Aqueous Humor Biopsy for Retinoblastoma

New methods could facilitate diagnosis for children with retinoblastoma.

A study by a team of researchers at the Vision Center of Children’s Hospital Los Angeles (CHLA) and the University of Southern California (USC) Roski Eye Institute provides proof of concept for a safe and effective way to derive genetic information from retinoblastoma tumors. Results of the study were recently published in JAMA Ophthalmology.

In treating the small particles or “seeds” that break off from the main tumor, ocular oncologists now inject chemotherapy directly into the eye. As part of this procedure, it is first necessary to remove a small amount of aqueous humor from the front of the eye to decrease the pressure within the eye prior to injection of the medication.

The study reported on 6 samples from 3 eyes affected with retinoblastoma, in children younger than 3 years of age. Aqueous humor was taken from all 3 eyes and allowed investigators to compare tumor DNA in the aqueous humor to DNA found in the retinoblastoma tumor.

“The most exciting aspect of this research is to finally have access to retinoblastoma tumor DNA in eyes that have not been enucleated,” said Jesse Berry, MD, ocular oncologist at CHLA, assistant professor of clinical ophthalmology at the USC Roski Eye Institute, and first author on the study. “While we know a significant amount of the genetic underpinning of this cancer we have never before been able to harness it without removing the eye. This paper, while early research, demonstrates that the aqueous humor hold tremendous potential to serve as a surrogate tumor biopsy which is the first step towards precision medicine for children suffering from this blinding — and deadly — ocular cancer.”

In an invited commentary that appeared in the same issue of JAMA Ophthalmology, J. William Harbour, MD, of the Oncology Service of Bascom Palmer Eye Institute, noted several limitations to study, including the small size of the case series and short follow-up period. He also pointed out that the study encompassed advanced tumors with vitreous seeding and hypothesized that liquid biopsy might not work in less advanced tumors, which contain small concentrations of DNA/RNA. Another limitation he noted was that the USC-CHLA collaboration study did contain some enucleated samples. Finally, he noted that liquid biopsy would be difficult in RB1 mutations that are notoriously challenging because of the large size of the gene and the multiple variations the mutations can take.

The team of investigators plans future studies to compare tumor DNA from eyes that have been saved to those that need to be removed due to tumor recurrence.
“This research has the potential to completely transform how we treat children with retinoblastoma,” said Jonathan W. Kim, MD, director of the retinoblastoma program at CHLA and director of the ocular oncology service at USC Roski Eye Institute in a news release. “This is one of the most significant findings in retinoblastoma research in the past 20 years.”