Arteriosclerotic retinopathy is an ontology-backed name for funduscopically visible sclerosis of retinal arterioles. Contemporary screening studies more often call the finding retinal or fundus arteriosclerosis and grade it with a modified Scheie S scale or retinal arteriosclerosis index. It is primarily a retinal vascular morphology, often detected incidentally, rather than a syndrome defined by visual symptoms. It correlates with age, hypertension, and several systemic vascular or metabolic conditions, but cross-sectional associations must not be interpreted as proof that the retinal finding directly causes or specifically measures systemic atherosclerosis.
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Conditions with similar clinical presentations that must be differentiated from Arteriosclerotic Retinopathy:
name: Arteriosclerotic Retinopathy
creation_date: "2026-05-06T17:24:49Z"
description: >-
Arteriosclerotic retinopathy is an ontology-backed name for funduscopically
visible sclerosis of retinal arterioles. Contemporary screening studies more
often call the finding retinal or fundus arteriosclerosis and grade it with a
modified Scheie S scale or retinal arteriosclerosis index. It is primarily a
retinal vascular morphology, often detected incidentally, rather than a
syndrome defined by visual symptoms. It correlates with age, hypertension,
and several systemic vascular or metabolic conditions, but cross-sectional
associations must not be interpreted as proof that the retinal finding
directly causes or specifically measures systemic atherosclerosis.
category: Complex
disease_term:
preferred_term: arteriosclerotic retinopathy
term:
id: MONDO:0042495
label: arteriosclerotic retinopathy
parents:
- Arteriosclerosis disorder
- Retinal vascular disorder
synonyms:
- Retinal arteriosclerosis
- Fundus arteriosclerosis
- Arteriosclerosis disorder of retina
- Retina arteriosclerosis disorder
- Retinopathy, arteriosclerotic
prevalence:
- population: South Korean tertiary-center health-screening cohort, 2003-2010
measure_type: POINT_PREVALENCE
prevalence_class: ABOVE_1_IN_1000
rate_per_100000: 4500.0
percentage: 4.5
notes: >-
This is the prevalence of high-grade retinal arteriosclerosis index (RAI
grade 2 or higher) among 74,608 screened adults, not a global disease
prevalence. Selection into health screening, the modified grading system,
and the study population limit generalization.
evidence:
- reference: PMID:42193361
reference_title: "Retinal Arteriosclerosis in a Large Health Screening Cohort: Associations with Systemic Vascular Comorbidities and Stroke in Young Adults."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: High-grade RAI was prespecified as ≥2.
explanation: This supplies the threshold used for the cohort-specific estimate.
- reference: PMID:42193361
reference_title: "Retinal Arteriosclerosis in a Large Health Screening Cohort: Associations with Systemic Vascular Comorbidities and Stroke in Young Adults."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: High-grade RAI was present in 4.5% of the participants and increased with age.
explanation: This supplies the observed high-grade RAI prevalence in the screened cohort.
pathophysiology:
- name: Fundus-defined retinal arteriolar sclerosis
biological_scale: TISSUE
mechanism_confidence: ESTABLISHED
description: >-
The curated disease identity is the chronic arteriolar-wall phenotype
operationalized by modified Scheie atherosclerotic/S grading. The visible
pattern includes alteration of the arteriolar light reflex and
arteriovenous crossing signs. The available population studies establish
the imaging phenotype and its correlates, but do not establish a unique
molecular lesion or prove that every such sign represents systemic plaque
atherosclerosis.
locations:
- preferred_term: retina
term:
id: UBERON:0000966
label: retina
- preferred_term: retinal arteriole
term:
id: UBERON:0001980
label: arteriole
biological_processes:
- preferred_term: blood vessel remodeling
modifier: ABNORMAL
term:
id: GO:0001974
label: blood vessel remodeling
evidence:
- reference: PMID:42193361
reference_title: "Retinal Arteriosclerosis in a Large Health Screening Cohort: Associations with Systemic Vascular Comorbidities and Stroke in Young Adults."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Retinal arteriosclerosis was graded (0-4) by masked readers with a modified
Scheie classification; a higher eye grade was defined as a person-level grade.
explanation: >-
The current large screening study operationalizes retinal
arteriosclerosis as a graded fundus phenotype.
- reference: PMID:33239480
reference_title: Examination of Large Artery Atherosclerosis could Reveal Small Artery Retinopathy in Untreated Middle-Aged Individuals.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The absence or presence and extent of retinopathy were characterized by
ophthalmologists as hypertensive (H0-4) and atherosclerotic grades (S0-4)
based on Scheie classification.
explanation: >-
Scheie grading explicitly records separate hypertensive and
atherosclerotic axes rather than treating them as interchangeable.
downstream:
- target: Enhanced retinal arteriolar light reflex
causal_link_type: UNKNOWN
description: >-
Enhanced wall reflex is part of the visible arteriosclerotic pattern, but
its optical and histologic specificity is limited and the population
evidence is observational.
evidence:
- reference: PMID:17070582
reference_title: "Prevalence and associations of enhanced retinal arteriolar light reflex: a new look at an old sign."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The enhanced arteriolar light reflex sign was found in 1053 participants
(31.7%, including 28.8% graded as mild and 2.9% as marked).
explanation: >-
This establishes the graded fundus sign but not a one-to-one causal or
histologic mapping to retinal arteriosclerosis.
- target: Arteriovenous crossing sign
causal_link_type: UNKNOWN
description: >-
Arteriovenous nicking or crossing change clusters with enhanced arteriolar
wall reflex, but the available cohort evidence supports association rather
than a uniquely attributable causal pathway.
evidence:
- reference: PMID:17070582
reference_title: "Prevalence and associations of enhanced retinal arteriolar light reflex: a new look at an old sign."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Strong associations were demonstrated between presence of mildly enhanced
light reflex and either arteriovenous nicking (OR 3.12) or retinopathy
(OR 1.96).
explanation: >-
The population study supports co-occurrence of the two fundus signs but
not causal direction or disease specificity.
phenotypes:
- category: Ophthalmologic
name: Enhanced retinal arteriolar light reflex
diagnostic: true
description: >-
Broadening or intensification of the central arteriolar light reflex is a
classic visible vessel-wall sign. The sign is not specific: in a general
older population it was common, and only the marked grade correlated with
elevated blood pressure after adjustment.
evidence:
- reference: PMID:17070582
reference_title: "Prevalence and associations of enhanced retinal arteriolar light reflex: a new look at an old sign."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In this older population, the enhanced retinal arteriolar light reflex sign
was a relatively common finding.
explanation: This directly identifies the classic arteriolar wall-reflex sign.
- reference: PMID:17070582
reference_title: "Prevalence and associations of enhanced retinal arteriolar light reflex: a new look at an old sign."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Although some associations of this sign with vascular risk factors were
found, only a marked level of enhanced light reflex was correlated with
elevated blood pressure, but not with poor survival.
explanation: >-
This bounds the sign's specificity and prognostic interpretation.
- category: Ophthalmologic
name: Arteriovenous crossing sign
diagnostic: true
description: >-
Arteriovenous nicking is a crossing-site change that can accompany the
arteriosclerotic wall-reflex phenotype. It also occurs with cumulative
hypertensive vascular injury and therefore does not distinguish etiology by
itself.
phenotype_term:
preferred_term: Arteriovenous crossing sign
term:
id: HP:6001216
label: Arteriovenous crossing sign
evidence:
- reference: PMID:17070582
reference_title: "Prevalence and associations of enhanced retinal arteriolar light reflex: a new look at an old sign."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Strong associations were demonstrated between presence of mildly enhanced
light reflex and either arteriovenous nicking (OR 3.12) or retinopathy
(OR 1.96).
explanation: This directly supports arteriovenous nicking as a co-occurring retinal sign.
- reference: PMID:11525792
reference_title: "Retinal microvascular abnormalities and their relationship with hypertension, cardiovascular disease, and mortality."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Generalized arteriolar narrowing and arteriovenous nicking also appear to
be irreversible long-term markers of hypertension, related not only to
current but past blood pressure levels as well.
explanation: >-
This shows why arteriovenous nicking cannot be interpreted as specific to
atherosclerotic disease or current blood pressure.
environmental:
- name: Hypertension and cumulative blood-pressure exposure
presence: Positive
description: >-
Hypertension is strongly associated with high-grade retinal
arteriosclerosis, and arteriovenous nicking can reflect past as well as
current blood pressure. These data support a vascular-risk context, not a
claim that every Scheie S sign is caused only by hypertension.
evidence:
- reference: PMID:42193361
reference_title: "Retinal Arteriosclerosis in a Large Health Screening Cohort: Associations with Systemic Vascular Comorbidities and Stroke in Young Adults."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
After adjustment, high-grade RAI was associated with hypertension (OR,
2.97; 95% CI, 2.73-3.23)
explanation: >-
The large current screening cohort establishes an adjusted association
between hypertension and high-grade RAI.
- reference: PMID:11525792
reference_title: "Retinal microvascular abnormalities and their relationship with hypertension, cardiovascular disease, and mortality."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Retinal microvascular abnormalities, such as generalized and focal
arteriolar narrowing, arteriovenous nicking and retinopathy, reflect
cumulative vascular damage from hypertension, aging, and other processes.
explanation: >-
The review supports cumulative pressure exposure and aging as contributors
while explicitly allowing other processes.
- name: Type 2 diabetes and metabolic syndrome
presence: Associated
description: >-
High-grade RAI was associated with type 2 diabetes and metabolic syndrome in
the large screening cohort. These cross-sectional correlations do not show
that the finding is diabetic retinopathy or establish causal direction.
evidence:
- reference: PMID:42193361
reference_title: "Retinal Arteriosclerosis in a Large Health Screening Cohort: Associations with Systemic Vascular Comorbidities and Stroke in Young Adults."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
After adjustment, high-grade RAI was associated with hypertension (OR,
2.97; 95% CI, 2.73-3.23), diabetes mellitus (OR, 1.35; 95% CI,
1.22-1.50), cardiovascular disease (OR, 1.46; 95% CI, 1.25-1.71),
metabolic syndrome (OR, 1.63; 95% CI, 1.49-1.78), and stroke (OR, 1.98;
95% CI, 1.41-2.79) but not with hyperlipidemia.
explanation: >-
The study provides adjusted cross-sectional associations with diabetes and
metabolic syndrome and also shows that hyperlipidemia was not associated.
diagnosis:
- name: Modified Scheie S-grade fundus assessment
description: >-
Dilated fundus examination or color fundus photography can identify and
grade retinal arteriosclerotic signs. The S or retinal-arteriosclerosis axis
must be recorded separately from the Scheie H hypertensive-retinopathy axis.
Modern cohorts use modified protocols, so a grade is method-dependent rather
than a universal molecular diagnosis.
diagnosis_term:
preferred_term: eye examination
term:
id: NCIT:C38060
label: Eye Examination
results: >-
Modified Scheie S or RAI grade 0-4 based on fundus-defined arteriolar
sclerosis; report the eye-level method, reader protocol, and threshold.
evidence:
- reference: PMID:42193361
reference_title: "Retinal Arteriosclerosis in a Large Health Screening Cohort: Associations with Systemic Vascular Comorbidities and Stroke in Young Adults."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Retinal arteriosclerosis was graded (0-4) by masked readers with a modified
Scheie classification; a higher eye grade was defined as a person-level grade.
explanation: This directly supports masked modified-Scheie grading from fundus images.
- reference: PMID:33239480
reference_title: Examination of Large Artery Atherosclerosis could Reveal Small Artery Retinopathy in Untreated Middle-Aged Individuals.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The absence or presence and extent of retinopathy were characterized by
ophthalmologists as hypertensive (H0-4) and atherosclerotic grades (S0-4)
based on Scheie classification.
explanation: This directly supports separate H and S grading by ophthalmologists.
differential_diagnoses:
- name: Hypertensive retinopathy
description: >-
Hypertensive retinopathy reflects pressure-related retinal vascular and, in
severe disease, parenchymal injury. Arteriolar narrowing belongs primarily
to the hypertensive axis, while hemorrhages, hard exudates, cotton-wool spots,
and optic-disc edema indicate more severe acute hypertensive injury. Chronic
wall-reflex and crossing changes can coexist, so blood pressure and the
complete fundus pattern must be interpreted together.
distinguishing_features:
- Modified Scheie H and S grades are separate axes and should both be reported when used.
- Generalized or focal arteriolar narrowing favors the hypertensive vascular response rather than isolated arteriosclerotic S grading.
- Retinal hemorrhages, hard exudates, cotton-wool spots, or optic-disc edema indicate parenchymal hypertensive injury and should not be collapsed into arteriosclerotic retinopathy.
evidence:
- reference: PMID:24121878
reference_title: "[Hypertensive changes of the fundus]."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Hypertensive retinopathy causes vascular constriction of retinal arterioles
and typical fundus findings, such as blot hemorrhages, hard exudates and
cotton wool spots resulting from ischemia within the nerve fiber layer.
explanation: >-
The review distinguishes constrictive and parenchymal hypertensive changes
from the chronic arteriosclerotic wall phenotype.
- reference: PMID:24121878
reference_title: "[Hypertensive changes of the fundus]."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Therefore, early stages with pure vascular pathology should be differentiated
from severe forms of hypertensive retinopathy with parenchymal changes of
the fundus.
explanation: This explicitly supports separating vascular signs from severe hypertensive retinopathy.
discussions:
- discussion_id: arteriosclerotic_retinopathy_nomenclature_and_scope
prompt: >-
Should arteriosclerotic retinopathy be treated as a distinct clinical
diagnosis, or as a graded retinal arteriolar morphology within broader
hypertensive and vascular-risk assessment?
kind: CONTROVERSY
status: OPEN
attaches_to:
- pathophysiology#Fundus-defined retinal arteriolar sclerosis
- diagnosis#Modified Scheie S-grade fundus assessment
rationale: >-
MONDO retains the disease label, whereas current clinical cohorts more often
use retinal arteriosclerosis, fundus arteriosclerosis, RAI, or modified
Scheie S grading. H and S axes overlap clinically but are not interchangeable,
and grading systems vary across studies.
evidence:
- reference: PMID:33239480
reference_title: Examination of Large Artery Atherosclerosis could Reveal Small Artery Retinopathy in Untreated Middle-Aged Individuals.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The absence or presence and extent of retinopathy were characterized by
ophthalmologists as hypertensive (H0-4) and atherosclerotic grades (S0-4)
based on Scheie classification.
explanation: The study demonstrates the continuing but separate use of H and S axes.
- reference: PMID:42193361
reference_title: "Retinal Arteriosclerosis in a Large Health Screening Cohort: Associations with Systemic Vascular Comorbidities and Stroke in Young Adults."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Retinal arteriosclerosis was graded (0-4) by masked readers with a modified
Scheie classification; a higher eye grade was defined as a person-level grade.
explanation: The current study uses retinal arteriosclerosis and RAI terminology rather than a symptom-defined retinopathy syndrome.
- discussion_id: systemic_biomarker_causality_and_treatment_gap
prompt: >-
Do retinal arteriosclerotic grades independently predict future systemic
vascular events, and does treatment of systemic risk factors alter the
retinal grade or patient outcomes?
kind: KNOWLEDGE_GAP
status: OPEN
attaches_to:
- diagnosis#Modified Scheie S-grade fundus assessment
rationale: >-
Recent cohorts show adjusted cross-sectional associations, but the available
evidence does not establish temporal direction, independent causal
specificity for systemic atherosclerosis, or a lesion-directed treatment
effect. No disease-specific ocular therapy is curated without intervention
evidence.
evidence:
- reference: PMID:42193361
reference_title: "Retinal Arteriosclerosis in a Large Health Screening Cohort: Associations with Systemic Vascular Comorbidities and Stroke in Young Adults."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
These findings support the potential role of retinal vascular changes as
cross-sectional correlates of systemic vascular health. Longitudinal studies
are needed to clarify temporal relationships and causality.
explanation: The newest large cohort explicitly limits its conclusions to cross-sectional correlation.
- reference: PMID:11525792
reference_title: "Retinal microvascular abnormalities and their relationship with hypertension, cardiovascular disease, and mortality."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
There are data supporting an association between retinal microvascular
abnormalities and stroke, but there is no convincing evidence of an
independent or direct association with atherosclerosis, ischemic heart
disease, or cardiovascular mortality.
explanation: >-
The review records the longstanding uncertainty about direct systemic
atherosclerosis and cardiovascular-outcome specificity.
review_notes: >-
Re-review treated the MONDO class as a retinal arteriolar morphology that is
still used in modified Scheie/RAI screening literature, while recognizing
that the standalone label is not a standardized contemporary symptomatic
syndrome. Retinal arteriolar narrowing, hemorrhages, hard exudates,
cotton-wool spots, and optic-disc edema were not normalized as core phenotypes
because they belong chiefly to hypertensive or other retinal injury patterns.
OCT/OCTA cardiovascular analytics, serum urate, alcohol, and lipid associations
were not promoted to diagnostic or causal mechanisms. No genetic cause,
disease-specific biochemical biomarker, lesion-specific treatment, or clinical
trial is asserted. The hypertensive-retinopathy differential is left without a
structured disease binding because its current MONDO identifier does not pass
the project's DiseaseTerm closure. Deep-research reports were treated only as
leads; retained claims were checked against cached primary or review literature.
Arteriosclerotic retinopathy denotes chronic retinal arteriolar remodeling/“hardening” related to arteriosclerosis/atherosclerosis and long-standing vascular risk exposure. In one clinical definition used in CKD/hemodialysis research, arteriosclerotic retinopathy is described as a lesion characterized by “medial layer hypertrophy, hyalinization of the intima, and hyperplasia of the endothelial layer of the vessel wall.” (nokiba2015associationbetweenophthalmological pages 1-3)
In practice, the term overlaps with chronic components of hypertensive retinopathy (arteriolar sclerosis) and with population screening terms such as “fundus arteriosclerosis.” (liu2023sexspecificassociationbetween pages 3-4, sugiura2022examinationoflarge media a2b302a2)
Commonly used overlapping terms in the retrieved literature: * Fundus arteriosclerosis (liu2023sexspecificassociationbetween pages 3-4) * Retinal arteriosclerosis / atherosclerotic retinopathy (Scheie S grading) (sugiura2022examinationoflarge pages 2-4, sugiura2022examinationoflarge media a2b302a2) * Arteriolar light reflex enhancement / copper-wiring / silver-wiring (as a sign within arteriosclerotic/hypertensive grading) (kaushik2007prevalenceandassociations pages 1-3, sugiura2022examinationoflarge media a2b302a2)
The information above is derived from aggregated disease-level resources in cohort studies, systematic reviews, and clinical definitions rather than single case reports. (kaushik2007prevalenceandassociations pages 1-3, liu2023sexspecificassociationbetween pages 3-4, rusu2024retinalstructuraland pages 1-2, geng2023sexspecificassociationof pages 1-2)
Arteriosclerotic retinopathy is best understood as a microvascular end-organ manifestation of chronic systemic vascular stressors rather than a single causal gene disorder. Mechanistically, the phenotype reflects chronic arteriolar wall remodeling and sclerosis (see §6). (nokiba2015associationbetweenophthalmological pages 1-3)
Metabolic and vascular risk factors are consistently associated with arteriosclerotic retinal signs:
Clear protective factors are less consistently reported; however, biomarkers sometimes proposed as protective against systemic atherosclerosis can show complex/sex-specific associations in retinal endpoints.
Direct gene–environment interaction evidence specific to arteriosclerotic retinopathy was not captured in the retrieved texts. Some broader retinal microvascular biomarker literature acknowledges genetic influences on retinal traits, but disease-specific G×E results were not retrievable here. (iorga2024noninvasiveretinalvessel pages 5-7)
The most widely operationalized phenotype definition in the retrieved sources is Scheie atherosclerotic retinopathy S0–S4 and hypertensive retinopathy H0–H4, evaluated from fundus examination/photography.
Scheie atherosclerotic retinopathy (S) grading (definitions): * S0: Normal * S1: Broadening of the light reflex from the arteriole with minimal/no AV compression * S2: Light reflex and crossing changes more prominent * S3: “Copper wire” appearance with more prominent AV compression * S4: “Silver” appearance with most severe AV crossing changes (sugiura2022examinationoflarge media a2b302a2)
Scheie hypertensive retinopathy (H) grading (definitions): * H0: Normal * H1: Barely detectable arterial narrowing * H2: Obvious arterial narrowing with focal irregularities plus light reflex changes * H3: H2 plus retinal hemorrhages and/or exudates * H4: H3 plus papilledema (sugiura2022examinationoflarge media a2b302a2)
A figure region containing the above grading definitions was retrieved from the Sugiura et al. paper (visual evidence). (sugiura2022examinationoflarge media a2b302a2)
Arteriosclerotic retinopathy is often asymptomatic until complications occur (e.g., occlusive disease, macular edema in related conditions). The retrieved evidence focused on imaging signs and systemic associations rather than patient-reported quality-of-life instruments; no EQ-5D/SF-36 metrics were found in the available texts. (liu2023sexspecificassociationbetween pages 3-4, rusu2024retinalstructuraland pages 1-2)
(These are ontology suggestions; exact HPO IDs should be verified in HPO.) * Retinal arteriolar narrowing (sign) (supported conceptually by Scheie H grades and retinal arteriolar narrowing) (sugiura2022examinationoflarge media a2b302a2) * Arteriovenous nicking (sign) (kaushik2007prevalenceandassociations pages 1-3, sugiura2022examinationoflarge media a2b302a2) * Increased retinal arteriolar light reflex / copper wiring / silver wiring (sign) (kaushik2007prevalenceandassociations pages 1-3, sugiura2022examinationoflarge media a2b302a2) * Retinal hemorrhage / hard exudates / cotton wool spots / papilledema (primarily severe hypertensive retinopathy features) (sugiura2022examinationoflarge media a2b302a2)
No causal genes or pathogenic variants were identified in the retrieved sources for arteriosclerotic retinopathy as a discrete genetic disorder. The current evidence base in this tool run supports arteriosclerotic retinopathy as a complex trait/end-organ phenotype rather than a Mendelian condition. (iorga2024noninvasiveretinalvessel pages 5-7)
Not identified in the retrieved evidence. (iorga2024noninvasiveretinalvessel pages 5-7)
No infectious etiology is supported in retrieved texts. (nokiba2015associationbetweenophthalmological pages 1-3)
Chronic systemic vascular risk exposure (hypertension, diabetes, dyslipidemia, CKD-related mineral/inflammatory milieu) → endothelial dysfunction and vascular remodeling → retinal arteriolar wall thickening/sclerosis (medial hypertrophy, intimal hyalinization, endothelial hyperplasia) → ophthalmoscopic signs (increased light reflex “copper/silver wiring”, AV crossing changes, arteriolar narrowing) → associations with systemic arterial stiffness and atherosclerotic burden. (nokiba2015associationbetweenophthalmological pages 1-3, nokiba2015associationbetweenophthalmological pages 3-4, sugiura2022examinationoflarge media a2b302a2)
A clinical pathologic description in CKD/hemodialysis literature emphasizes that arteriosclerotic retinopathy reflects vascular wall remodeling with “medial layer hypertrophy, hyalinization of the intima, and hyperplasia of the endothelial layer.” (nokiba2015associationbetweenophthalmological pages 1-3)
Evidence supports that retinal arteriosclerotic findings track systemic vascular disease: * In hemodialysis patients (n=44), Scheie S grade correlated with arterial stiffness (PWV) and past CVD (reported p=0.001 and p=0.045). (nokiba2015associationbetweenophthalmological pages 1-3) * In untreated middle-aged adults (n=7,730), measures of large-artery atherosclerosis/stiffness—carotid IMT and CAVI—were independently associated with Scheie-defined retinopathy; carotid IMT per 0.1 mm showed ORs around ~1.18 for retinopathy in multivariable models. (sugiura2022examinationoflarge pages 7-9, sugiura2022examinationoflarge pages 6-7) * In a large cross-sectional health-exam sample (n=20,836), fundus arteriosclerosis was associated with carotid atherosclerosis (adjusted OR 1.17). (liu2023sexspecificassociationbetween pages 3-4)
The retrieved texts emphasize general vascular mechanisms (endothelial dysfunction, oxidative stress, inflammation) in the context of systemic vascular disease and retinal microvasculature but do not provide disease-specific retinal transcriptomic/proteomic signatures for arteriosclerotic retinopathy. (nokiba2015associationbetweenophthalmological pages 1-3, bisen2025retinalimagingas pages 5-8)
GO (biological process) suggestions (verify IDs): * Blood vessel remodeling; extracellular matrix organization; regulation of vascular smooth muscle cell proliferation; response to oxidative stress; inflammatory response (conceptually consistent with sclerosis/remodeling and inflammation noted as risk factors). (nokiba2015associationbetweenophthalmological pages 1-3)
CL (cell type) suggestions (verify IDs): * Vascular endothelial cell; vascular smooth muscle cell/pericyte (arteriolar wall remodeling). (nokiba2015associationbetweenophthalmological pages 1-3)
UBERON suggestions (verify IDs): retina; retinal blood vessel; retinal arteriole.
Generally bilateral in systemic disease, but laterality was not specified in retrieved texts.
Arteriosclerotic retinal changes are typically chronic/insidious and accumulate with age and vascular risk exposure. In middle-aged workers (mean ~45 years), Scheie S1+S2 prevalence was already ~13.6%, supporting early/midlife detectability. (sugiura2022examinationoflarge pages 12-13, sugiura2022examinationoflarge pages 1-2)
Scheie S0–S4 provides a practical staging framework from normal through copper/silver wiring and severe AV crossing changes. (sugiura2022examinationoflarge media a2b302a2)
Population-based frequencies depend heavily on definitions: * Enhanced arteriolar light reflex prevalence: 31.7% in a ≥49-year cohort. (kaushik2007prevalenceandassociations pages 1-3) * Scheie-defined atherosclerotic retinopathy (S1+S2): 13.6% in untreated workers aged 35–61. (sugiura2022examinationoflarge pages 12-13)
Incidence data from a longitudinal study: * Retinal arteriosclerosis events over ~9.5 years: 295 men and 97 women among 4,324 adults initially free of retinal arteriosclerosis. (geng2023sexspecificassociationof pages 1-2)
Sex-specific associations have been reported for biochemical predictors (e.g., SUA trajectories and TBIL associations stronger in men). (geng2023sexspecificassociationof pages 1-2, nokiba2015associationbetweenophthalmological pages 1-3)
Fundus examination / fundus photography is the core diagnostic modality for Scheie and KWB grading. * Sugiura et al. used non-mydriatic fundus photographs graded by ophthalmologists according to Scheie H and S grades. (sugiura2022examinationoflarge pages 2-4, sugiura2022examinationoflarge media a2b302a2) * Liu et al. used standardized nonmydriatic fundus photography with two trained ophthalmologists grading KWB-based fundus arteriosclerosis. (liu2023sexspecificassociationbetween pages 3-4)
OCT and OCTA (modern developments; 2024 evidence): * A 2024 systematic review/meta-analysis of CAD studies supports that OCT/OCTA capture retinal structural and microvascular signatures in systemic CAD, including reduced RNFL thickness and reduced vessel density with expanded FAZ in CAD. (rusu2024retinalstructuraland pages 1-2) * A 2024 review describes limitations and strengths of OCTA vs fundus-photo vessel measurement and summarizes normative CRAE/CRVE/AVR metrics. (iorga2024noninvasiveretinalvessel pages 5-7)
Biochemical predictors investigated in recent cohorts include serum uric acid trajectories (incident retinal arteriosclerosis in men) and total bilirubin quartiles (risk in males). (geng2023sexspecificassociationof pages 1-2, nokiba2015associationbetweenophthalmological pages 1-3)
Not systematically addressed in retrieved texts, but clinically overlaps with: * Hypertensive retinopathy (acute and chronic stages) * Diabetic retinopathy (microaneurysms/hemorrhages/exudates) * Retinal vein/artery occlusions (acute ischemic presentations)
The current evidence set emphasizes that arteriosclerotic signs (light reflex and crossing changes) are often embedded within hypertensive retinopathy staging systems. (sugiura2022examinationoflarge media a2b302a2)
Arteriosclerotic retinal signs and retinal microvascular biomarkers are repeatedly associated with systemic vascular disease burden: * Fundus arteriosclerosis associated with carotid atherosclerosis (adjusted OR 1.17). (liu2023sexspecificassociationbetween pages 3-4) * Scheie grades correlated with arterial stiffness and CVD history in hemodialysis patients. (nokiba2015associationbetweenophthalmological pages 1-3)
The retrieved texts did not provide direct longitudinal estimates of vision loss attributable specifically to arteriosclerotic retinopathy without occlusive events. However, retinal microvascular compromise is positioned as part of a continuum toward ischemic retinal complications and systemic vascular events. (bisen2025retinalimagingas pages 5-8, rusu2024retinalstructuraland pages 1-2)
No disease-specific ocular therapy for isolated arteriosclerotic retinopathy is established in the retrieved literature; management typically targets systemic risk factor modification and surveillance.
Given strong associations with hypertension, diabetes, dyslipidemia, and CKD, real-world management aligns with cardiovascular risk reduction. Supporting evidence includes the strong unadjusted associations of these conditions with Scheie-defined retinopathy in population screening. (sugiura2022examinationoflarge pages 12-13)
Screening and risk stratification using fundus photography and retinal analytics is an active area: * A 2023 deep-learning meta-analysis supports that retinal-image-based models can predict multiple CVD risk-related outcomes and future CVD events with AUROC ~0.68–0.81 in some studies, but emphasizes need for validation for real-world adoption. (nokiba2015associationbetweenophthalmological pages 1-3) * A 2024 review argues retinal microvascular biomarkers (e.g., CRAE/CRVE/AVR; dynamic retinal vessel analysis; AI systems) could aid screening and treatment monitoring for CVD. (iorga2024noninvasiveretinalvessel pages 5-7)
No naturally occurring veterinary analogs were identified in the retrieved evidence set for “arteriosclerotic retinopathy” as a named entity.
No specific model organism papers for retinal arteriosclerosis were retrieved in the available evidence. Mechanistic modeling is likely to rely on hypertension/atherosclerosis animal models with retinal vascular endpoints, but this could not be substantiated with the current evidence set.
1) Large observational datasets are increasingly treating fundus arteriosclerosis as a quantitative marker linked to systemic atherosclerosis (e.g., carotid ultrasound associations; sex-specific effects). (liu2023sexspecificassociationbetween pages 3-4, geng2023sexspecificassociationof pages 1-2) 2) OCT/OCTA biomarkers are being consolidated in systematic reviews as potential non-invasive correlates of coronary artery disease (reduced vessel density; larger FAZ; thinner RNFL/choroid). (rusu2024retinalstructuraland pages 1-2) 3) AI/deep learning and “retinal analytics” for cardiovascular risk prediction has matured into systematic evidence syntheses, with performance competitive with but not clearly superior to standard risk scores in current studies. (nokiba2015associationbetweenophthalmological pages 1-3)
The following table consolidates the most relevant quantitative studies and syntheses captured in this run.
| Study (first author, year) | Design/Population (N, setting) | Retinal phenotype definition (Scheie/KWB, vessel measures) | Main findings with effect sizes (OR/HR/WMD etc.) | Publication date | PMID | URL |
|---|---|---|---|---|---|---|
| Geng 2023 | Population-based longitudinal study; N=4,324 adults aged 18–60 without retinal arteriosclerosis at baseline; exposure window 2006–2010, follow-up 2011–2019; Chinese health-examination cohort | Incident retinal arteriosclerosis; study evaluated sex-specific serum uric acid (SUA) trajectory groups (low, moderate, moderate-high, high) as predictors of later retinal arteriosclerosis | During median 9.54-year follow-up, 97 women and 295 men developed retinal arteriosclerosis. In men, moderate-high SUA trajectory vs low: HR 1.76 (95% CI 1.17–2.65); high trajectory vs low: HR 1.81 (95% CI 1.04–3.17). No significant increase in women for moderate-high trajectory: HR 0.77 (95% CI 0.39–1.52) (geng2023sexspecificassociationof pages 1-2) | 2023-02-28 | https://doi.org/10.3389/fcvm.2023.1116486 | |
| Liu 2023 | Retrospective cross-sectional study; N=20,836 Chinese health-examination participants (13,050 male; 7,786 female) | Fundus arteriosclerosis graded from standardized nonmydriatic fundus photographs using Keith–Wagener–Barker (KWB) grades 1–4; any grade 1–4 counted as fundus arteriosclerosis; carotid atherosclerosis assessed by Doppler ultrasound | Carotid atherosclerosis incidence was higher in those with fundus arteriosclerosis (52.94% vs 47.06%). Adjusted association between fundus arteriosclerosis and carotid atherosclerosis: OR 1.17 (95% CI 1.02–1.34; p=0.0262); association significant in males but not females (liu2023sexspecificassociationbetween pages 3-4) | 2023-11 | https://doi.org/10.1186/s40001-023-01508-6 | |
| Dong 2023 | Retrospective cohort study; N=27,477 Chinese participants, follow-up 2006–2019 | Incident fundus arteriosclerosis; exposure was quartiles of serum total bilirubin (TBIL); fundus arteriosclerosis assessed in routine examinations | In males, higher TBIL quartiles associated with higher fundus arteriosclerosis risk vs Q1: Q2 HR 1.217 (95% CI 1.095–1.354), Q3 HR 1.255 (95% CI 1.128–1.396), Q4 HR 1.396 (95% CI 1.254–1.555); linear dose-response reported. No significant association in females (nokiba2015associationbetweenophthalmological pages 1-3) | 2023-07 | https://doi.org/10.1038/s41598-023-38378-1 | |
| Rusu 2024 | Systematic review and meta-analysis; 11 studies of CAD vs controls | OCT/OCTA retinal structural and vascular biomarkers rather than classic Scheie/KWB lesions; included retinal thickness, RNFL, choroid, vessel density, FAZ | CAD associated with thinner RNFL (WMD −3.11), thinner subfoveal choroid (WMD −58.79), lower overall retinal thickness (WMD −4.61), lower superficial foveal vessel density (WMD −2.19; p<0.0001), and larger FAZ (WMD 52.73; p=0.02), supporting retinal vascularization as a noninvasive CAD biomarker (rusu2024retinalstructuraland pages 1-2) | 2024-03 | https://doi.org/10.3390/life14040448 | |
| Iorga 2024 | Narrative/systematic-style review of non-invasive retinal vessel analysis in cardiovascular disease | Retinal vessel analysis metrics: CRAE, CRVE, AVR; fundus photography, dynamic retinal vessel analysis, OCTA | Summarized normative Gutenberg Health Study metrics: mean CRAE 178.37 µm, CRVE 212.30 µm, AVR 0.84. Review notes uncontrolled hypertension example values CRAE 172.28 µm and AVR 0.81; hypertension strongly associated with lower AVR/CRAE, with tabulated ORs 2.703 for AVR and 2.881 for CRAE (p=0.001). Emphasizes AI systems (e.g., QUARTZ, SIVA-DLS) for scalable extraction of retinal vascular biomarkers (iorga2024noninvasiveretinalvessel pages 5-7) | 2024-05 | https://doi.org/10.3390/jpm14050501 | |
| Girach 2024 | Systematic review of prospective studies assessing retinal imaging biomarkers for stroke risk; 24 studies included | Retinal imaging biomarkers including vessel caliber, fractal dimension, tortuosity, retinopathy, emboli, AV nicking; fundus photography and limited OCT studies | Review found wider retinal venules, lower fractal dimension, increased arteriolar tortuosity, retinopathy, and retinal emboli associated with higher stroke risk; evidence weaker for narrower arterioles and isolated AV nicking. AI models performed similarly to conventional risk scores but did not clearly outperform them (nokiba2015associationbetweenophthalmological pages 1-3) | 2024-03 | https://doi.org/10.1007/s00415-023-12171-6 | |
| Hu 2023 | Systematic review and meta-analysis of deep learning for CVD risk prediction from retinal images; 26 studies | Retinal-image-based DL using fundus photographs and retinal vascular morphology/geometry features rather than disease-specific Scheie grading | Future CVD-event prediction studies reported AUROC 0.68–0.81. Pooled performance for related tasks: age MAE 3.19 years; gender AUROC 0.96; diabetes AUROC 0.80; CKD AUROC 0.86. Authors conclude real-world applicability requires further validation despite promise of noninvasive retinal-image-based risk prediction (nokiba2015associationbetweenophthalmological pages 1-3) | 2023-07 | https://doi.org/10.1167/tvst.12.7.14 | |
| Colcombe 2023 | Targeted narrative review of retinal findings and cardiovascular risk | Reviewed retinal disease states and imaging biomarkers including AV nicking, vessel caliber changes, OCT/OCTA biomarkers | Concludes retinal findings and retinal bioimaging biomarkers may aid cardiovascular prognostication and personalized counseling; notes classic retinopathy findings such as arteriovenous nicking have been incorporated into cardiovascular/stroke risk literature, but emphasizes heterogeneity and need for validation before routine implementation (nokiba2015associationbetweenophthalmological pages 1-3) | 2023-10 | https://doi.org/10.3390/jpm13111564 |
Table: This table summarizes recent quantitative studies and reviews relevant to arteriosclerotic retinopathy, fundus arteriosclerosis, and related retinal vascular biomarkers. It highlights study design, retinal phenotype definitions, effect sizes, and links to cardiovascular outcomes or risk stratification.
References
(nokiba2015associationbetweenophthalmological pages 1-3): Hirohiko Nokiba, Takashi Takei, Chikako Suto, and Kosaku Nitta. Association between ophthalmological changes and cardiovascular diseases in patients with chronic kidney disease undergoing hemodialysis. Journal of atherosclerosis and thrombosis, 22 12:1248-54, Dec 2015. URL: https://doi.org/10.5551/jat.30601, doi:10.5551/jat.30601. This article has 9 citations and is from a peer-reviewed journal.
(sugiura2022examinationoflarge media a2b302a2): Tomonori Sugiura, Yasuaki Dohi, Yasuyuki Takagi, Takashi Yokochi, Naofumi Yoshikane, Kenji Suzuki, Takamasa Tomiishi, Takashi Nagami, Mitsunori Iwase, Hiroyuki Takase, Yoshihiro Seo, and Nobuyuki Ohte. Examination of large artery atherosclerosis could reveal small artery retinopathy in untreated middle-aged individuals. Journal of Atherosclerosis and Thrombosis, 29:11-23, Jan 2022. URL: https://doi.org/10.5551/jat.59857, doi:10.5551/jat.59857. This article has 8 citations and is from a peer-reviewed journal.
(liu2023sexspecificassociationbetween pages 3-4): Chunxing Liu, Xiaolong Yang, Mengmeng Ji, Xiaowei Zhang, Xiyun Bian, Tingli Chen, Yihan Li, Xing Qi, Jianfeng Wu, Jing Wang, and Zaixiang Tang. Sex-specific association between carotid atherosclerosis and fundus arteriosclerosis in a chinese population: a retrospective cross-sectional study. European Journal of Medical Research, Nov 2023. URL: https://doi.org/10.1186/s40001-023-01508-6, doi:10.1186/s40001-023-01508-6. This article has 5 citations and is from a peer-reviewed journal.
(rusu2024retinalstructuraland pages 1-2): Alexandra Cristina Rusu, Karin Ursula Horvath, Grigore Tinica, Raluca Ozana Chistol, Andra-Irina Bulgaru-Iliescu, Ecaterina Tomaziu Todosia, and Klara Brînzaniuc. Retinal structural and vascular changes in patients with coronary artery disease: a systematic review and meta-analysis. Life, 14:448, Mar 2024. URL: https://doi.org/10.3390/life14040448, doi:10.3390/life14040448. This article has 23 citations.
(sugiura2022examinationoflarge pages 2-4): Tomonori Sugiura, Yasuaki Dohi, Yasuyuki Takagi, Takashi Yokochi, Naofumi Yoshikane, Kenji Suzuki, Takamasa Tomiishi, Takashi Nagami, Mitsunori Iwase, Hiroyuki Takase, Yoshihiro Seo, and Nobuyuki Ohte. Examination of large artery atherosclerosis could reveal small artery retinopathy in untreated middle-aged individuals. Journal of Atherosclerosis and Thrombosis, 29:11-23, Jan 2022. URL: https://doi.org/10.5551/jat.59857, doi:10.5551/jat.59857. This article has 8 citations and is from a peer-reviewed journal.
(kaushik2007prevalenceandassociations pages 1-3): Shweta Kaushik, Ava Grace Tan, Paul Mitchell, and Jie Jin Wang. Prevalence and associations of enhanced retinal arteriolar light reflex: a new look at an old sign. Ophthalmology, 114 1:113-20, Jan 2007. URL: https://doi.org/10.1016/j.ophtha.2006.06.046, doi:10.1016/j.ophtha.2006.06.046. This article has 37 citations and is from a highest quality peer-reviewed journal.
(geng2023sexspecificassociationof pages 1-2): Ruirui Geng, Qinbei Feng, Mengmeng Ji, Yongfei Dong, Shuanshuan Xu, Chunxing Liu, Yufeng He, and Zaixiang Tang. Sex-specific association of serum uric acid trajectories with risk of incident retinal arteriosclerosis in chinese population: a population-based longitudinal study. Frontiers in Cardiovascular Medicine, Feb 2023. URL: https://doi.org/10.3389/fcvm.2023.1116486, doi:10.3389/fcvm.2023.1116486. This article has 2 citations and is from a peer-reviewed journal.
(sugiura2022examinationoflarge pages 12-13): Tomonori Sugiura, Yasuaki Dohi, Yasuyuki Takagi, Takashi Yokochi, Naofumi Yoshikane, Kenji Suzuki, Takamasa Tomiishi, Takashi Nagami, Mitsunori Iwase, Hiroyuki Takase, Yoshihiro Seo, and Nobuyuki Ohte. Examination of large artery atherosclerosis could reveal small artery retinopathy in untreated middle-aged individuals. Journal of Atherosclerosis and Thrombosis, 29:11-23, Jan 2022. URL: https://doi.org/10.5551/jat.59857, doi:10.5551/jat.59857. This article has 8 citations and is from a peer-reviewed journal.
(iorga2024noninvasiveretinalvessel pages 5-7): Raluca Eugenia Iorga, Damiana Costin, Răzvana Sorina Munteanu-Dănulescu, Elena Rezuș, and Andreea Dana Moraru. Non-invasive retinal vessel analysis as a predictor for cardiovascular disease. Journal of Personalized Medicine, 14:501, May 2024. URL: https://doi.org/10.3390/jpm14050501, doi:10.3390/jpm14050501. This article has 21 citations.
(nokiba2015associationbetweenophthalmological pages 3-4): Hirohiko Nokiba, Takashi Takei, Chikako Suto, and Kosaku Nitta. Association between ophthalmological changes and cardiovascular diseases in patients with chronic kidney disease undergoing hemodialysis. Journal of atherosclerosis and thrombosis, 22 12:1248-54, Dec 2015. URL: https://doi.org/10.5551/jat.30601, doi:10.5551/jat.30601. This article has 9 citations and is from a peer-reviewed journal.
(sugiura2022examinationoflarge pages 7-9): Tomonori Sugiura, Yasuaki Dohi, Yasuyuki Takagi, Takashi Yokochi, Naofumi Yoshikane, Kenji Suzuki, Takamasa Tomiishi, Takashi Nagami, Mitsunori Iwase, Hiroyuki Takase, Yoshihiro Seo, and Nobuyuki Ohte. Examination of large artery atherosclerosis could reveal small artery retinopathy in untreated middle-aged individuals. Journal of Atherosclerosis and Thrombosis, 29:11-23, Jan 2022. URL: https://doi.org/10.5551/jat.59857, doi:10.5551/jat.59857. This article has 8 citations and is from a peer-reviewed journal.
(sugiura2022examinationoflarge pages 6-7): Tomonori Sugiura, Yasuaki Dohi, Yasuyuki Takagi, Takashi Yokochi, Naofumi Yoshikane, Kenji Suzuki, Takamasa Tomiishi, Takashi Nagami, Mitsunori Iwase, Hiroyuki Takase, Yoshihiro Seo, and Nobuyuki Ohte. Examination of large artery atherosclerosis could reveal small artery retinopathy in untreated middle-aged individuals. Journal of Atherosclerosis and Thrombosis, 29:11-23, Jan 2022. URL: https://doi.org/10.5551/jat.59857, doi:10.5551/jat.59857. This article has 8 citations and is from a peer-reviewed journal.
(bisen2025retinalimagingas pages 5-8): Jay Bharatsingh Bisen, Hayden Sikora, Anushree Aneja, Sanjiv J. Shah, and Rukhsana G. Mirza. Retinal imaging as a window into cardiovascular health: towards harnessing retinal analytics for precision cardiovascular medicine. Journal of Cardiovascular Development and Disease, 12:230, Jun 2025. URL: https://doi.org/10.3390/jcdd12060230, doi:10.3390/jcdd12060230. This article has 6 citations.
(sugiura2022examinationoflarge pages 1-2): Tomonori Sugiura, Yasuaki Dohi, Yasuyuki Takagi, Takashi Yokochi, Naofumi Yoshikane, Kenji Suzuki, Takamasa Tomiishi, Takashi Nagami, Mitsunori Iwase, Hiroyuki Takase, Yoshihiro Seo, and Nobuyuki Ohte. Examination of large artery atherosclerosis could reveal small artery retinopathy in untreated middle-aged individuals. Journal of Atherosclerosis and Thrombosis, 29:11-23, Jan 2022. URL: https://doi.org/10.5551/jat.59857, doi:10.5551/jat.59857. This article has 8 citations and is from a peer-reviewed journal.