Proliferative Vitreoretinopathy

Acquired MONDO:0700115 Pathograph 4 Show in embeddings browser Retinal disorder

Proliferative vitreoretinopathy (PVR) is an abnormal wound-healing response that complicates rhegmatogenous retinal detachment, ocular trauma, or retinal detachment surgery. Retinal pigment epithelial (RPE) cells and glial cells disperse into the vitreous cavity and undergo epithelial-mesenchymal transition into myofibroblast-like cells, which proliferate and contract to form fibrocellular membranes on the retinal surfaces and posterior vitreous cortex. Membrane contraction produces traction on the retina, causing fixed folds and tractional (re)detachment, and is the leading cause of anatomic failure after retinal reattachment surgery.

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4
Pathophys.
4
Phenotypes
4
Pathograph
2
Medical Actions
3
Datasets
⚙

Pathophysiology

4
Retinal Break and RPE Cell Dispersion into Vitreous
A full-thickness retinal break, detachment, or surgical/traumatic injury breaches the retina and the retinal pigment epithelial monolayer. RPE cells lose contact with Bruch's membrane and disperse into the vitreous cavity and subretinal space, where local injury triggers an inflammatory response that induces the formation of multilayered groups of migratory RPE cells.
Retinal Pigment Epithelial Cell CL:0002586 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Retinal Pigment Epithelial Cell (CL:0002586). CL:0002586 is a cell type from the Cell Ontology.
Cell Migration GO:0016477 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased Cell Migration (GO:0016477). GO:0016477 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. vitreous body UBERON:0001798 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in vitreous body (UBERON:0001798). UBERON:0001798 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
RPE Epithelial-Mesenchymal Transition
Show evidence (2 references)
PMID:12101449 SUPPORT Human Clinical
"injury of the retina induces an inflammatory response that upregulates HGF expression inducing the formation of multilayered groups of migratory retinal pigment epithelial cells (RPE)"
Establishes the model of retinal injury triggering RPE cell dispersion and migration as the initiating step of PVR pathogenesis.
PMID:26562474 SUPPORT Human Clinical
"retinal pigment epithelial (RPE) cells are indicated to play the primary role in the pathogenesis of PVR"
Confirms RPE cells as the primary cellular driver of PVR pathogenesis, consistent with dispersion from the injured retina.
RPE Epithelial-Mesenchymal Transition
Dispersed RPE cells lose epithelial cell-cell contacts and undergo epithelial-mesenchymal transition (EMT) into matrix-producing, contractile myofibroblast-like cells. TGF-beta activated in the vitreous upregulates connective tissue growth factor (CTGF), and under the combined influence of TGF-beta and CTGF, RPE cells become myofibroblastic.
Retinal Pigment Epithelial Cell CL:0002586 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Retinal Pigment Epithelial Cell (CL:0002586). CL:0002586 is a cell type from the Cell Ontology. Myofibroblast CL:0000186 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Myofibroblast, annotated with myofibroblast cell (CL:0000186). CL:0000186 is a cell type from the Cell Ontology.
Epithelial to Mesenchymal Transition GO:0001837 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased Epithelial to Mesenchymal Transition (GO:0001837). GO:0001837 is a biological process from the Gene Ontology. ↑ INCREASED TGF-beta Receptor Signaling GO:0007179 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased TGF-beta Receptor Signaling, annotated with transforming growth factor beta receptor signaling pathway (GO:0007179). GO:0007179 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Contractile Fibrocellular Membrane Formation
Show evidence (2 references)
PMID:26562474 SUPPORT Human Clinical
"RPE cells undergo a process named epithelial-mesenchymal transition (EMT), by which differentiated epithelial cells go through a phenotypic conversion that gives rise to the matrix-producing fibroblasts and myofibroblasts"
Directly describes the RPE-to-myofibroblast EMT conversion, the central effector step of PVR pathogenesis.
PMID:12101449 SUPPORT Human Clinical
"The TGF-beta is activated, upregulating expression of CTGF. Under the influence of TGF-beta and CTGF, RPE become myofibroblastic and fibrosis ensues."
Identifies TGF-beta/CTGF signaling as the proximate driver of RPE myofibroblastic transdifferentiation.
Contractile Fibrocellular Membrane Formation
Myofibroblast-like RPE cells, together with glial cells (notably Muller cells) recruited from the retina, proliferate and deposit extracellular matrix, forming contractile fibrocellular membranes on the retinal surfaces and posterior vitreous cortex. Vitreous TGF-beta2 levels rise in proportion to the degree of intraocular fibrosis, and elevated vitreous cytokines are predictive of membrane formation.
Retinal Pigment Epithelial Cell CL:0002586 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Retinal Pigment Epithelial Cell (CL:0002586). CL:0002586 is a cell type from the Cell Ontology. Muller Cell CL:0000636 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Muller Cell, annotated with Mueller cell (CL:0000636). CL:0000636 is a cell type from the Cell Ontology.
Extracellular Matrix Organization GO:0030198 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased Extracellular Matrix Organization (GO:0030198). GO:0030198 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Tractional Retinal Redetachment
Show evidence (2 references)
PMID:2708527 SUPPORT Human Clinical
"vitreous aspirates from eyes with intraocular fibrosis associated with PVR have more than three times the amount of TGF-beta"
Demonstrates that vitreous TGF-beta (predominantly TGF-beta2) levels correlate with the degree of intraocular fibrotic membrane formation.
PMID:10067974 SUPPORT Human Clinical
"Multivariate logistic regression analysis showed IL-6 and protein to be significant (P < 0.05), independent, predictive risk factors for the development of PVR."
Shows that elevated vitreous cytokines (IL-6) independently predict subsequent PVR membrane formation.
Tractional Retinal Redetachment
Contraction of the fibrocellular membranes exerts traction on the underlying retina, producing fixed retinal folds and epiretinal/subretinal membranes that progress to tractional (re)detachment. Severity is staged clinically by the 1991 Retina Society classification (Grades A-C, subdivided anterior/posterior and by clock hour extent), which remains the basis for current OCT-correlated staging.
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.
Show evidence (2 references)
PMID:1867299 SUPPORT Human Clinical
"A more detailed description of posterior and anterior contractions has been made possible by adding contraction types such as focal, diffuse, subretinal, circumferential contraction, and anterior displacement."
Defines the membrane-contraction-driven traction patterns underlying the clinical staging of PVR-associated redetachment.
PMID:40311677 SUPPORT Human Clinical
"Proliferative vitreoretinopathy C (27/100) was clinically divided into patients with subretinal (SR) membranes"
Confirms fixed retinal folds and subretinal membranes as the OCT- and clinically-observed correlates of traction in Grade C PVR.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Proliferative Vitreoretinopathy 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

4
Vitreous haze Ophthalmologic HP:0030652 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Vitreous haze (HP:0030652). HP:0030652 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:1867299 SUPPORT Human Clinical
"There are three grades describing increasing severity of the disease."
Establishes the graded clinical staging (A-C) of which vitreous haze/cells is the earliest (Grade A) sign.
Retinal folds Ophthalmologic HP:0008052 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Retinal fold (HP:0008052). HP:0008052 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:40311677 SUPPORT Human Clinical
"patients with fixed retinal folds (intraretinal"
Documents fixed retinal folds as a clinically observed PVR feature.
Epiretinal and subretinal membranes Ophthalmologic HP:0100014 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Epiretinal membrane (HP:0100014). HP:0100014 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:40311677 SUPPORT Human Clinical
"they had a thick hyperreflective membrane emanating from the retinal pigment epithelium and extending along the outer retinal surface"
Confirms fibrocellular membrane formation on the retinal surface as the OCT correlate of Grade C PVR.
Tractional retinal detachment Ophthalmologic HP:0007917 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Tractional retinal detachment (HP:0007917). HP:0007917 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:2708527 SUPPORT Human Clinical
"Approximately 1 out of every 10 eyes undergoing surgery for retinal detachment develops excessive intraocular fibrosis that can lead to traction retinal detachment and ultimate blindness."
Establishes tractional retinal detachment as the clinically significant end-stage outcome of PVR-associated fibrosis.
💊

Medical Actions

2
Pars Plana Vitrectomy with Membrane Peeling and Tamponade
Action: VitrectomyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Vitrectomy (NCIT:C50837). NCIT:C50837 is a clinical intervention from the NCI Thesaurus. NCIT:C50837
Surgical removal of the vitreous and dissection/peeling of contractile fibrocellular membranes, followed by tamponade with silicone oil or long-acting gas, is the only proven management for established PVR; there is no proven pharmacologic treatment.
Show evidence (1 reference)
PMID:30585928 SUPPORT Human Clinical
"At this time, surgery is the only management option for PVR as there is no proven pharmacologic agent for the treatment or prevention of PVR."
Establishes vitrectomy-based surgery as the sole proven treatment for established PVR.
Adjuvant Intravitreal 5-Fluorouracil and Low-Molecular-Weight Heparin
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: 5-fluorouracil CHEBI:46345 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses 5-fluorouracil (CHEBI:46345). CHEBI:46345 is a therapeutic agent from Chemical Entities of Biological Interest. heparin CHEBI:28304 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses heparin (CHEBI:28304). CHEBI:28304 is a therapeutic agent from Chemical Entities of Biological Interest.
Combined perioperative 5-fluorouracil (5-FU) and low-molecular-weight heparin (LMWH) has been trialed as an antiproliferative adjuvant to vitrectomy surgery. Evidence is mixed: an early single-center trial found a reduced incidence of postoperative PVR when used prophylactically in high-risk eyes, but a trial in established Grade C PVR and a larger, more recent multicenter prevention trial found no significant benefit.
Show evidence (3 references)
PMID:11425671 SUPPORT Human Clinical
"The incidence of postoperative PVR was significantly lower (P = 0.02) in the 5-FU and LMWH therapy compared with the placebo group."
Early single-center trial supporting prophylactic 5-FU/LMWH in high-risk eyes undergoing primary vitrectomy.
PMID:15582080 REFUTE Human Clinical
"There was no significant difference in success in the primary outcome measure (56%, treatment group; 51%, placebo group; P = 0.59)"
Multicenter trial in established Grade C PVR found no significant benefit of adjuvant 5-FU/LMWH on surgical success.
PMID:35680097 REFUTE Human Clinical
"Rate of PVR did not differ between adjuvant therapy with 5-FU and LMWH and placebo treatment in eyes with RRD."
Larger, more recent multicenter (PRIVENT) trial found no preventive benefit of adjuvant 5-FU/LMWH, contradicting the earlier single-center prevention trial.
🔬

Diagnosis

2
Dilated fundus examination with Retina Society grading
Indirect ophthalmoscopy with staging by the 1991 Retina Society classification (Grades A, B, C anterior/posterior by clock hour) is the standard clinical diagnostic method.
clinical assessment NCIT:C124351 NCI Thesaurus (NCIT)
Results: PVR grade A (vitreous haze), B (retinal folds/wrinkling), or C (anterior/posterior membranes, staged by clock hours).
Show evidence (1 reference)
PMID:1867299 SUPPORT Human Clinical
"Posterior and anterior location of the proliferations have been emphasized."
Describes the clinical staging system used for diagnosis and grading.
Swept-source OCT microstructural assessment
Swept-source OCT can characterize retinal microstructural correlates of PVR (outer retinal corrugations, hyperreflective membranes, bacillary layer changes) and distinguish subretinal-membrane from intraretinal-fold subtypes of Grade C disease.
optical coherence tomography NCIT:C20828 NCI Thesaurus (NCIT)
Results: Outer retinal corrugations, hyperreflective preretinal/subretinal membranes, tractional folds of the outer retina.
Show evidence (1 reference)
PMID:40311677 SUPPORT Human Clinical
"Ultra-widefield fundus imaging was staged per the Retina Society 1991 PVR Classification and correlated with retinal microstructural changes assessed with SS-OCT."
Demonstrates OCT as a complementary quantitative diagnostic tool alongside clinical staging.
📊

Prevalence

1
Eyes undergoing surgery for retinal detachment
Point Prevalence 10000.0 per 100,000 >1 in 1,000
Classic estimate of PVR as a complication of retinal detachment surgery; more recent reviews report a similar 5-10% range depending on risk factors such as trauma or prior vitrectomy.
Show evidence (1 reference)
PMID:2708527 SUPPORT Human Clinical
"Approximately 1 out of every 10 eyes undergoing surgery for retinal detachment develops excessive intraocular fibrosis that can lead to traction retinal detachment and ultimate blindness."
Direct quantitative estimate of PVR incidence following retinal detachment surgery.
📊

Related Datasets

3
Transcriptional Characterisation of Proliferative Vitreoretinopathy geo:GSE179603
Purpose: The development of vitreoretinal scars remains an unsolved challenge in clinical practice and often leads to repeated revision surgery and blindness due to lack of efficient therapy. The aim of this study was to characterize the cellular and molecular environment in vitreoretinal scar tissue from patients with proliferative vitreoretinopathy (PVR) in comparison to membranes of the vitreoretinal junction, in order to subsequently identify potential drug treatment options using bioinformatics techniques.
human BULK RNA SEQ n=27
PMID:35579905
Identified by GEO DataSets index search for Proliferative Vitreoretinopathy (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.
Expression profile of peripheral immune cells-derived coding and long non-coding RNAs in patients with proliferative vitreoretinopathy geo:GSE164208
Peripheral immune response has been revealed to play a critical role in proliferative vitreoretinopathy (PVR). However, the reliable immune-related factors that are acting as prognostic indicators or therapeutic targets for PVR remain to explore further. Methods: In the current study, we applied whole-transcriptome sequencing to profile peripheral blood mononuclear cells (PBMCs) from PVR patients and also analyzed lncRNA-mRNA interactions in peripheral immune cells to explore the pathways that might mediate immunopathology and resultant retinal damage in PVR.
human BULK RNA SEQ n=24
PMID:33509158
Identified by GEO DataSets index search for Proliferative Vitreoretinopathy (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.
Absent in melanoma 2: a potent suppressor of retinal pigment epithelial-mesenchymal transition and experimental proliferative vitreoretinopathy geo:GSE282859
Epithelial-to-mesenchymal transition (EMT) is a critical and complex process involved in normal embryonic development, tissue regeneration, and tumor progression. It also contributes to retinal diseases, such as age-related macular degeneration (AMD) and proliferative vitreoretinopathy (PVR). Although absent in melanoma 2 (AIM2) has been linked to inflammatory disorders, autoimmune diseases, and cancers, its role in the EMT of the retinal pigment epithelium (RPE-EMT) and retinal diseases remains unclear. The present study demonstrated that AIM2 functions as a potent suppressor of RPE cell proliferation and EMT to maintain retinal homeostasis.
human BULK RNA SEQ n=6
PMID:39870644
Identified by GEO DataSets index search for Proliferative Vitreoretinopathy (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: Proliferative Vitreoretinopathy
creation_date: "2026-07-16T00:00:00Z"
description: >-
  Proliferative vitreoretinopathy (PVR) is an abnormal wound-healing response
  that complicates rhegmatogenous retinal detachment, ocular trauma, or
  retinal detachment surgery. Retinal pigment epithelial (RPE) cells and
  glial cells disperse into the vitreous cavity and undergo
  epithelial-mesenchymal transition into myofibroblast-like cells, which
  proliferate and contract to form fibrocellular membranes on the retinal
  surfaces and posterior vitreous cortex. Membrane contraction produces
  traction on the retina, causing fixed folds and tractional
  (re)detachment, and is the leading cause of anatomic failure after retinal
  reattachment surgery.
category: Acquired
disease_term:
  preferred_term: proliferative vitreoretinopathy
  term:
    id: MONDO:0700115
    label: proliferative vitreoretinopathy
synonyms:
- PVR
- massive periretinal proliferation
parents:
- Retinal disorder
pathophysiology:
- name: Retinal Break and RPE Cell Dispersion into Vitreous
  description: >-
    A full-thickness retinal break, detachment, or surgical/traumatic injury
    breaches the retina and the retinal pigment epithelial monolayer. RPE
    cells lose contact with Bruch's membrane and disperse into the vitreous
    cavity and subretinal space, where local injury triggers an inflammatory
    response that induces the formation of multilayered groups of migratory
    RPE cells.
  role: trigger
  locations:
  - preferred_term: retina
    term:
      id: UBERON:0000966
      label: retina
  - preferred_term: vitreous body
    term:
      id: UBERON:0001798
      label: vitreous body
  cell_types:
  - preferred_term: Retinal Pigment Epithelial Cell
    term:
      id: CL:0002586
      label: retinal pigment epithelial cell
  biological_processes:
  - preferred_term: Cell Migration
    term:
      id: GO:0016477
      label: cell migration
    modifier: INCREASED
  evidence:
  - reference: PMID:12101449
    reference_title: Novel growth factors involved in the pathogenesis of proliferative vitreoretinopathy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      injury of the retina induces an inflammatory response that upregulates
      HGF expression inducing the formation of multilayered groups of
      migratory retinal pigment epithelial cells (RPE)
    explanation: >-
      Establishes the model of retinal injury triggering RPE cell dispersion
      and migration as the initiating step of PVR pathogenesis.
  - reference: PMID:26562474
    reference_title: Mechanisms of epithelial-mesenchymal transition in proliferative vitreoretinopathy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      retinal pigment epithelial (RPE) cells are indicated to play the
      primary role in the pathogenesis of PVR
    explanation: >-
      Confirms RPE cells as the primary cellular driver of PVR pathogenesis,
      consistent with dispersion from the injured retina.
  downstream:
  - target: RPE Epithelial-Mesenchymal Transition

- name: RPE Epithelial-Mesenchymal Transition
  conforms_to: "fibrotic_response#Mesenchymal Cell Activation"
  description: >-
    Dispersed RPE cells lose epithelial cell-cell contacts and undergo
    epithelial-mesenchymal transition (EMT) into matrix-producing,
    contractile myofibroblast-like cells. TGF-beta activated in the
    vitreous upregulates connective tissue growth factor (CTGF), and under
    the combined influence of TGF-beta and CTGF, RPE cells become
    myofibroblastic.
  role: central_effector
  cell_types:
  - preferred_term: Retinal Pigment Epithelial Cell
    term:
      id: CL:0002586
      label: retinal pigment epithelial cell
  - preferred_term: Myofibroblast
    term:
      id: CL:0000186
      label: myofibroblast cell
  biological_processes:
  - preferred_term: Epithelial to Mesenchymal Transition
    term:
      id: GO:0001837
      label: epithelial to mesenchymal transition
    modifier: INCREASED
  - preferred_term: TGF-beta Receptor Signaling
    term:
      id: GO:0007179
      label: transforming growth factor beta receptor signaling pathway
    modifier: INCREASED
  evidence:
  - reference: PMID:26562474
    reference_title: Mechanisms of epithelial-mesenchymal transition in proliferative vitreoretinopathy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      RPE cells undergo a process named epithelial-mesenchymal transition
      (EMT), by which differentiated epithelial cells go through a
      phenotypic conversion that gives rise to the matrix-producing
      fibroblasts and myofibroblasts
    explanation: >-
      Directly describes the RPE-to-myofibroblast EMT conversion, the
      central effector step of PVR pathogenesis.
  - reference: PMID:12101449
    reference_title: Novel growth factors involved in the pathogenesis of proliferative vitreoretinopathy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The TGF-beta is activated, upregulating expression of CTGF. Under the
      influence of TGF-beta and CTGF, RPE become myofibroblastic and
      fibrosis ensues.
    explanation: >-
      Identifies TGF-beta/CTGF signaling as the proximate driver of RPE
      myofibroblastic transdifferentiation.
  downstream:
  - target: Contractile Fibrocellular Membrane Formation

- name: Contractile Fibrocellular Membrane Formation
  description: >-
    Myofibroblast-like RPE cells, together with glial cells (notably Muller
    cells) recruited from the retina, proliferate and deposit extracellular
    matrix, forming contractile fibrocellular membranes on the retinal
    surfaces and posterior vitreous cortex. Vitreous TGF-beta2 levels rise
    in proportion to the degree of intraocular fibrosis, and elevated
    vitreous cytokines are predictive of membrane formation.
  role: amplifier
  cell_types:
  - preferred_term: Retinal Pigment Epithelial Cell
    term:
      id: CL:0002586
      label: retinal pigment epithelial cell
  - preferred_term: Muller Cell
    term:
      id: CL:0000636
      label: Mueller cell
  biological_processes:
  - preferred_term: Extracellular Matrix Organization
    term:
      id: GO:0030198
      label: extracellular matrix organization
    modifier: INCREASED
  evidence:
  - reference: PMID:2708527
    reference_title: Correlation of fibrosis and transforming growth factor-beta type 2 levels in the eye.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      vitreous aspirates from eyes with intraocular fibrosis associated with
      PVR have more than three times the amount of TGF-beta
    explanation: >-
      Demonstrates that vitreous TGF-beta (predominantly TGF-beta2) levels
      correlate with the degree of intraocular fibrotic membrane formation.
  - reference: PMID:10067974
    reference_title: "Expression of vitreous cytokines in proliferative vitreoretinopathy: a prospective study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Multivariate logistic regression analysis showed IL-6 and protein to
      be significant (P < 0.05), independent, predictive risk factors for
      the development of PVR.
    explanation: >-
      Shows that elevated vitreous cytokines (IL-6) independently predict
      subsequent PVR membrane formation.
  downstream:
  - target: Tractional Retinal Redetachment

- name: Tractional Retinal Redetachment
  description: >-
    Contraction of the fibrocellular membranes exerts traction on the
    underlying retina, producing fixed retinal folds and
    epiretinal/subretinal membranes that progress to tractional
    (re)detachment. Severity is staged clinically by the 1991 Retina Society
    classification (Grades A-C, subdivided anterior/posterior and by clock
    hour extent), which remains the basis for current OCT-correlated
    staging.
  role: outcome
  locations:
  - preferred_term: retina
    term:
      id: UBERON:0000966
      label: retina
  evidence:
  - reference: PMID:1867299
    reference_title: An updated classification of retinal detachment with proliferative vitreoretinopathy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      A more detailed description of posterior and anterior contractions
      has been made possible by adding contraction types such as focal,
      diffuse, subretinal, circumferential contraction, and anterior
      displacement.
    explanation: >-
      Defines the membrane-contraction-driven traction patterns underlying
      the clinical staging of PVR-associated redetachment.
  - reference: PMID:40311677
    reference_title: "Assessment of Proliferative Vitreoretinopathy in Rhegmatogenous Retinal Detachment with OCT: Revisiting the 1991 Retina Society Classification."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Proliferative vitreoretinopathy C (27/100) was clinically divided into
      patients with subretinal (SR) membranes
    explanation: >-
      Confirms fixed retinal folds and subretinal membranes as the OCT- and
      clinically-observed correlates of traction in Grade C PVR.

phenotypes:
- category: Ophthalmologic
  name: Vitreous haze
  description: >-
    Vitreous cells and pigment clumps (Grade A) are the earliest clinical
    sign of PVR, reflecting dispersed RPE cells and inflammatory cells in
    the vitreous cavity.
  phenotype_term:
    preferred_term: Vitreous haze
    term:
      id: HP:0030652
      label: Vitreous haze
  evidence:
  - reference: PMID:1867299
    reference_title: An updated classification of retinal detachment with proliferative vitreoretinopathy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      There are three grades describing increasing severity of the disease.
    explanation: >-
      Establishes the graded clinical staging (A-C) of which vitreous
      haze/cells is the earliest (Grade A) sign.
- category: Ophthalmologic
  name: Retinal folds
  description: >-
    Fixed or rolled retinal folds (Grade B) reflect subclinical contraction
    of preretinal membranes and inner retinal wrinkling.
  phenotype_term:
    preferred_term: Retinal fold
    term:
      id: HP:0008052
      label: Retinal fold
  evidence:
  - reference: PMID:40311677
    reference_title: "Assessment of Proliferative Vitreoretinopathy in Rhegmatogenous Retinal Detachment with OCT: Revisiting the 1991 Retina Society Classification."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      patients with fixed retinal folds (intraretinal
    explanation: Documents fixed retinal folds as a clinically observed PVR feature.
- category: Ophthalmologic
  name: Epiretinal and subretinal membranes
  description: >-
    Preretinal and subretinal fibrocellular membranes (Grade C) are the
    contractile tissue responsible for traction on the retina.
  phenotype_term:
    preferred_term: Epiretinal membrane
    term:
      id: HP:0100014
      label: Epiretinal membrane
  evidence:
  - reference: PMID:40311677
    reference_title: "Assessment of Proliferative Vitreoretinopathy in Rhegmatogenous Retinal Detachment with OCT: Revisiting the 1991 Retina Society Classification."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      they had a thick hyperreflective membrane emanating from the retinal
      pigment epithelium and extending along the outer retinal surface
    explanation: >-
      Confirms fibrocellular membrane formation on the retinal surface as
      the OCT correlate of Grade C PVR.
- category: Ophthalmologic
  name: Tractional retinal detachment
  description: >-
    Membrane contraction produces traction on the retina, leading to
    tractional (re)detachment, the end-stage outcome of PVR and the primary
    cause of failed retinal reattachment surgery.
  phenotype_term:
    preferred_term: Tractional retinal detachment
    term:
      id: HP:0007917
      label: Tractional retinal detachment
  evidence:
  - reference: PMID:2708527
    reference_title: Correlation of fibrosis and transforming growth factor-beta type 2 levels in the eye.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Approximately 1 out of every 10 eyes undergoing surgery for retinal
      detachment develops excessive intraocular fibrosis that can lead to
      traction retinal detachment and ultimate blindness.
    explanation: >-
      Establishes tractional retinal detachment as the clinically
      significant end-stage outcome of PVR-associated fibrosis.

prevalence:
- population: Eyes undergoing surgery for retinal detachment
  measure_type: POINT_PREVALENCE
  prevalence_class: ABOVE_1_IN_1000
  rate_per_100000: 10000.0
  notes: >-
    Classic estimate of PVR as a complication of retinal detachment surgery;
    more recent reviews report a similar 5-10% range depending on risk
    factors such as trauma or prior vitrectomy.
  evidence:
  - reference: PMID:2708527
    reference_title: Correlation of fibrosis and transforming growth factor-beta type 2 levels in the eye.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Approximately 1 out of every 10 eyes undergoing surgery for retinal
      detachment develops excessive intraocular fibrosis that can lead to
      traction retinal detachment and ultimate blindness.
    explanation: Direct quantitative estimate of PVR incidence following retinal detachment surgery.

diagnosis:
- name: Dilated fundus examination with Retina Society grading
  description: >-
    Indirect ophthalmoscopy with staging by the 1991 Retina Society
    classification (Grades A, B, C anterior/posterior by clock hour) is the
    standard clinical diagnostic method.
  diagnosis_term:
    preferred_term: clinical assessment
    term:
      id: NCIT:C124351
      label: Clinical Evaluation
  results: "PVR grade A (vitreous haze), B (retinal folds/wrinkling), or C (anterior/posterior membranes, staged by clock hours)."
  evidence:
  - reference: PMID:1867299
    reference_title: An updated classification of retinal detachment with proliferative vitreoretinopathy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Posterior and anterior location of the proliferations have been
      emphasized.
    explanation: Describes the clinical staging system used for diagnosis and grading.
- name: Swept-source OCT microstructural assessment
  description: >-
    Swept-source OCT can characterize retinal microstructural correlates of
    PVR (outer retinal corrugations, hyperreflective membranes, bacillary
    layer changes) and distinguish subretinal-membrane from
    intraretinal-fold subtypes of Grade C disease.
  diagnosis_term:
    preferred_term: optical coherence tomography
    term:
      id: NCIT:C20828
      label: Optical Coherence Tomography
  results: "Outer retinal corrugations, hyperreflective preretinal/subretinal membranes, tractional folds of the outer retina."
  evidence:
  - reference: PMID:40311677
    reference_title: "Assessment of Proliferative Vitreoretinopathy in Rhegmatogenous Retinal Detachment with OCT: Revisiting the 1991 Retina Society Classification."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Ultra-widefield fundus imaging was staged per the Retina Society 1991
      PVR Classification and correlated with retinal microstructural
      changes assessed with SS-OCT.
    explanation: Demonstrates OCT as a complementary quantitative diagnostic tool alongside clinical staging.

treatments:
- name: Pars Plana Vitrectomy with Membrane Peeling and Tamponade
  description: >-
    Surgical removal of the vitreous and dissection/peeling of contractile
    fibrocellular membranes, followed by tamponade with silicone oil or
    long-acting gas, is the only proven management for established PVR;
    there is no proven pharmacologic treatment.
  treatment_term:
    preferred_term: Vitrectomy
    term:
      id: NCIT:C50837
      label: Vitrectomy
  evidence:
  - reference: PMID:30585928
    reference_title: "Proliferative Vitreoretinopathy: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      At this time, surgery is the only management option for PVR as there
      is no proven pharmacologic agent for the treatment or prevention of
      PVR.
    explanation: Establishes vitrectomy-based surgery as the sole proven treatment for established PVR.
- name: Adjuvant Intravitreal 5-Fluorouracil and Low-Molecular-Weight Heparin
  description: >-
    Combined perioperative 5-fluorouracil (5-FU) and low-molecular-weight
    heparin (LMWH) has been trialed as an antiproliferative adjuvant to
    vitrectomy surgery. Evidence is mixed: an early single-center trial
    found a reduced incidence of postoperative PVR when used prophylactically
    in high-risk eyes, but a trial in established Grade C PVR and a larger,
    more recent multicenter prevention trial found no significant benefit.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: 5-fluorouracil
      term:
        id: CHEBI:46345
        label: 5-fluorouracil
    - preferred_term: heparin
      term:
        id: CHEBI:28304
        label: heparin
  evidence:
  - reference: PMID:11425671
    reference_title: "Adjuvant 5-fluorouracil and heparin prevents proliferative vitreoretinopathy : Results from a randomized, double-blind, controlled clinical trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The incidence of postoperative PVR was significantly lower (P = 0.02)
      in the 5-FU and LMWH therapy compared with the placebo group.
    explanation: >-
      Early single-center trial supporting prophylactic 5-FU/LMWH in
      high-risk eyes undergoing primary vitrectomy.
  - reference: PMID:15582080
    reference_title: A randomized controlled trial of combined 5-fluorouracil and low-molecular-weight heparin in management of established proliferative vitreoretinopathy.
    supports: REFUTE
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      There was no significant difference in success in the primary outcome
      measure (56%, treatment group; 51%, placebo group; P = 0.59)
    explanation: >-
      Multicenter trial in established Grade C PVR found no significant
      benefit of adjuvant 5-FU/LMWH on surgical success.
  - reference: PMID:35680097
    reference_title: "Intravitreal 5-Fluorouracil and Heparin to Prevent Proliferative Vitreoretinopathy: Results from a Randomized Clinical Trial."
    supports: REFUTE
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Rate of PVR did not differ between adjuvant therapy with 5-FU and LMWH
      and placebo treatment in eyes with RRD.
    explanation: >-
      Larger, more recent multicenter (PRIVENT) trial found no preventive
      benefit of adjuvant 5-FU/LMWH, contradicting the earlier single-center
      prevention trial.
datasets:
- accession: geo:GSE179603
  title: Transcriptional Characterisation of Proliferative Vitreoretinopathy
  description: 'Purpose: The development of vitreoretinal scars remains an unsolved challenge in clinical practice and often leads to repeated revision surgery and blindness due to lack of efficient therapy. The aim of this study was to characterize the cellular and molecular environment in vitreoretinal scar tissue from patients with proliferative vitreoretinopathy (PVR) in comparison to membranes of the vitreoretinal junction, in order to subsequently identify potential drug treatment options using bioinformatics techniques.'
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_count: 27
  publication: PMID:35579905
  notes: Identified by GEO DataSets index search for Proliferative Vitreoretinopathy (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.
- accession: geo:GSE164208
  title: Expression profile of peripheral immune cells-derived coding and long non-coding RNAs in patients with proliferative vitreoretinopathy
  description: 'Peripheral immune response has been revealed to play a critical role in proliferative vitreoretinopathy (PVR). However, the reliable immune-related factors that are acting as prognostic indicators or therapeutic targets for PVR remain to explore further. Methods: In the current study, we applied whole-transcriptome sequencing to profile peripheral blood mononuclear cells (PBMCs) from PVR patients and also analyzed lncRNA-mRNA interactions in peripheral immune cells to explore the pathways that might mediate immunopathology and resultant retinal damage in PVR.'
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_count: 24
  publication: PMID:33509158
  notes: Identified by GEO DataSets index search for Proliferative Vitreoretinopathy (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.
- accession: geo:GSE282859
  title: 'Absent in melanoma 2: a potent suppressor of retinal pigment epithelial-mesenchymal transition and experimental proliferative vitreoretinopathy'
  description: Epithelial-to-mesenchymal transition (EMT) is a critical and complex process involved in normal embryonic development, tissue regeneration, and tumor progression. It also contributes to retinal diseases, such as age-related macular degeneration (AMD) and proliferative vitreoretinopathy (PVR). Although absent in melanoma 2 (AIM2) has been linked to inflammatory disorders, autoimmune diseases, and cancers, its role in the EMT of the retinal pigment epithelium (RPE-EMT) and retinal diseases remains unclear. The present study demonstrated that AIM2 functions as a potent suppressor of RPE cell proliferation and EMT to maintain retinal homeostasis.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_count: 6
  publication: PMID:39870644
  notes: Identified by GEO DataSets index search for Proliferative Vitreoretinopathy (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.