Evidence map›Paper›PMID 34448806›Full record

ArticleInvestigative ophthalmology & visual science2021

Hyperreflective Foci, Optical Coherence Tomography Progression Indicators in Age-Related Macular Degeneration, Include Transdifferentiated Retinal Pigment Epithelium.

Dongfeng Cao, Belinda Leong, Jeffrey D Messinger, Deepayan Kar, Thomas Ach, Lawrence A Yannuzzi, K Bailey Freund, Christine A Curcio

Open access · goldAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed
16.1field-weighted citation impact, top 1% 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

89 citing papers in PubMed, 126 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Non neovascular Age - related macular degeneration - Review on clinical and imaging advances.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026
    Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Time Course of Structural, Functional, Complement Changes and Inflammatory Processes in a Sodium Iodate Rat Model of Geographic Atrophy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  18. Spatial distribution of Intra-retinal Hyper-reflective foci and impact on progression in eyes with intermediate Age-related macular degeneration.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2025
    Article
  19. Article
  20. Article

29 more citing papers are in PubMed but not listed here.

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

8 authors at 5 institutions in 2 countries.

Dongfeng CaoDepartment of Ophthalmology and Visual Sciences, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States.
Belinda LeongVitreous Retina Macula Consultants of New York, New York, New York, United States.
Jeffrey D MessingerDepartment of Ophthalmology and Visual Sciences, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States.
Deepayan KarDepartment of Ophthalmology and Visual Sciences, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States.
Thomas AchDepartment of Ophthalmology, University Hospital Bonn, Bonn, Germany.
Lawrence A YannuzziVitreous Retina Macula Consultants of New York, New York, New York, United States.
K Bailey FreundVitreous Retina Macula Consultants of New York, New York, New York, United States.
Christine A CurcioDepartment of Ophthalmology and Visual Sciences, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States.
University of Alabama at Birmingham · USManhattan Eye, Ear and Throat Hospital · USRetina Associates · USUniversity Hospital Bonn · DEVitreous Retina Macula Consultants of New York · US

Funding

Visual Phenotyping CoreP30EY003039 · NEI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Paul Douglas Gamlin · 1985 to 2026
$16.9M
Validated Autofluorescence in Age-Related Macular DegenerationR01EY015520 · NEI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI SMITH, ROLAND THEODORE · 2005 to 2018
$6.0M
A hyperspectral approach to RPE fluorophores in AMDR01EY027948 · NEI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI ACH, THOMAS, CURCIO, CHRISTINE A · 2017 to 2025
$3.8M
NEI NIH HHS R01 EY015520NEI NIH HHS R01 EY027948
6 · The paper itself

Abstract

Purpose: By optical coherence tomography (OCT) imaging, hyperreflective foci (HRF) indicate progression risk for advanced age-related macular degeneration (AMD) and are in part attributable to ectopic retinal pigment epithelium (RPE). We hypothesized that ectopic RPE are molecularly distinct from in-layer cells and that their cross-retinal course follows Müller glia. Methods: In clinical OCT (61 eyes, 44 patients with AMD, 79.4 ± 7.7 years; 29 female; follow-up = 4.7 ± 0.9 years), one HRF type, RPE plume (n = 129 in 4 morphologies), was reviewed. Twenty eyes of 20 donors characterized by ex vivo OCT were analyzed by histology (normal, 4; early/intermediate AMD, 7; geographic atrophy, 6; neovascular AMD, 3). Cryosections were stained with antibodies to retinoid (RPE65, CRALPB) and immune (CD68, CD163) markers. In published RPE cellular phenotypes, red immunoreactivity was assessed semiquantitatively by one observer (none, some cells, all cells). Results: Plume morphology evolved over time and many resolved (40%). Trajectories of RPE plume and cellular debris paralleled Müller glia, including near atrophy borders. RPE corresponding to HRF lost immunoreactivity for retinoid markers and gained immunoreactivity for immune markers. Aberrant immunoreactivity appeared in individual in-layer RPE cells and extended to all abnormal phenotypes. Müller glia remained CRALBP positive. Plume cells approached and contacted retinal capillaries. Conclusions: HRF are indicators not predictors of overall disease activity. Gain and loss of function starts with individual in-layer RPE cells and extends to all abnormal phenotypes. Evidence for RPE transdifferentiation, possibly due to ischemia, supports a proposed process of epithelial-mesenchyme transition. Data can propel new biomarkers and therapeutic strategies for AMD.

Indexed as

AgedAged, 80 and overCell TransdifferentiationDisease ProgressionFemaleFluorescein AngiographyFollow-Up StudiesFundus OculiHumansMalePrognosisRefraction, OcularRetinal Pigment EpitheliumTime FactorsTomography, Optical CoherenceWet Macular Degeneration

Identifiers

PMID34448806
PMCPMC8399556
OpenAlexW3193777758

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.