Evidence map›Paper›PMID 27471039›Full record

Trial reportThe British journal of ophthalmology2016

Response to AREDS supplements according to genetic factors: survival analysis approach using the eye as the unit of analysis.

Johanna M Seddon, Rachel E Silver, Bernard Rosner

Registry-linked trialAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The British journal of ophthalmology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00594672 (Age-Related Eye Disease Study), which is not on this map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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.

NCT00594672 active not recruitingnot on this map

Age-Related Eye Disease Study (AREDS) and AREDS2 Follow-Up

TypeobservationalSponsorNational Eye Institute (NEI)Ran2008Enrolled110ConditionsAge-Related Macular Degeneration, Cataract
3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Trial
  4. Proceedings of the National Academy of Sciences of the United States of America · 2018
    Trial
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  7. Article
  8. Review
  9. Article
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  15. Article
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  17. Risk factors for progression of age-related macular degeneration.Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists) · 2020
    Review
  18. Review
  19. Review
  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

3 authors.

Johanna M SeddonOphthalmic Epidemiology and Genetics Service, New England Eye Center, Tufts Medical Center, Boston, Massachusetts, USA.
Rachel E SilverOphthalmic Epidemiology and Genetics Service, New England Eye Center, Tufts Medical Center, Boston, Massachusetts, USA.
Bernard RosnerChanning Division of Network Medicine, Harvard Medical School, Harvard University, Boston, Massachusetts, USA.

Funding

ETIOLOGIC STUDIES OF AGE-RELATED MACULAR DEGENERATIONR01EY011309 · NEI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI SEDDON, JOHANNA M · 2003 to 2017
$9.3M
Use of Correlated Data Methods in OphthalmologyR01EY022445 · NEI · BRIGHAM AND WOMEN'S HOSPITAL · PI ROSNER, BERNARD A · 2013 to 2025
$4.6M
NEI NIH HHS R01 EY011309NEI NIH HHS R01 EY022445
6 · The paper itself

Abstract

BACKGROUND/

aimsThe Age-Related Eye Disease Study (AREDS) reported the beneficial impact of antioxidant and zinc supplements on the risk of progression to advanced stages of age-related macular degeneration (AMD). We evaluated the role of genetic variants in modifying the relationship between supplementation and progression to advanced AMD.

methodsAmong 4124 eyes (2317 subjects with a genetic specimen), 882 progressed from no AMD, early or intermediate AMD to overall advanced disease, including geographic atrophy (GA) and neovascular disease (NV) over the course of the clinical trial. Survival analysis using individual eyes as the unit of analysis was used to assess the effect of supplementation on AMD outcomes, with adjustment for demographic, environmental, ocular and genetic covariates. Interaction effects between supplement groups and individual complement factor H (CFH) Y402H and age-related maculopathy susceptibility 2 (ARMS2) genotypes, and composite genetic risk groups combining the number of risk alleles for both loci, were evaluated for their association with progression.

resultsAmong antioxidant and zinc supplement users compared with the placebo group, subjects with a non-risk genotype for CFH (TT) had a lower risk of progression to advanced AMD (HR: 0.55, 95% CI 0.32 to 0.95, p=0.033). No significant treatment effect was apparent among subjects who were homozygous for the CFH risk allele (CC). A protective effect was observed among high-risk ARMS2 (TT) carriers (HR: 0.52, 95% CI 0.33 to 0.82, p=0.005). Similar results were seen for the NV subtype but not GA.

conclusionsThe effectiveness of antioxidant and zinc supplementation appears to differ by genotype. Further study is needed to determine the biological basis for this interaction. TRIAL REGISTRATION NUMBER: NCT00594672, pre-results.

Indexed as

Polymorphism, Single NucleotideAgedAllelesAntioxidantsComplement Factor HDietary SupplementsDisease ProgressionDNADouble-Blind MethodFemaleFollow-Up StudiesGenotypeGeographic AtrophyHumansMaleMiddle AgedAntioxidantsARMS2 protein, humanCFH protein, humanComplement Factor HDNAProteinsZinc CompoundsEpidemiologyGeneticsMaculaTreatment other

Identifiers

PMID27471039
PMCPMC6570490

What OpenQuestion holds

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Registered trials

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.