain OCT (SD-OCT) enables monitoring of tumor growth and its relationship with surrounding structures, including the foveal pit and optic nerve head. Foveal localization relative to the tumor influences treatment selection (chemotherapy vs. primary focal therapy), laser choice (532- vs. 810-nm), and technique (sequential targeted laser therapy), while also providing insights into visual potential.[2]
For peripapillary tumors, OCT may raise suspicion of optic nerve invasion, although it cannot always distinguish between tumor and papilledema. OCT also helps map choroidal invasion to assess metastasis risk and is superior to clinical examination in detecting macular pathologies such as surface wrinkling maculopathy, macular edema, subfoveal fluid, retinal thinning, and retinal pigment epithelium detachment.
Compared to ultrasonography, OCT demonstrates higher sensitivity in detecting surface wrinkling maculopathy, non-cystoid macular edema, and subfoveal fluid. However, ultrasonography offers greater penetration, making it more effective for large tumors exceeding 1.6 mm in thickness.
COMPARISON OF IMAGING MODALITIES IN RETINOBLASTOMA MANAGEMENT
Table 1 shows the comparative analysis between different modalities in Retinoblastoma Management.
| Feature | Optical coherence tomography | Indirect ophthalmoscopy | Ultrasonography | MRI |
|---|---|---|---|---|
| Small tumor detection (<100 μm) | Excellent | Poor | Poor | Poor |
| Tumor margin definition | Excellent | Good | Moderate | Moderate |
| Calcification detection | Good (indirect signs) | Moderate | Excellent | Moderate |
| Vitreous seed visualization | Good | Good | Moderate | Poor |
| Optic nerve invasion assessment | Limited | Limited | Moderate | Excellent |
| Extraocular extension evaluation | Poor | Poor | Good | Excellent |
| Foveal relationship assessment | Excellent | Moderate | Poor | Poor |
| Retinal layer analysis | Excellent | Poor | Poor | Poor |
| Deep lesion penetration | Limited (<1.6mm) | Moderate | Excellent | Excellent |
| Peripheral lesion detection | Limited with handheld | Good | Good | Good |
| Real-time guidance for treatment | Excellent | Good | Limited | Not applicable |
| Cost | High | Low | Moderate | Very high |
| Availability in clinical settings | Limited | Widely available | Widely available | Limited |
| Radiation exposure | None | None | None | None (but requires contrast) |
| Sensitivity for recurrence | High (95%) | Moderate | Moderate | Low |
| Specificity for active vs. inactive lesions | Moderate (87%) | Moderate | Poor | Poor |
MRI: Magnetic resonance imaging
TREATMENT
OCT has transformed treatment approaches for retinoblastoma in several important ways:
OCT-guided laser treatment
OCT-guided laser treatment for perifoveal tumors has demonstrated 100% accuracy in tumor localization through precise OCT mapping relative to landmarks such as blood vessels. Immediate post-laser OCT confirms complete tumor coverage by revealing visible retinal whitening without geographic misses or skipped areas, allowing for additional laser application.[12]
Complete tumor treatment is verified through a final OCT scan showing characteristic post-laser signs: Tumor swelling, hyperreflectiveness, and shadowing extending to the retinal pigment epithelium. These signs should extend at least one OCT frame beyond the originally uninvolved margins on each side of the tumor.
Foveal-sparing laser photocoagulation
OCT enables foveal-sparing laser photocoagulation following tumor chemoreduction for retinoblastoma (IIRC groups B/C/D or T1b/T2a/T2b according to the eighth edition TNMH classification).[13] This approach results in superior anatomical preservation and functional vision compared to traditional laser treatments that may damage the fovea and cause post-laser scarring, particularly when foveal localization is imprecise.[14]
This technique avoids direct laser application to the foveolar edge of perifoveal tumors while still controlling the tumor by targeting its blood supply, operating on the principle that the foveal avascular zone would not contribute to tumor vascularization. A study from the Hospital for Sick Children (Toronto, Canada) reported the following outcomes:[15]
Juxtafoveal tumors (n=14)
Foveal pit preservation in 13/14 cases (93%)
≥500 μm of perifoveal retina preserved and scar-free
Median visual acuity of 20/40 (0.5 logMAR)
Acceptable visual acuity (≥1.0 logMAR) in 12/14 eyes (86%)
Good visual acuity (≥0.5 logMAR) in 8/14 eyes (57%)
No tumor recurrence detected
Foveolar tumors (n=8)
Failed to restore foveal pit or perifoveal retina in all cases (8/8)
Median visual acuity of 20/160
Visual acuity of 0.1 or better in 5/8 eyes (63%)
No eyes achieved visual acuity of 0.3 or better
Recurrence detected in 5/8 eyes (63%)
These findings underscore the significant visual benefits of OCT-guided foveal-sparing approaches, particularly for juxtafoveal tumors.
FOLLOW-UP
OCT plays a crucial role in the follow-up management of retinoblastoma:
Early detection of recurrence
OCT facilitates the detection of early subclinical tumor recurrence through regular monitoring of each scar for at least 6 months following treatment. Recurrences appear as solid, homogeneous, elevated, rounded, or ovoid hyperreflective lesions. This early detection enables prompt intervention at the subclinical level, often requiring only focal laser therapy and avoiding more aggressive treatments like systemic or intra-arterial chemotherapy for central tumors, with their associated complications.[2]
In tumors with mixed or fish-flesh regression patterns, differentiating active from inactive areas may be challenging except through serial OCT monitoring for stability. Some clinicians adopt a conservative approach, treating all suspicious areas as active when they are small and amenable to laser therapy, rather than waiting 4–5 weeks for follow-up only to encounter larger recurrences requiring more intensive treatment.[2]
Scar evaluation
OCT enhances clinical judgment during tumor scar evaluation. At 3-month post-laser completion, tumor scars typically show expansion in all directions by less than 20% of initial dimensions. Expansion exceeding this threshold, such as the 50% expansion observed in one case, may indicate true scar migration. Pigmentary changes are commonly detected in all scars.[12]
OCT also helps distinguish gliosis and scar formation from tumor recurrence. Tumors typically appear homogeneous and hyporeflective compared to scars, which display a dome shape, loss of retinal layers, and flat surface. This distinction is particularly valuable with white choroidal scars where visual detection of recurrence is challenging.[2]
COMPREHENSIVE ASSESSMENT
OCT provides detailed pre- and post-laser assessments, including:
Fovea identification
Foveolar thickness (normal or atrophic)
Mean fovea-tumor and fovea-scar distances (uninvolved perifoveal retina)
Photoreceptor inner-outer segment (IS-OS) junction preservation
Secondary macular changes (retinoschisis, cysts, atrophy, traction, or detachment)
Preservation of perifoveal retina within a 2-disc-diameter circle centered on the fovea, indicating good visual potential.[2]
OCT also detects various retinal changes, including subretinal exudates, macular intraretinal and subretinal edema, flat scars indicating no further treatment is needed, subclinical tumor recurrences, and differentiation between gliosis and tumor recurrence, preventing unnecessary treatment of inactive lesions.[2]
CHEMOTHERAPY MONITORING
OCT helps assess central retinal thickness before and after intravitreal melphalan administration in cases not involving the macula. While eyes with grade I toxicity show no significant change in central retinal thickness, those with grade IV and V toxicity demonstrate clinically evident thinning with inner and outer retinal atrophy and loss of foveal contour, although data remain limited.[16] Some studies have also noted reduced subfoveal choroidal thickness following intra-arterial melphalan administration.[17]
OCT ANGIOGRAPHY APPLICATIONS
OCT angiography enables assessment of the deep capillary plexus before and after systemic chemotherapy, documenting vascular alterations induced by treatment.[18] This emerging application provides valuable insights into the microvascular changes and potential ischemic effects of chemotherapeutic agents, which may have implications for visual function and long-term outcomes.
CONTRALATERAL EYE ASSESSMENT
OCT facilitates objective assessment of the contralateral unaffected eye in unilateral retinoblastoma patients by evaluating optic nerve head parameters, peripapillary nerve fiber layer (pRNFL) thickness, and macular metrics including total macular thickness, central foveal thickness (CFT), ganglion cell layer (GCL), ganglion cell complex (GCC), and macular RNFL thickness.
Studies have shown that the contralateral unaffected eyes of unilateral retinoblastoma patients exhibit thinning of CFT, GCL, and GCC without significant differences in pRNFL thickness or optic nerve head parameters. Following unilateral enucleation of the affected eye, the contralateral eye demonstrates increased thickness in macular GCC and pRNFL.[19]
REGRESSION PATTERN MONITORING
OCT enables the detection and monitoring of regression pattern types according to the Wills Eye Institute classification:[20]
Type 0: No tumor remnant/no visible retinal scar
Type I: Completely calcified remnant (cottage cheese scar)
Type II: Completely non-calcified fish flesh tumor remnant
Type III: Mixed type with both calcified and fish flesh components
Type IV: Flat chorioretinal scar.
Following chemoreduction, the most common regression pattern is a non-calcified fish flesh remnant, which may evolve into a calcified remnant, particularly during the first 6 months after completing chemotherapy.[21]
EMERGING TECHNOLOGIES AND FUTURE DIRECTIONS
Advanced OCT applications
Recent advancements in OCT technology have expanded its applications in retinoblastoma management:
Swept-source OCT (SS-OCT)
With its longer wavelength (1050 nm versus 840 nm in conventional SD-OCT), SS-OCT offers deeper penetration and improved visualization of choroidal invasion, a critical prognostic factor. Early studies suggest that SS-OCT may detect subtle choroidal changes not visible with conventional OCT, potentially improving staging accuracy.[22]
OCT angiography (OCTA)
This non-invasive technology provides detailed visualization of retinal and choroidal vasculature without contrast agents. OCTA can detect tumor-associated vascular changes, including abnormal vascular networks within and surrounding tumors, helping differentiate retinoblastoma from other vascular lesions. Furthermore, OCTA has revealed microischemic changes in the deep capillary plexus following systemic chemotherapy, offering insights into treatment-related vascular toxicity.[23]
Artificial intelligence integration
Machine learning algorithms applied to OCT imaging show promise for automated detection of small retinoblastomas and differentiate them from mimicking lesions. These tools may enhance screening efficiency, particularly in regions with limited access to specialized ophthalmologists.[24]
Intraoperative OCT
This emerging technology provides real-time guidance during surgical interventions, potentially improving precision in complex cases involving the macula or optic nerve.[25]
TRANSLATIONAL RESEARCH APPLICATIONS
OCT is increasingly valuable in translational retinoblastoma research:
Biomarker development
OCT features such as the “fishtail” and “shark fin” signs may serve as biomarkers for early detection and prognosis. Ongoing research is exploring correlations between specific OCT patterns and genetic mutations or treatment response.[23]
Treatment response assessment
Standardized OCT protocols for evaluating treatment response could facilitate a more objective comparison of therapeutic approaches across clinical trials.[26]
Integrated multimodal imaging
Combining OCT with other imaging modalities such as fundus autofluorescence, fluorescein angiography, and molecular imaging techniques offers a comprehensive approach to tumor characterization and treatment planning.[24]
LIMITATIONS OF OCT IN RETINOBLASTOMA
Despite its numerous advantages, OCT has several limitations in retinoblastoma management:
Limited penetration
Large tumors exceeding 1.6 mm in thickness or those located in the far periphery may not be fully visualized due to signal absorption and attenuation. Areas beneath calcifications also cannot be seen in detail due to signal shadowing.
Differentiation challenges
OCT alone cannot definitively differentiate active from inactive retinoblastomas in all cases, requiring clinical expertise and follow-up assessments.
Media opacity dependence
The technology relies on clear ocular media, limiting its utility in cases with significant opacities.
Accessibility and cost
Handheld OCT remains expensive and less widely available than ultrasonography, limiting its implementation in resource-constrained settings.
Functional limitations
OCT lacks built-in functionality for comprehensive macular thickness mapping in standard clinical applications.
Interpretation complexities
While black lesions with strong light scattering typically indicate calcifications, blood vessels can produce similar effects, necessitating OCT angiography for differentiation.
Prognostic limitations
Visual prognosis depends on various factors beyond OCT findings, including tumor regression type, foveal calcification, amblyopia therapy, tumor-foveola distance, fellow eye status, and final foveal architecture.
Understanding these limitations is crucial for appropriate interpretation and optimal utilization of OCT in retinoblastoma management.
CONCLUSION
OCT has emerged as an invaluable tool in retinoblastoma management, yielding significant improvements in patient outcomes while reducing treatment costs. Earlier tumor detection in familial cases and decreased reliance on systemic therapies contribute to substantial cost savings. OCT’s ability to precisely localize small tumors minimizes treatment-related scarring, preserves normal retinal architecture, and enhances visual potential.
The most substantial benefits of OCT are evident during follow-up, where it facilitates monitoring of treatment effects, regression patterns, and potential recurrences. However, clinicians must remain cognizant of OCT’s limitations when incorporating this technology into their practice.
Looking forward, the integration of pre- and post-treatment OCT imaging data promises to provide a comprehensive view of tumor development and treatment response. This holistic approach, combined with emerging technologies such as OCT angiography and artificial intelligence integration, holds tremendous potential for further refining treatment strategies and improving overall management of this challenging disease.
Ethical approval:
Institutional Review Board approval is not required.
Declaration of patient consent:
Patient’s consent not required as there are no patients in this study.
Conflicts of interest:
There are no conflicts of interest.
Use of artificial intelligence (AI)-assisted technology for manuscript preparation:
The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.
Financial support and sponsorship: Nil.
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