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. 2025 Mar 19:S0161-6420(25)00180-0.
doi: 10.1016/j.ophtha.2025.03.018. Online ahead of print.

Safety Assessment of Aqueous Humor Liquid Biopsy in Retinoblastoma: A Multicenter Study of 1203 Procedures

Douglas Chigane  1 , Drishti Pandya  1 , Muskaan Singh  2 , Brianne Brown  1 , Michelle Lin  1 , Liya Xu  3 , Andrew W Stacey  4 , Alyssa C Bonnell  4 , G Baker Hubbard 3rd  5 , Hans Grossniklaus  5 , Alison H Skalet  6 , Kellyn N Bellsmith  6 , Sara E Lally  7 , Margarida Simão-Rafael  8 , Cristina Jou Muñoz  8 , Jaume Català-Mora  8 , Denis Malaise  9 , Livia Lumbroso-Le Rouic  9 , Alexandre Matet  10 , Guillermo L Chantada  8 , Nathalie Cassoux  10 , Carol L Shields  7 , Jesse L Berry  11
Affiliations

Safety Assessment of Aqueous Humor Liquid Biopsy in Retinoblastoma: A Multicenter Study of 1203 Procedures

Douglas Chigane et al. Ophthalmology. .

Abstract

Purpose: To evaluate the safety profile of aqueous humor (AH) liquid biopsy in pediatric patients with retinoblastoma and retinoblastoma-simulating lesions through a multicenter analysis of paracentesis procedures.

Design: Retrospective multicenter study.

Participants: A total of 1203 paracentesis procedures were performed on 484 eyes of 425 pediatric patients, including 352 patients with retinoblastoma and 73 patients with retinoblastoma-simulating lesions.

Methods: Medical records were reviewed retrospectively to identify complications from anterior chamber paracentesis performed to obtain AH for liquid biopsy. Procedures were conducted during routine examination under anesthesia. Aqueous humor samples were extracted using a 32-gauge needle and underwent cell-free DNA analysis. Complications were classified as mild, moderate, or severe based on clinical impact and required interventions.

Main outcome measures: Incidence and severity of complications related to the paracentesis procedure.

Results: Among 1203 procedures, 1 mild complication was identified, representing an overall complication rate of 0.08%. No moderate or severe complications, including vision, eye loss, extraocular tumor spread, or death, were observed at a median follow-up of 16 months. The procedure demonstrated an excellent safety profile across multiple centers, with no permanent adverse outcomes.

Conclusions: Aqueous humor liquid biopsy via anterior chamber paracentesis is a safe and well-tolerated procedure in pediatric patients with retinoblastoma when performed by trained ocular surgeons under general anesthesia. This large-scale analysis supports the procedure's use as a minimally invasive diagnostic tool with minimal risk, providing valuable molecular insights for retinoblastoma management. These findings offer reassurance to clinicians and parents regarding the safety of AH liquid biopsy for retinoblastoma.

Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Keywords: Aqueous humor; Liquid biopsy; Retinoblastoma; Safety.

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