Evidence map›Paper›PMID 28814675›Full record

ArticleJCI insight2017

Retinal amyloid pathology and proof-of-concept imaging trial in Alzheimer's disease.

Yosef Koronyo, David Biggs, Ernesto Barron, David S Boyer, Joel A Pearlman, William J Au, Shawn J Kile, Austin Blanco, Dieu-Trang Fuchs, Adeel Ashfaq and 7 more

2 registry-linked trialsOpen access · goldAbstract read
In one paragraph

Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 323 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
323citing papers in PubMed, 3 pooled it
25.7field-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.

NCT05062486 phase2completednot on this mapstarted 2021, after this paper: background citation

An Open-Label, Randomized, Double Arm, Phase 2 Study to Evaluate the Safety and Efficacy of C and RQC for Preventing Progression in Age-Related Macular Degeneration

TypeinterventionalSponsorPaul A Knepper, MD PhDRan2021 to 2024Enrolled55ConditionsAge-related Macular DegenerationArmsResveratrol, Quercetin, Curcumin (RQC), Curcumin
NCT06470061 phase2not yet recruitingnot on this mapstarted 2024, after this paper: background citation

A Randomized Phase II Study to Evaluate Oral RQC for the Prevention of Alzheimer's Disease and Retinal Amyloid-β

TypeinterventionalSponsorZaparackas and Knepper LTDRan2024 to 2027Enrolled200ConditionsAlzheimer Disease, Mild Cognitive Impairment, Cognitive DeclineArmsResveratrol, Quercetin, and Curcumin (RQC), Curcumin
3 · Its place in the literature

Who cites it

323 citing papers in PubMed, 3 syntheses or guidelines pooled it, 509 citations in OpenAlex.

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  20. Complement in brain and eye disease: shared mechanisms, convergent pathologies, and common therapeutic opportunities.Mammalian genome : official journal of the International Mammalian Genome Society · 2026
    Review

263 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

17 authors at 8 institutions in 1 country.

Yosef KoronyoDepartment of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
David BiggsNeuroVision Imaging LLC, Sacramento, California, USA.
Ernesto BarronDoheny Eye Institute, Los Angeles, California, USA.
David S BoyerRetina Vitreous Associates Medical Group, Beverly Hills, California, USA.
Joel A PearlmanRetinal Consultants Medical Group, Sacramento, California, USA.
William J AuSutter Neuroscience Institute, Sacramento, California, USA.
Shawn J KileSutter Neuroscience Institute, Sacramento, California, USA.
Austin BlancoNeuroVision Imaging LLC, Sacramento, California, USA.
Dieu-Trang FuchsDepartment of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Adeel AshfaqDavid Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Sally FrautschyDepartments of Neurology and Medicine, University of California, Los Angeles, Los Angeles, California, USA; Geriatric Research Education and Clinical Center, Los Angeles, California, USA; and Veterans Greater Los Angeles Healthcare System, Los Angeles, California, USA.
Gregory M ColeDepartments of Neurology and Medicine, University of California, Los Angeles, Los Angeles, California, USA; Geriatric Research Education and Clinical Center, Los Angeles, California, USA; and Veterans Greater Los Angeles Healthcare System, Los Angeles, California, USA.
Carol A MillerDepartment of Pathology Program in Neuroscience, Keck School of Medicine, and.
David R HintonDepartments of Pathology and Ophthalmology, USC Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Steven R VerdoonerNeuroVision Imaging LLC, Sacramento, California, USA.
Keith L BlackDepartment of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Maya Koronyo-HamaouiDepartment of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Cedars-Sinai Medical Center · USNVision Eye Centers (United States) · USUniversity of California, Los Angeles · USSutter Medical Center · USCalifornia Retina Consultants · USDoheny Eye Institute · USRetina Vitreous Associates Medical Group · USSouthern California Eye Institute · US

Funding

VASCULAR RISK AND COGNITIVE STATUS IN A LATINO POPULATIONP50AG005142 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ARANDA, MARIA P. · 1985 to 2019
$41.0M
Alzheimer's Disease Hallmark Pathology and Associated Inflammation in the RetinaR01AG055865 · NIA · CEDARS-SINAI MEDICAL CENTER · PI Maya Koronyo-Hamaoui · 2018 to 2026
$4.9M
Retinal Imaging of Alzheimer's Disease PathologyR01AG056478 · NIA · CEDARS-SINAI MEDICAL CENTER · PI KORONYO-HAMAOUI, MAYA · 2017 to 2021
$2.5M
A noninvasive optical imaging of retinal amyloid beta deposits in AD patientsR41AG044897 · NIA · NEUROVISION IMAGING, LLC · PI KORONYO-HAMAOUI, MAYA · 2013 to 2013
$151k
NIA NIH HHS P50 AG005142NIA NIH HHS R01 AG055865NIA NIH HHS R01 AG056478NIA NIH HHS R41 AG044897
6 · The paper itself

Abstract

backgroundNoninvasive detection of Alzheimer's disease (AD) with high specificity and sensitivity can greatly facilitate identification of at-risk populations for earlier, more effective intervention. AD patients exhibit a myriad of retinal pathologies, including hallmark amyloid β-protein (Aβ) deposits.

methodsBurden, distribution, cellular layer, and structure of retinal Aβ plaques were analyzed in flat mounts and cross sections of definite AD patients and controls (n = 37). In a proof-of-concept retinal imaging trial (n = 16), amyloid probe curcumin formulation was determined and protocol was established for retinal amyloid imaging in live patients.

resultsHistological examination uncovered classical and neuritic-like Aβ deposits with increased retinal Aβ42 plaques (4.7-fold; P = 0.0063) and neuronal loss (P = 0.0023) in AD patients versus matched controls. Retinal Aβ plaque mirrored brain pathology, especially in the primary visual cortex (P = 0.0097 to P = 0.0018; Pearson's r = 0.84-0.91). Retinal deposits often associated with blood vessels and occurred in hot spot peripheral regions of the superior quadrant and innermost retinal layers. Transmission electron microscopy revealed retinal Aβ assembled into protofibrils and fibrils. Moreover, the ability to image retinal amyloid deposits with solid-lipid curcumin and a modified scanning laser ophthalmoscope was demonstrated in live patients. A fully automated calculation of the retinal amyloid index (RAI), a quantitative measure of increased curcumin fluorescence, was constructed. Analysis of RAI scores showed a 2.1-fold increase in AD patients versus controls (P = 0.0031).

conclusionThe geometric distribution and increased burden of retinal amyloid pathology in AD, together with the feasibility to noninvasively detect discrete retinal amyloid deposits in living patients, may lead to a practical approach for large-scale AD diagnosis and monitoring.

fundingNational Institute on Aging award (AG044897) and The Saban and The Marciano Family Foundations.

Indexed as

NeuroscienceOphthalmology

Identifiers

PMID28814675
PMCPMC5621887
OpenAlexW2750510345

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.