A multidisciplinary team at Children’s Hospital Los Angeles (CHLA) has demonstrated how a liquid biopsy test developed at the hospital can significantly improve the diagnosis and clinical management of tumors in the eye, including retinoblastoma.1
In a study published in npj Precision Oncology, CHLA researchers report that an aqueous humor liquid biopsy platform can identify tumor-specific genetic information with up to 98% accuracy, helping clinicians distinguish between malignant and non-malignant eye lesions and tailor treatment decisions more precisely.2
The study, titled “Prospective implementation of an aqueous humor liquid biopsy platform informs clinical diagnosis and management of retinoblastoma and other intraocular lesions,” was led by Laura Kagami, MD, a postdoctoral research fellow in CHLA’s Cancer and Blood Disease Institute. The research was conducted in collaboration with investigators from CHLA’s Amy Elizabeth Corwin Aqueous Humor Liquid Biopsy Laboratory and the Center for Personalized Medicine (CPM), including Jaclyn Biegel, PhD, FACMG, Jesse L. Berry, MD, and Liya Xu, PhD.
Retinoblastoma presents a unique diagnostic challenge because tumor tissue cannot be directly biopsied at diagnosis due to the risk of spreading cancer cells within the eye or to other parts of the body. Traditionally, tumor-specific genetic information could only be obtained after removal of the eye. In 2017, CHLA researchers discovered that aqueous humor contains DNA shed from tumors located in the back of the eye. This discovery led to the development of aqueous humor liquid biopsy, a safer method for accessing tumor genetics.
“Sampling the clear fluid in the front of the eye can be safely performed and enables molecular analysis of retinoblastoma tumors,” Dr. Kagami said. “This gives us information we could not previously access without removing the eye.”
The team later clinically validated the test as LBSeq4Kids, allowing it to be used to guide real-time clinical decision-making.
The new study evaluated 147 aqueous humor samples from 60 patients with intraocular lesions referred between January 2023 and January 2025. Using LBSeq4Kids, the researchers confirmed retinoblastoma in 41 patients. Among the remaining cases, the test identified other intraocular malignancies—such as leukemia and lymphoma—as well as non-malignant conditions known as “RB mimickers,” which can resemble retinoblastoma on imaging.
Beyond distinguishing cancer from non-cancer, the liquid biopsy revealed critical genetic insights, including:
RB1 gene variants that drive retinoblastoma development
Chromosomal alterations explaining why tumors in each eye may respond differently to therapy
Additional tumor-driving genes such as BCOR and MDM4
Genetic signatures of leukemia or lymphoma involving the eye
“These genetic details are incredibly valuable,” said Dr. Berry, director of CHLA’s Vision Center. “In some cases, we’ve been able to determine that a child is not at risk for other cancers later in life—information we simply couldn’t obtain before.”
The test’s high specificity also helps clinicians determine whether retinoblastoma is active or inactive, whether a new lesion represents tumor recurrence or a new growth, and whether treatment is working. Importantly, it can confidently identify non-cancerous RB mimickers, allowing surgeons to operate quickly and safely when needed.
According to Dr. Biegel, CHLA is currently the only pediatric academic medical center offering a liquid biopsy platform that combines copy number profiling with targeted sequencing. “This allows us to examine each tumor in detail and understand the combination of genetic alterations driving its development,” she said.
References
1. Danowski P. New CHLA Study Explores Expanded Diagnostic Capabilities of Aqueous Humor Liquid Biopsy. Children’s Hospital Los Angeles Blog. Published February 12, 2026. Accessed February 16, 2026. https://www.chla.org/blog/research-and-breakthroughs/new-chla-study-explores-expanded-diagnostic-capabilities-aqueous
2. Kagami LAT, Christodoulou E, Yellapantula V, et al. Prospective implementation of an aqueous humor liquid biopsy platform informs clinical diagnosis and management of retinoblastoma and other intraocular lesions. npj Precis Oncol. 2026;10:53. doi:10.1038/s41698-025-01255-3.