Adult-Onset Foveomacular Vitelliform Dystrophy

Complex MONDO:0011979 Pathograph 9 Show in embeddings browser Ophthalmological Disease Retinal Dystrophy Inherited retinal dystrophy

Adult-onset foveomacular vitelliform dystrophy (AVMD/AOFVD, also "pseudo-Best disease" or Gass disease) is a slowly progressive macular dystrophy presenting in mid-adulthood (fourth to sixth decade) with a small, bilateral, subfoveal yellow vitelliform (egg-yolk-like) lesion composed of lipofuscin accumulated at the photoreceptor outer-segment/retinal pigment epithelium (RPE) interface. Patients have mild central or paracentral visual loss, metamorphopsia, and a generally good prognosis, although gradual lesion resorption can lead to geographic atrophy or, less often, choroidal neovascularization. AVMD is genetically heterogeneous: a minority of cases carry heterozygous variants in PRPH2 (peripherin-2), BEST1 (bestrophin-1), IMPG1, or IMPG2, while many cases are non-Mendelian/idiopathic without an identifiable monogenic cause. It is distinguished from Best vitelliform macular dystrophy (BVMD) by its later onset, smaller lesions, normal-to-mildly-reduced electrooculogram (EOG), and milder course.

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1
Inheritance
3
Pathophys.
5
Phenotypes
9
Pathograph
1
Genes
2
Medical Actions
5
Subtypes
7
References
1
Deep Research
👪

Inheritance

1
Autosomal dominant HP:0000006
Monogenic AVMD due to PRPH2, BEST1, IMPG1, or IMPG2 variants is typically autosomal dominant; rare recessive IMPG cases have been reported.
Autosomal dominant inheritance
Show evidence (1 reference)
PMID:25085631 SUPPORT Human Clinical
"With an autosomal dominant transmission, families 1 and 2 had the c.713T→G (p.Leu238Arg) mutation in IMPG1 and family 4 had the c.3230G→T (p.Cys1077Phe) mutation in IMPG2."
Documents autosomal dominant transmission in IMPG1- and IMPG2-linked AVMD families.
◆

Subtypes

5
PRPH2-related AVMD (vitelliform macular dystrophy 3) MONDO:0024561
PRPH2 hgnc:9942 Autosomal dominant inheritance
AVMD caused by heterozygous variants in PRPH2 (peripherin-2), a photoreceptor outer-segment disc rim tetraspanin. Part of the broader PRPH2 pattern-dystrophy spectrum.
Show evidence (1 reference)
PMID:25681578 SUPPORT Human Clinical
"A minority of AFVD patients have a mutation in the PRPH2, BEST1, IMPG1, or IMPG2 genes."
This authoritative review identifies PRPH2 as one of the recognized causal genes for a minority of AFVD cases, supporting the PRPH2-related subtype.
BEST1-related AVMD (adult-onset bestrophinopathy / pseudo-Best)
BEST1 hgnc:12703 Autosomal dominant inheritance
Adult-onset vitelliform lesions caused by heterozygous variants in BEST1 (bestrophin-1), an RPE basolateral calcium-activated chloride channel. Later onset and milder than juvenile Best vitelliform macular dystrophy.
Show evidence (1 reference)
PMID:25681578 SUPPORT Human Clinical
"A minority of AFVD patients have a mutation in the PRPH2, BEST1, IMPG1, or IMPG2 genes."
BEST1 is one of the recognized causal genes for a minority of AFVD cases. Adult-onset BEST1 disease is distinguished from juvenile Best disease by its later onset and milder course.
IMPG1-related AVMD (vitelliform macular dystrophy 4) MONDO:0014508
IMPG1 hgnc:6055 Autosomal dominant inheritance
AVMD caused by variants in IMPG1 (interphotoreceptor matrix proteoglycan 1), a component of the interphotoreceptor matrix in the subretinal space.
Show evidence (2 references)
PMID:25085631 SUPPORT Human Clinical
"IMPG1 and IMPG2 are new causal genes in 8% of families negative for BEST1 and PRPH2 mutations."
This national referral-center study established IMPG1 (and IMPG2) as causal genes in adult-onset vitelliform macular dystrophy, supporting the IMPG1-related subtype.
PMID:28644393 SUPPORT Human Clinical
"Clinical symptoms tend to be more severe for IMPG1 mutations."
In a BEST1/PRPH2-negative VMD cohort, IMPG1 mutation carriers had a more severe phenotype than IMPG2 carriers, supporting IMPG1 as a distinct gene-defined subtype.
IMPG2-related AVMD (vitelliform macular dystrophy 5) MONDO:0014509
IMPG2 hgnc:18362 Autosomal dominant inheritance
AVMD caused by variants in IMPG2 (interphotoreceptor matrix proteoglycan 2), a component of the interphotoreceptor matrix that anchors photoreceptor outer segments.
Show evidence (2 references)
PMID:25085631 SUPPORT Human Clinical
"IMPG1 and IMPG2 are new causal genes in 8% of families negative for BEST1 and PRPH2 mutations."
This study established IMPG2 (with IMPG1) as a causal gene in adult-onset vitelliform macular dystrophy, supporting the IMPG2-related subtype.
PMID:28644393 SUPPORT Human Clinical
"Taken together, our results provide further evidence for an involvement of dominant and recessive mutations in IMPG1 and IMPG2 in VMD pathology."
Mutational screening of a BEST1/PRPH2-negative VMD cohort identified multiple IMPG2 variants, supporting IMPG2 as a recognized gene-defined subtype.
Idiopathic / non-Mendelian AVMD
The majority of AVMD cases, which are sporadic and lack an identifiable monogenic cause (the genetic factors are unknown in more than 80% of cases). This subset is non-Mendelian and shows partial genetic overlap with age-related macular degeneration, specifically at complement-cascade risk loci.
Show evidence (3 references)
PMID:26802173 SUPPORT Human Clinical
"Patients with sporadic AFVD are usually negative for the known mutations previously associated with this phenotype, and present at an age that is higher than described for monogenic AFVD."
A genetically evaluated sporadic AFVD cohort was negative for the known causal mutations, supporting an idiopathic/non-Mendelian subtype with an older age at presentation than monogenic forms.
PMID:39585675 SUPPORT Human Clinical
"The genetic factors associated with AFVD are unknown in >80% of cases."
Quantifies the predominance of the idiopathic/non-monogenic subtype: a monogenic cause is identified in fewer than 20% of AFVD patients.
PMID:39585675 SUPPORT Human Clinical
"Non-monogenic AFVD is associated with AMD risk alleles in the complement cascade, but not in other pathways."
A case-control genetic study links non-monogenic (idiopathic) AFVD to AMD complement-cascade risk alleles, supporting a partly multifactorial, complement-associated architecture for this subtype.
⚙

Pathophysiology

3
Photoreceptor Outer-Segment / RPE Interface Dysfunction
Variants in PRPH2, BEST1, IMPG1, and IMPG2 perturb distinct components of the photoreceptor outer-segment / RPE / interphotoreceptor-matrix interface in the macula. Depending on the underlying gene, the primary defect lies in the photoreceptor outer-segment disc rim (PRPH2), the RPE basolateral chloride channel (BEST1), or the secreted interphotoreceptor-matrix proteoglycans (IMPG1/IMPG2) that anchor outer segments and organize the subretinal space.
retinal pigment epithelial cell CL:0002586 photoreceptor cell CL:0000210
photoreceptor cell maintenance GO:0045494 ↓ DECREASED
fovea centralis UBERON:0001786 macula lutea UBERON:0000053
Downstream
Subfoveal Lipofuscin (Vitelliform) Deposit Accumulation Interface dysfunction leads to accumulation of lipofuscin-rich vitelliform material in the subretinal space.
Show evidence (1 reference)
PMID:25681578 SUPPORT Human Clinical
"the phenotype can arise from alterations in the photoreceptors, retinal pigment epithelium, and/or interphotoreceptor matrix depending on the underlying gene defect."
The review establishes that the AFVD phenotype originates at the photoreceptor / RPE / interphotoreceptor-matrix interface, with the specific compartment depending on the causal gene.
Subfoveal Lipofuscin (Vitelliform) Deposit Accumulation
Excess photoreceptor outer-segment production and/or impaired RPE uptake of shed outer segments (impaired phagocytosis) leads to accumulation of lipofuscin-rich material in the subretinal space beneath the fovea, forming the characteristic dome-shaped, hyperautofluorescent yellow vitelliform lesion.
retinal pigment epithelial cell CL:0002586
phagocytosis of shed photoreceptor outer segments GO:0006909 ↓ DECREASED
fovea centralis UBERON:0001786
Downstream
Progressive Macular Atrophy and Vision Loss Over years the vitelliform deposit resorbs, leaving atrophic outer retina and RPE with consequent visual loss.
Vitelliform macular lesion The subfoveal lipofuscin-rich deposit is the visible vitelliform macular lesion.
Show evidence (2 references)
PMID:25681578 SUPPORT Human Clinical
"Excess photoreceptor outer segment production and/or impaired outer segment uptake due to impaired phagocytosis are likely underlying mechanisms."
Directly supports impaired phagocytic clearance of outer segments and/or their overproduction as the mechanism generating the subretinal vitelliform deposit.
PMID:25681578 SUPPORT Human Clinical
"Vitelliform lesions are hyperautofluorescent and initially have a dome-shaped appearance on optical coherence tomography."
Supports the lipofuscin-rich (hyperautofluorescent), dome-shaped character of the vitelliform deposit.
Progressive Macular Atrophy and Vision Loss
The vitelliform lesion gradually increases and then decreases in size over years, leaving an area of atrophic outer retina and retinal pigment epithelium accompanied by loss of visual acuity. A subset of patients develops choroidal neovascularization.
photoreceptor cell CL:0000210 retinal pigment epithelial cell CL:0002586
retina homeostasis GO:0001895 ↓ DECREASED
macula lutea UBERON:0000053
Downstream
Reduced visual acuity Progressive outer-retinal and RPE atrophy causes central visual acuity loss.
Metamorphopsia Macular distortion from the vitelliform lesion can produce distorted central vision.
Macular atrophy Resorption of the vitelliform lesion leaves atrophic outer retina and RPE in the macula.
Choroidal neovascularization A subset of progressive AOFVD cases develops subfoveal choroidal neovascularization.
Show evidence (2 references)
PMID:25681578 SUPPORT Human Clinical
"The lesions gradually increase and then decrease in size over the years, leaving an area of atrophic outer retina and retinal pigment epithelium."
Supports the slow evolution of the vitelliform lesion toward outer-retinal and RPE atrophy.
PMID:26802173 SUPPORT Human Clinical
"Sporadic AFVD is a slowly progressing macular degeneration of older people."
Longitudinal cohort data support the slowly progressive macular degeneration phenotype.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Adult-Onset Foveomacular Vitelliform Dystrophy 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

5
Eye 2
Reduced visual acuity Reduced visual acuity HP:0007663
Course: PROGRESSIVE
Show evidence (1 reference)
PMID:25681578 SUPPORT Human Clinical
"This process is accompanied by a loss of visual acuity."
The natural course of AFVD involves progressive loss of visual acuity as the lesion evolves to atrophy.
Macular atrophy Macular atrophy HP:0007401
Show evidence (1 reference)
PMID:25681578 SUPPORT Human Clinical
"leaving an area of atrophic outer retina and retinal pigment epithelium"
The lesion resorbs to leave outer-retinal and RPE atrophy in the macula.
Other 3
Vitelliform macular lesion Vitelliform-like macular lesions HP:0007677
Show evidence (1 reference)
PMID:28644393 SUPPORT Human Clinical
"bilateral, central, dome-shaped foveal accumulation of yellowish material with preserved integrity of the retinal pigment epithelium (RPE)"
Describes the characteristic bilateral central dome-shaped foveal vitelliform deposit in mutation carriers.
Metamorphopsia Metamorphopsia HP:0012508
Show evidence (1 reference)
PMID:16567277 SUPPORT Human Clinical
"Patients with AOFVD typically present with symptoms of blurred vision or mild metamorphopsia."
The clinical review explicitly identifies mild metamorphopsia as a typical presenting symptom of AOFVD.
Choroidal neovascularization Choroidal neovascularization HP:0011506
Show evidence (2 references)
PMID:25681578 PARTIAL Human Clinical
"Phenocopies are also associated with other ocular disorders, such as vitreomacular traction, age-related macular degeneration, pseudodrusen, and central serous chorioretinopathy."
Indirect support: the review situates AFVD among macular disorders with neovascular complications; choroidal neovascularization is captured in MONDO/Orphanet as an AVMD complication (synonym "adult-onset foveomacular dystrophy with choroidal neovascularization"). Marked PARTIAL because the abstract does not explicitly quantify CNV in AFVD.
PMID:16567277 SUPPORT Human Clinical
"patients can develop dramatically decreased vision owing to subfoveal choroidal neovascularization (CNV)."
The clinical review explicitly supports choroidal neovascularization as a severe AOFVD complication.
🧬

Genetic Associations

1
Genetic heterogeneity
Show evidence (1 reference)
PMID:25681578 SUPPORT Human Clinical
"A single-nucleotide polymorphism in the HTRA1 gene has also been associated with this phenotype."
Beyond the four monogenic genes, an HTRA1 SNP has been associated with AFVD, underscoring the genetic heterogeneity and partly non-Mendelian architecture of the disorder.
💊

Medical Actions

2
Anti-VEGF Therapy for Choroidal Neovascularization
Action: Pharmacotherapy NCIT:C15986
Agent: angiogenesis inhibitor (anti-VEGF) NCIT:C1742 bevacizumab NCIT:C2039
Intravitreal anti-VEGF agents (e.g., bevacizumab, ranibizumab) are the standard of care for choroidal neovascularization complicating AVMD and are associated with stabilization of vision in most treated eyes. There is no disease-modifying therapy for the underlying dystrophy itself.
Target Phenotypes: Choroidal neovascularization HP:0011506
Show evidence (1 reference)
PMID:25681578 SUPPORT Human Clinical
"At present, no cure is available for AFVD."
Supports the absence of a disease-modifying therapy; management is directed at complications such as choroidal neovascularization.
Multimodal Imaging Surveillance
Action: supportive care MAXO:0000950
Because severe visual loss in AVMD is driven by choroidal neovascularization and macular atrophy, management centers on periodic multimodal imaging (SD-OCT, fundus autofluorescence, OCT angiography) to detect treatable complications early.
Show evidence (1 reference)
PMID:38983024 SUPPORT Human Clinical
"Advancements in retinal imaging over the past 15 years have enabled improved characterization of the different stages of AOFVD."
Multimodal retinal imaging is central to staging AOFVD and to monitoring for complications.
{ }

Source YAML

click to show 
name: Adult-Onset Foveomacular Vitelliform Dystrophy
creation_date: "2026-06-08T00:00:00Z"
category: Complex
description: >-
  Adult-onset foveomacular vitelliform dystrophy (AVMD/AOFVD, also "pseudo-Best
  disease" or Gass disease) is a slowly progressive macular dystrophy presenting
  in mid-adulthood (fourth to sixth decade) with a small, bilateral, subfoveal
  yellow vitelliform (egg-yolk-like) lesion composed of lipofuscin accumulated at
  the photoreceptor outer-segment/retinal pigment epithelium (RPE) interface.
  Patients have mild central or paracentral visual loss, metamorphopsia, and a
  generally good prognosis, although gradual lesion resorption can lead to
  geographic atrophy or, less often, choroidal neovascularization. AVMD is
  genetically heterogeneous: a minority of cases carry heterozygous variants in
  PRPH2 (peripherin-2), BEST1 (bestrophin-1), IMPG1, or IMPG2, while many cases
  are non-Mendelian/idiopathic without an identifiable monogenic cause. It is
  distinguished from Best vitelliform macular dystrophy (BVMD) by its later onset,
  smaller lesions, normal-to-mildly-reduced electrooculogram (EOG), and milder
  course.
disease_term:
  preferred_term: adult-onset foveomacular vitelliform dystrophy
  term:
    id: MONDO:0011979
    label: adult-onset foveomacular vitelliform dystrophy
synonyms:
- AVMD
- AOFVD
- AOFMD
- adult-onset vitelliform macular dystrophy
- pseudo-Best disease
- Gass disease
- pseudo-vitelliform macular dystrophy
parents:
- Ophthalmological Disease
- Retinal Dystrophy
- Inherited retinal dystrophy
notes: >-
  AVMD overlaps clinically and genetically with the broader pattern-dystrophy and
  vitelliform spectrum. MONDO places vitelliform macular dystrophy 1, 3 (PRPH2), 4
  (IMPG1), and 5 (IMPG2) as direct children of MONDO:0011979. BEST1-related
  adult-onset disease ("pseudo-Best"/adult-onset bestrophinopathy) is captured
  here as a gene-defined subtype distinct from juvenile Best disease (BVMD), which
  is modeled separately in BEST1_Bestrophinopathies.yaml.
has_subtypes:
- name: PRPH2-related
  display_name: PRPH2-related AVMD (vitelliform macular dystrophy 3)
  subtype_term:
    preferred_term: vitelliform macular dystrophy 3
    term:
      id: MONDO:0024561
      label: vitelliform macular dystrophy 3
  description: >-
    AVMD caused by heterozygous variants in PRPH2 (peripherin-2), a photoreceptor
    outer-segment disc rim tetraspanin. Part of the broader PRPH2 pattern-dystrophy
    spectrum.
  genes:
  - preferred_term: PRPH2
    term:
      id: hgnc:9942
      label: PRPH2
  inheritance:
  - name: Autosomal dominant
    inheritance_term:
      preferred_term: Autosomal dominant inheritance
      term:
        id: HP:0000006
        label: Autosomal dominant inheritance
  evidence:
  - reference: PMID:25681578
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A minority of AFVD patients have a mutation in the PRPH2, BEST1, IMPG1, or IMPG2 genes."
    explanation: >-
      This authoritative review identifies PRPH2 as one of the recognized causal
      genes for a minority of AFVD cases, supporting the PRPH2-related subtype.
- name: BEST1-related
  display_name: BEST1-related AVMD (adult-onset bestrophinopathy / pseudo-Best)
  description: >-
    Adult-onset vitelliform lesions caused by heterozygous variants in BEST1
    (bestrophin-1), an RPE basolateral calcium-activated chloride channel. Later
    onset and milder than juvenile Best vitelliform macular dystrophy.
  genes:
  - preferred_term: BEST1
    term:
      id: hgnc:12703
      label: BEST1
  inheritance:
  - name: Autosomal dominant
    inheritance_term:
      preferred_term: Autosomal dominant inheritance
      term:
        id: HP:0000006
        label: Autosomal dominant inheritance
  evidence:
  - reference: PMID:25681578
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A minority of AFVD patients have a mutation in the PRPH2, BEST1, IMPG1, or IMPG2 genes."
    explanation: >-
      BEST1 is one of the recognized causal genes for a minority of AFVD cases.
      Adult-onset BEST1 disease is distinguished from juvenile Best disease by
      its later onset and milder course.
- name: IMPG1-related
  display_name: IMPG1-related AVMD (vitelliform macular dystrophy 4)
  subtype_term:
    preferred_term: vitelliform macular dystrophy 4
    term:
      id: MONDO:0014508
      label: vitelliform macular dystrophy 4
  description: >-
    AVMD caused by variants in IMPG1 (interphotoreceptor matrix proteoglycan 1),
    a component of the interphotoreceptor matrix in the subretinal space.
  genes:
  - preferred_term: IMPG1
    term:
      id: hgnc:6055
      label: IMPG1
  inheritance:
  - name: Autosomal dominant
    inheritance_term:
      preferred_term: Autosomal dominant inheritance
      term:
        id: HP:0000006
        label: Autosomal dominant inheritance
  evidence:
  - reference: PMID:25085631
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "IMPG1 and IMPG2 are new causal genes in 8% of families negative for BEST1 and PRPH2 mutations."
    explanation: >-
      This national referral-center study established IMPG1 (and IMPG2) as causal
      genes in adult-onset vitelliform macular dystrophy, supporting the
      IMPG1-related subtype.
  - reference: PMID:28644393
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Clinical symptoms tend to be more severe for IMPG1 mutations."
    explanation: >-
      In a BEST1/PRPH2-negative VMD cohort, IMPG1 mutation carriers had a more
      severe phenotype than IMPG2 carriers, supporting IMPG1 as a distinct
      gene-defined subtype.
- name: IMPG2-related
  display_name: IMPG2-related AVMD (vitelliform macular dystrophy 5)
  subtype_term:
    preferred_term: vitelliform macular dystrophy 5
    term:
      id: MONDO:0014509
      label: vitelliform macular dystrophy 5
  description: >-
    AVMD caused by variants in IMPG2 (interphotoreceptor matrix proteoglycan 2),
    a component of the interphotoreceptor matrix that anchors photoreceptor outer
    segments.
  genes:
  - preferred_term: IMPG2
    term:
      id: hgnc:18362
      label: IMPG2
  inheritance:
  - name: Autosomal dominant
    inheritance_term:
      preferred_term: Autosomal dominant inheritance
      term:
        id: HP:0000006
        label: Autosomal dominant inheritance
  evidence:
  - reference: PMID:25085631
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "IMPG1 and IMPG2 are new causal genes in 8% of families negative for BEST1 and PRPH2 mutations."
    explanation: >-
      This study established IMPG2 (with IMPG1) as a causal gene in adult-onset
      vitelliform macular dystrophy, supporting the IMPG2-related subtype.
  - reference: PMID:28644393
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Taken together, our results provide further evidence for an involvement of dominant and recessive mutations in IMPG1 and IMPG2 in VMD pathology."
    explanation: >-
      Mutational screening of a BEST1/PRPH2-negative VMD cohort identified
      multiple IMPG2 variants, supporting IMPG2 as a recognized gene-defined
      subtype.
- name: Idiopathic
  display_name: Idiopathic / non-Mendelian AVMD
  description: >-
    The majority of AVMD cases, which are sporadic and lack an identifiable
    monogenic cause (the genetic factors are unknown in more than 80% of cases).
    This subset is non-Mendelian and shows partial genetic overlap with
    age-related macular degeneration, specifically at complement-cascade risk
    loci.
  evidence:
  - reference: PMID:26802173
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Patients with sporadic AFVD are usually negative for the known mutations previously associated with this phenotype, and present at an age that is higher than described for monogenic AFVD."
    explanation: >-
      A genetically evaluated sporadic AFVD cohort was negative for the known
      causal mutations, supporting an idiopathic/non-Mendelian subtype with an
      older age at presentation than monogenic forms.
  - reference: PMID:39585675
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The genetic factors associated with AFVD are unknown in >80% of cases."
    explanation: >-
      Quantifies the predominance of the idiopathic/non-monogenic subtype: a
      monogenic cause is identified in fewer than 20% of AFVD patients.
  - reference: PMID:39585675
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Non-monogenic AFVD is associated with AMD risk alleles in the complement cascade, but not in other pathways."
    explanation: >-
      A case-control genetic study links non-monogenic (idiopathic) AFVD to
      AMD complement-cascade risk alleles, supporting a partly multifactorial,
      complement-associated architecture for this subtype.
pathophysiology:
- name: Photoreceptor Outer-Segment / RPE Interface Dysfunction
  description: >-
    Variants in PRPH2, BEST1, IMPG1, and IMPG2 perturb distinct components of the
    photoreceptor outer-segment / RPE / interphotoreceptor-matrix interface in the
    macula. Depending on the underlying gene, the primary defect lies in the
    photoreceptor outer-segment disc rim (PRPH2), the RPE basolateral chloride
    channel (BEST1), or the secreted interphotoreceptor-matrix proteoglycans
    (IMPG1/IMPG2) that anchor outer segments and organize the subretinal space.
  locations:
  - preferred_term: fovea centralis
    term:
      id: UBERON:0001786
      label: fovea centralis
  - preferred_term: macula lutea
    term:
      id: UBERON:0000053
      label: macula lutea
  cell_types:
  - preferred_term: retinal pigment epithelial cell
    term:
      id: CL:0002586
      label: retinal pigment epithelial cell
  - preferred_term: photoreceptor cell
    term:
      id: CL:0000210
      label: photoreceptor cell
  biological_processes:
  - preferred_term: photoreceptor cell maintenance
    term:
      id: GO:0045494
      label: photoreceptor cell maintenance
    modifier: DECREASED
  evidence:
  - reference: PMID:25681578
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the phenotype can arise from alterations in the photoreceptors, retinal pigment epithelium, and/or interphotoreceptor matrix depending on the underlying gene defect."
    explanation: >-
      The review establishes that the AFVD phenotype originates at the
      photoreceptor / RPE / interphotoreceptor-matrix interface, with the
      specific compartment depending on the causal gene.
  downstream:
  - target: Subfoveal Lipofuscin (Vitelliform) Deposit Accumulation
    description: >-
      Interface dysfunction leads to accumulation of lipofuscin-rich vitelliform
      material in the subretinal space.
- name: Subfoveal Lipofuscin (Vitelliform) Deposit Accumulation
  description: >-
    Excess photoreceptor outer-segment production and/or impaired RPE uptake of
    shed outer segments (impaired phagocytosis) leads to accumulation of
    lipofuscin-rich material in the subretinal space beneath the fovea, forming
    the characteristic dome-shaped, hyperautofluorescent yellow vitelliform
    lesion.
  locations:
  - preferred_term: fovea centralis
    term:
      id: UBERON:0001786
      label: fovea centralis
  cell_types:
  - preferred_term: retinal pigment epithelial cell
    term:
      id: CL:0002586
      label: retinal pigment epithelial cell
  biological_processes:
  - preferred_term: phagocytosis of shed photoreceptor outer segments
    term:
      id: GO:0006909
      label: phagocytosis
    modifier: DECREASED
  evidence:
  - reference: PMID:25681578
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Excess photoreceptor outer segment production and/or impaired outer segment uptake due to impaired phagocytosis are likely underlying mechanisms."
    explanation: >-
      Directly supports impaired phagocytic clearance of outer segments and/or
      their overproduction as the mechanism generating the subretinal
      vitelliform deposit.
  - reference: PMID:25681578
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Vitelliform lesions are hyperautofluorescent and initially have a dome-shaped appearance on optical coherence tomography."
    explanation: >-
      Supports the lipofuscin-rich (hyperautofluorescent), dome-shaped character
      of the vitelliform deposit.
  downstream:
  - target: Progressive Macular Atrophy and Vision Loss
    description: >-
      Over years the vitelliform deposit resorbs, leaving atrophic outer retina
      and RPE with consequent visual loss.
  - target: Vitelliform macular lesion
    description: The subfoveal lipofuscin-rich deposit is the visible vitelliform macular lesion.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:28644393
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "bilateral, central, dome-shaped foveal accumulation of yellowish material with preserved integrity of the retinal pigment epithelium (RPE)"
      explanation: >-
        The clinical cohort describes the visible vitelliform lesion produced by
        subfoveal material accumulation.
- name: Progressive Macular Atrophy and Vision Loss
  description: >-
    The vitelliform lesion gradually increases and then decreases in size over
    years, leaving an area of atrophic outer retina and retinal pigment
    epithelium accompanied by loss of visual acuity. A subset of patients
    develops choroidal neovascularization.
  locations:
  - preferred_term: macula lutea
    term:
      id: UBERON:0000053
      label: macula lutea
  cell_types:
  - preferred_term: photoreceptor cell
    term:
      id: CL:0000210
      label: photoreceptor cell
  - preferred_term: retinal pigment epithelial cell
    term:
      id: CL:0002586
      label: retinal pigment epithelial cell
  biological_processes:
  - preferred_term: retina homeostasis
    term:
      id: GO:0001895
      label: retina homeostasis
    modifier: DECREASED
  evidence:
  - reference: PMID:25681578
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The lesions gradually increase and then decrease in size over the years, leaving an area of atrophic outer retina and retinal pigment epithelium."
    explanation: >-
      Supports the slow evolution of the vitelliform lesion toward outer-retinal
      and RPE atrophy.
  - reference: PMID:26802173
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Sporadic AFVD is a slowly progressing macular degeneration of older people."
    explanation: >-
      Longitudinal cohort data support the slowly progressive macular
      degeneration phenotype.
  downstream:
  - target: Reduced visual acuity
    description: Progressive outer-retinal and RPE atrophy causes central visual acuity loss.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:25681578
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "This process is accompanied by a loss of visual acuity."
      explanation: >-
        The review directly links lesion evolution and atrophy to visual acuity
        loss.
  - target: Metamorphopsia
    description: Macular distortion from the vitelliform lesion can produce distorted central vision.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - foveal lesion distortion
    evidence:
    - reference: PMID:16567277
      reference_title: Adult-onset foveomacular vitelliform dystrophy.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Patients with AOFVD typically present with symptoms of blurred vision or
        mild metamorphopsia.
      explanation: >-
        The clinical review supports metamorphopsia as a presenting symptom of
        the macular dystrophy.
  - target: Macular atrophy
    description: Resorption of the vitelliform lesion leaves atrophic outer retina and RPE in the macula.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:25681578
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "leaving an area of atrophic outer retina and retinal pigment epithelium"
      explanation: >-
        The review directly supports macular outer-retinal and RPE atrophy as a
        downstream stage of lesion evolution.
  - target: Choroidal neovascularization
    description: A subset of progressive AOFVD cases develops subfoveal choroidal neovascularization.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:16567277
      reference_title: Adult-onset foveomacular vitelliform dystrophy.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        patients can develop dramatically decreased vision owing to subfoveal
        choroidal neovascularization (CNV).
      explanation: >-
        The clinical review supports choroidal neovascularization as a severe
        downstream complication of AOFVD.
phenotypes:
- name: Vitelliform macular lesion
  description: >-
    Bilateral, central, dome-shaped subfoveal accumulation of yellowish
    (egg-yolk-like) vitelliform material, the hallmark of AVMD.
  phenotype_term:
    preferred_term: Vitelliform macular lesion
    term:
      id: HP:0007677
      label: Vitelliform-like macular lesions
  evidence:
  - reference: PMID:28644393
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "bilateral, central, dome-shaped foveal accumulation of yellowish material with preserved integrity of the retinal pigment epithelium (RPE)"
    explanation: >-
      Describes the characteristic bilateral central dome-shaped foveal
      vitelliform deposit in mutation carriers.
- name: Reduced visual acuity
  description: >-
    Mild to moderate central visual impairment that progresses slowly over years.
  phenotype_term:
    preferred_term: Reduced visual acuity
    term:
      id: HP:0007663
      label: Reduced visual acuity
    clinical_course: PROGRESSIVE
  evidence:
  - reference: PMID:25681578
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "This process is accompanied by a loss of visual acuity."
    explanation: >-
      The natural course of AFVD involves progressive loss of visual acuity as
      the lesion evolves to atrophy.
- name: Metamorphopsia
  description: Distortion of central vision.
  phenotype_term:
    preferred_term: Metamorphopsia
    term:
      id: HP:0012508
      label: Metamorphopsia
  evidence:
  - reference: PMID:16567277
    reference_title: Adult-onset foveomacular vitelliform dystrophy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Patients with AOFVD typically present with symptoms of blurred vision or
      mild metamorphopsia.
    explanation: >-
      The clinical review explicitly identifies mild metamorphopsia as a typical
      presenting symptom of AOFVD.
- name: Macular atrophy
  category: Ophthalmic
  description: >-
    Atrophy of the outer retina and retinal pigment epithelium in the macula,
    developing as the vitelliform lesion resorbs.
  phenotype_term:
    preferred_term: Macular atrophy
    term:
      id: HP:0007401
      label: Macular atrophy
  evidence:
  - reference: PMID:25681578
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "leaving an area of atrophic outer retina and retinal pigment epithelium"
    explanation: >-
      The lesion resorbs to leave outer-retinal and RPE atrophy in the macula.
- name: Choroidal neovascularization
  description: >-
    A minority of AVMD patients develop choroidal neovascularization, a recognized
    complication that can cause acute visual loss.
  phenotype_term:
    preferred_term: Choroidal neovascularization
    term:
      id: HP:0011506
      label: Choroidal neovascularization
  evidence:
  - reference: PMID:25681578
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "Phenocopies are also associated with other ocular disorders, such as vitreomacular traction, age-related macular degeneration, pseudodrusen, and central serous chorioretinopathy."
    explanation: >-
      Indirect support: the review situates AFVD among macular disorders with
      neovascular complications; choroidal neovascularization is captured in
      MONDO/Orphanet as an AVMD complication (synonym "adult-onset foveomacular
      dystrophy with choroidal neovascularization"). Marked PARTIAL because the
      abstract does not explicitly quantify CNV in AFVD.
  - reference: PMID:16567277
    reference_title: Adult-onset foveomacular vitelliform dystrophy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      patients can develop dramatically decreased vision owing to subfoveal
      choroidal neovascularization (CNV).
    explanation: >-
      The clinical review explicitly supports choroidal neovascularization as a
      severe AOFVD complication.
genetic:
- name: Genetic heterogeneity
  notes: >-
    AVMD is genetically heterogeneous; a minority of cases carry heterozygous
    variants in PRPH2, BEST1, IMPG1, or IMPG2, while most are idiopathic.
  evidence:
  - reference: PMID:25681578
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A single-nucleotide polymorphism in the HTRA1 gene has also been associated with this phenotype."
    explanation: >-
      Beyond the four monogenic genes, an HTRA1 SNP has been associated with
      AFVD, underscoring the genetic heterogeneity and partly non-Mendelian
      architecture of the disorder.
inheritance:
- name: Autosomal dominant
  inheritance_term:
    preferred_term: Autosomal dominant inheritance
    term:
      id: HP:0000006
      label: Autosomal dominant inheritance
  description: >-
    Monogenic AVMD due to PRPH2, BEST1, IMPG1, or IMPG2 variants is typically
    autosomal dominant; rare recessive IMPG cases have been reported.
  evidence:
  - reference: PMID:25085631
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "With an autosomal dominant transmission, families 1 and 2 had the c.713T→G (p.Leu238Arg) mutation in IMPG1 and family 4 had the c.3230G→T (p.Cys1077Phe) mutation in IMPG2."
    explanation: >-
      Documents autosomal dominant transmission in IMPG1- and IMPG2-linked AVMD
      families.
treatments:
- name: Anti-VEGF Therapy for Choroidal Neovascularization
  description: >-
    Intravitreal anti-VEGF agents (e.g., bevacizumab, ranibizumab) are the
    standard of care for choroidal neovascularization complicating AVMD and are
    associated with stabilization of vision in most treated eyes. There is no
    disease-modifying therapy for the underlying dystrophy itself.
  therapeutic_modality: MONOCLONAL_ANTIBODY
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: angiogenesis inhibitor (anti-VEGF)
      term:
        id: NCIT:C1742
        label: Angiogenesis Inhibitor
    - preferred_term: bevacizumab
      term:
        id: NCIT:C2039
        label: Bevacizumab
  target_phenotypes:
  - preferred_term: Choroidal neovascularization
    term:
      id: HP:0011506
      label: Choroidal neovascularization
  evidence:
  - reference: PMID:25681578
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "At present, no cure is available for AFVD."
    explanation: >-
      Supports the absence of a disease-modifying therapy; management is
      directed at complications such as choroidal neovascularization.
- name: Multimodal Imaging Surveillance
  description: >-
    Because severe visual loss in AVMD is driven by choroidal neovascularization
    and macular atrophy, management centers on periodic multimodal imaging
    (SD-OCT, fundus autofluorescence, OCT angiography) to detect treatable
    complications early.
  treatment_term:
    preferred_term: supportive care
    term:
      id: MAXO:0000950
      label: supportive care
  evidence:
  - reference: PMID:38983024
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Advancements in retinal imaging over the past 15 years have enabled improved characterization of the different stages of AOFVD."
    explanation: >-
      Multimodal retinal imaging is central to staging AOFVD and to monitoring
      for complications.
epidemiology:
- name: Prevalence
  description: >-
    AOFVD is a relatively common macular dystrophy that may affect up to roughly
    1 in 7,400 individuals, although its prevalence is poorly characterized and
    confounded by frequent misdiagnosis as age-related macular degeneration.
  evidence:
  - reference: PMID:38983024
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Adult-onset foveomacular dystrophy (AOFVD) is a retinal pattern dystrophy that may affect up to 1 in 7,400 individuals."
    explanation: >-
      Provides the most-cited prevalence estimate for AOFVD.
progression:
- phase: Four-stage imaging-defined natural history
  notes: >-
    AOFVD evolves through four imaging-defined stages (vitelliform,
    pseudohypopyon, vitelliruptive, and atrophic), with most patients progressing
    slowly; severe visual loss is typically linked to choroidal neovascularization
    or macular atrophy.
  evidence:
  - reference: PMID:38983024
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "There is much that is unknown regarding this disease's epidemiology, risk factors for development, and rate of progression through its four stages."
    explanation: >-
      Establishes the four-stage progression framework used to characterize the
      natural history of AOFVD.
references:
- reference: PMID:25681578
  title: "Adult-onset foveomacular vitelliform dystrophy: A fresh perspective."
- reference: PMID:25085631
  title: "Frequency and clinical pattern of vitelliform macular dystrophy caused by mutations of interphotoreceptor matrix IMPG1 and IMPG2 genes."
- reference: PMID:38983024
  title: "Adult-onset foveomacular vitelliform dystrophy: epidemiology, pathophysiology, imaging, and prognosis."
- reference: PMID:39585675
  title: "Adult Onset Foveomacular Vitelliform Dystrophy Shows Genetic Overlap With Age-Related Macular Degeneration."
- reference: PMID:28644393
  title: "Mutations in the Genes for Interphotoreceptor Matrix Proteoglycans, IMPG1 and IMPG2, in Patients with Vitelliform Macular Lesions."
- reference: PMID:26802173
  title: "Characterising the phenotype and progression of sporadic adult-onset foveomacular vitelliform dystrophy."
- reference: PMID:16567277
  title: "Adult-onset foveomacular vitelliform dystrophy."
📚

References & Deep Research

References

7
PMID:25681578
Adult-onset foveomacular vitelliform dystrophy: A fresh perspective.
No top-level findings curated for this source.
PMID:25085631
Frequency and clinical pattern of vitelliform macular dystrophy caused by mutations of interphotoreceptor matrix IMPG1 and IMPG2 genes.
No top-level findings curated for this source.
PMID:38983024
Adult-onset foveomacular vitelliform dystrophy: epidemiology, pathophysiology, imaging, and prognosis.
No top-level findings curated for this source.
PMID:39585675
Adult Onset Foveomacular Vitelliform Dystrophy Shows Genetic Overlap With Age-Related Macular Degeneration.
No top-level findings curated for this source.
PMID:28644393
Mutations in the Genes for Interphotoreceptor Matrix Proteoglycans, IMPG1 and IMPG2, in Patients with Vitelliform Macular Lesions.
No top-level findings curated for this source.
PMID:26802173
Characterising the phenotype and progression of sporadic adult-onset foveomacular vitelliform dystrophy.
No top-level findings curated for this source.
PMID:16567277
Adult-onset foveomacular vitelliform dystrophy.
No top-level findings curated for this source.

Deep Research

1
Falcon ▸
Adult-Onset Foveomacular Vitelliform Dystrophy (AOFVD/AFVD) — Disease Characteristics Research Report
Edison Scientific Literature 31 citations 2026-06-08T18:22:03.492146

Adult-Onset Foveomacular Vitelliform Dystrophy (AOFVD/AFVD) — Disease Characteristics Research Report

Executive summary (current understanding; 2023–2024 emphasis)

Adult-onset foveomacular vitelliform dystrophy (AOFVD; also AFVD/AVMD in parts of the literature) is a macular pattern dystrophy characterized by subfoveal “vitelliform” material in the subretinal space, typically presenting in mid-to-late adulthood and progressing through four imaging-defined stages (vitelliform → pseudohypopyon → vitelliruptive → atrophic). It is frequently misdiagnosed as age-related macular degeneration (AMD), but management differs because AOFVD itself has no proven disease-modifying therapy; treatment is directed mainly at complications such as macular neovascularization/choroidal neovascularization (CNV/MNV). (nipp2023adultonsetfoveomacularvitelliform pages 1-2, nipp2023adultonsetfoveomacularvitelliform pages 2-3, tesfaw2023clinicalandoptical pages 1-2)

Genetically, AOFVD is heterogeneous and often sporadic; reported monogenic contributors include PRPH2, BEST1, IMPG1, and IMPG2, but known genes explain a minority of cases in many cohorts. (nipp2023adultonsetfoveomacularvitelliform pages 2-3) A major 2024 development is evidence that non-monogenic AFVD is enriched for AMD complement-pathway risk alleles (e.g., CFH; C2/CFB/SKIV2L), suggesting a polygenic overlap with AMD and raising complement inhibition as a potential future therapeutic avenue. (jaskoll2024adultonsetfoveomacular pages 1-2)

Target disease metadata

  • Disease name: Adult-Onset Foveomacular Vitelliform Dystrophy
  • Category: Mendelian (genetically heterogeneous; many cases non-monogenic/sporadic)
  • MONDO ID: Not found in the retrieved sources (requires targeted ontology lookup beyond current evidence).

1. Disease information

1.1 Definition/overview

AOFVD is described as a “retinal pattern dystrophy” that “may affect up to 1 in 7,400 individuals,” with improved characterization enabled by modern imaging (SD-OCT, OCTA). (nipp2023adultonsetfoveomacularvitelliform pages 1-2)

A mechanistic definition used in a 2023 review: AOFVD is “a clinical spectrum of disease that results from the disordered metabolism of RPE cells, resulting in the accumulation of material in the subretinal space.” (nipp2023adultonsetfoveomacularvitelliform pages 2-3)

1.2 Common synonyms / alternative names

Historical and still-used labels include “adult vitelliform macular degeneration,” “pseudovitelliform macular degeneration,” and “adult-onset foveomacular pigment epithelial dystrophy,” among others; the term “adult-onset foveomacular vitelliform dystrophy” was first used in 1996 and became widely accepted later. (nipp2023adultonsetfoveomacularvitelliform pages 1-2)

The lesion is also referred to as an acquired vitelliform lesion (AVL) in parts of the staging literature. (nipp2023adultonsetfoveomacularvitelliform pages 2-3)

1.3 Key identifiers (availability in retrieved sources)

  • OMIM/Orphanet/ICD/MeSH/MONDO: Not explicitly provided in the retrieved excerpts.
  • Gene-level OMIM references were present in a pattern-dystrophy genetic testing report (e.g., PRPH2 OMIM gene 179605; BEST1 OMIM gene 607854; IMPG1 OMIM gene 602870; IMPG2 OMIM gene 607056). (abeshi2017genetictestingfor pages 1-2)

1.4 Evidence sources: individual vs aggregated

  • Aggregated disease-level resource: 2023 review in Frontiers in Ophthalmology synthesizing epidemiology, imaging, pathophysiology, and management. (nipp2023adultonsetfoveomacularvitelliform pages 1-2)
  • Human clinical cohorts/case series: 2023 retrospective cohort with multimodal imaging and stage counts (12 patients/19 eyes). (tesfaw2023clinicalandoptical pages 1-2)
  • Human genetic association study (2024): AFVD (n=50) vs AMD (n=917) vs controls (n=432), targeted genotyping and pathway genetic risk scores. (jaskoll2024adultonsetfoveomacular pages 1-2)

2. Etiology

2.1 Disease causal factors (genetic/mechanistic)

AOFVD is linked to genes involved in photoreceptor outer segment structure (PRPH2), RPE ion channel function (BEST1), and interphotoreceptor matrix/extracellular matrix adhesion (IMPG1/IMPG2). (nipp2023adultonsetfoveomacularvitelliform pages 2-3)

AOFVD is often sporadic rather than clearly autosomal dominant. (nipp2023adultonsetfoveomacularvitelliform pages 1-2)

Primary-gene evidence example (IMPG1)

A landmark human genetics study concluded: “IMPG1 mutations cause both autosomal-dominant and -recessive forms of VMD, thus indicating that impairment of the interphotoreceptor matrix might be a general cause of VMD.” (manes2013mutationsinimpg1 pages 1-2)

This paper identified multiple pathogenic variant classes (missense, splice-site, nonsense) including c.713T>G (p.Leu238Arg) and additional recessive variants. (manes2013mutationsinimpg1 pages 1-2)

2.2 Risk factors

Genetic risk factors

  • PRPH2: encodes peripherin-2; mutations are the “most common gene mutations identified in AOFVD patients” but explain “only 2–18% of all patients.” (nipp2023adultonsetfoveomacularvitelliform pages 2-3)
  • IMPG1/IMPG2: in one summary, frequency among familial AOFVD patients lacking PRPH2/BEST1 mutations was “4 in 49, or approximately 8%,” and likely <8% among all AOFVD. (nipp2023adultonsetfoveomacularvitelliform pages 2-3)
  • 2024 polygenic/complement risk: AFVD (non-monogenic) associated with AMD complement alleles including CFH rs570618 and C2/CFB/SKIV2L rs116503776, rs114254831, with a positive association for a complement genetic risk score (GRS). (jaskoll2024adultonsetfoveomacular pages 1-2)

Environmental/other risk factors

The 2023 review highlights that much remains unknown about “risk factors for development,” and misdiagnosis/coding issues complicate epidemiology. (nipp2023adultonsetfoveomacularvitelliform pages 1-2)

2.3 Protective factors

No specific protective factors (genetic or environmental) were identified in the retrieved sources.

2.4 Gene–environment interactions

Not identified in the retrieved sources.

3. Phenotypes

3.1 Core symptom/sign phenotype spectrum

Typical presentation includes mild blurred central vision and/or metamorphopsia; lesions are classically small, yellow, subretinal, centered at or near the fovea, often with central pigmentation. (tesfaw2023clinicalandoptical pages 1-2)

A 2023 cohort reported presenting visual acuity “ranged from 20/100 to 20/20.” (tesfaw2023clinicalandoptical pages 1-2)

3.2 Age of onset, severity, progression

  • Age range: Gass proposed onset in “3rd to 5th decades,” but later studies suggest many are diagnosed at 50–70 years, with reported ranges up to ~80. (nipp2023adultonsetfoveomacularvitelliform pages 2-3)
  • Disease stages: AOFVD “progresses through four clinical stages” described by Querques et al. using SD-OCT. (nipp2023adultonsetfoveomacularvitelliform pages 2-3)

3.3 Stage-specific phenotypes and frequencies (example cohort)

In a 2023 retrospective cohort (12 patients; 19 eyes): - Stage distribution: vitelliform 10/19; pseudohypopyon 5/19; vitelliruptive 4/19; no atrophic stage in that cohort. (tesfaw2023clinicalandoptical pages 2-4, tesfaw2023clinicalandoptical pages 1-2) - OCT: IS/OS (ellipsoid zone) disruption in 8/19 eyes; “optically clear (non-reflective) subretinal lesions” in 6/19 eyes, mainly pseudohypopyon. (tesfaw2023clinicalandoptical pages 1-2)

3.4 Quality-of-life impact

Direct QoL instruments (EQ-5D/SF-36/PROMIS) were not present in the retrieved sources. Functionally, significant impairment is tied to CNV and macular atrophy rather than early stages. (nipp2023adultonsetfoveomacularvitelliform pages 7-8)

3.5 Suggested HPO terms (curated suggestions)

(These are ontology mapping suggestions for KB use; not claims of exact ontology IDs from the cited papers.) - Decreased visual acuity; Metamorphopsia; Central scotoma; Abnormal fundus autofluorescence; Macular dystrophy; Subretinal deposits; Choroidal neovascularization; Retinal pigment epithelium atrophy; Abnormal color vision.

4. Genetic / molecular information

4.1 Causal/associated genes (human)

  • PRPH2: peripherin-2, photoreceptor outer segment disc morphogenesis/stability. (nipp2023adultonsetfoveomacularvitelliform pages 2-3)
  • BEST1: bestrophin-1, RPE-expressed transmembrane protein; ion channel/calcium signaling role; implicated in Best disease and some AOFVD cases. (nipp2023adultonsetfoveomacularvitelliform pages 2-3)
  • IMPG1 / IMPG2: secreted extracellular matrix/interphotoreceptor matrix proteins involved in retinal adhesion. (nipp2023adultonsetfoveomacularvitelliform pages 2-3)

4.2 Pathogenic variant types and examples

  • IMPG1 (primary evidence, 2013): c.713T>G (p.Leu238Arg) (dominant); c.807+1G>T (splice-site; recessive); c.461T>C (p.Leu154Pro) + c.1519C>T (p.Arg507*) (compound heterozygous). (manes2013mutationsinimpg1 pages 1-2)

4.3 Variant classification / allele frequency

ACMG-style variant classification and population allele frequencies were not provided in the retrieved excerpts.

4.4 Modifier genes

Not established in the retrieved sources.

4.5 Epigenetics / chromosomal abnormalities

Not established in the retrieved sources.

5. Environmental information

No AOFVD-specific environmental toxins/exposures or infectious triggers were identified in the retrieved sources.

6. Mechanism / pathophysiology

6.1 Proposed causal chain (integrated from 2023–2024 evidence)

1) Primary tissue dysfunction: AOFVD is framed as disordered RPE metabolism leading to accumulation of material in the subretinal space. (nipp2023adultonsetfoveomacularvitelliform pages 2-3) 2) Material composition (clinicopathologic): Subretinal material includes “pigment-laden cells, lipofuscin granules, photoreceptor debris, and RPE cells,” consistent with impaired outer segment handling and RPE/photoreceptor interface stress. (tesfaw2023clinicalandoptical pages 1-2) 3) Structural progression: Stage-specific OCT/FAF/FA changes reflect lesion maturation, sedimentation (pseudohypopyon), fragmentation (vitelliruptive), and in some eyes eventual photoreceptor and RPE atrophy. (nipp2023adultonsetfoveomacularvitelliform pages 7-8) 4) Complications: CNV/MNV and macular atrophy drive major visual decline. (nipp2023adultonsetfoveomacularvitelliform pages 7-8) 5) Genetic contributors: - PRPH2 variants may predispose by disrupting outer segment disc structure. (nipp2023adultonsetfoveomacularvitelliform pages 2-3) - IMPG1/IMPG2 variants implicate the interphotoreceptor matrix; the IMPG1 genetics paper highlights interphotoreceptor matrix impairment as a general causal mechanism in vitelliform macular dystrophy. (manes2013mutationsinimpg1 pages 1-2) 6) 2024 complement-genetics hypothesis: Non-monogenic AFVD shows association with AMD complement risk alleles and complement GRS, supporting a potential role for complement biology in some AFVD cases (even though systemic complement activation did not differ by plasma assays in that study). (jaskoll2024adultonsetfoveomacular pages 1-2, jaskoll2024adultonsetfoveomacular pages 6-8)

6.2 Suggested GO biological process terms (curated suggestions)

  • Phagocytosis of photoreceptor outer segments; Visual perception; Extracellular matrix organization; Complement activation (alternative pathway); Retina development/maintenance.

6.3 Suggested Cell Ontology (CL) terms (curated suggestions)

  • Retinal pigment epithelial cell; Rod photoreceptor cell; Cone photoreceptor cell; (optional for lesion biology) macrophage/mononuclear phagocyte.

6.4 Omics / single-cell / spatial / screens

No AOFVD-specific omics or single-cell/spatial transcriptomics evidence was present in the retrieved sources.

7. Anatomical structures affected

7.1 Organ/system level

  • Primary: Eye—retina, particularly the macula/fovea. (tesfaw2023clinicalandoptical pages 1-2)

7.2 Tissue/cell level

  • Key tissues/cells: RPE and photoreceptors; lesion material resides in the subretinal space. (nipp2023adultonsetfoveomacularvitelliform pages 2-3, tesfaw2023clinicalandoptical pages 1-2)

7.3 Subcellular level (inferred from mechanisms)

  • Outer segment disc morphogenesis (PRPH2) and ion-channel/calcium signaling in RPE (BEST1) are implicated in genetic subsets. (nipp2023adultonsetfoveomacularvitelliform pages 2-3)

7.4 Localization and laterality

AOFVD is commonly bilateral, though unilateral/asymmetric cases occur. (tesfaw2023clinicalandoptical pages 1-2)

Suggested UBERON terms (curated suggestions)

  • Retina; Macula; Fovea centralis; Retinal pigment epithelium; Subretinal space.

8. Temporal development

8.1 Onset pattern

Typically insidious, adult-onset; many are diagnosed at 50–70 years. (nipp2023adultonsetfoveomacularvitelliform pages 2-3)

8.2 Progression / stages

Four-stage progression is widely used (vitelliform, pseudohypopyon, vitelliruptive, atrophic), originally described using SD-OCT. (nipp2023adultonsetfoveomacularvitelliform pages 2-3)

8.3 Remission patterns

Not established. Lesion material may be reabsorbed; not all eyes with resorption become atrophic. (nipp2023adultonsetfoveomacularvitelliform pages 2-3)

9. Inheritance and population

9.1 Epidemiology

  • Prevalence estimates reported: ~1:7,400 to 1:8,200 in a local population estimate cited in the 2023 review; prevalence otherwise “remains undescribed” and is confounded by misdiagnosis/miscoding as AMD. (nipp2023adultonsetfoveomacularvitelliform pages 1-2)

9.2 Inheritance

Early articles suggested autosomal dominant inheritance, but “most cases of AOFVD are sporadic and do not follow a clear inheritance pattern,” despite multiple associated genes. (nipp2023adultonsetfoveomacularvitelliform pages 1-2)

9.3 Population demographics

No robust race/ethnicity/sex ratio data were available in the retrieved excerpts; the 2023 review notes many studies do not report race/ethnicity and that cohorts are geographically diverse. (nipp2023adultonsetfoveomacularvitelliform pages 1-2)

10. Diagnostics

10.1 Clinical criteria (practical)

Diagnosis is strongly imaging-based: a subfoveal round yellow lesion with subretinal hyperreflective material on OCT was used as inclusion in a 2023 case series. (tesfaw2023clinicalandoptical pages 1-2)

A differential diagnosis rule summarized in the 2023 review: patients with vitelliform lesions and drusen not meeting consensus AMD criteria should be diagnosed as AOFVD rather than AMD. (nipp2023adultonsetfoveomacularvitelliform pages 8-9)

10.2 Imaging

A central reference for staging-by-imaging is Table 1 from the 2023 review (color fundus photography, FAF, FA, SD-OCT, OCTA), including hallmark “egg-yolk” and “scrambled egg” appearances and stage-specific FAF/FA/OCT patterns. (nipp2023adultonsetfoveomacularvitelliform media 8bbaddb3)

An example of complication evolution (progression to CNV with OCT/FAF and response to anti-VEGF) is shown in Figure 4. (nipp2023adultonsetfoveomacularvitelliform media 7d1bcfc8)

Key modality notes: - FAF: vitelliform lesions typically hyperautofluorescent; later stages increasingly hypoautofluorescent. (nipp2023adultonsetfoveomacularvitelliform pages 7-8) - FA: can show a “non-fluorescent central spot” with a “hyperfluorescent spoked ring” in vitelliform stage; late staining can mimic CNV. (nipp2023adultonsetfoveomacularvitelliform pages 7-8) - SD-OCT: dome-shaped subretinal hyperreflective material is typical; pseudohypopyon may show an “optically clear” space superiorly, distinguishing it from neovascular AMD fluid patterns in some cases. (tesfaw2023clinicalandoptical pages 1-2) - OCTA: can be more sensitive for CNV detection; one cited report detected CNV on OCTA not seen on FA (1/8 eyes). (nipp2023adultonsetfoveomacularvitelliform pages 7-8)

10.3 Functional testing

A practical differentiator vs Best disease: Best disease typically shows abnormal EOG with reduced Arden ratio, whereas EOG is normal in the majority of AOFVD patients. (nipp2023adultonsetfoveomacularvitelliform pages 8-9)

10.4 Genetic testing strategy

A 2017 pattern-dystrophy genetic testing report describes a targeted multi-gene approach: - NGS panel of coding exons/splice regions of BEST1, CTNNA1, IMPG1, IMPG2, PRPH2, OTX2, with Sanger confirmation and segregation testing; MLPA for BEST1/PRPH2 copy-number changes. Reported NGS analytical sensitivity >99% (≥10×) and specificity 99.99%. (abeshi2017genetictestingfor pages 2-3)

The 2023 review notes “no formal guidelines for genetic testing” in AOFVD and suggests considering testing when multiple family members are affected. (nipp2023adultonsetfoveomacularvitelliform pages 9-10)

11. Outcome / prognosis

AOFVD “generally progresses slowly,” with severe loss typically linked to CNV or macular atrophy. (nipp2023adultonsetfoveomacularvitelliform pages 1-2)

Quantitative examples summarized in the 2023 review: - In 28 eyes followed 1–5 years: 10 stable, 11 worse, 4 improved. (nipp2023adultonsetfoveomacularvitelliform pages 7-8) - Stabilization at vitelliform stage corresponded to BCVA change from 20/36 → 20/39, whereas progression to vitelliruptive/atrophic stages corresponded to 20/50 → 20/104. (nipp2023adultonsetfoveomacularvitelliform pages 7-8)

Mortality/survival impacts are not applicable (ocular disease) and not reported.

12. Treatment

12.1 Standard of care / real-world management

  • No disease-modifying therapy: “no therapies currently slow disease progression,” so management focuses on complications. (nipp2023adultonsetfoveomacularvitelliform pages 9-10)

12.2 Treatment of CNV/MNV

  • Anti-VEGF (bevacizumab, ranibizumab): cited as standard of care for CNV secondary to AOFVD and associated with stabilization in most eyes. In one study summarized in the 2023 review, 87.5% lost fewer than three lines of vision at one year. (nipp2023adultonsetfoveomacularvitelliform pages 9-10)
  • Photodynamic therapy (PDT): “has shown no benefit in AOFVD and may worsen BCVA.” (nipp2023adultonsetfoveomacularvitelliform pages 9-10)

12.3 Surgical/interventional

  • Macular translocation has been reported but had high surgical risk and no distance-vision improvement; risks considered to outweigh benefits. (nipp2023adultonsetfoveomacularvitelliform pages 9-10)

12.4 Clinical trials / experimental development (selected)

  • NCT01965041 (2013; Manhattan Eye, Ear & Throat Hospital): intravitreal aflibercept for pattern dystrophy–associated adult-onset vitelliform detachments; withdrawn, enrollment=0, no results. (NCT01965041 chunk 1)
  • NCT01432847 (NEI; recruiting; last update 2026-06-05): biospecimen collection for inherited retinal diseases (including Best disease) to generate iPSC-derived RPE/retinal models and enable drug screening. (NCT01432847 chunk 1)
  • NCT02162953 (Mayo Clinic; completed; Feb 2014–Dec 31, 2022): stem-cell models of Best disease/bestrophinopathies; skin + blood to derive iPSC-RPE models (enrolled 48). (NCT02162953 chunk 1)
  • NCT05809635 (Columbia; recruiting; published record; started 2021-03-30): BEST1 vitelliform macular dystrophy natural history to develop endpoints for future trials (OCT, FAF, ERG/EOG, etc.). (NCT05809635 chunk 1)
  • NCT05258032 (Barcelona Macula Foundation; primary completion estimated 2024-11-24): structural/functional characterization of rare ocular diseases including Best disease/pattern dystrophy; endpoints include BCVA, microperimetry, OCT thickness. (NCT05258032 chunk 1)

12.5 MAXO term suggestions (curated)

  • Anti-VEGF therapy; Optical coherence tomography monitoring; Genetic testing; Low-vision rehabilitation; Intravitreal injection; Fluorescein angiography; OCT angiography.

13. Prevention

No primary-prevention strategies were identified (genetic/degenerative macular disease). Secondary prevention is primarily monitoring for CNV and atrophy using multimodal imaging and treating CNV when present. (nipp2023adultonsetfoveomacularvitelliform pages 9-10, nipp2023adultonsetfoveomacularvitelliform pages 7-8)

Genetic counseling/cascade testing may be considered in families with multiple affected members, but formal testing guidelines are not established for AOFVD. (nipp2023adultonsetfoveomacularvitelliform pages 9-10)

14. Other species / natural disease

No naturally occurring AOFVD in other species was identified in the retrieved sources.

15. Model organisms / experimental systems

While classical animal-model papers were not retrieved, active translational modeling relies on patient-derived iPSC systems: - NEI biospecimen repository to generate iPSC lines differentiated into RPE and neural retina for mechanistic studies and drug screening (NCT01432847). (NCT01432847 chunk 1) - Mayo Clinic iPSC-RPE disease models for bestrophinopathies (NCT02162953). (NCT02162953 chunk 1)

Key recent developments (2023–2024) and expert interpretation

1) 2023 consolidation of staging and imaging-driven differential diagnosis: the 2023 open-access review emphasizes improved characterization and differentiation from AMD/Best disease using SD-OCT and OCTA, alongside a four-stage framework with modality-specific signatures. (nipp2023adultonsetfoveomacularvitelliform pages 1-2, nipp2023adultonsetfoveomacularvitelliform media 8bbaddb3) 2) 2024 genetic overlap with AMD complement cascade: a 2024 IOVS study reports AFVD association with complement-pathway variants and a complement GRS (e.g., CFH rs570618 OR 2.73; complement GRS OR 1.42), concluding: “Non-monogenic AFVD is associated with AMD risk alleles in the complement cascade… Further research is needed to explore complement inhibition for AFVD.” (jaskoll2024adultonsetfoveomacular pages 1-2)

High-density summary table

The following table compiles the most directly evidenced identifiers, genetics, staging/imaging hallmarks, and 2024 developments.

Domain Key points Quantitative data Key source (include DOI/URL + year)
Definition / classification AOFVD/AFVD is a retinal pattern dystrophy characterized by subfoveal vitelliform material on fundus exam and multimodal imaging; often bilateral; slow progression but can lead to vision loss from CNV or macular atrophy. Debate persists about strict inclusion among pattern dystrophies because inheritance is often not clearly autosomal dominant. Synonyms used in the literature include adult vitelliform macular degeneration, adult macular vitelliform degeneration, pseudovitelliform macular degeneration, adult-onset foveomacular pigment epithelial dystrophy, adult foveomacular vitelliform dystrophy, and adult vitelliform macular dystrophy. (nipp2023adultonsetfoveomacularvitelliform pages 1-2, jabłonski2026adultonsetfoveomacularvitelliform pages 1-2) Approximate prevalence reported as 1:7,400 to 1:8,200; AFVD described as the common phenotype among pattern dystrophies. (nipp2023adultonsetfoveomacularvitelliform pages 1-2, jabłonski2026adultonsetfoveomacularvitelliform pages 1-2, jaskoll2024adultonsetfoveomacular pages 1-2) Nipp et al., 2023, Front. Ophthalmol., DOI: 10.3389/fopht.2023.1237788, https://doi.org/10.3389/fopht.2023.1237788; Jaskoll et al., 2024, IOVS, DOI: 10.1167/iovs.65.13.53, https://doi.org/10.1167/iovs.65.13.53
Epidemiology / onset Most patients are diagnosed between ages 50–70, although reported onset ranges extend from ~30 to 80 years; AFVD is frequently misdiagnosed as AMD. (nipp2023adultonsetfoveomacularvitelliform pages 2-3) Mean age in one 2023 case series: 62.75 years (12 patients, 19 eyes). In the 2024 genetics cohort: AFVD mean age 73 ± 10 years (n=50). (tesfaw2023clinicalandoptical pages 1-2, jaskoll2024adultonsetfoveomacular pages 1-2) Tesfaw & Bernstein, 2023, JOECSA, DOI: 10.64666/joecsa.2023.81, https://doi.org/10.64666/joecsa.2023.81; Jaskoll et al., 2024, https://doi.org/10.1167/iovs.65.13.53
Gene evidence: PRPH2 PRPH2 encodes peripherin-2, important for rod/cone outer segment disc formation and stabilization. It is the most commonly reported mutated gene in AOFVD but is not present in most cases; some authors consider it more of a predisposing factor in many patients than a universal monogenic cause. Pattern dystrophies are mainly autosomal dominant, and PRPH2 is associated with almost all pattern dystrophies. (nipp2023adultonsetfoveomacularvitelliform pages 2-3, abeshi2017genetictestingfor pages 1-2) Reported to account for only 2%–18% of AOFVD patients. (nipp2023adultonsetfoveomacularvitelliform pages 2-3) Nipp et al., 2023, https://doi.org/10.3389/fopht.2023.1237788; Abeshi et al., 2017, DOI: 10.24190/issn2564-615x/2017/s1.27, https://doi.org/10.24190/issn2564-615x/2017/s1.27
Gene evidence: BEST1 BEST1 (formerly VMD2) encodes bestrophin-1, an RPE-predominant transmembrane protein involved in ion channel function and intracellular calcium signaling. BEST1 mutations are classic for Best disease and have also been reported in some AOFVD/AVMD cases; some late-onset mild cases may represent mild Best disease. However, BEST1 mutations are absent in most AOFVD patients, so AFVD remains largely a clinical diagnosis with no formal genetic-testing guideline. (nipp2023adultonsetfoveomacularvitelliform pages 2-3, nipp2023adultonsetfoveomacularvitelliform pages 9-10, abeshi2017genetictestingfor pages 1-2) In a testing-focused review, BEST1 variants were reported as common in AVMD: 96% with positive family history and 50%–70% of sporadic cases, but this estimate comes from the testing review context and not all clinically defined AOFVD cohorts. (abeshi2017genetictestingfor pages 2-3) Nipp et al., 2023, https://doi.org/10.3389/fopht.2023.1237788; Abeshi et al., 2017, https://doi.org/10.24190/issn2564-615x/2017/s1.27
Gene evidence: IMPG1 IMPG1 and IMPG2 encode extracellular/interphotoreceptor matrix proteins involved in retinal adhesion. Primary genetic evidence shows IMPG1 mutations cause vitelliform macular dystrophies, including both autosomal dominant and autosomal recessive forms. Reported IMPG1 variants include missense, splice-site, and nonsense changes; disease mechanism implicates impaired interphotoreceptor matrix biology. (manes2013mutationsinimpg1 pages 1-2, manes2013mutationsinimpg1 pages 4-5, manes2013mutationsinimpg1 pages 7-8) In familial AOFVD patients lacking PRPH2/BEST1 mutations, IMPG1/2 mutations were found in 4/49 (~8%); likely <8% among all AOFVD. Primary IMPG1 report identified recurrent p.Leu238Arg and additional c.807+1G>T, p.Leu154Pro, p.Arg507*. (nipp2023adultonsetfoveomacularvitelliform pages 2-3, manes2013mutationsinimpg1 pages 1-2) Manes et al., 2013, Am J Hum Genet, DOI: 10.1016/j.ajhg.2013.07.018, https://doi.org/10.1016/j.ajhg.2013.07.018; Nipp et al., 2023, https://doi.org/10.3389/fopht.2023.1237788
Gene evidence: IMPG2 IMPG2 is also implicated in AOFVD/AVMD and, like IMPG1, encodes an extracellular matrix protein important for retinal adhesion/interphotoreceptor matrix structure. Evidence supports its contribution in a minority of cases and in familial disease lacking PRPH2/BEST1 mutations. (nipp2023adultonsetfoveomacularvitelliform pages 2-3, abeshi2017genetictestingfor pages 1-2, nipp2023adultonsetfoveomacularvitelliform pages 11-12) Combined IMPG1/IMPG2 frequency in familial AOFVD without PRPH2/BEST1 mutations: 4/49 (~8%). (nipp2023adultonsetfoveomacularvitelliform pages 2-3) Nipp et al., 2023, https://doi.org/10.3389/fopht.2023.1237788; Abeshi et al., 2017, https://doi.org/10.24190/issn2564-615x/2017/s1.27
Clinical stage 1: Vitelliform Classic “egg-yolk” lesion: yellowish-white, rounded, centered on the fovea. OCT shows dome-shaped homogeneous subretinal hyperreflective material between RPE and neurosensory retina. FAF is hyperautofluorescent. FA shows a non-fluorescent central spot with a hyperfluorescent spoked ring and no leakage. (nipp2023adultonsetfoveomacularvitelliform pages 7-8, nipp2023adultonsetfoveomacularvitelliform pages 3-5, gomezbenlloch2024opticalcoherencetomography pages 10-11) In one 2023 series, 10/19 eyes were stage I. (tesfaw2023clinicalandoptical pages 1-2) Nipp et al., 2023, https://doi.org/10.3389/fopht.2023.1237788; Tesfaw & Bernstein, 2023, https://doi.org/10.64666/joecsa.2023.81
Clinical stage 2: Pseudohypopyon Layering of vitelliform material within the lesion. OCT shows two zones: upper hyporeflective/optically clear space and lower homogeneous hyperreflective material; intraretinal pseudocysts may occur. FAF shows hyperautofluorescent inferior half and hypoautofluorescent superior half. FA may show a “stars-in-the-sky” appearance. The optically clear space may help distinguish AFVD from neovascular AMD. (nipp2023adultonsetfoveomacularvitelliform pages 7-8, tesfaw2023clinicalandoptical pages 1-2) In one 2023 series, 5/19 eyes were stage II; optically clear subretinal spaces were seen in 6/19 eyes overall, including 5 pseudohypopyon eyes; 4/5 pseudohypopyon eyes had intact IS/OS interfaces. (tesfaw2023clinicalandoptical pages 1-2) Nipp et al., 2023, https://doi.org/10.3389/fopht.2023.1237788; Tesfaw & Bernstein, 2023, https://doi.org/10.64666/joecsa.2023.81
Clinical stage 3: Vitelliruptive “Scrambled egg” stage with breakup and reabsorption of the lesion. OCT shows fragmented vitelliform material with mixed hyper-/hyporeflective spaces, hyperreflective clumps, and increasing photoreceptor loss/ellipsoid zone disruption. FAF becomes hypoautofluorescent; FA may retain a “stars-in-the-sky” pattern. (nipp2023adultonsetfoveomacularvitelliform pages 7-8, nipp2023adultonsetfoveomacularvitelliform pages 3-5, gomezbenlloch2024opticalcoherencetomography pages 10-11) In one 2023 series, 4/19 eyes were stage III; IS/OS disruption was seen in 8/19 eyes total, including 4 stage III eyes. (tesfaw2023clinicalandoptical pages 1-2) Nipp et al., 2023, https://doi.org/10.3389/fopht.2023.1237788; Tesfaw & Bernstein, 2023, https://doi.org/10.64666/joecsa.2023.81
Clinical stage 4: Atrophic Final stage after lesion resorption; not all eyes with lesion resorption become atrophic. OCT shows widespread photoreceptor-layer loss and RPE atrophy/cRORA. FAF is hypoautofluorescent. FA shows late hyperfluorescence of the atrophic area; color photography may show pale fundus/visible choroidal vessels. (nipp2023adultonsetfoveomacularvitelliform pages 7-8, nipp2023adultonsetfoveomacularvitelliform pages 2-3) No atrophic eyes were present in the 19-eye 2023 Ethiopian series. (tesfaw2023clinicalandoptical pages 2-4, tesfaw2023clinicalandoptical pages 1-2) Nipp et al., 2023, https://doi.org/10.3389/fopht.2023.1237788; Tesfaw & Bernstein, 2023, https://doi.org/10.64666/joecsa.2023.81
Imaging / differential diagnosis SD-OCT and OCTA are central for diagnosis and for distinguishing AFVD from AMD and Best disease. OCTA may detect CNV not seen on FA; one cited example detected CNV in 1/8 eyes on OCTA not seen on FA. EOG and full-field ERG are often normal or only mildly abnormal, supporting focal rather than generalized dysfunction. (nipp2023adultonsetfoveomacularvitelliform pages 7-8, nipp2023adultonsetfoveomacularvitelliform pages 9-10, jabłonski2026adultonsetfoveomacularvitelliform pages 1-2) OCTA-detected CNV missed by FA: 1/8 eyes in one cited report. In the 2023 19-eye series, presenting VA ranged from 20/100 to 20/20. (nipp2023adultonsetfoveomacularvitelliform pages 7-8, tesfaw2023clinicalandoptical pages 1-2) Nipp et al., 2023, https://doi.org/10.3389/fopht.2023.1237788; Tesfaw & Bernstein, 2023, https://doi.org/10.64666/joecsa.2023.81
Prognosis / complications Visual course is often relatively benign, but decline is greater with stage progression, CNV, or macular atrophy. Reported complications include CNV, macular atrophy, PED, retinal folds, macular coloboma, and RPE aperture. (nipp2023adultonsetfoveomacularvitelliform pages 7-8) Example natural-history data: in 28 eyes followed 1–5 years, 10 stable, 11 worse, 4 improved; progression to vitelliruptive/atrophic stages reduced BCVA from 20/50 to 20/104 versus minimal change when stable at vitelliform stage (20/36 to 20/39). CNV prevalence around 15% is reported in review summaries. (nipp2023adultonsetfoveomacularvitelliform pages 7-8, jabłonski2026adultonsetfoveomacularvitelliform pages 1-2) Nipp et al., 2023, https://doi.org/10.3389/fopht.2023.1237788; Jabłoński & Mackiewicz, 2026, https://doi.org/10.5114/oku/215545
2024 development: AFVD genetic overlap with AMD/complement A 2024 IOVS study examined non-monogenic AFVD and found partial genetic overlap with AMD, especially in complement-related loci, while major AMD loci such as ARMS2/HTRA1 were not similarly associated with AFVD. The study suggests complement dysregulation may contribute to a subset of AFVD and raises complement inhibition as a future research direction. (jaskoll2024adultonsetfoveomacular pages 1-2, jaskoll2024adultonsetfoveomacular pages 6-8, jaskoll2024adultonsetfoveomacular pages 8-10) Cohort: 50 AFVD, 917 AMD, 432 controls; 52 AMD-linked SNPs tested. AFVD-associated loci vs controls: CFH rs570618 OR 2.73 (95% CI 1.32–5.73; P=0.01); C2/CFB/SKIV2L rs116503776 OR 0.31 (0.14–0.71; P=0.0036); rs114254831 OR 0.41 (0.22–0.74; P=0.0025); MIR6130/RORB rs10781182 OR 0.13 (0.06–0.25; P<0.0001) vs controls and OR 0.19 (0.10–0.34; P<0.0001) vs AMD. Complement GRS OR 1.42 (1.04–1.95; P=0.03); other-pathways GRS OR 0.46 (0.21–0.98; P=0.04). Plasma complement activation did not differ significantly among AFVD, AMD, and controls. (jaskoll2024adultonsetfoveomacular pages 1-2, jaskoll2024adultonsetfoveomacular pages 6-8, jaskoll2024adultonsetfoveomacular pages 8-10) Jaskoll et al., 2024, Invest. Ophthalmol. Vis. Sci., DOI: 10.1167/iovs.65.13.53, https://doi.org/10.1167/iovs.65.13.53

Table: This table condenses the most evidence-supported findings on adult-onset foveomacular vitelliform dystrophy, including nomenclature, genetics, multimodal imaging stages, prognosis, and the major 2024 complement-genetics development. It is useful as a high-density reference for disease knowledge-base curation.

Notes on evidence limitations vs requested template

  • MONDO/MeSH/ICD/Orphanet IDs were not present in retrieved excerpts; a targeted ontology lookup is required.
  • PMIDs: Some papers in the evidence set did not include PMIDs in the retrieved text. One cited PMID available in excerpts is Meunier et al. Ophthalmology 2014 (PMID: 25085631) referenced in the genetic testing report; additional primary sources would be needed to populate complete PMID coverage. (abeshi2017genetictestingfor pages 3-3)
  • Protective factors, GxE, epigenetics, omics: not identified in the retrieved sources.

References

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  2. (nipp2023adultonsetfoveomacularvitelliform pages 2-3): Grace E. Nipp, Terry Lee, Kubra Sarici, Goldis Malek, and Majda Hadziahmetovic. Adult-onset foveomacular vitelliform dystrophy: epidemiology, pathophysiology, imaging, and prognosis. Frontiers in Ophthalmology, Aug 2023. URL: https://doi.org/10.3389/fopht.2023.1237788, doi:10.3389/fopht.2023.1237788. This article has 14 citations.

  3. (tesfaw2023clinicalandoptical pages 1-2): Alemu Kerie Tesfaw and Paul S. Bernstein. Clinical and optical coherence tomography features of adult-onset foveo-macular vitelliform dystrophy mimicking age-related macular degeneration. Journal of Ophthalmology of Eastern, Central and Southern Africa (JOECSA), Jul 2023. URL: https://doi.org/10.64666/joecsa.2023.81, doi:10.64666/joecsa.2023.81. This article has 0 citations.

  4. (jaskoll2024adultonsetfoveomacular pages 1-2): Shlomit Jaskoll, Adi Kramer, Sarah Elbaz-Hayoun, Batya Rinsky, Chiara M. Eandi, Michelle Grunin, Yahel Shwartz, Liran Tiosano, Iris M. Heid, Thomas Winkler, and Itay Chowers. Adult onset foveomacular vitelliform dystrophy shows genetic overlap with age-related macular degeneration. Investigative Ophthalmology & Visual Science, 65:53, Nov 2024. URL: https://doi.org/10.1167/iovs.65.13.53, doi:10.1167/iovs.65.13.53. This article has 4 citations and is from a domain leading peer-reviewed journal.

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  7. (tesfaw2023clinicalandoptical pages 2-4): Alemu Kerie Tesfaw and Paul S. Bernstein. Clinical and optical coherence tomography features of adult-onset foveo-macular vitelliform dystrophy mimicking age-related macular degeneration. Journal of Ophthalmology of Eastern, Central and Southern Africa (JOECSA), Jul 2023. URL: https://doi.org/10.64666/joecsa.2023.81, doi:10.64666/joecsa.2023.81. This article has 0 citations.

  8. (nipp2023adultonsetfoveomacularvitelliform pages 7-8): Grace E. Nipp, Terry Lee, Kubra Sarici, Goldis Malek, and Majda Hadziahmetovic. Adult-onset foveomacular vitelliform dystrophy: epidemiology, pathophysiology, imaging, and prognosis. Frontiers in Ophthalmology, Aug 2023. URL: https://doi.org/10.3389/fopht.2023.1237788, doi:10.3389/fopht.2023.1237788. This article has 14 citations.

  9. (jaskoll2024adultonsetfoveomacular pages 6-8): Shlomit Jaskoll, Adi Kramer, Sarah Elbaz-Hayoun, Batya Rinsky, Chiara M. Eandi, Michelle Grunin, Yahel Shwartz, Liran Tiosano, Iris M. Heid, Thomas Winkler, and Itay Chowers. Adult onset foveomacular vitelliform dystrophy shows genetic overlap with age-related macular degeneration. Investigative Ophthalmology & Visual Science, 65:53, Nov 2024. URL: https://doi.org/10.1167/iovs.65.13.53, doi:10.1167/iovs.65.13.53. This article has 4 citations and is from a domain leading peer-reviewed journal.

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  12. (nipp2023adultonsetfoveomacularvitelliform media 7d1bcfc8): Grace E. Nipp, Terry Lee, Kubra Sarici, Goldis Malek, and Majda Hadziahmetovic. Adult-onset foveomacular vitelliform dystrophy: epidemiology, pathophysiology, imaging, and prognosis. Frontiers in Ophthalmology, Aug 2023. URL: https://doi.org/10.3389/fopht.2023.1237788, doi:10.3389/fopht.2023.1237788. This article has 14 citations.

  13. (abeshi2017genetictestingfor pages 2-3): Andi Abeshi, Pamela Coppola, Tommaso Beccari, Munis Dundar, Maura Di Nicola, Francesco Viola, Leonardo Colombo, and Matteo Bertelli. Genetic testing for pattern dystrophies. The EuroBiotech Journal, 1:86-88, Oct 2017. URL: https://doi.org/10.24190/issn2564-615x/2017/s1.27, doi:10.24190/issn2564-615x/2017/s1.27. This article has 2 citations.

  14. (nipp2023adultonsetfoveomacularvitelliform pages 9-10): Grace E. Nipp, Terry Lee, Kubra Sarici, Goldis Malek, and Majda Hadziahmetovic. Adult-onset foveomacular vitelliform dystrophy: epidemiology, pathophysiology, imaging, and prognosis. Frontiers in Ophthalmology, Aug 2023. URL: https://doi.org/10.3389/fopht.2023.1237788, doi:10.3389/fopht.2023.1237788. This article has 14 citations.

  15. (NCT01965041 chunk 1): Intravitreal Aflibercept Injections In The Treatment Of Pattern Dystrophy. Manhattan Eye, Ear & Throat Hospital. 2013. ClinicalTrials.gov Identifier: NCT01965041

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