Intraocular Oncology and Retinoblastoma Management

Intraocular oncology encompasses the diagnosis and treatment of neoplasms arising within the globe, of which retinoblastoma is the most prevalent in early childhood. This malignancy originates from retinal progenitor cells following biallelic inactivation of the RB1 tumour suppressor gene or, less commonly, MYCN amplification. Clinical signs often include leukocoria and strabismus, with advanced disease manifesting as extraocular extension and metastatic spread. Management objectives balance life preservation with globe and vision salvage. Traditional approaches such as enucleation and external beam radiotherapy have given way to systemic chemotherapy, focal therapies (laser photocoagulation, cryotherapy, brachytherapy) and targeted local drug delivery via intra-arterial and intravitreal routes. Recent developments leverage molecular profiling, patient-derived organoid models and refined staging to individualise treatment, optimise outcomes and minimise toxicity. Nevertheless, global disparities in diagnosis timing and access to specialised care continue to affect survival and visual prognosis in low-resource settings.

Research from Nature Portfolio

Multi-omics integration has delineated two principal retinoblastoma subtypes. One subtype retains differentiated cone-like characteristics, harbours few alterations beyond RB1 loss and is associated with better clinical outcomes. The other exhibits cone dedifferentiation, neuronal and stem-like gene expression, frequent MYCN amplification and additional copy number alterations, correlating with greater aggressiveness and metastatic propensity. These findings pave the way for subtype-tailored therapeutic strategies. Complementary genomic studies confirm that retinoblastoma possesses a remarkably low single nucleotide variant burden, with tumour evolution chiefly driven by subclonal gains and losses of chromosomal material. The observed heterogeneity and developmental timing of these copy number alterations inform the design of combination therapies aimed at eradicating both dominant and subclonal tumour cell populations.

Intraocular Oncology and Retinoblastoma Management publication trend

The graph below shows the total number of articles in intraocular oncology and retinoblastoma management across all publications each year (not limited to Nature Index journals).

Technical terms

Retinoblastoma: A malignant intraocular tumour of childhood arising after inactivation of both RB1 alleles or MYCN amplification.

Intra-arterial chemotherapy: Administration of chemotherapeutic agents directly into the ophthalmic artery to concentrate drug delivery within the eye.

Intravitreal chemotherapy: Injection of cytotoxic drugs into the vitreous humour to treat seeding while limiting systemic exposure.

Globe salvage: Preservation of the eyeball and, when possible, functional vision, thereby avoiding enucleation.

Copy number alteration: A genomic event involving gains or losses of chromosomal segments that drive tumour growth and heterogeneity.

Organoids: Three-dimensional cultures derived from patient tumour cells that recapitulate key histological and genetic features for preclinical testing.

References

1. A high-risk retinoblastoma subtype with stemness features, dedifferentiated cone states and neuronal/ganglion cell gene expression. Nature Communications (2021).
2. Somatic genomic alterations in retinoblastoma beyond RB1 are rare and limited to copy number changes. Scientific Reports (2016).
3. Sunitinib efficacy with minimal toxicity in patient-derived retinoblastoma organoids. Journal of Experimental & Clinical Cancer Research (2023).
4. The Global Retinoblastoma Outcome Study: a prospective, cluster-based analysis of 4064 patients from 149 countries. The Lancet Global Health (2022).
5. Intra-Arterial Chemotherapy (Ophthalmic Artery Chemosurgery) for Group D Retinoblastoma. PLOS ONE (2016).