Aqueous humor biopsy for retinoblastoma shows promise

This study finds that aqueous humor from retinoblastoma eyes contains tumor-derived DNA that can be analyzed as an alternative to tissue biopsy.

Study design

Investigators obtained aqueous humor samples from 3 eyes with retinoblastoma, including 2 after primary enucleation. Samples from the third eye were obtained while the child was undergoing melphalan treatment for vitreous seeding.

The authors extracted cell-free DNA from the samples, which were analyzed for DNA, RNA and micro-RNA. They also performed whole genome sequencing and genome-wide chromosomal copy number variation profiling.

Outcomes

Evaluation of aqueous humor demonstrated tumor-derived, cell-free DNA and regions of chromosomal gains and losses, representing changes in the tumor. These findings suggest that aqueous humor can serve as a surrogate tumor biopsy for analyses of tumor-derived DNA in retinoblastoma eyes.

Limitations

This is a small exploratory analysis performed at a single center, and the findings will need to be confirmed in a larger study. Furthermore, the genetic analysis requires specialized equipment and expertise.

Clinical significance

The traditional method of tissue biopsy in retinoblastoma eyes can induce extraocular seeding of tumor cells. A transzonular approach may reduce this risk but is technically demanding.

Aqueous humor biopsy may be an improvement over existing methods, as it could require less advanced technical skills and carry a lower risk of causing ocular or systemic comorbidity. This new technique may enable a more precise analysis of treatment response in these patients — especially those undergoing salvage therapy, in which tumor tissue is unavailable.

In an interview earlier this month, lead author Dr. Jesse Berry discusses why her research could represent a paradigm shift in the treatment of children with retinoblastoma.