Evidence map›Paper›PMID 38040321›Full record

Observational studyAmerican journal of ophthalmology2024

Aqueous Humor Liquid Biopsy as a Companion Diagnostic for Retinoblastoma: Implications for Diagnosis, Prognosis, and Therapeutic Options: Five Years of Progress.

Jesse L Berry, Sarah Pike, Rachana Shah, Mark W Reid, Chen-Ching Peng, Yingfei Wang, Venkata Yellapantula, Jaclyn Biegel, Peter Kuhn, James Hicks and 1 more

Open access · bronzeAbstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in American journal of ophthalmology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 2 pooled it
8.1field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 29 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Review
  5. Digital PCR Quantification of a CirculatingInternational journal of molecular sciences · 2026
    Article
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  16. Update on Retinoblastoma Therapies.Medicina (Kaunas, Lithuania) · 2025
    Review
  17. SOX4 as a Key Oncogene Driving Tumor Invasion in Retinoblastoma.Investigative ophthalmology & visual science · 2025
    Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Jesse L BerryFrom the Vision Center, Children's Hospital Los Angeles (J.L.B., S.P., M.W.R., C.-C.P., L.X.); USC Roski Eye Institute, Keck School of Medicine of the University of Southern California (J.L.B., S.P., M.W.R., C.-C.P., L.X.); the Saban Research Institute, Children's Hospital Los Angeles (J.L.B., V.Y., J.B., L.X.); Norris Comprehensive Cancer Center, Keck School of Medicine of the University of Southern California (J.L.B., P.K., J.H.). Electronic address: jesse.berrymd@gmail.com.
Sarah PikeFrom the Vision Center, Children's Hospital Los Angeles (J.L.B., S.P., M.W.R., C.-C.P., L.X.); USC Roski Eye Institute, Keck School of Medicine of the University of Southern California (J.L.B., S.P., M.W.R., C.-C.P., L.X.).
Rachana ShahCancer and Blood Disease Institute, Children's Hospital Los Angeles (R.S.).
Mark W ReidFrom the Vision Center, Children's Hospital Los Angeles (J.L.B., S.P., M.W.R., C.-C.P., L.X.); USC Roski Eye Institute, Keck School of Medicine of the University of Southern California (J.L.B., S.P., M.W.R., C.-C.P., L.X.).
Chen-Ching PengFrom the Vision Center, Children's Hospital Los Angeles (J.L.B., S.P., M.W.R., C.-C.P., L.X.); USC Roski Eye Institute, Keck School of Medicine of the University of Southern California (J.L.B., S.P., M.W.R., C.-C.P., L.X.).
Yingfei WangCancer and Blood Disease Institute, Children's Hospital Los Angeles (R.S.); Department of Quantitative and Computational Biology, University of Southern California (Y.W.).
Venkata Yellapantulathe Saban Research Institute, Children's Hospital Los Angeles (J.L.B., V.Y., J.B., L.X.); Center for Personalized Medicine, Children's Hospital Los Angeles (V.Y., J.B.).
Jaclyn Biegelthe Saban Research Institute, Children's Hospital Los Angeles (J.L.B., V.Y., J.B., L.X.).
Peter KuhnNorris Comprehensive Cancer Center, Keck School of Medicine of the University of Southern California (J.L.B., P.K., J.H.); USC Michelson Center for Convergent Biosciences and Department of Biological Sciences (P.K., J.H.), Los Angeles, California, USA.
James HicksNorris Comprehensive Cancer Center, Keck School of Medicine of the University of Southern California (J.L.B., P.K., J.H.); USC Michelson Center for Convergent Biosciences and Department of Biological Sciences (P.K., J.H.), Los Angeles, California, USA.
Liya XuFrom the Vision Center, Children's Hospital Los Angeles (J.L.B., S.P., M.W.R., C.-C.P., L.X.); USC Roski Eye Institute, Keck School of Medicine of the University of Southern California (J.L.B., S.P., M.W.R., C.-C.P., L.X.); the Saban Research Institute, Children's Hospital Los Angeles (J.L.B., V.Y., J.B., L.X.).
University of Southern California · USChildren's Hospital of Los Angeles · US

Funding

Validation of an aqueous humor liquid biopsy for molecular prognostication and monitoring of children with retinoblastoma.R01CA282759 · NCI · CHILDREN'S HOSPITAL OF LOS ANGELES · PI Jesse L Berry · 2023 to 2026
$2.2M
Development of a surrogate liquid biopsy from the aqueous humor in retinoblastoma eyes.K08CA232344 · NCI · CHILDREN'S HOSPITAL OF LOS ANGELES · PI BERRY, JESSE L · 2018 to 2022
$1.1M
NCI NIH HHS K08 CA232344NCI NIH HHS R01 CA282759
6 · The paper itself

Abstract

purposeTo define the prospective use of the aqueous humor (AH) as a molecular diagnostic and prognostic liquid biopsy for retinoblastoma (RB).

methodsThis is a prospective, observational study wherein an AH liquid biopsy is performed at diagnosis and longitudinally through therapy for patients with RB. Tumor-derived cell-free DNA is isolated and sequenced for single nucleotide variant analysis of the RB1 gene and detection of somatic copy number alterations (SCNAs). The SCNAs are used to determine tumor fraction (TFx). Specific SCNAs, including 6p gain and focal MycN gain, along with TFx, are prospectively correlated with intraocular tumor relapse, response to therapy, and globe salvage.

resultsA total of 26 eyes of 21 patients were included with AH taken at diagnosis. Successful ocular salvage was achieved in 19 of 26 (73.1%) eyes. Mutational analysis of 26 AH samples identified 23 pathogenic RB1 variants and 2 focal RB1 deletions; variant allele fraction ranged from 30.5% to 100% (median 93.2%). At diagnosis, SCNAs were detectable in 17 of 26 (65.4%) AH samples. Eyes with 6p gain and/or focal MycN gain had significantly greater odds of poor therapeutic outcomes (odds ratio = 6.75, 95% CI = 1.06-42.84, P = .04). Higher AH TFx was observed in eyes with vitreal progression (TFx = 46.0% ± 40.4) than regression (22.0 ± 29.1; difference: -24.0; P = .049).

conclusionsEstablishing an AH liquid biopsy for RB is aimed at addressing (1) our inability to biopsy tumor tissue and (2) the lack of molecular biomarkers for intraocular prognosis. Current management decisions for RB are made based solely on clinical features without objective molecular testing. This prognostic study shows great promise for using AH as a companion diagnostic. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Indexed as

Aqueous HumorRetinal NeoplasmsRetinoblastomaBiomarkers, TumorChildChild, PreschoolDNA Copy Number VariationsDNA Mutational AnalysisDNA, NeoplasmFemaleHumansInfantLiquid BiopsyMalePrognosisProspective StudiesBiomarkers, TumorDNA, NeoplasmRB1 protein, humanRetinoblastoma Binding ProteinsUbiquitin-Protein Ligases

Identifiers

PMID38040321
PMCPMC11148850
OpenAlexW4389210405

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.