Evidence map›Paper›PMID 39983974›Full record

ReviewExperimental eye research2025

Dissecting the biological complexity of age-related macular degeneration: Is it one disease, multiple separate diseases, or a spectrum?

Jason M L Miller, Benjamin R Thompson, James T Handa, Philip Luthert, Usha Chakravarthy, Karl G Csaky, Alan Bird, Benjamin K Young, Sudha K Iyengar, Jiwon Baek and 8 more

Abstract readReview
In one paragraph

Review in Experimental eye research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–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.

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

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Tomographic phenotypes and conditional time to atrophic conversion in dry age-related macular degeneration among progressors: an interval-censored study.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026
    Article
  4. Article
  5. 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

18 authors.

Jason M L MillerUniversity of Michigan, Kellogg Eye Center and Cellular and Molecular Biology Program, Ann Arbor, MI, USA. Electronic address: miljason@umich.edu.
Benjamin R ThompsonNorthwestern University Feinberg School of Medicine, Department of Ophthalmology and Feinberg Cardiovascular and Renal Research Inst., Chicago, IL, USA.
James T HandaJohns Hopkins Medical School, Wilmer Eye Institute, Baltimore, MD, USA.
Philip LuthertUCL Institute of Ophthalmology, London, United Kingdom.
Usha ChakravarthyQueens University of Belfast, Center for Public Health, Belfast, Ireland.
Karl G CsakyRetina Foundation of the Southwest, Dallas, TX, USA.
Alan BirdUCL Institute of Ophthalmology, London, United Kingdom.
Benjamin K YoungOregon Health Sciences University, Department of Ophthalmology, Portland, OR, USA.
Sudha K IyengarCase Western Reserve University, Department of Population and Quantitative Health Sciences, Cleveland, OH, USA.
Jiwon BaekDepartment of Ophthalmology, College of Medicine, The Catholic University of Korea, South Korea.
Moussa A ZouacheUniversity of Utah, Department of Ophthalmology and Visual Sciences, Salt Lake City, UT, USA.
Burt T RichardsUniversity of Utah, Department of Ophthalmology and Visual Sciences, Salt Lake City, UT, USA.
Gregory S HagemanUniversity of Utah, Department of Ophthalmology and Visual Sciences, Salt Lake City, UT, USA.
Gerry RodriguesAllergan/Abbvie, Ophthalmology Discovery Research, Laguna Niguel, CA, USA.
Kapil BhartiNational Eye Institute, National Institutes of Health, Bethesda, MD, USA.
John G FlanneryUniversity of California, Berkeley, Department of Neuroscience, Berkeley, CA, USA.
Michael B GorinDavid Geffen School of Medicine, Stein Eye Institute, Los Angeles, CA, USA. Electronic address: gorin@jsei.ucla.edu.
Catherine Bowes RickmanDuke University Medical Center, Departments of Ophthalmology and of Cell Biology, Durham, NC, USA. Electronic address: bowes007@duke.edu.

Funding

A Resource for Genetic Epidemiology Research in Adult Health and AgingRC2AG036607 · NIA · KAISER FOUNDATION RESEARCH INSTITUTE · PI RISCH, NEIL J., SCHAEFER, CATHERINE ANN · 2009 to 2010
$24.8M
VISION RESEARCHP30EY005722 · NEI · DUKE UNIVERSITY · PI Goldis Malek · 1985 to 2026
$19.3M
Understanding the molecular mechanisms that contribute to neuropsychiatric symptoms in Alzheimer DiseaseR01AG067025 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI FINKBEINER, STEVEN M, HAROUTUNIAN, VAHRAM · 2019 to 2023
$11.8M
Higher Order Chromatin and Genetic Risk for Alzheimer's DiseaseR01AG050986 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ROUSSOS, PANAGIOTIS · 2015 to 2025
$11.2M
Understanding the protective and neuroinflammatory role of human brain immune cells in Alzheimer DiseaseR01AG065582 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HAROUTUNIAN, VAHRAM, ROUSSOS, PANAGIOTIS · 2020 to 2024
$9.9M
The 3D genome in transcriptional regulation across the postnatal life span, with implications for schizophrenia and bipolar disorderU01MH116442 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AKBARIAN, SCHAHRAM, DRACHEVA, STELLA · 2018 to 2022
$5.9M
Multiethnic genomic epigenomic and transcriptomic fine-mapping and functional validation analysis of schizophrenia and bipolar disorder risk lociR01MH125246 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ROUSSOS, PANAGIOTIS · 2021 to 2025
$5.0M
International Advancing genomics through the AMD Genomics Consortium (IAMDGC)R01EY022310 · NEI · VANDERBILT UNIVERSITY · PI BLANTON, SUSAN HALLORAN, HAINES, JONATHAN L · 2012 to 2024
$4.9M
Nrf2 signaling and oxidative stress in Age-related macular degenerationR01EY019904 · NEI · JOHNS HOPKINS UNIVERSITY · PI HANDA, JAMES T · 2010 to 2016
$4.1M
Complement factor H modulates lipoprotein clearance in AMDR01EY031748 · NEI · DUKE UNIVERSITY · PI BOWES RICKMAN, CATHERINE · 2020 to 2024
$2.8M
Oxidative stress and innate immunity impair the visual cycleR01EY027691 · NEI · JOHNS HOPKINS UNIVERSITY · PI HANDA, JAMES T · 2017 to 2021
$2.7M
The role of Angiopoietin-TEK signaling in polypoidal choroidal vasculopathyR01EY032609 · NEI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI THOMSON, BENJAMIN R. · 2021 to 2025
$2.0M
BLRD VA I01 BX003364BLRD VA I01 BX004189BLRD VA I01 BX004557BLRD VA IK6 BX005233BLRD VA IK6 BX005787NEI NIH HHS K08 EY033420NEI NIH HHS P30 EY005722NEI NIH HHS R01 EY019904NEI NIH HHS R01 EY022310NEI NIH HHS R01 EY027004NEI NIH HHS R01 EY027691NEI NIH HHS R01 EY031748NEI NIH HHS R01 EY032609NEI NIH HHS R01 EY035805NIA NIH HHS R01 AG050986NIA NIH HHS R01 AG065582NIA NIH HHS R01 AG067025NIA NIH HHS RC2 AG036607NIMH NIH HHS K08 MH122911NIMH NIH HHS R01 MH125246NIMH NIH HHS U01 MH116442
6 · The paper itself

Abstract

Clinicians recognize the heterogeneity of age-related macular degeneration (AMD) in presentation, progression, and treatment response, as well as the challenges in distinguishing it from other macular degenerations. As part of the 2024 Ryan Initiative for Macular Research meeting, a group of clinician-scientists and basic scientists were convened to consider the question of whether AMD should be classified as a single disorder or a spectrum of conditions. To answer this question, we reviewed research on several "dimensions" that constitute AMD risk or pathogenesis: genetics, ancestry, retinal imaging findings, diet and environment, aging, and outer retinal molecular and cellular pathways. The group reached a consensus that AMD represents a heterogeneous collection of disease states arising from the interplay of these dimensions. This heterogeneity can be conceived of as a "cloud" of AMD phenotypes. Defining subtypes within this "cloud" requires longitudinal cohorts of well-genotyped and phenotyped patients who progress from no AMD through late AMD, analyzed by unsupervised learning. Comparing the AMD subtypes that emerge from this analysis, especially -omics data from each subtype, will illuminate biology that is applicable to certain subtypes of AMD patients and molecular pathogenic mechanisms that universally apply to all AMD. This knowledge will, in turn, drive improved drug development.

Indexed as

Macular DegenerationDisease ProgressionHumansAgingAncestryDietEnvironmentGeneticsRPESubgroups of AMD

Identifiers

PMID39983974
PMCPMC12066171

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.