Evidence map›Paper›PMID 25439613›Full record

Observational studyOphthalmology2015

Identification of torque teno virus in culture-negative endophthalmitis by representational deep DNA sequencing.

Aaron Y Lee, Lakshmi Akileswaran, Michael D Tibbetts, Sunir J Garg, Russell N Van Gelder

Open access · greenAbstract readObservational Study
In one paragraph

Observational study in Ophthalmology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 1 pooled it
5.2field-weighted citation impact, top 5% 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

45 citing papers in PubMed, 1 synthesis or guideline pooled it, 123 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Paucibacterial Microbiome and Resident DNA Virome of the Healthy Conjunctiva.Investigative ophthalmology & visual science · 2016
    Trial
  4. Article
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  8. Review
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  14. Investigating the Ocular Surface Microbiome: What Can It Tell Us?Clinical ophthalmology (Auckland, N.Z.) · 2023
    Review
  15. Article
  16. Article
  17. Review
  18. Review
  19. Article
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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

5 authors at 3 institutions in 1 country.

Aaron Y LeeDepartment of Ophthalmology and Visual Science, Washington University, St. Louis, Missouri.
Lakshmi AkileswaranDepartment of Ophthalmology, University of Washington, Seattle, Washington.
Michael D TibbettsThe Retina Service of Wills Eye Hospital, MidAtlantic Retina, Philadelphia, Pennsylvania.
Sunir J GargThe Retina Service of Wills Eye Hospital, MidAtlantic Retina, Philadelphia, Pennsylvania.
Russell N Van GelderDepartment of Ophthalmology, University of Washington, Seattle, Washington; Department of Biological Structure, University of Washington, Seattle, Washington; Department of Pathology, University of Washington, Seattle, Washington. Electronic address: russvg@u.washington.edu.
University of Washington · USWills Eye Hospital · USWashington University in St. Louis · US

Funding

Vision Research CoreP30EY001730 · NEI · UNIVERSITY OF WASHINGTON · PI MAUREEN E NEITZ · 1985 to 2026
$23.5M
Diversity and Dynamic Stability of the Ocular Surface MicrobiomeR01EY022038 · NEI · UNIVERSITY OF WASHINGTON · PI SHESTOPALOV, VALERY I, VAN GELDER, RUSSELL N. · 2012 to 2016
$3.2M
NEI NIH HHS P30 EY001730NEI NIH HHS P30EY001730NEI NIH HHS R01 EY022038NEI NIH HHS R01EY022038
6 · The paper itself

Abstract

purposeTo test the hypothesis that uncultured organisms may be present in cases of culture-negative endophthalmitis by use of deep DNA sequencing of vitreous biopsies.

designSingle-center, consecutive, prospective, observational study.

participantsAqueous or vitreous biopsies from 21 consecutive patients presenting with presumed infectious endophthalmitis and 7 vitreous samples from patients undergoing surgery for noninfectious retinal disorders.

methodsTraditional bacterial and fungal culture, 16S quantitative polymerase chain reaction (qPCR), and a representational deep-sequencing method (biome representational in silico karyotyping [BRiSK]) were applied in parallel to samples to identify DNA sequences corresponding to potential pathogens.

main outcome measuresPresence of potential pathogen DNA in ocular samples.

resultsZero of 7 control eyes undergoing routine vitreous surgery yielded positive results for bacteria or virus by culture or 16S polymerase chain reaction (PCR). A total of 14 of the 21 samples (66.7%) from eyes harboring suspected infectious endophthalmitis were culture-positive, the most common being Staphylococcal and Streptococcal species. There was good agreement among culture, 16S bacterial PCR, and BRiSK methodologies for culture-positive cases (Fleiss' kappa of 0.621). 16S PCR did not yield a recognizable pathogen sequence in any culture-negative sample, whereas BRiSK suggested the presence of Streptococcus in 1 culture-negative sample. With the use of BRiSK, 57.1% of culture-positive and 100% of culture-negative samples demonstrated the presence of torque teno virus (TTV) sequences, compared with none in the controls (P=0.0005, Fisher exact test). The presence of TTV viral DNA was confirmed in 7 cases by qPCR. No other known viruses or potential pathogens were identified in these samples.

conclusionsCulture, 16S qPCR, and BRiSK provide complementary information in presumed infectious endophthalmitis. The majority of culture-negative endophthalmitis samples did not contain significant levels of bacterial DNA. "Culture negativity" does not seem to be due to failure of growth of fastidious bacteria. The small DNA virus TTV was unexpectedly found in all culture-negative samples and some culture-positive samples. This study cannot distinguish whether TTV is a direct intraocular pathogen, an adjuvant for inflammation, a general marker of inflammation, or a commensal virus but provides a testable hypothesis for a pathogenic mechanism in culture-negative endophthalmitis.

Indexed as

Sequence Analysis, DNAAgedAqueous HumorBacteriological TechniquesDNA, BacterialDNA, FungalDNA, ViralDNA Virus InfectionsEndophthalmitisEye Infections, ViralFemaleHigh-Throughput Nucleotide SequencingHumansKaryotypingMaleMetagenomeDNA, BacterialDNA, FungalDNA, ViralRNA, Ribosomal, 16S

Identifiers

PMID25439613
PMCPMC4339625
OpenAlexW1968634605

What OpenQuestion 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 OpenQuestion graph.