Acute Macular Neuroretinopathy

Acquired MONDO:0044627 Pathograph 3 Show in embeddings browser Retinal disorder

Acute macular neuroretinopathy (AMN) is a rare acute retinal disorder, classically affecting young women, characterized by sudden paracentral scotomas corresponding to reddish-brown, wedge-shaped parafoveal lesions pointing toward the fovea. Modern multimodal imaging (OCT, near-infrared reflectance, OCT angiography) has established a microvascular etiology: ischemia of the deep capillary plexus of the retina infarcts the outer plexiform and outer nuclear layers, producing acute OCT hyperreflectivity that evolves into persistent outer nuclear layer thinning and long-term paracentral visual field deficits. AMN has been associated with febrile/viral illness (including dengue, influenza, and COVID-19), oral contraceptive use, and other vasoconstrictive or hypercoagulable states, though no proven treatment exists.

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3
Pathophys.
3
Phenotypes
2
Hypotheses
3
Pathograph
1
Medical Actions
1
Datasets
1
Deep Research
◈

Mechanistic Hypotheses

2
Canonical Deep Capillary Plexus Ischemia Model
canonical_deep_capillary_plexus_ischemia_model CANONICAL
Evidence balance 1 support
Ischemia/microvascular occlusion of the retinal deep capillary plexus infarcts the outer plexiform and outer nuclear layers, producing the characteristic acute OCT hyperreflectivity and long-term photoreceptor layer thinning. This is the predominant model in the current literature, supported by OCT angiography studies directly localizing the flow deficit to the deep capillary plexus.
Show evidence (1 reference)
PMID:29561336 SUPPORT Human Clinical
"Optical coherence tomography angiography illustrated a flow void in the deep retinal capillary plexus associated with the AMN lesion."
Direct OCTA evidence for the deep capillary plexus ischemia model.
Emerging Choriocapillaris Perfusion Deficit Model
emerging_choriocapillaris_perfusion_deficit_model EMERGING
Evidence balance 1 support
An alternative hypothesis proposes that the primary perfusion deficit in AMN lies in the choriocapillaris and choroid rather than the deep capillary plexus, based on quantitative OCTA vessel-area-density analysis finding no retinal-layer flow differences but significantly reduced choriocapillaris and choroidal density in COVID-19-associated AMN cases.
Based on a single small retrospective series (n=6) of SARS-CoV-2-related AMN; the authors themselves note this contradicts "the predominant hypothesis in current literature." Retained as EMERGING pending independent replication and confirmation in non-COVID AMN cohorts.
Show evidence (1 reference)
PMID:38512510 SUPPORT Human Clinical
"Our data suggests that a perfusion deficit in the choroidal layers is responsible for AMN rather than in the DCP, which is the predominant hypothesis in current literature."
Primary evidence for the emerging choriocapillaris/choroidal perfusion-deficit alternative to the canonical DCP-ischemia model.
⚙

Pathophysiology

3
Retinal Deep Capillary Plexus Ischemia
In predisposed individuals, transient microvascular occlusion/ischemia develops in the deep capillary plexus (DCP) of the retina, the vascular bed supplying the outer plexiform and outer nuclear layers. OCT angiography directly demonstrates a flow void in the DCP co-localized with the acute lesion, with partial recovery of flow signal on follow-up in most cases.
Retinal Blood Vessel Endothelial Cell CL:0002585 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Retinal Blood Vessel Endothelial Cell (CL:0002585). CL:0002585 is a cell type from the Cell Ontology.
Cellular Response to Hypoxia GO:0071456 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased Cellular Response to Hypoxia (GO:0071456). GO:0071456 is a biological process from the Gene Ontology. ↑ INCREASED
retina UBERON:0000966 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in retina (UBERON:0000966). UBERON:0000966 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Outer Retinal Photoreceptor Layer Infarction
Show evidence (2 references)
PMID:29561336 SUPPORT Human Clinical
"Optical coherence tomography angiography illustrated a flow void in the deep retinal capillary plexus associated with the AMN lesion."
Directly demonstrates deep capillary plexus flow deficit at the site of the AMN lesion via OCT angiography.
PMID:30025133 SUPPORT Human Clinical
"All five eyes had reduced DCP flow signal, along with normal SCP, MCP, and choriocapillaris flow signal in the area of the lesion"
Projection-resolved OCTA localizes the AMN flow deficit specifically to the deep capillary plexus, distinguishing it from the more superficial plexus involvement seen in paracentral acute middle maculopathy (PAMM).
Outer Retinal Photoreceptor Layer Infarction
Deep capillary plexus ischemia infarcts the outer plexiform layer (OPL) and outer nuclear layer (ONL), producing acute hyperreflectivity at the OPL/ONL junction on OCT that enlarges over the first week, with disruption of the ellipsoid zone and outer segment/RPE junction. The lesion is best visualized as a dark area on near-infrared reflectance imaging.
Photoreceptor Cell CL:0000210 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Photoreceptor Cell (CL:0000210). CL:0000210 is a cell type from the Cell Ontology.
outer plexiform layer of retina UBERON:0001790 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in outer plexiform layer of retina (UBERON:0001790). UBERON:0001790 is an anatomical location from the Uberon multi-species anatomy ontology. outer nuclear layer of retina UBERON:0001789 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in outer nuclear layer of retina (UBERON:0001789). UBERON:0001789 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Persistent Outer Nuclear Layer Thinning and Visual Field Defect
Show evidence (2 references)
PMID:22846801 SUPPORT Human Clinical
"Two patients were seen within the first 1 to 2 days of symptoms, and both showed outer nuclear and outer plexiform layer hyperreflectivity."
Establishes acute OPL/ONL hyperreflectivity as the earliest OCT finding, with lesion enlargement over the following week.
PMID:38200478 SUPPORT Human Clinical
"hyperreflective lesions at the level of the outer plexiform layer (OPL) and outer nuclear layer (ONL) and disruption of the ellipsoid zone (EZ) on spectral domain optical coherence tomography (SD-OCT) B-scans"
Confirms the OPL/ONL hyperreflectivity and ellipsoid zone disruption pattern as the characteristic acute OCT signature of AMN.
Persistent Outer Nuclear Layer Thinning and Visual Field Defect
Lesions wider than 100 micrometers develop persistent thinning of the outer nuclear layer that correlates with long-term visual field deficits (paracentral scotomas). Visual acuity often recovers within weeks, but scotomas frequently persist for months or longer.
outer nuclear layer of retina UBERON:0001789 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in outer nuclear layer of retina (UBERON:0001789). UBERON:0001789 is an anatomical location from the Uberon multi-species anatomy ontology.
Show evidence (2 references)
PMID:22846801 SUPPORT Human Clinical
"Thinning of the outer nuclear layer persisted in all patients with lesions >100 μm width, and in one patient this thinning worsened over the course of follow-up"
Demonstrates the size-dependent persistence of ONL thinning and its correlation with long-term functional (visual field) deficits.
PMID:38200478 SUPPORT Human Clinical
"all patients achieved a BCVA of 20/40 or better, but 9 patients (81.8%) continued to experience persistent scotomas"
Shows that visual acuity typically recovers while paracentral scotomas frequently persist, consistent with the structural ONL thinning outcome.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Acute Macular Neuroretinopathy Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

3
Paracentral scotoma Ophthalmologic HP:0030528 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Paracentral scotoma (HP:0030528). HP:0030528 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:26973287 SUPPORT Human Clinical
"Acute onset of paracentral scotomas corresponding to the clinically evident lesions is both common and characteristic."
Establishes paracentral scotoma as the characteristic presenting symptom.
Acute photoreceptor layer disruption Ophthalmologic HP:0030609 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Photoreceptor layer loss on macular OCT (HP:0030609), qualified as temporality acute. HP:0030609 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Show evidence (1 reference)
PMID:38200478 SUPPORT Human Clinical
"hyperreflective lesions at the level of the outer plexiform layer (OPL) and outer nuclear layer (ONL) and disruption of the ellipsoid zone (EZ) on spectral domain optical coherence tomography (SD-OCT) B-scans"
Documents the acute OCT photoreceptor-layer disruption finding.
Persistent outer nuclear layer thinning Ophthalmologic HP:6000367 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Central thinning of the outer nuclear layer of the retina (HP:6000367), qualified as temporality chronic. HP:6000367 is a phenotype from the Human Phenotype Ontology.
Temporal: CHRONIC
Show evidence (1 reference)
PMID:22846801 SUPPORT Human Clinical
"Thinning of the outer nuclear layer persisted in all patients with lesions >100 μm width"
Documents persistent ONL thinning as a long-term structural sequela.
💊

Medical Actions

1
Observation and supportive management
Action: supportive careNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is supportive care (NCIT:C15747). NCIT:C15747 is a clinical intervention from the NCI Thesaurus. Ontology label: Supportive Care NCIT:C15747
No pharmacologic or interventional treatment has proven effective for AMN; management consists of observation and monitoring, since surgery and pharmacotherapy have no established role in this ischemic outer retinal condition.
Show evidence (1 reference)
PMID:26973287 SUPPORT Human Clinical
"Although the pathogenesis of acute macular neuroretinopathy is complex, recent research suggests a microvascular etiology."
Underscores that despite advances in understanding AMN's microvascular etiology, no proven pharmacologic treatment has emerged; management remains observational.
🌍

Environmental Factors

2
Oral Contraceptive Use
Oral contraceptive exposure ECTO:0000509 Environmental Conditions, Treatments and Exposures Ontology (ECTO) Relation: this environmental factor is this exposure This environmental factor is Oral contraceptive exposure, annotated with exposure to drug (ECTO:0000509). ECTO:0000509 is an exposure from the Environmental Conditions, Treatments and Exposures Ontology.
AMN was originally described in young women using oral contraceptives, and oral contraceptive use remains a recognized association, consistent with a role for hormonally-mediated hypercoagulability/vasoconstriction in the microvascular ischemic mechanism.
Show evidence (1 reference)
PMID:1180301 SUPPORT Human Clinical
"An unrecognized acute macular affection occurred in four women, 24 to 35 years old, using oral contraceptives who complained of a sudden decrease of visual acuity or paracentral scotomas."
The original 1975 case series defining AMN identified oral contraceptive use as a shared exposure among all four affected women.
Preceding Febrile/Viral Illness or Vaccination
Infectious agent exposure ECTO:3000000 Environmental Conditions, Treatments and Exposures Ontology (ECTO) Relation: this environmental factor is this exposure This environmental factor is Infectious agent exposure, annotated with exposure to organism (ECTO:3000000). ECTO:3000000 is an exposure from the Environmental Conditions, Treatments and Exposures Ontology.
AMN has been repeatedly reported to follow a preceding systemic febrile or viral illness (influenza, dengue, SARS-CoV-2) or vaccination by days, consistent with a trigger-driven microvascular ischemic event.
Show evidence (1 reference)
PMID:38200478 SUPPORT Human Clinical
"AMN is a rare retinal disease that has been reported to occur following dengue fever, influenza virus infection, and influenza vaccination, but the exact mechanisms underlying this association remain unknown."
Documents the recurring association between AMN onset and a preceding febrile/viral illness or vaccination across multiple pathogens.
🔬

Diagnosis

2
Near-infrared reflectance and OCT imaging
Near-infrared reflectance imaging best visualizes the dark parafoveal lesion, while spectral-domain OCT shows the characteristic acute OPL/ONL hyperreflectivity evolving to outer nuclear layer thinning and ellipsoid zone disruption.
optical coherence tomography NCIT:C20828 NCI Thesaurus (NCIT)
Results: Dark wedge-shaped parafoveal lesion on near-infrared reflectance; OPL/ONL hyperreflectivity evolving to ONL thinning and ellipsoid zone disruption on OCT.
Show evidence (1 reference)
PMID:22846801 SUPPORT Human Clinical
"Infrared reflectance highlights the lesion best, and abnormalities on near IR autofluorescence may be present."
Establishes near-infrared reflectance as the most sensitive imaging modality for AMN lesion detection.
OCT angiography of the deep capillary plexus
OCT angiography localizes reduced flow signal to the deep capillary plexus at the site of the lesion, distinguishing AMN from the more superficial vascular involvement of paracentral acute middle maculopathy.
optical coherence tomography NCIT:C20828 NCI Thesaurus (NCIT)
Results: Reduced/absent flow signal in the deep capillary plexus co-localized with the OCT/near-infrared lesion, with partial recovery on follow-up.
Show evidence (1 reference)
PMID:30025133 SUPPORT Human Clinical
"All three eyes with AMN and follow-up had recovery of DCP flow."
Documents OCTA-detectable deep capillary plexus flow deficit and its partial recovery.
📊

Prevalence

1
Cases in the English and non-English language literature, 1975-2014
Cases In Literature Not yet documented
AMN is a rare condition with no population-based prevalence studies; the 2016 comprehensive literature review identified 101 reported cases across nearly 40 years.
Show evidence (1 reference)
PMID:26973287 SUPPORT Human Clinical
"We review 101 reported cases in the English and non-English language literature identified from 1975, when acute macular neuroretinopathy was first described, to December, 2014."
Documents the rarity of AMN via the total literature case count.
📊

Related Datasets

1
Neutrophil extracellular traps aggravate COVID-19 related acute macular neuroretinopathy by promoting immune microthrombosis geo:GSE328399
To observe retinal and peripheral blood bioinformatic characteristics of COVID-19 infected individuals with or without suffering acute macular neuroretinopathy (AMN)
human BULK RNA SEQ n=6
Identified by GEO DataSets index search for Acute Macular Neuroretinopathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
{ }

Source YAML

click to show 
name: Acute Macular Neuroretinopathy
creation_date: "2026-07-16T00:00:00Z"
description: >-
  Acute macular neuroretinopathy (AMN) is a rare acute retinal disorder,
  classically affecting young women, characterized by sudden paracentral
  scotomas corresponding to reddish-brown, wedge-shaped parafoveal lesions
  pointing toward the fovea. Modern multimodal imaging (OCT, near-infrared
  reflectance, OCT angiography) has established a microvascular etiology:
  ischemia of the deep capillary plexus of the retina infarcts the outer
  plexiform and outer nuclear layers, producing acute OCT hyperreflectivity
  that evolves into persistent outer nuclear layer thinning and long-term
  paracentral visual field deficits. AMN has been associated with febrile/viral
  illness (including dengue, influenza, and COVID-19), oral contraceptive use,
  and other vasoconstrictive or hypercoagulable states, though no proven
  treatment exists.
category: Acquired
disease_term:
  preferred_term: acute macular neuroretinopathy
  term:
    id: MONDO:0044627
    label: acute macular neuroretinopathy
synonyms:
- AMN
- AMNR
parents:
- Retinal disorder
pathophysiology:
- name: Retinal Deep Capillary Plexus Ischemia
  description: >-
    In predisposed individuals, transient microvascular occlusion/ischemia
    develops in the deep capillary plexus (DCP) of the retina, the vascular
    bed supplying the outer plexiform and outer nuclear layers. OCT
    angiography directly demonstrates a flow void in the DCP co-localized
    with the acute lesion, with partial recovery of flow signal on
    follow-up in most cases.
  role: trigger
  locations:
  - preferred_term: retina
    term:
      id: UBERON:0000966
      label: retina
  cell_types:
  - preferred_term: Retinal Blood Vessel Endothelial Cell
    term:
      id: CL:0002585
      label: retinal blood vessel endothelial cell
  biological_processes:
  - preferred_term: Cellular Response to Hypoxia
    term:
      id: GO:0071456
      label: cellular response to hypoxia
    modifier: INCREASED
  evidence:
  - reference: PMID:29561336
    reference_title: "OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF ACUTE MACULAR NEURORETINOPATHY REVEALS DEEP CAPILLARY ISCHEMIA."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Optical coherence tomography angiography illustrated a flow void in
      the deep retinal capillary plexus associated with the AMN lesion.
    explanation: >-
      Directly demonstrates deep capillary plexus flow deficit at the site
      of the AMN lesion via OCT angiography.
  - reference: PMID:30025133
    reference_title: Projection-Resolved OCT Angiography of Microvascular Changes in Paracentral Acute Middle Maculopathy and Acute Macular Neuroretinopathy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      All five eyes had reduced DCP flow signal, along with normal SCP,
      MCP, and choriocapillaris flow signal in the area of the lesion
    explanation: >-
      Projection-resolved OCTA localizes the AMN flow deficit specifically
      to the deep capillary plexus, distinguishing it from the more
      superficial plexus involvement seen in paracentral acute middle
      maculopathy (PAMM).
  downstream:
  - target: Outer Retinal Photoreceptor Layer Infarction

- name: Outer Retinal Photoreceptor Layer Infarction
  description: >-
    Deep capillary plexus ischemia infarcts the outer plexiform layer (OPL)
    and outer nuclear layer (ONL), producing acute hyperreflectivity at the
    OPL/ONL junction on OCT that enlarges over the first week, with
    disruption of the ellipsoid zone and outer segment/RPE junction. The
    lesion is best visualized as a dark area on near-infrared reflectance
    imaging.
  role: central_effector
  locations:
  - preferred_term: outer plexiform layer of retina
    term:
      id: UBERON:0001790
      label: outer plexiform layer of retina
  - preferred_term: outer nuclear layer of retina
    term:
      id: UBERON:0001789
      label: outer nuclear layer of retina
  cell_types:
  - preferred_term: Photoreceptor Cell
    term:
      id: CL:0000210
      label: photoreceptor cell
  evidence:
  - reference: PMID:22846801
    reference_title: "Acute macular neuroretinopathy: long-term insights revealed by multimodal imaging."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Two patients were seen within the first 1 to 2 days of symptoms, and
      both showed outer nuclear and outer plexiform layer hyperreflectivity.
    explanation: >-
      Establishes acute OPL/ONL hyperreflectivity as the earliest OCT
      finding, with lesion enlargement over the following week.
  - reference: PMID:38200478
    reference_title: The characteristics of acute macular neuroretinopathy following COVID-19 infection.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      hyperreflective lesions at the level of the outer plexiform layer
      (OPL) and outer nuclear layer (ONL) and disruption of the ellipsoid
      zone (EZ) on spectral domain optical coherence tomography (SD-OCT)
      B-scans
    explanation: >-
      Confirms the OPL/ONL hyperreflectivity and ellipsoid zone disruption
      pattern as the characteristic acute OCT signature of AMN.
  downstream:
  - target: Persistent Outer Nuclear Layer Thinning and Visual Field Defect

- name: Persistent Outer Nuclear Layer Thinning and Visual Field Defect
  description: >-
    Lesions wider than 100 micrometers develop persistent thinning of the
    outer nuclear layer that correlates with long-term visual field
    deficits (paracentral scotomas). Visual acuity often recovers within
    weeks, but scotomas frequently persist for months or longer.
  role: outcome
  locations:
  - preferred_term: outer nuclear layer of retina
    term:
      id: UBERON:0001789
      label: outer nuclear layer of retina
  evidence:
  - reference: PMID:22846801
    reference_title: "Acute macular neuroretinopathy: long-term insights revealed by multimodal imaging."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Thinning of the outer nuclear layer persisted in all patients with
      lesions >100 μm width, and in one patient this thinning worsened
      over the course of follow-up
    explanation: >-
      Demonstrates the size-dependent persistence of ONL thinning and its
      correlation with long-term functional (visual field) deficits.
  - reference: PMID:38200478
    reference_title: The characteristics of acute macular neuroretinopathy following COVID-19 infection.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      all patients achieved a BCVA of 20/40 or better, but 9 patients
      (81.8%) continued to experience persistent scotomas
    explanation: >-
      Shows that visual acuity typically recovers while paracentral
      scotomas frequently persist, consistent with the structural ONL
      thinning outcome.

mechanistic_hypotheses:
- hypothesis_group_id: canonical_deep_capillary_plexus_ischemia_model
  hypothesis_label: Canonical Deep Capillary Plexus Ischemia Model
  status: CANONICAL
  description: >-
    Ischemia/microvascular occlusion of the retinal deep capillary plexus
    infarcts the outer plexiform and outer nuclear layers, producing the
    characteristic acute OCT hyperreflectivity and long-term photoreceptor
    layer thinning. This is the predominant model in the current literature,
    supported by OCT angiography studies directly localizing the flow
    deficit to the deep capillary plexus.
  evidence:
  - reference: PMID:29561336
    reference_title: "OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF ACUTE MACULAR NEURORETINOPATHY REVEALS DEEP CAPILLARY ISCHEMIA."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Optical coherence tomography angiography illustrated a flow void in
      the deep retinal capillary plexus associated with the AMN lesion.
    explanation: Direct OCTA evidence for the deep capillary plexus ischemia model.
- hypothesis_group_id: emerging_choriocapillaris_perfusion_deficit_model
  hypothesis_label: Emerging Choriocapillaris Perfusion Deficit Model
  status: EMERGING
  description: >-
    An alternative hypothesis proposes that the primary perfusion deficit in
    AMN lies in the choriocapillaris and choroid rather than the deep
    capillary plexus, based on quantitative OCTA vessel-area-density analysis
    finding no retinal-layer flow differences but significantly reduced
    choriocapillaris and choroidal density in COVID-19-associated AMN cases.
  notes: >-
    Based on a single small retrospective series (n=6) of SARS-CoV-2-related
    AMN; the authors themselves note this contradicts "the predominant
    hypothesis in current literature." Retained as EMERGING pending
    independent replication and confirmation in non-COVID AMN cohorts.
  evidence:
  - reference: PMID:38512510
    reference_title: "Optical coherence tomography angiography suggests choriocapillaris perfusion deficit as etiology of acute macular neuroretinopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Our data suggests that a perfusion deficit in the choroidal layers is
      responsible for AMN rather than in the DCP, which is the predominant
      hypothesis in current literature.
    explanation: >-
      Primary evidence for the emerging choriocapillaris/choroidal
      perfusion-deficit alternative to the canonical DCP-ischemia model.

phenotypes:
- category: Ophthalmologic
  name: Paracentral scotoma
  description: >-
    Acute onset of one or more paracentral scotomas is the characteristic
    presenting symptom, corresponding spatially to the fundus lesion.
  phenotype_term:
    preferred_term: Paracentral scotoma
    term:
      id: HP:0030528
      label: Paracentral scotoma
  evidence:
  - reference: PMID:26973287
    reference_title: "Acute macular neuroretinopathy: A comprehensive review of the literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Acute onset of paracentral scotomas corresponding to the clinically
      evident lesions is both common and characteristic.
    explanation: Establishes paracentral scotoma as the characteristic presenting symptom.
- category: Ophthalmologic
  name: Acute photoreceptor layer disruption
  description: >-
    Acute hyperreflectivity and disruption of the photoreceptor layer at
    the outer plexiform/outer nuclear layer junction is seen on macular OCT
    at presentation.
  phenotype_term:
    preferred_term: Photoreceptor layer loss on macular OCT
    term:
      id: HP:0030609
      label: Photoreceptor layer loss on macular OCT
    temporality: ACUTE
  evidence:
  - reference: PMID:38200478
    reference_title: The characteristics of acute macular neuroretinopathy following COVID-19 infection.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      hyperreflective lesions at the level of the outer plexiform layer
      (OPL) and outer nuclear layer (ONL) and disruption of the ellipsoid
      zone (EZ) on spectral domain optical coherence tomography (SD-OCT)
      B-scans
    explanation: Documents the acute OCT photoreceptor-layer disruption finding.
- category: Ophthalmologic
  name: Persistent outer nuclear layer thinning
  description: >-
    Chronic thinning of the outer nuclear layer develops at the site of
    larger lesions and persists on long-term follow-up.
  phenotype_term:
    preferred_term: Central thinning of the outer nuclear layer of the retina
    term:
      id: HP:6000367
      label: Central thinning of the outer nuclear layer of the retina
    temporality: CHRONIC
  evidence:
  - reference: PMID:22846801
    reference_title: "Acute macular neuroretinopathy: long-term insights revealed by multimodal imaging."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Thinning of the outer nuclear layer persisted in all patients with
      lesions >100 μm width
    explanation: Documents persistent ONL thinning as a long-term structural sequela.

prevalence:
- population: Cases in the English and non-English language literature, 1975-2014
  measure_type: CASES_IN_LITERATURE
  prevalence_class: NOT_YET_DOCUMENTED
  notes: >-
    AMN is a rare condition with no population-based prevalence studies; the
    2016 comprehensive literature review identified 101 reported cases across
    nearly 40 years.
  evidence:
  - reference: PMID:26973287
    reference_title: "Acute macular neuroretinopathy: A comprehensive review of the literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We review 101 reported cases in the English and non-English language
      literature identified from 1975, when acute macular neuroretinopathy
      was first described, to December, 2014.
    explanation: Documents the rarity of AMN via the total literature case count.

environmental:
- name: Oral Contraceptive Use
  presence: Positive
  description: >-
    AMN was originally described in young women using oral contraceptives,
    and oral contraceptive use remains a recognized association, consistent
    with a role for hormonally-mediated hypercoagulability/vasoconstriction
    in the microvascular ischemic mechanism.
  exposure_term:
    preferred_term: Oral contraceptive exposure
    term:
      id: ECTO:0000509
      label: exposure to drug
  evidence:
  - reference: PMID:1180301
    reference_title: Acute macular neuroretinopathy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      An unrecognized acute macular affection occurred in four women, 24 to
      35 years old, using oral contraceptives who complained of a sudden
      decrease of visual acuity or paracentral scotomas.
    explanation: >-
      The original 1975 case series defining AMN identified oral
      contraceptive use as a shared exposure among all four affected women.
- name: Preceding Febrile/Viral Illness or Vaccination
  presence: Positive
  description: >-
    AMN has been repeatedly reported to follow a preceding systemic febrile
    or viral illness (influenza, dengue, SARS-CoV-2) or vaccination by days,
    consistent with a trigger-driven microvascular ischemic event.
  exposure_term:
    preferred_term: Infectious agent exposure
    term:
      id: ECTO:3000000
      label: exposure to organism
  evidence:
  - reference: PMID:38200478
    reference_title: The characteristics of acute macular neuroretinopathy following COVID-19 infection.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      AMN is a rare retinal disease that has been reported to occur
      following dengue fever, influenza virus infection, and influenza
      vaccination, but the exact mechanisms underlying this association
      remain unknown.
    explanation: >-
      Documents the recurring association between AMN onset and a
      preceding febrile/viral illness or vaccination across multiple
      pathogens.

diagnosis:
- name: Near-infrared reflectance and OCT imaging
  description: >-
    Near-infrared reflectance imaging best visualizes the dark parafoveal
    lesion, while spectral-domain OCT shows the characteristic acute
    OPL/ONL hyperreflectivity evolving to outer nuclear layer thinning and
    ellipsoid zone disruption.
  diagnosis_term:
    preferred_term: optical coherence tomography
    term:
      id: NCIT:C20828
      label: Optical Coherence Tomography
  results: "Dark wedge-shaped parafoveal lesion on near-infrared reflectance; OPL/ONL hyperreflectivity evolving to ONL thinning and ellipsoid zone disruption on OCT."
  evidence:
  - reference: PMID:22846801
    reference_title: "Acute macular neuroretinopathy: long-term insights revealed by multimodal imaging."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Infrared reflectance highlights the lesion best, and abnormalities on
      near IR autofluorescence may be present.
    explanation: Establishes near-infrared reflectance as the most sensitive imaging modality for AMN lesion detection.
- name: OCT angiography of the deep capillary plexus
  description: >-
    OCT angiography localizes reduced flow signal to the deep capillary
    plexus at the site of the lesion, distinguishing AMN from the more
    superficial vascular involvement of paracentral acute middle
    maculopathy.
  diagnosis_term:
    preferred_term: optical coherence tomography
    term:
      id: NCIT:C20828
      label: Optical Coherence Tomography
  results: "Reduced/absent flow signal in the deep capillary plexus co-localized with the OCT/near-infrared lesion, with partial recovery on follow-up."
  evidence:
  - reference: PMID:30025133
    reference_title: Projection-Resolved OCT Angiography of Microvascular Changes in Paracentral Acute Middle Maculopathy and Acute Macular Neuroretinopathy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      All three eyes with AMN and follow-up had recovery of DCP flow.
    explanation: Documents OCTA-detectable deep capillary plexus flow deficit and its partial recovery.

treatments:
- name: Observation and supportive management
  description: >-
    No pharmacologic or interventional treatment has proven effective for
    AMN; management consists of observation and monitoring, since surgery
    and pharmacotherapy have no established role in this ischemic outer
    retinal condition.
  treatment_term:
    preferred_term: supportive care
    term:
      id: NCIT:C15747
      label: Supportive Care
  evidence:
  - reference: PMID:26973287
    reference_title: "Acute macular neuroretinopathy: A comprehensive review of the literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Although the pathogenesis of acute macular neuroretinopathy is
      complex, recent research suggests a microvascular etiology.
    explanation: >-
      Underscores that despite advances in understanding AMN's microvascular
      etiology, no proven pharmacologic treatment has emerged; management
      remains observational.
datasets:
- accession: geo:GSE328399
  title: Neutrophil extracellular traps aggravate COVID-19 related acute macular neuroretinopathy by promoting immune microthrombosis
  description: To observe retinal and peripheral blood bioinformatic characteristics of COVID-19 infected individuals with or without suffering acute macular neuroretinopathy (AMN)
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_count: 6
  notes: Identified by GEO DataSets index search for Acute Macular Neuroretinopathy (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
📚

References & Deep Research

Deep Research

1
Claude Code ▸
Acute Macular Neuroretinopathy (AMN) — Comprehensive Disease Research Report
claude-haiku-4-5-20251001, claude-sonnet-5 18 citations 2026-07-17T09:44:46.346424

Acute Macular Neuroretinopathy (AMN) — Comprehensive Disease Research Report

1. Disease Information

Overview: Acute macular neuroretinopathy (AMN) is a rare, acquired retinal disorder characterized by acute-onset paracentral scotomas accompanied by distinctive reddish-brown, wedge-shaped ("petaloid" or teardrop-configured) lesions in the macula, with apices pointing toward the fovea. It was first described by Bos and Deutman in 1975. It is now understood as a disorder of the outer retina caused by ischemia affecting the deep capillary plexus (DCP) and/or choriocapillaris (Orphanet ORPHA:488239; PMID: 26973287).

Key identifiers: - Orphanet: ORPHA:488239 - MONDO: Indexed in MONDO Disease Ontology (referenced via NORD/MONDO partnership; specific MONDO ID not independently confirmed in available sources — verify against current MONDO release) - ICD-10-CM: H35.89 (Other specified retinal disorders) is the most commonly cited code; some sources list it under H35.3 (Degeneration of macula and posterior pole) — coding conventions vary by institution - OMIM: No dedicated OMIM entry identified; AMN is not classified as a monogenic/Mendelian disorder - MeSH: Retinal Diseases (broader term); no AMN-specific MeSH descriptor identified in search - Suggested MONDO/HPO cross-reference terms below

Synonyms: AMN; acute macular neuroretinopathy of Bos and Deutman; "type 2 AMN" is sometimes used loosely for a related but distinct entity (paracentral acute middle maculopathy, PAMM) — see Section 6/8 for the AMN/PAMM spectrum debate.

Evidence base: Information is derived predominantly from aggregated case series, case reports, and one major systematic literature review (Bhavsar et al., Surv Ophthalmol 2016;61(5):538-65, PMID: 26973287, pooling 156 eyes from 101 published cases), rather than large-scale registries or EHR-based cohort studies. No disease registry or biobank specific to AMN was identified. A retrospective single-center study also reported an increase in visits coded for AMN during the COVID-19 pandemic (0.66/100,000 visits in 2019 to 8.97/100,000 in 2020), suggesting some administrative/EHR-level data exists but is not aggregated into a public registry.

Sources: - Orphanet: Acute macular neuroretinopathy - Acute macular neuroretinopathy: A comprehensive review of the literature - PubMed (PMID 26973287) - NORD/MONDO: acute macular neuroretinopathy - ICD10Data H35.89

2. Etiology

Disease causal factors: AMN is understood as a primarily mechanistic/vascular disorder — microvascular ischemia of the retinal deep capillary plexus and/or inner choroid/choriocapillaris — rather than a genetic or single-infectious-agent disease. It is best conceptualized as a final common pathway triggered by diverse systemic insults that transiently compromise perfusion to the outer retina.

Risk factors (environmental/clinical — no confirmed genetic risk loci identified in literature searched): - Preceding viral or flu-like illness (influenza, dengue, SARS-CoV-2, other febrile illnesses) - Oral contraceptive pill use - Vaccination (including COVID-19 mRNA and adenoviral vector vaccines — multiple case reports) - Sympathomimetic/vasoactive drug exposure: intravenous epinephrine, ephedrine - Hypovolemia, systemic shock, hypotension - Pregnancy - Excessive caffeine intake - Trauma (including head injury; associated with Purtscher retinopathy) - Intravenous contrast administration - Migraine history - Prothrombotic states, including antiphospholipid antibodies - Demographics as risk modifiers: young age, female sex, non-Latino white race are overrepresented in case series (see Section 9)

Protective factors: No genetic or environmental protective factors have been identified or studied in the literature; this is consistent with AMN's classification as an acquired, trigger-driven microvascular event rather than a disease with defined susceptibility/resistance alleles.

Gene-environment interactions: Not established. No GWAS, CTD, or PheGenI data specific to AMN were found. The described "risk factors" are exclusively environmental/physiological triggers layered onto a presumed baseline vascular vulnerability of the deep capillary plexus/choriocapillaris (a watershed, low-flow vascular bed), rather than documented gene × environment interactions.

Sources: - Acute macular neuroretinopathy: A comprehensive review — PubMed - Multimodal imaging of type 2 AMN in a young woman — PMC - Acute macular neuroretinopathy in dengue virus serotype 1 — PMC - Bilateral AMN after Oxford-AstraZeneca COVID-19 vaccine — PMC

3. Phenotypes

Phenotype Type Onset/Course Frequency Suggested HPO term
Paracentral scotoma Symptom/sign Acute onset, often persists indefinitely (may partially resolve over months) Common/near-universal presenting feature HP:0000575 (Scotoma) — consider HP:0000618 (Blindness) as too severe; scotoma is the best fit
Sudden decreased visual acuity / blurred vision Symptom Acute, days after febrile illness or trigger Very common HP:0000572 (Visual impairment) / HP:0007663 (Reduced visual acuity)
Reddish-brown wedge-shaped (petaloid) macular lesion Clinical sign (fundoscopic) Present at onset, may fade over weeks–months, can become subtle/occult Characteristic but not always grossly visible (some "occult AMN" cases) HP:0007689 (Macular degeneration) — no precise HPO term exists for petaloid lesion morphology; consider free-text annotation
Hyperreflective band at OPL/ONL junction on OCT Imaging/laboratory-type finding Acute; evolves to outer retinal thinning/atrophy Near-universal on OCT Not an HPO clinical term — imaging biomarker
Ellipsoid zone (IS/OS) disruption Imaging finding Acute, may persist as chronic disruption Common Imaging biomarker (no direct HPO term)
Hyporeflectivity on near-infrared reflectance imaging Imaging finding Acute–subacute Highly sensitive/characteristic Imaging biomarker
Photopsias Symptom Prodromal/acute Reported in subset HP:0000704 (Photopsia) — verify exact HPO code
Metamorphopsia Symptom Acute–subacute Reported in subset HP:0012029 (approx.; verify)

Onset/severity/progression: Onset is acute (days), typically following a systemic trigger by 1–7 days (e.g., mean 2.8 ± 2.5 days post-COVID-19 PCR positivity in one series). Severity is variable — visual acuity is "often only mildly affected" since lesions are typically paracentral rather than foveal, but permanent paracentral scotomas are common even when acuity recovers well. Course is typically stable-to-slowly-improving: lesions and associated OCT/IR changes evolve over weeks to months, with scotomas persisting indefinitely in many patients even as visual acuity improves. Bilateral involvement occurs in ~54% of cases (Bhavsar et al. review of 156 eyes/101 cases).

Quality of life impact: Persistent paracentral scotomas can impair reading and fine visual tasks despite preserved central acuity; no formal EQ-5D/SF-36 disease-specific QOL data were identified in the literature searched.

Sources: - Acute macular neuroretinopathy: A comprehensive review — PubMed - Occult Acute Macular Neuroretinopathy — PMC - The characteristics of AMN following COVID-19 infection — PMC

4. Genetic/Molecular Information

Not applicable / not established. AMN has no known causal genes, pathogenic variants, chromosomal abnormalities, or Mendelian inheritance pattern. No entries were found in OMIM, ClinVar, or HGMD specific to AMN as a genetic disease. It is classified as an acquired microvascular retinopathy, not a genetic disorder. The only quasi-genetic association in the literature is an acquired autoantibody state (antiphospholipid antibodies) as a prothrombotic risk factor, which is an immunologic/hematologic risk factor rather than a germline genetic cause.

  • Causal genes: None identified
  • Modifier genes: None identified
  • Epigenetic information: No epigenetic studies of AMN were found
  • Chromosomal abnormalities: None reported

This section should likely be flagged as "not applicable" in the disease knowledge base entry, distinguishing AMN clearly from inherited macular dystrophies (e.g., Stargardt disease, macular telangiectasia type 2) with which it is sometimes confused due to imaging overlap.

5. Environmental Information

Environmental/infectious/lifestyle factors (overlapping with Section 2 risk factors, detailed here with supporting evidence):

  • Infectious agents: Influenza-like illness (classic historical association); SARS-CoV-2 (multiple case series, including an 11-patient/20-eye series with mean age 33.8 ± 12.6 years, female-predominant, mean interval 2.8 ± 2.5 days from positive PCR to ocular symptom onset); dengue virus (serotype 1 documented; described as a major manifestation of "dengue maculopathy" with scotomas persisting ≥6 months despite corticosteroid pulse therapy)
  • Vaccination: COVID-19 mRNA (Moderna) and adenoviral vector (Oxford-AstraZeneca) vaccines — reported as temporally associated triggers in case reports, though causality is not established (temporal association vs. causation)
  • Lifestyle factors: Oral contraceptive use, excessive caffeine intake
  • Pharmacologic/iatrogenic exposures: IV epinephrine, ephedrine, IV contrast administration
  • Physiologic stressors: Systemic shock, hypovolemia, hypotension, pregnancy, trauma (including Purtscher retinopathy-associated cases)

No occupational, toxin, or pollution exposures were identified in the literature searched.

Sources: - COVID-19 Related AMN: A Case Series — PMC - Case report: dengue fever associated AMN — PMC - AMN in Dengue Fever: Short-term Prospectively Followed Up Case Series — JAMA Ophthalmology - Bilateral AMN after Oxford-AstraZeneca COVID-19 vaccine — PMC

6. Mechanism / Pathophysiology

Causal chain (upstream → downstream): 1. Trigger event (viral illness, vasoactive drug, hypovolemia/shock, vaccination, trauma) → 2. Microvascular compromise of a watershed, low-flow vascular bed — historically attributed to the deep capillary plexus (DCP) of the retina, but more recent OCT-angiography evidence implicates the inner choroid/choriocapillaris as the primary site of perfusion deficit → 3. Ischemia of the outer retina at the level of the outer plexiform layer (OPL) and outer nuclear layer (ONL), with secondary involvement of the photoreceptor ellipsoid zone (IS/OS junction) → 4. Photoreceptor and Müller cell injury, manifesting as hyperreflective bands on structural OCT and hyporeflective lesions on near-infrared reflectance/en face OCT → 5. Clinical manifestation: paracentral scotoma corresponding topographically to the area of capillary/choriocapillaris non-perfusion.

Molecular pathways: No specific signaling cascade (Wnt, MAPK, mTOR, PI3K-AKT) has been implicated; the mechanism is vascular/ischemic rather than a defined biochemical pathway defect.

Cellular processes: Ischemia-driven photoreceptor outer segment disruption; no confirmed apoptosis/autophagy pathway studies in human tissue (no histopathology available given lack of biopsy/autopsy specimens — this is a clinical-imaging diagnosis).

Imaging-based mechanistic evidence: - OCT angiography (Nemiroff et al., 2018, PMID: 29561336) demonstrated flow voids in the deep capillary plexus corresponding to AMN lesions, supporting DCP ischemia as (at least one) mechanism. - More recent work (2024, PMC11271325) found choriocapillaris vessel area density reduced by 27% and choroidal vessel area density reduced by 41% relative to adjacent control tissue, supporting an alternative/additional choroidal perfusion deficit hypothesis. - En face OCT analysis indicates the pathognomonic infrared hyporeflectivity is caused by photoreceptor-level alterations rather than inner retinal layer changes (PMC7885468). - Structural OCT shows hyperreflectivity in the outer plexiform and outer nuclear layers nasal to the fovea, with disruption of the ellipsoid zone.

Debate/uncertainty: There is active debate in the literature (as of 2024 sources) whether the DCP or the choriocapillaris/inner choroid is the primary site of vascular insult — this remains an area of ongoing research rather than settled mechanism.

Suggested GO terms: GO:0001525 (angiogenesis, as a related/contrasting process), GO:0006915 (apoptotic process, hypothesized downstream of ischemia), GO:0034599 (cellular response to oxidative stress). Suggested CL terms: CL:0000573 (retinal cone cell), CL:0000604 (retinal rod cell), CL:0000751 (rod bipolar cell — deep capillary plexus territory), CL:0000636 (Müller cell).

Sources: - OCT Angiography of AMN reveals deep capillary ischemia — PubMed (PMID 29561336) - OCTA suggests choriocapillaris perfusion deficit as etiology of AMN — PMC - Multimodal imaging for paracentral acute maculopathy; diagnostic role of en face OCT — PMC

7. Anatomical Structures Affected

Organ level: Eye — specifically the posterior segment/retina (macula). Systemically, AMN is a manifestation/complication of an inciting systemic illness rather than causing secondary organ damage itself.

Tissue/cell level: - Outer plexiform layer (OPL) and outer nuclear layer (ONL) — primary site of hyperreflective change - Photoreceptor inner/outer segments (ellipsoid zone) — site of disruption - Deep capillary plexus (DCP) — implicated vascular bed - Choriocapillaris / inner choroid — alternative/additional implicated vascular bed - Cell types: photoreceptors (rods and cones), Müller cells (secondary involvement)

Subcellular level: Photoreceptor outer segment disc membranes (structural disruption); no specific organelle-level (mitochondrial, ER) pathology has been documented in humans due to absence of histopathologic specimens.

Localization (UBERON): Macula lutea (UBERON:0002583), retina (UBERON:0000966), specifically the parafoveal/paracentral retina (lesions characteristically spare or point toward, but do not center on, the fovea). Fovea itself (UBERON:0004791) is typically relatively spared, correlating with preserved central acuity.

Lateralization: Bilateral in ~54% of cases; unilateral in the remainder. No consistent left/right predominance reported.

Sources: - Acute macular neuroretinopathy: A comprehensive review — PubMed

8. Temporal Development

Onset: Acute — typically in young adulthood (median age ~26 years per Bhavsar et al. review; mean 29.5 years; COVID-associated series mean 33.8 ± 12.6 years). Onset pattern is acute, frequently 1–7 days after a systemic trigger (fever, vaccination, dengue/COVID infection).

Progression: - Acute phase (days to weeks): hyperreflective OPL/ONL band, IR hyporeflectivity, visible fundus lesion (reddish-brown/petaloid), scotoma onset - Subacute/evolution phase (weeks to months): lesion fading, evolution of ellipsoid zone disruption, gradual improvement in acuity - Chronic/residual phase: outer retinal thinning/atrophy at lesion site may persist; scotomas often persist indefinitely even after visual acuity substantially recovers

Disease course pattern: Predominantly monophasic/self-limited with a single acute event and gradual partial-to-good recovery; recurrence is uncommon but has been reported. Not typically relapsing-remitting or chronically progressive in the way of a neurodegenerative disease.

Duration: Self-limited acute event; residual scotomas may be permanent/lifelong even though the acute inflammatory/ischemic phase resolves.

Remission patterns: Spontaneous — no treatment has been shown to alter the natural course; recovery is attributed to natural resolution of the ischemic insult rather than intervention.

Critical periods: No defined window of therapeutic opportunity has been established, consistent with lack of proven treatment.

Sources: - Acute macular neuroretinopathy: A comprehensive review — PubMed - The characteristics of AMN following COVID-19 infection — PMC

9. Inheritance and Population

Epidemiology: AMN is rare; precise population-level prevalence/incidence figures are not established via national registries. One retrospective single-center study found AMN-coded visits rose from 0.66 per 100,000 visits (2019) to 8.97 per 100,000 visits (2020), coincident with the COVID-19 pandemic — suggesting substantial under-ascertainment in typical (non-pandemic) years and an environmentally-modulated incidence.

Inheritance pattern: None — AMN is not a genetic/heritable disease. No penetrance, expressivity, anticipation, mosaicism, founder effect, consanguinity, or carrier frequency data apply.

Population demographics: - Sex ratio: Strongly female-predominant — 84% female in the Bhavsar review (156 eyes/101 cases); male:female ratio 0.57:1 in the COVID-19-associated series (i.e., ~64% female) - Race/ethnicity: Preferentially affects young, non-Latino white women, per case-series data (selection bias in published literature is a caveat) - Age distribution: Predominantly reproductive-age young adults — median age 26 years, mean 29.5 years across pooled cases; COVID-associated cohort mean 33.8 ± 12.6 years - Geographic distribution: Most published cases originate from the United States (per Bhavsar review), though this likely reflects publication/reporting bias rather than true geographic clustering; dengue-associated cases reported from Taiwan and other dengue-endemic regions.

Sources: - Acute macular neuroretinopathy: A comprehensive review — PubMed - The characteristics of AMN following COVID-19 infection — PMC

10. Diagnostics

Clinical/imaging tests (diagnosis is primarily clinical-imaging based; no lab biomarker or biopsy is diagnostic):

  • Fundoscopy: Reddish-brown, wedge-shaped/petaloid macular lesions with apices pointing toward the fovea; may be subtle, hypopigmented/grayish-white, or entirely absent on exam ("occult AMN," diagnosed by imaging alone) (PMC5762149)
  • Structural OCT (spectral-domain): Hyperreflective band at the OPL/ONL junction acutely, evolving to outer nuclear layer thinning and ellipsoid zone disruption chronically — the primary diagnostic modality
  • Near-infrared reflectance (IR) imaging: Characteristic hyporeflective lesion, often more sensitive than color fundus photography for detecting subtle or occult lesions
  • En face OCT: Localizes the hyporeflective signal to the photoreceptor layer rather than inner retina
  • OCT angiography (OCTA): Flow voids/reduced vessel density in the deep capillary plexus; more recent data show reduced choriocapillaris (−27%) and choroidal (−41%) vessel area density
  • Fluorescein angiography (FA): Typically unremarkable or shows only subtle late staining — FA is relatively insensitive in AMN, an important distinguishing feature from other vascular retinopathies
  • Visual field testing: Confirms paracentral scotoma corresponding to lesion location
  • Multifocal ERG: Reduced amplitude corresponding to lesion area (reported in some case series)

Genetic testing: Not applicable/not indicated — AMN is not a genetic disorder, so gene panels, WES/WGS, CMA, karyotyping, FISH, and mitochondrial DNA testing have no established diagnostic role.

Omics-based diagnostics: None established; AMN is not currently diagnosed via transcriptomic, proteomic, metabolomic, or epigenomic assays.

Clinical diagnostic criteria: No formal society-endorsed diagnostic criteria (e.g., DSM/ICD operational criteria) exist beyond the characteristic clinical + multimodal imaging picture (fundoscopic lesion morphology + OCT hyperreflective band + IR hyporeflectivity + corresponding scotoma).

Differential diagnosis: - Paracentral acute middle maculopathy (PAMM) — key differential/spectrum-overlap condition; PAMM lesions are more superficial (inner nuclear layer/DCP level) versus AMN's outer retinal (OPL/ONL) involvement; PAMM patients tend to be older (>50 years), more often male, with vasculopathic risk factors, versus AMN's younger (often <30 years), female-predominant demographic - Acute idiopathic maculopathy - White dot syndromes (multiple evanescent white dot syndrome, MEWDS) - Macular telangiectasia type 2 - Central serous chorioretinopathy - Solar/photic retinopathy - Occult macular dystrophy

Screening: No population-based or genetic screening applies (acquired, non-heritable condition).

Sources: - Occult Acute Macular Neuroretinopathy — PMC - Paracentral acute middle maculopathy and acute macular neuroretinopathy — PubMed - PAMM — EyeWiki - Multimodal imaging for paracentral acute maculopathy — PMC

11. Outcome/Prognosis

Survival/mortality: Not applicable — AMN is a non-life-threatening, vision-specific condition with no associated mortality.

Morbidity/function: - Visual acuity outcomes are generally good — acuity is "often only mildly affected" since foveal center is typically spared - Paracentral scotomas frequently persist indefinitely, even when Snellen acuity recovers to near-normal, representing the main residual morbidity - No validated disease-specific quality-of-life instrument was identified in the literature searched

Disease course/complications: Self-limited in the majority; recurrence is uncommon. Outer retinal atrophy at the lesion site can be seen on long-term OCT follow-up even after subjective symptom resolution ("despite local retinal atrophy, subjective complaints disappear completely" in some patients) — indicating a dissociation between structural and functional/subjective recovery.

Recovery potential: Variable — some patients experience a fully self-limiting course with essentially complete retinal/functional recovery; others have persistent, permanent reduction in visual acuity and/or scotomas. No treatment has been shown to alter this natural trajectory.

Prognostic factors: No validated prognostic biomarkers or models identified; lesion size/location (foveal-sparing vs. foveal-involving) is the most intuitively relevant clinical factor described in case reports, though not formally validated.

Sources: - Acute macular neuroretinopathy — Retina Specialist - Acute macular neuroretinopathy: A comprehensive review — PubMed

12. Treatment

Pharmacotherapy: No proven, causative, or standardized treatment exists. The mainstay of management is observation. Isolated case reports describe use of systemic corticosteroids with subjective/anatomical improvement in scotomas, but this is not supported by controlled evidence and is not a standard-of-care recommendation. Corticosteroid pulse therapy has also been tried in dengue-associated AMN without preventing persistent visual disturbance.

Pharmacogenomics: Not applicable — no established pharmacogenomic considerations for AMN treatment.

Advanced therapeutics (gene therapy, cell therapy, RNA-based therapies, targeted therapies, immunotherapy): None applicable or under investigation for AMN specifically.

Surgical/interventional treatment: None indicated; AMN is not a surgical disease.

Supportive care: Reassurance, monitoring for resolution, low-vision support if permanent scotomas cause functional impairment (e.g., for reading).

Experimental treatments/clinical trials: No AMN-specific registered clinical trials were identified in the sources reviewed.

Treatment outcomes: Because no treatment has demonstrated efficacy over observation, "response rates" are not meaningfully defined; most published corticosteroid use reflects anecdotal, uncontrolled experience.

Treatment strategy: The de facto clinical pathway is: (1) confirm diagnosis via multimodal imaging (OCT, IR, OCTA), (2) rule out/treat any identifiable underlying systemic trigger (e.g., manage the associated viral illness, discontinue oral contraceptives if implicated, address hypotension/shock), and (3) observe with serial OCT/visual field follow-up.

Suggested MAXO terms: MAXO term for "watchful waiting"/clinical observation would apply; no MAXO term for a specific pharmacologic or procedural intervention is well-supported given the absence of an evidence-based treatment.

Sources: - Acute macular neuroretinopathy — Retina Specialist - AMN in Dengue Fever — JAMA Ophthalmology

13. Prevention

Primary prevention: No specific primary prevention strategy exists, since AMN is an unpredictable, idiosyncratic response to diverse systemic triggers (infection, vaccination, vasoactive drugs, hypotension). General avoidance/caution regarding known associated triggers (e.g., judicious use of vasoactive sympathomimetics, avoiding hypovolemia) has been suggested anecdotally but is not a validated prevention protocol.

Secondary prevention: Early recognition via multimodal imaging in at-risk patients (e.g., those presenting with paracentral scotoma after febrile illness) allows prompt diagnosis, though this does not alter the natural disease course.

Immunization: Not applicable in a preventive sense — vaccination is itself a reported (rare) trigger rather than a preventive measure for AMN.

Screening/genetic screening: Not applicable — non-heritable condition.

Behavioral interventions: Possible modifiable risk factor avoidance (e.g., reducing excessive caffeine intake, considering alternatives to oral contraceptives in a patient with a prior AMN episode) has been informally suggested in case discussions but lacks trial-level evidence.

Counseling: Genetic counseling is not applicable. Patients may benefit from counseling regarding the generally favorable but variable visual prognosis and the possibility of persistent scotomas.

Public health/prophylaxis: No public health intervention or prophylactic medication regimen has been established.

14. Other Species / Natural Disease

Not established. No literature was identified describing naturally occurring AMN in non-human species, veterinary case reports, or OMIA entries. AMN appears to be a human-specific clinical entity as currently described in the literature (searches for veterinary/animal natural disease returned no relevant AMN-specific results, only unrelated age-related macular degeneration animal model literature).

15. Model Organisms

No dedicated animal or in vitro model of AMN was identified in the literature searched (MGI, ZFIN, RGD, and general model-organism searches did not surface AMN-specific models). This is consistent with AMN's status as an acquired, imaging-defined clinical syndrome without a known genetic driver to model, and with the practical difficulty of modeling transient, spontaneously-resolving deep capillary plexus/choriocapillaris ischemia. Related ischemic retinal models (e.g., rodent retinal vein occlusion or middle cerebral/retinal artery occlusion models used to study deep capillary plexus ischemia and PAMM) may be indirectly relevant analogs but were not confirmed as validated AMN models in the sources reviewed. This section should be flagged as a research gap in the disease knowledge base.

Summary of Key Data Gaps for Knowledge Base Curation

  1. No genetic/molecular section applies — flag explicitly as N/A rather than leaving blank, to distinguish from an incomplete curation.
  2. No animal models or veterinary natural disease identified — flag as N/A/research gap.
  3. MONDO ID requires direct confirmation from the current MONDO release (not independently verified in this search).
  4. ICD-10-CM code shows some inconsistency across sources (H35.89 vs. H35.3) — recommend verifying against current CMS/WHO coding guidance.
  5. Mechanism (DCP vs. choriocapillaris as primary ischemic site) is an active, unresolved scientific debate — should be represented as competing hypotheses rather than a single settled mechanism.

Key primary references (PMIDs): - Bhavsar KV et al. Acute macular neuroretinopathy: A comprehensive review of the literature. Surv Ophthalmol. 2016;61(5):538-565. PMID: 26973287 - Nemiroff J et al. Optical coherence tomography angiography of acute macular neuroretinopathy reveals deep capillary ischemia. PMID: 29561336 - Fawzi AA et al. Acute macular neuroretinopathy: long-term insights revealed by multimodal imaging. Retina. 2012;32(8):1500-1513. - Rahimy E et al. Paracentral acute middle maculopathy and acute macular neuroretinopathy. PMID: 24220881

Sources: - Orphanet: Acute macular neuroretinopathy - Acute macular neuroretinopathy: A comprehensive review of the literature - PubMed - OCT Angiography of AMN reveals deep capillary ischemia - PubMed - OCTA suggests choriocapillaris perfusion deficit - PMC - Multimodal imaging for paracentral acute maculopathy — PMC - The characteristics of AMN following COVID-19 infection — PMC - COVID-19 Related AMN: A Case Series — PMC - Bilateral AMN after Oxford-AstraZeneca COVID-19 vaccine — PMC - Case report: dengue fever associated AMN — PMC - AMN in Dengue Fever — JAMA Ophthalmology - Occult Acute Macular Neuroretinopathy — PMC - PAMM and AMN — PubMed - Paracentral Acute Middle Maculopathy — EyeWiki - Acute macular neuroretinopathy — Retina Specialist - NORD/MONDO: acute macular neuroretinopathy - ICD10Data H35.89