Uveitis

Complex MONDO:0020283 Pathograph 18 Show in embeddings browser Eye disorder Inflammatory Disease

Uveitis is intraocular inflammation of the uveal tract (iris, ciliary body, and choroid), classified anatomically by the Standardization of Uveitis Nomenclature (SUN) Working Group into anterior, intermediate, posterior, and panuveitis. It is a leading cause of preventable vision loss and is mechanistically heterogeneous: distinct disorders converge on this final common anatomic phenotype through either a non-infectious autoimmune route (breakdown of ocular immune privilege with autoreactive Th1/Th17 T cell activation, as in HLA-B27-associated disease, juvenile idiopathic arthritis, Behcet's disease, Vogt-Koyanagi-Harada disease, and sarcoidosis) or a distinct infectious route (direct pathogen invasion or antigen-driven inflammatory response, as in toxoplasmosis, cytomegalovirus, herpetic, and tuberculous uveitis). This root entry models the two arms as separate causal chains rather than blending them into a single mechanism, and links to disorder-specific entries that are already fully curated elsewhere in this knowledge base.

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5
Pathophys.
11
Phenotypes
18
Pathograph
2
Genes
6
Medical Actions
15
Subtypes
3
Trials
1
Deep Research
◆

Subtypes

15
anatomic (SUN)
Anterior Uveitis MONDO:0006651
Inflammation of the iris and ciliary body (iritis/iridocyclitis), the most common anatomic class of uveitis. Etiologies span idiopathic, HLA-B27/spondyloarthritis-associated, juvenile idiopathic arthritis-associated, and infectious (chiefly herpetic) disease.
  • HLA-B27-Associated Anterior Uveitis
  • JIA-Associated Uveitis
  • Herpetic Anterior Uveitis
Show evidence (1 reference)
PMID:40434762 SUPPORT Human Clinical
"Anterior uveitis affects the iris and ciliary body (41%-60% of cases)"
This review reports anterior uveitis as the most frequent anatomic class and defines its anatomic scope.
Intermediate Uveitis MONDO:0006806
Inflammation centered on the pars plana and peripheral retina/vitreous, often idiopathic (pars planitis) but also associated with multiple sclerosis and sarcoidosis.
  • Pars Planitis
Show evidence (1 reference)
PMID:40434762 SUPPORT Human Clinical
"intermediate uveitis affects the pars plana (attachment point of vitreous humor) and peripheral retina (9%-15%)"
Defines the anatomic scope and reported frequency of intermediate uveitis.
Posterior Uveitis MONDO:0006918
Inflammation involving the choroid and/or retina, frequently infectious (toxoplasmosis, cytomegalovirus, tuberculosis) but also caused by non-infectious entities such as sarcoidosis and Behcet's disease.
  • Choroiditis
  • Ocular Toxoplasmosis
  • Cytomegalovirus Retinitis
  • Tuberculous Uveitis
Show evidence (1 reference)
PMID:40434762 SUPPORT Human Clinical
"posterior uveitis involves the choroid and/or retina (17%-23%)"
Defines the anatomic scope and reported frequency of posterior uveitis.
Choroiditis MONDO:0001280
Focal, multifocal, or diffuse inflammation of the choroid, a form of posterior uveitis that may be infectious or non-infectious in origin. Fully curated in `Choroiditis.yaml`.
Panuveitis MONDO:0017255
Inflammation involving all uveal layers, considered a high-risk form of uveitis because of frequent sight-threatening complications. Commonly caused by systemic autoimmune/autoinflammatory disease (Behcet's disease, Vogt-Koyanagi-Harada disease, sarcoidosis) or infection (ocular toxoplasmosis, tuberculosis). Fully curated in `Panuveitis.yaml`, which carries the detailed pan-uveal inflammation pathophysiology.
  • Behcet Uveitis
  • Vogt-Koyanagi-Harada Uveitis
  • Sarcoid Uveitis
Show evidence (1 reference)
PMID:40434762 SUPPORT Human Clinical
"panuveitis involves all uveal layers (7%-32%)"
Defines the anatomic scope and reported frequency of panuveitis.
etiologic (genetic/autoimmune)
HLA-B27-Associated Acute Anterior Uveitis
HLA-B27 hgnc:4932 HUGO Gene Nomenclature Committee (hgnc) Relation: this subtype is caused by variation in this gene This subtype is caused by variation in HLA-B27, annotated with HLA-B (hgnc:4932). hgnc:4932 is a gene from the HUGO Gene Nomenclature Committee.
Recurrent, typically unilateral-alternating acute anterior uveitis associated with HLA-B27 and the spondyloarthropathies (notably ankylosing spondylitis). The single most frequently identified cause of acute anterior uveitis. Fully curated as the ocular manifestation of `Ankylosing_Spondylitis.yaml`; this stub links that systemic-disease pathophysiology into the uveitis anatomic classification.
Show evidence (2 references)
PMID:19027424 SUPPORT Human Clinical
"human leukocyte antigen-B27-related diseases being the most common identified cause"
A population-based cohort identifies HLA-B27-related disease as the leading identified cause of anterior uveitis.
PMID:27245590 SUPPORT Human Clinical
"Patients with ankylosing spondylitis (AS) and AAU share other genetic markers, such as ERAP-1, which show strong evidence of gene-gene interaction and point to new mechanisms of disease pathogenesis."
Directly supports the shared HLA-B27/ERAP1 genetic basis linking ankylosing spondylitis and acute anterior uveitis.
etiologic (autoimmune, pediatric)
Juvenile Idiopathic Arthritis-Associated Uveitis
Chronic, often clinically asymptomatic anterior uveitis occurring most commonly in ANA-positive, young-onset oligoarticular juvenile idiopathic arthritis, requiring regular screening because it can progress silently to sight-threatening complications. Fully curated as part of `Juvenile_Idiopathic_Arthritis.yaml`.
Show evidence (2 references)
PMID:42184063 SUPPORT Human Clinical
"Particularly, early onset of the disease, female gender, positive ANA status, and articular relapses should be considered warning signs for uveitis."
A JIA cohort study identifies the classic risk-factor profile (young onset, female sex, ANA positivity) for JIA-associated uveitis.
PMID:42184063 SUPPORT Human Clinical
"Juvenile Idiopathic Arthritis uveitis (JIA-U) can progress without obvious clinical signs and cause permanent damage if left untreated, therefore early detection through regular screening is crucial"
Supports the characteristic silent/asymptomatic course of JIA-associated uveitis that drives systematic screening recommendations.
etiologic (infectious, viral)
Herpesvirus-Associated Anterior Uveitis
Acute or recurrent anterior uveitis caused by reactivation of herpes simplex virus, varicella zoster virus, or (less commonly) cytomegalovirus within the anterior chamber, often with elevated intraocular pressure, sectoral iris atrophy, and keratic precipitates. No dedicated dismech entry currently exists for herpes simplex/varicella zoster virus infection, so the viral mechanism is curated directly here rather than linked to a sibling file.
Show evidence (2 references)
PMID:37862684 SUPPORT Human Clinical
"The viral pathogens most commonly associated with infectious anterior uveitis include Herpes Simplex Virus, Varicella-Zoster Virus, Cytomegalovirus, and Rubella Virus."
Identifies herpesviruses as the leading viral causes of infectious anterior uveitis.
PMID:29543540 SUPPORT Human Clinical
"the herpes viruses cause an acute lytic infection and inflammation"
Describes the acute lytic infection mechanism that distinguishes herpetic anterior uveitis from other viral causes.
Cytomegalovirus Retinitis MONDO:0000878
Necrotizing retinitis caused by cytomegalovirus reactivation, occurring almost exclusively in severely immunocompromised patients. Fully curated in `Cytomegalovirus_Retinitis.yaml`.
etiologic (idiopathic)
Pars Planitis MONDO:0011644
The idiopathic subset of intermediate uveitis, characterized by vitreous snowballs and peripheral retinal snowbanking without an identifiable infectious or systemic cause. Fully curated in `Pars_Planitis.yaml`.
etiologic (infectious, parasitic)
Ocular Toxoplasmosis MONDO:0005879
Necrotizing retinochoroiditis due to reactivation of latent Toxoplasma gondii cysts in the retina, the most common identifiable cause of infectious posterior uveitis worldwide. Systemic and congenital toxoplasma infection is fully curated in `Toxoplasmosis.yaml`; this stub links the ocular manifestation into the posterior uveitis anatomic class.
Show evidence (1 reference)
PMID:40456390 SUPPORT Human Clinical
"in posterior uveitis various microorganisms are involved, among them Toxoplasma gondii, Cytomegalovirus, Plasmodium spp. and Candida spp."
Identifies Toxoplasma gondii as a leading infectious cause of posterior uveitis.
etiologic (infectious, mycobacterial)
Tuberculous Uveitis
Granulomatous uveitis caused by Mycobacterium tuberculosis, presenting as choroidal tubercles, tuberculoma, serpiginous-like choroiditis, or panuveitis, particularly in endemic regions and immunocompromised patients. Systemic tuberculosis is fully curated in `Tuberculosis.yaml`.
Show evidence (1 reference)
PMID:40434762 SUPPORT Human Clinical
"toxoplasmosis, herpes, tuberculosis, and HIV comprising 11% to 21% of infectious cases in high-income countries and 50% in low- and middle-income countries"
Quantifies tuberculosis as a major contributor to infectious uveitis, especially in low- and middle-income countries.
etiologic (autoimmune, vasculitic)
Behcet's Disease-Associated Panuveitis
Bilateral, chronic, recurrent, non-granulomatous panuveitis with retinal vasculitis, a hallmark manifestation of Behcet's disease. Fully curated as part of `Behcets_Disease.yaml`.
Show evidence (1 reference)
PMID:38778397 SUPPORT Human Clinical
"Behcet's uveitis (BU) is a common manifestation of BD, occurring in over two-thirds of the patients."
Establishes uveitis, typically panuveitis, as a common and defining manifestation of Behcet's disease.
etiologic (autoimmune, melanocyte-directed)
Vogt-Koyanagi-Harada Disease-Associated Panuveitis
Bilateral granulomatous panuveitis with exudative retinal detachment driven by T cell-mediated autoimmunity against melanocyte antigens, progressing without treatment to a chronic recurrent anterior uveitis with "sunset glow fundus." Fully curated in `Vogt-Koyanagi-Harada_Disease.yaml`.
Show evidence (1 reference)
PMID:34869409 SUPPORT Human Clinical
"Patients with initial-onset acute uveitis present with granulomatous choroiditis with secondary exudative retinal detachment resulting from impairment of the retinal pigment epithelium caused by choroidal inflammation"
Describes the granulomatous panuveitis with exudative retinal detachment characteristic of acute VKH disease.
etiologic (autoimmune, granulomatous)
Sarcoidosis-Associated Uveitis
Granulomatous ocular inflammation in sarcoidosis that can affect any uveal segment but most often presents as panuveitis. Fully curated as part of `Sarcoidosis.yaml` and `Neurosarcoidosis.yaml`.
Show evidence (1 reference)
PMID:33173272 SUPPORT Human Clinical
"Twelve had uveitis of which panuveitis was the most common subtype."
A sarcoidosis cohort study reports panuveitis as the most common uveitis subtype among ocular sarcoidosis cases.
⚙

Pathophysiology

5
Breakdown of Ocular Immune Privilege
The eye is normally shielded from systemic immunity by physical barriers (blood-aqueous and blood-retinal), a locally immunosuppressive microenvironment, and tolerance circuits such as anterior chamber-associated immune deviation. Non-infectious (autoimmune) uveitis arises when these layered controls fail, permitting autoreactive lymphocyte access to intraocular antigens. This node begins the autoimmune arm of uveitis pathogenesis, modeled separately from the infectious arm below.
establishment of blood-retinal barrier GO:1990963 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased establishment of blood-retinal barrier (GO:1990963). GO:1990963 is a biological process from the Gene Ontology. ↓ DECREASED
Downstream
Autoreactive Th1/Th17 T Cell Priming and Uveal Infiltration Loss of ocular immune privilege permits systemic activation and intraocular entry of autoreactive T cells.
Show evidence (1 reference)
PMID:41877771 SUPPORT Human Clinical
"Layered mechanisms normally restrain inflammation: physical barriers (blood-aqueous and blood-retina), a locally immunosuppressive milieu, and systemic tolerance circuits such as anterior chamber-associated immune deviation."
Describes the layered immune-privilege mechanisms whose failure is the entry point for autoimmune uveitis.
Autoreactive Th1/Th17 T Cell Priming and Uveal Infiltration
Genetic susceptibility (HLA class I/II alleles and peptide-trimming enzymes such as ERAP1) shapes antigen presentation and lowers the activation threshold for autoreactive T cells directed against ocular or cross-reactive antigens. These T cells are primed toward Th1/Th17 phenotypes in draining lymphoid tissue, then infiltrate the eye where they are restimulated by resident microglia and recruited macrophages. This is the mechanism underlying HLA-B27-associated and juvenile idiopathic arthritis-associated anterior uveitis and contributes to Behcet's disease- and Vogt-Koyanagi-Harada disease-associated panuveitis. Experimental autoimmune uveitis (EAU) models in rodents are the primary source of mechanistic detail for this pathway.
CD4-positive, alpha-beta T cell CL:0000624 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves CD4-positive, alpha-beta T cell (CL:0000624). CL:0000624 is a cell type from the Cell Ontology. T-helper 17 cell CL:0000899 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves T-helper 17 cell (CL:0000899). CL:0000899 is a cell type from the Cell Ontology. microglial cell CL:0000129 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves microglial cell (CL:0000129). CL:0000129 is a cell type from the Cell Ontology.
T-helper 1 type immune response GO:0042088 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased T-helper 1 type immune response (GO:0042088). GO:0042088 is a biological process from the Gene Ontology. ↑ INCREASED T-helper 17 type immune response GO:0072538 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased T-helper 17 type immune response (GO:0072538). GO:0072538 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Cytokine-Driven Leukocyte Recruitment and Barrier Disruption Restimulated effector T cells and resident myeloid cells drive cytokine cascades that recruit further leukocytes and damage ocular barriers.
Show evidence (2 references)
PMID:18317764 SUPPORT Model Organism
"Th17 cells elicit EAU, can be found in uveitic eyes along with Th1 cells, and are dominant in some types of EAU. In other types of EAU, Th1 cells have a dominant role."
Rodent experimental autoimmune uveitis studies establish the dual Th1/Th17 effector basis of autoimmune uveitis.
PMID:27245590 SUPPORT Human Clinical
"Studies of patients with AAU and animal models of disease indicate a role for innate immunity, the IL-23 cytokine pathway and exogenous factors, in the pathogenesis of both SpA and acute anterior uveitis."
Supports genetic-pathway (IL-23/Th17 axis) involvement in human HLA-B27-associated anterior uveitis.
Cytokine-Driven Leukocyte Recruitment and Barrier Disruption
Effector T cell and myeloid cytokine production amplifies leukocyte recruitment into the aqueous, vitreous, retina, and choroid while further disrupting the blood-retinal barrier, producing the clinical signs and sight-threatening complications common to non-infectious uveitis of any anatomic class.
leukocyte migration GO:0050900 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased leukocyte migration (GO:0050900). GO:0050900 is a biological process from the Gene Ontology. ↑ INCREASED inflammatory response GO:0006954 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Ocular pain Intraocular inflammation and elevated intraocular pressure produce pain.
Photophobia Anterior chamber and ciliary inflammation causes light sensitivity.
Blurred vision Vitreous haze and macular edema reduce visual clarity.
Macular edema Leukocyte infiltration and cytokine-driven vascular permeability promote macular edema.
Show evidence (1 reference)
PMID:41877771 SUPPORT Human Clinical
"effector T-cells are restimulated by resident microglia and recruited macrophages, driving cytokine cascades that disrupt the blood-retina barrier and amplify leukocyte recruitment"
Directly supports the cytokine-driven leukocyte recruitment and barrier disruption mechanism of autoimmune uveitis.
Ocular Pathogen Invasion or Reactivation
Infectious uveitis is triggered by direct invasion or reactivation of an infectious agent within the eye, mechanistically distinct from the autoimmune arm above. The responsible organism differs by anatomic class: herpesviruses (herpes simplex virus, varicella zoster virus) predominate in infectious anterior uveitis; Toxoplasma gondii, cytomegalovirus, and Mycobacterium tuberculosis predominate in infectious posterior uveitis and panuveitis. This node begins the infectious arm of uveitis pathogenesis and is modeled as a separate causal chain rather than merged with the autoimmune arm.
Downstream
Pathogen Antigen-Driven Uveal Inflammatory Damage Ongoing pathogen replication or antigen persistence drives a destructive local inflammatory response.
Show evidence (2 references)
PMID:40456390 SUPPORT Human Clinical
"Infectious uveitis is an inflammation of the uveal tract, corresponding to the middle layer of the eye, triggered by a response against an infectious agent."
Establishes the direct infectious-trigger mechanism that distinguishes this arm from autoimmune uveitis.
PMID:41877771 SUPPORT Human Clinical
"Infectious uveitis reflects direct intraocular infection or reactivation."
Confirms direct infection or pathogen reactivation, rather than autoimmunity, as the trigger for this arm.
Pathogen Antigen-Driven Uveal Inflammatory Damage
Persistent pathogen replication or retained antigen drives ocular infiltration by T cells and B/plasma cells and local production of proinflammatory cytokines and chemokines, causing necrotizing or granulomatous tissue damage and the same downstream clinical complications seen in the autoimmune arm, despite the distinct upstream trigger.
lymphocyte CL:0000542 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves lymphocyte (CL:0000542). CL:0000542 is a cell type from the Cell Ontology. macrophage CL:0000235 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves macrophage (CL:0000235). CL:0000235 is a cell type from the Cell Ontology.
inflammatory response GO:0006954 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology. ↑ INCREASED defense response GO:0006952 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased defense response (GO:0006952). GO:0006952 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Ocular pain Active infectious inflammation produces pain and redness.
Floaters Vitreous inflammatory infiltrate produces floaters.
Blurred vision Retinochoroiditis and vitreous haze reduce visual clarity.
Retinal detachment Necrotizing retinochoroiditis can lead to retinal detachment.
Show evidence (1 reference)
PMID:29543540 SUPPORT Human Clinical
"These viral infections are commonly associated with ocular infiltration of T cells and B/plasma cells, and expression of cytokines and chemokines typical of a proinflammatory immune response."
Directly supports pathogen-driven lymphocyte infiltration and proinflammatory cytokine expression as the tissue-damage mechanism of infectious uveitis.
⬡

Pathograph

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

11
Cardiovascular 1
Eye redness Conjunctival hyperemia HP:0030953 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Conjunctival hyperemia (HP:0030953). HP:0030953 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:40434762 SUPPORT Human Clinical
"eye redness, pain, photophobia, floaters, and blurred vision"
This review lists eye redness among common presenting symptoms of uveitis.
Eye 9
Uveitis HP:0000554 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Uveitis (HP:0000554). HP:0000554 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:36164924 SUPPORT Human Clinical
"The uveitides are a collection of over 30 diseases characterised by intraocular inflammation."
SUN establishes uveitis as intraocular inflammation spanning a large, anatomically classified group of diseases.
Photophobia HP:0000613 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Photophobia (HP:0000613). HP:0000613 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:40434762 SUPPORT Human Clinical
"eye redness, pain, photophobia, floaters, and blurred vision"
This review lists photophobia among common presenting symptoms of uveitis.
Floaters Vitreous floaters HP:0100832 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Floaters, annotated with Vitreous floaters (HP:0100832). HP:0100832 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:40434762 SUPPORT Human Clinical
"eye redness, pain, photophobia, floaters, and blurred vision"
This review lists floaters among common presenting symptoms of uveitis.
Blurred vision HP:0000622 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Blurred vision (HP:0000622). HP:0000622 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:40434762 SUPPORT Human Clinical
"eye redness, pain, photophobia, floaters, and blurred vision"
This review lists blurred vision among common presenting symptoms of uveitis.
Macular edema HP:0040049 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Macular edema (HP:0040049). HP:0040049 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:40434762 SUPPORT Human Clinical
"cataracts, glaucoma, macular edema, retinal detachment, optic nerve damage, and vision loss"
This review lists macular edema among major complications of untreated uveitis.
Retinal detachment HP:0000541 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Retinal detachment (HP:0000541). HP:0000541 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:40434762 SUPPORT Human Clinical
"cataracts, glaucoma, macular edema, retinal detachment, optic nerve damage, and vision loss"
This review lists retinal detachment among major complications of untreated uveitis.
Cataract HP:0000518 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Cataract (HP:0000518). HP:0000518 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:40434762 SUPPORT Human Clinical
"cataracts, glaucoma, macular edema, retinal detachment, optic nerve damage, and vision loss"
This review lists cataracts among major complications of untreated uveitis.
Glaucoma HP:0000501 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Glaucoma (HP:0000501). HP:0000501 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:40434762 SUPPORT Human Clinical
"cataracts, glaucoma, macular edema, retinal detachment, optic nerve damage, and vision loss"
This review lists glaucoma among major complications of untreated uveitis.
Visual impairment HP:0000505 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Visual impairment (HP:0000505). HP:0000505 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:40434762 SUPPORT Human Clinical
"cataracts, glaucoma, macular edema, retinal detachment, optic nerve damage, and vision loss"
This review lists vision loss among major complications of untreated uveitis.
Constitutional 1
Ocular pain HP:0200026 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Ocular pain (HP:0200026). HP:0200026 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:40434762 SUPPORT Human Clinical
"eye redness, pain, photophobia, floaters, and blurred vision"
This review lists pain among common presenting symptoms of uveitis.
🧬

Genetic Associations

2
HLA-B27 (Strong Risk Factor)
Gene: HLA-B hgnc:4932 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is HLA-B (hgnc:4932). hgnc:4932 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: RISK_FACTOR
Show evidence (2 references)
PMID:19027424 SUPPORT Human Clinical
"human leukocyte antigen-B27-related diseases being the most common identified cause"
A population-based cohort identifies HLA-B27-related disease as the leading identified cause of anterior uveitis.
PMID:40434762 SUPPORT Human Clinical
"Incidence and prevalence of uveitis are influenced by genetic factors (eg, human leukocyte antigen–B27)"
Identifies HLA-B27 as a genetic factor influencing uveitis incidence and prevalence broadly.
ERAP1 (Risk Factor)
Gene: ERAP1 hgnc:18173 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is ERAP1 (hgnc:18173). hgnc:18173 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: SUSCEPTIBILITY
Show evidence (1 reference)
PMID:27245590 SUPPORT Human Clinical
"Patients with ankylosing spondylitis (AS) and AAU share other genetic markers, such as ERAP-1, which show strong evidence of gene-gene interaction and point to new mechanisms of disease pathogenesis."
Directly supports ERAP1 as a shared genetic modifier contributing to HLA-B27-associated acute anterior uveitis via gene-gene interaction.
💊

Medical Actions

6
Etiology-Directed Antimicrobial Therapy
Action: antimicrobial pharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is antimicrobial pharmacotherapy, annotated with Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. Ontology label: Pharmacotherapy NCIT:C15986
Infectious uveitis requires treatment directed at the causative organism (antiviral, antiparasitic, or antimycobacterial therapy), typically combined with anti-inflammatory therapy once pathogen load is controlled.
Mechanism Target:
INHIBITS Ocular Pathogen Invasion or Reactivation — Antimicrobial therapy directly targets the causative infectious agent underlying this arm of uveitis.
Show evidence (1 reference)
PMID:40434762 SUPPORT Human Clinical
"Infectious uveitis requires systemic antimicrobial treatment."
Directly supports organism-directed antimicrobial therapy as the mainstay treatment of infectious uveitis.
Topical Corticosteroid Therapy
Action: topical corticosteroid therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is topical corticosteroid therapy (NCIT:C122078). NCIT:C122078 is a clinical intervention from the NCI Thesaurus. Ontology label: Topical Corticosteroid Therapy NCIT:C122078
Topical corticosteroid eye drops are first-line therapy for non-infectious anterior uveitis, delivering high local drug concentration to the anterior segment while limiting systemic exposure.
Mechanism Target:
INHIBITS Cytokine-Driven Leukocyte Recruitment and Barrier Disruption — Topical corticosteroids suppress the cytokine-driven leukocyte recruitment and inflammation that damages ocular tissue in non-infectious anterior uveitis.
Show evidence (1 reference)
PMID:40434762 SUPPORT Human Clinical
"corticosteroid eyedrops are first-line treatment"
States that topical corticosteroid eye drops are first-line therapy for noninfectious anterior uveitis.
Systemic Corticosteroid Therapy
Action: systemic corticosteroid therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is systemic corticosteroid therapy (NCIT:C122080). NCIT:C122080 is a clinical intervention from the NCI Thesaurus. Ontology label: Systemic Corticosteroid Therapy NCIT:C122080
Systemic corticosteroids rapidly suppress non-infectious intraocular inflammation in patients with moderate-to-severe intermediate, posterior, or panuveitis who are at high risk of sight-threatening complications.
Mechanism Target:
INHIBITS Cytokine-Driven Leukocyte Recruitment and Barrier Disruption — Systemic corticosteroids suppress the cytokine-driven leukocyte recruitment and inflammation that damages ocular tissue in non-infectious uveitis.
Show evidence (1 reference)
PMID:40434762 SUPPORT Human Clinical
"require systemic and/or intravitreal corticosteroids and immunosuppressive agents"
Directly supports systemic corticosteroids for moderate-to-severe non-infectious uveitis.
Local (Intravitreal) Corticosteroid Therapy
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: corticosteroid CHEBI:50858 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses corticosteroid (CHEBI:50858). CHEBI:50858 is a therapeutic agent from Chemical Entities of Biological Interest.
Locally delivered intravitreal corticosteroids are used, as an alternative or adjunct to systemic therapy, for moderate-to-severe non-infectious intermediate, posterior, or panuveitis, achieving high intraocular drug concentration while limiting systemic corticosteroid exposure. No NCIT clinical-action term specifically names the intravitreal route (the closest candidate, Localized Corticosteroid Therapy NCIT:C121367, is explicitly defined as intraarticular, topical, or inhaled only), so this treatment uses the generic Pharmacotherapy action term with a corticosteroid therapeutic agent instead of overclaiming a route-specific NCIT term.
Mechanism Target:
INHIBITS Cytokine-Driven Leukocyte Recruitment and Barrier Disruption — Locally delivered intravitreal corticosteroids suppress the cytokine-driven leukocyte recruitment and inflammation that damages ocular tissue in non-infectious uveitis, without the systemic exposure of oral or intravenous therapy.
Show evidence (1 reference)
PMID:40434762 SUPPORT Human Clinical
"require systemic and/or intravitreal corticosteroids and immunosuppressive agents"
Directly supports intravitreal corticosteroids as a local-delivery option for moderate-to-severe non-infectious uveitis.
Steroid-Sparing Immunosuppressive Therapy
Action: immune suppressant agent therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is immune suppressant agent therapy, annotated with Immunosuppressive Therapy (NCIT:C15261). NCIT:C15261 is a clinical intervention from the NCI Thesaurus. Ontology label: Immunosuppressive Therapy NCIT:C15261
Chronic, recurrent, bilateral, or vision-threatening non-infectious uveitis commonly requires steroid-sparing immunosuppression such as methotrexate or mycophenolate mofetil.
Mechanism Target:
INHIBITS Cytokine-Driven Leukocyte Recruitment and Barrier Disruption — Immunosuppressive therapy reduces recurrent autoimmune ocular inflammation while limiting corticosteroid exposure.
Show evidence (1 reference)
PMID:40434762 SUPPORT Human Clinical
"For posterior uveitis, first-line therapy with disease-modifying antirheumatic drugs such as methotrexate achieved remission of inflammation in 52.1% (95% CI, 38.6%-67.1%) of patients, and mycophenolate mofetil controlled inflammation in 70.9% (95% CI, 57.1%-83.5%)"
Provides quantitative human clinical outcome data for steroid-sparing immunosuppressive therapy in non-infectious uveitis.
Adalimumab
Action: anti-TNF biologic therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is anti-TNF biologic therapy, annotated with Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. Ontology label: Pharmacotherapy NCIT:C15986
Agent: Adalimumab NCIT:C65216 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses Adalimumab (NCIT:C65216). NCIT:C65216 is a therapeutic agent from the NCI Thesaurus.
Platform: Monoclonal antibody
Adalimumab is a steroid-sparing anti-TNF biologic for active or inactive non-infectious intermediate, posterior, or panuveitis when inflammation is not adequately controlled with corticosteroid-based therapy.
Mechanism Target:
INHIBITS Cytokine-Driven Leukocyte Recruitment and Barrier Disruption — Anti-TNF therapy inhibits the cytokine cascade that drives leukocyte recruitment and barrier disruption in non-infectious uveitis.
Show evidence (2 references)
PMID:27602665 SUPPORT Human Clinical
"median time to treatment failure was 24 weeks in the adalimumab group and 13 weeks in the placebo group"
The VISUAL I trial supports adalimumab efficacy in active non-infectious intermediate, posterior, or panuveitis.
PMID:39157460 SUPPORT Human Clinical
"TNF-α inhibitors, anti-CD20 therapy and alkylating agents have shown considerable efficacy"
This review confirms TNF-alpha inhibitors as an effective biologic option for non-infectious uveitis refractory to corticosteroids.
🌍

Environmental Factors

1
Immune checkpoint inhibitor therapy
immune checkpoint inhibitor therapy Relation: this environmental factor is this exposure This environmental factor is immune checkpoint inhibitor therapy.
ECTO was searched (via OLS, ontology=ecto) for "immune checkpoint inhibitor" and "checkpoint inhibitor"; no suitable exposure term was found, so `term:` is intentionally left unbound.
Show evidence (1 reference)
PMID:38264654 SUPPORT Human Clinical
"Associated Kaplan-Meier curves showed significantly increased uveitis risk among the ICI group for all follow-up years (p<0.001)."
Establishes immune checkpoint inhibitor therapy as a documented uveitis exposure in its own right, with risk elevated across the whole follow-up period. This attests the exposure entry; the separate evidence on the influences_mechanisms link attests that it acts on ocular immune privilege.
Mechanism Target:
TRIGGERS Breakdown of Ocular Immune Privilege — Immune checkpoint inhibitor therapy releases the checkpoints that normally restrain autoreactive T cells, precipitating loss of ocular immune privilege and drug-induced uveitis.
Show evidence (1 reference)
PMID:38264654 SUPPORT Human Clinical
"The risk of uveitis was also higher among the ICI group during the 144-month follow-up period with a hazard ratio (HR) of 2.39 (95% CI: 2.07-2.75)."
A matched TriNetX cohort study of 71,931 exposed and 71,931 unexposed cancer patients found a significantly elevated hazard ratio for new-onset uveitis among immune checkpoint inhibitor recipients, supporting a direct causal trigger role.
🔬

Diagnosis

2
SUN Anatomic Classification
Diagnosis begins with ophthalmic examination establishing the SUN anatomic class (anterior, intermediate, posterior, panuveitis), followed by directed evaluation to distinguish infectious from non-infectious (autoimmune) etiology.
clinical assessment NCIT:C124351 NCI Thesaurus (NCIT)
Results: Anatomic classification narrows the differential; systemic and infectious workup then determines the causal arm and specific etiology.
Show evidence (1 reference)
PMID:36164924 SUPPORT Human Clinical
"The SUN "Developing Classification Criteria for the Uveitides" project used a rigorous, multi-phase approach to develop classification criteria for 25 of the most common uveitic diseases."
Describes the SUN classification project that underlies anatomic and etiologic diagnosis of uveitis.
Intraocular Fluid Pathogen PCR Testing
Polymerase chain reaction testing of aqueous or vitreous fluid supports identification of the infectious arm when clinical features suggest a herpetic, toxoplasmic, or other infectious etiology.
polymerase chain reaction testing NCIT:C17003 NCI Thesaurus (NCIT)
Results: A positive intraocular PCR result for a specific pathogen supports infectious rather than autoimmune uveitis and directs antimicrobial therapy.
Show evidence (1 reference)
PMID:40456390 SUPPORT Human Clinical
"polymerase chain reaction (PCR) on ocular specimens for Herpes simplex virus has a sensitivity of 91.3% and specificity of 98.8%, while for toxoplasmosis the sensitivity is 43.1% and specificity 98.5%"
Reports the diagnostic performance of intraocular PCR testing used to confirm infectious etiologies of uveitis.
📊

Prevalence

7
Northern California health maintenance organization members, USA
Annual Incidence 52.4 per 100,000 1–9 per 10,000 per year
Northern California Epidemiology of Uveitis Study.
Show evidence (1 reference)
PMID:15019324 SUPPORT Human Clinical
"These data yielded an incidence of 52.4/100 000 person-years and a period prevalence of 115.3/100 000 persons."
Reports incidence in the largest US population-based uveitis study to date.
Northern California health maintenance organization members, USA
Period Prevalence 115.3 per 100,000 >1 in 1,000
Northern California Epidemiology of Uveitis Study.
Show evidence (1 reference)
PMID:15019324 SUPPORT Human Clinical
"These data yielded an incidence of 52.4/100 000 person-years and a period prevalence of 115.3/100 000 persons."
Reports period prevalence in the largest US population-based uveitis study to date.
Kaiser Permanente Hawaii health plan members, USA
Annual Incidence 24.9 per 100,000 1–9 per 10,000 per year
Pacific Ocular Inflammation Study.
Show evidence (1 reference)
PMID:24008391 SUPPORT Human Clinical
"The overall uveitis incidence rate was 24.9 cases per 100,000 person-years."
Reports incidence in a Hawaiian managed-care population.
Kaiser Permanente Hawaii health plan members, USA (2006)
Period Prevalence 57.5 per 100,000 1–9 per 10,000
Pacific Ocular Inflammation Study, annual (calendar-year) prevalence for 2006.
Show evidence (1 reference)
PMID:24008391 SUPPORT Human Clinical
"The annual prevalence rates for 2006 and 2007 were 57.5 and 58.0 per 100,000 persons, respectively."
Reports annual (calendar-year) prevalence for 2006 in a Hawaiian managed-care population.
Kaiser Permanente Hawaii health plan members, USA (2007)
Period Prevalence 58.0 per 100,000 1–9 per 10,000
Pacific Ocular Inflammation Study, annual (calendar-year) prevalence for 2007.
Show evidence (1 reference)
PMID:24008391 SUPPORT Human Clinical
"The annual prevalence rates for 2006 and 2007 were 57.5 and 58.0 per 100,000 persons, respectively."
Reports annual (calendar-year) prevalence for 2007 in a Hawaiian managed-care population.
Veterans Affairs Medical Centers, Oregon and Washington, USA
Annual Incidence 25.6 per 100,000 1–9 per 10,000 per year
VA Pacific Northwest study.
Show evidence (1 reference)
PMID:19027424 SUPPORT Human Clinical
"This study found a crude incidence of 25.6 cases/100,000 person-years and a crude prevalence of 69 cases/100,000 persons."
Reports incidence in a VA Pacific Northwest population.
Veterans Affairs Medical Centers, Oregon and Washington, USA
Period Prevalence 69 per 100,000 1–9 per 10,000
VA Pacific Northwest study.
Show evidence (1 reference)
PMID:19027424 SUPPORT Human Clinical
"This study found a crude incidence of 25.6 cases/100,000 person-years and a crude prevalence of 69 cases/100,000 persons."
Reports crude prevalence in a VA Pacific Northwest population.
🔬

Clinical Trials

3
NCT06431373 PHASE_III ACTIVE_NOT_RECRUITING
Randomized, double-masked, placebo-controlled trial of oral brepocitinib in adults with active, non-infectious intermediate, posterior, or panuveitis.
Show evidence (1 reference)
clinicaltrials:NCT06431373 SUPPORT Human Clinical
"The purpose of this study is to determine the safety and efficacy of brepocitinib in participants with active, non-anterior (intermediate, posterior, or pan) non-infectious uveitis (NIU)."
ClinicalTrials.gov record establishes the trial's objective of testing oral brepocitinib in non-anterior non-infectious uveitis.
NCT05384249 PHASE_II TERMINATED
Trial of izokibep, a selective interleukin-17A inhibitor, in subjects with active non-infectious intermediate-, posterior-, or pan-uveitis requiring high-dose steroids.
Show evidence (1 reference)
clinicaltrials:NCT05384249 SUPPORT Human Clinical
"Izokibep is a small protein molecule that acts as a selective, potent inhibitor of interleukin-17A, to which it binds with high affinity."
ClinicalTrials.gov record establishes izokibep's IL-17A-inhibitor mechanism as tested in non-infectious uveitis.
NCT02595398 PHASE_III COMPLETED
Randomized, masked, controlled trial of suprachoroidally administered triamcinolone acetonide injectable suspension (CLS-TA) for macular edema associated with non-infectious uveitis.
Target Phenotypes: Macular edema HP:0040049 Human Phenotype Ontology (HP) Relation: this clinical trial targets this phenotype This clinical trial targets Macular edema (HP:0040049). HP:0040049 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
clinicaltrials:NCT02595398 SUPPORT Human Clinical
"The study is designed to evaluate the safety and efficacy of suprachoroidally administered triamcinolone acetonide, CLS-TA, in subjects with macular edema associated with non-infectious uveitis."
ClinicalTrials.gov record establishes the trial's evaluation of suprachoroidal CLS-TA for uveitic macular edema.
{ }

Source YAML

click to show 
name: Uveitis
creation_date: "2026-08-26T22:00:00Z"
category: Complex
description: >-
  Uveitis is intraocular inflammation of the uveal tract (iris, ciliary body,
  and choroid), classified anatomically by the Standardization of Uveitis
  Nomenclature (SUN) Working Group into anterior, intermediate, posterior, and
  panuveitis. It is a leading cause of preventable vision loss and is
  mechanistically heterogeneous: distinct disorders converge on this final
  common anatomic phenotype through either a non-infectious autoimmune route
  (breakdown of ocular immune privilege with autoreactive Th1/Th17 T cell
  activation, as in HLA-B27-associated disease, juvenile idiopathic
  arthritis, Behcet's disease, Vogt-Koyanagi-Harada disease, and sarcoidosis)
  or a distinct infectious route (direct pathogen invasion or antigen-driven
  inflammatory response, as in toxoplasmosis, cytomegalovirus, herpetic, and
  tuberculous uveitis). This root entry models the two arms as separate
  causal chains rather than blending them into a single mechanism, and links
  to disorder-specific entries that are already fully curated elsewhere in
  this knowledge base.
disease_term:
  preferred_term: uveitis
  term:
    id: MONDO:0020283
    label: uveitis
parents:
- Eye disorder
- Inflammatory Disease
notes: >-
  Drug-induced uveitis (e.g. immune checkpoint inhibitor-associated uveitis,
  captured here as an environmental trigger) and masquerade syndromes (e.g.
  intraocular lymphoma mimicking uveitis) are recognized etiologic categories
  that are deliberately not modeled as `has_subtypes` entries in this pass;
  this is an intentional scoping decision for this curation round, not a gap
  to silently reopen without discussion.
has_subtypes:
- name: Anterior Uveitis
  subtype_term:
    preferred_term: anterior uveitis
    term:
      id: MONDO:0006651
      label: anterior uveitis
  classification: anatomic (SUN)
  children:
  - HLA-B27-Associated Anterior Uveitis
  - JIA-Associated Uveitis
  - Herpetic Anterior Uveitis
  description: >-
    Inflammation of the iris and ciliary body (iritis/iridocyclitis), the
    most common anatomic class of uveitis. Etiologies span idiopathic,
    HLA-B27/spondyloarthritis-associated, juvenile idiopathic
    arthritis-associated, and infectious (chiefly herpetic) disease.
  evidence:
  - reference: PMID:40434762
    reference_title: "Uveitis in Adults: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Anterior uveitis affects the iris and ciliary body (41%-60% of cases)"
    explanation: This review reports anterior uveitis as the most frequent anatomic class and defines its anatomic scope.
- name: HLA-B27-Associated Anterior Uveitis
  display_name: HLA-B27-Associated Acute Anterior Uveitis
  classification: etiologic (genetic/autoimmune)
  genes:
  - preferred_term: HLA-B27
    term:
      id: hgnc:4932
      label: HLA-B
  description: >-
    Recurrent, typically unilateral-alternating acute anterior uveitis
    associated with HLA-B27 and the spondyloarthropathies (notably ankylosing
    spondylitis). The single most frequently identified cause of acute
    anterior uveitis. Fully curated as the ocular manifestation of
    `Ankylosing_Spondylitis.yaml`; this stub links that systemic-disease
    pathophysiology into the uveitis anatomic classification.
  evidence:
  - reference: PMID:19027424
    reference_title: "Incidence and prevalence of uveitis in Veterans Affairs Medical Centers of the Pacific Northwest."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "human leukocyte antigen-B27-related diseases being the most common identified cause"
    explanation: A population-based cohort identifies HLA-B27-related disease as the leading identified cause of anterior uveitis.
  - reference: PMID:27245590
    reference_title: "HLA-B27 Anterior Uveitis: Immunology and Immunopathology."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Patients with ankylosing spondylitis (AS) and AAU share other genetic markers, such as ERAP-1, which show strong evidence of gene-gene interaction and point to new mechanisms of disease pathogenesis."
    explanation: Directly supports the shared HLA-B27/ERAP1 genetic basis linking ankylosing spondylitis and acute anterior uveitis.
- name: JIA-Associated Uveitis
  display_name: Juvenile Idiopathic Arthritis-Associated Uveitis
  classification: etiologic (autoimmune, pediatric)
  description: >-
    Chronic, often clinically asymptomatic anterior uveitis occurring most
    commonly in ANA-positive, young-onset oligoarticular juvenile idiopathic
    arthritis, requiring regular screening because it can progress silently
    to sight-threatening complications. Fully curated as part of
    `Juvenile_Idiopathic_Arthritis.yaml`.
  evidence:
  - reference: PMID:42184063
    reference_title: "Clinical characteristics and factors associated with uveitis in juvenile idiopathic arthritis: a long-term single-center experience."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Particularly, early onset of the disease, female gender, positive ANA status, and articular relapses should be considered warning signs for uveitis."
    explanation: A JIA cohort study identifies the classic risk-factor profile (young onset, female sex, ANA positivity) for JIA-associated uveitis.
  - reference: PMID:42184063
    reference_title: "Clinical characteristics and factors associated with uveitis in juvenile idiopathic arthritis: a long-term single-center experience."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Juvenile Idiopathic Arthritis uveitis (JIA-U) can progress without obvious clinical signs and cause permanent damage if left untreated, therefore early detection through regular screening is crucial"
    explanation: Supports the characteristic silent/asymptomatic course of JIA-associated uveitis that drives systematic screening recommendations.
- name: Herpetic Anterior Uveitis
  display_name: Herpesvirus-Associated Anterior Uveitis
  classification: etiologic (infectious, viral)
  description: >-
    Acute or recurrent anterior uveitis caused by reactivation of herpes
    simplex virus, varicella zoster virus, or (less commonly) cytomegalovirus
    within the anterior chamber, often with elevated intraocular pressure,
    sectoral iris atrophy, and keratic precipitates. No dedicated dismech
    entry currently exists for herpes simplex/varicella zoster virus
    infection, so the viral mechanism is curated directly here rather than
    linked to a sibling file.
  evidence:
  - reference: PMID:37862684
    reference_title: "Viral Anterior Uveitis: A Practical and Comprehensive Review of Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The viral pathogens most commonly associated with infectious anterior uveitis include Herpes Simplex Virus, Varicella-Zoster Virus, Cytomegalovirus, and Rubella Virus."
    explanation: Identifies herpesviruses as the leading viral causes of infectious anterior uveitis.
  - reference: PMID:29543540
    reference_title: "Immunopathology of Virus-Induced Anterior Uveitis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the herpes viruses cause an acute lytic infection and inflammation"
    explanation: Describes the acute lytic infection mechanism that distinguishes herpetic anterior uveitis from other viral causes.
- name: Intermediate Uveitis
  subtype_term:
    preferred_term: intermediate uveitis
    term:
      id: MONDO:0006806
      label: intermediate uveitis
  classification: anatomic (SUN)
  children:
  - Pars Planitis
  description: >-
    Inflammation centered on the pars plana and peripheral retina/vitreous,
    often idiopathic (pars planitis) but also associated with multiple
    sclerosis and sarcoidosis.
  evidence:
  - reference: PMID:40434762
    reference_title: "Uveitis in Adults: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "intermediate uveitis affects the pars plana (attachment point of vitreous humor) and peripheral retina (9%-15%)"
    explanation: Defines the anatomic scope and reported frequency of intermediate uveitis.
- name: Pars Planitis
  subtype_term:
    preferred_term: pars planitis
    term:
      id: MONDO:0011644
      label: pars planitis
  classification: etiologic (idiopathic)
  description: >-
    The idiopathic subset of intermediate uveitis, characterized by vitreous
    snowballs and peripheral retinal snowbanking without an identifiable
    infectious or systemic cause. Fully curated in `Pars_Planitis.yaml`.
- name: Posterior Uveitis
  subtype_term:
    preferred_term: posterior uveitis
    term:
      id: MONDO:0006918
      label: posterior uveitis
  classification: anatomic (SUN)
  children:
  - Choroiditis
  - Ocular Toxoplasmosis
  - Cytomegalovirus Retinitis
  - Tuberculous Uveitis
  description: >-
    Inflammation involving the choroid and/or retina, frequently infectious
    (toxoplasmosis, cytomegalovirus, tuberculosis) but also caused by
    non-infectious entities such as sarcoidosis and Behcet's disease.
  evidence:
  - reference: PMID:40434762
    reference_title: "Uveitis in Adults: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "posterior uveitis involves the choroid and/or retina (17%-23%)"
    explanation: Defines the anatomic scope and reported frequency of posterior uveitis.
- name: Choroiditis
  subtype_term:
    preferred_term: choroiditis
    term:
      id: MONDO:0001280
      label: choroiditis
  classification: anatomic (SUN)
  description: >-
    Focal, multifocal, or diffuse inflammation of the choroid, a form of
    posterior uveitis that may be infectious or non-infectious in origin.
    Fully curated in `Choroiditis.yaml`.
- name: Ocular Toxoplasmosis
  subtype_term:
    preferred_term: ocular toxoplasmosis
    term:
      id: MONDO:0005879
      label: ocular toxoplasmosis
  classification: etiologic (infectious, parasitic)
  description: >-
    Necrotizing retinochoroiditis due to reactivation of latent Toxoplasma
    gondii cysts in the retina, the most common identifiable cause of
    infectious posterior uveitis worldwide. Systemic and congenital
    toxoplasma infection is fully curated in `Toxoplasmosis.yaml`; this stub
    links the ocular manifestation into the posterior uveitis anatomic class.
  evidence:
  - reference: PMID:40456390
    reference_title: "Infectious uveitis: Epidemiology, etiology, diagnostic test performance and treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "in posterior uveitis various microorganisms are involved, among them Toxoplasma gondii, Cytomegalovirus, Plasmodium spp. and Candida spp."
    explanation: Identifies Toxoplasma gondii as a leading infectious cause of posterior uveitis.
- name: Cytomegalovirus Retinitis
  subtype_term:
    preferred_term: cytomegalovirus retinitis
    term:
      id: MONDO:0000878
      label: cytomegalovirus retinitis
  classification: etiologic (infectious, viral)
  description: >-
    Necrotizing retinitis caused by cytomegalovirus reactivation, occurring
    almost exclusively in severely immunocompromised patients. Fully curated
    in `Cytomegalovirus_Retinitis.yaml`.
- name: Tuberculous Uveitis
  classification: etiologic (infectious, mycobacterial)
  description: >-
    Granulomatous uveitis caused by Mycobacterium tuberculosis, presenting as
    choroidal tubercles, tuberculoma, serpiginous-like choroiditis, or
    panuveitis, particularly in endemic regions and immunocompromised
    patients. Systemic tuberculosis is fully curated in `Tuberculosis.yaml`.
  evidence:
  - reference: PMID:40434762
    reference_title: "Uveitis in Adults: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "toxoplasmosis, herpes, tuberculosis, and HIV comprising 11% to 21% of infectious cases in high-income countries and 50% in low- and middle-income countries"
    explanation: Quantifies tuberculosis as a major contributor to infectious uveitis, especially in low- and middle-income countries.
- name: Panuveitis
  subtype_term:
    preferred_term: panuveitis
    term:
      id: MONDO:0017255
      label: panuveitis
  classification: anatomic (SUN)
  children:
  - Behcet Uveitis
  - Vogt-Koyanagi-Harada Uveitis
  - Sarcoid Uveitis
  description: >-
    Inflammation involving all uveal layers, considered a high-risk form of
    uveitis because of frequent sight-threatening complications. Commonly
    caused by systemic autoimmune/autoinflammatory disease (Behcet's disease,
    Vogt-Koyanagi-Harada disease, sarcoidosis) or infection (ocular
    toxoplasmosis, tuberculosis). Fully curated in `Panuveitis.yaml`, which
    carries the detailed pan-uveal inflammation pathophysiology.
  evidence:
  - reference: PMID:40434762
    reference_title: "Uveitis in Adults: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "panuveitis involves all uveal layers (7%-32%)"
    explanation: Defines the anatomic scope and reported frequency of panuveitis.
- name: Behcet Uveitis
  display_name: Behcet's Disease-Associated Panuveitis
  classification: etiologic (autoimmune, vasculitic)
  description: >-
    Bilateral, chronic, recurrent, non-granulomatous panuveitis with retinal
    vasculitis, a hallmark manifestation of Behcet's disease. Fully curated
    as part of `Behcets_Disease.yaml`.
  evidence:
  - reference: PMID:38778397
    reference_title: "Decoding Behcet's Uveitis: an In-depth review of pathogenesis and therapeutic advances."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Behcet's uveitis (BU) is a common manifestation of BD, occurring in over two-thirds of the patients."
    explanation: Establishes uveitis, typically panuveitis, as a common and defining manifestation of Behcet's disease.
- name: Vogt-Koyanagi-Harada Uveitis
  display_name: Vogt-Koyanagi-Harada Disease-Associated Panuveitis
  classification: etiologic (autoimmune, melanocyte-directed)
  description: >-
    Bilateral granulomatous panuveitis with exudative retinal detachment
    driven by T cell-mediated autoimmunity against melanocyte antigens,
    progressing without treatment to a chronic recurrent anterior uveitis
    with "sunset glow fundus." Fully curated in
    `Vogt-Koyanagi-Harada_Disease.yaml`.
  evidence:
  - reference: PMID:34869409
    reference_title: "New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Patients with initial-onset acute uveitis present with granulomatous choroiditis with secondary exudative retinal detachment resulting from impairment of the retinal pigment epithelium caused by choroidal inflammation"
    explanation: Describes the granulomatous panuveitis with exudative retinal detachment characteristic of acute VKH disease.
- name: Sarcoid Uveitis
  display_name: Sarcoidosis-Associated Uveitis
  classification: etiologic (autoimmune, granulomatous)
  description: >-
    Granulomatous ocular inflammation in sarcoidosis that can affect any
    uveal segment but most often presents as panuveitis. Fully curated as
    part of `Sarcoidosis.yaml` and `Neurosarcoidosis.yaml`.
  evidence:
  - reference: PMID:33173272
    reference_title: "Ocular Manifestations of Sarcoidosis in a South Florida Population."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Twelve had uveitis of which panuveitis was the most common subtype."
    explanation: A sarcoidosis cohort study reports panuveitis as the most common uveitis subtype among ocular sarcoidosis cases.
pathophysiology:
- name: Breakdown of Ocular Immune Privilege
  biological_scale: TISSUE
  description: >-
    The eye is normally shielded from systemic immunity by physical
    barriers (blood-aqueous and blood-retinal), a locally immunosuppressive
    microenvironment, and tolerance circuits such as anterior
    chamber-associated immune deviation. Non-infectious (autoimmune)
    uveitis arises when these layered controls fail, permitting
    autoreactive lymphocyte access to intraocular antigens. This node
    begins the autoimmune arm of uveitis pathogenesis, modeled separately
    from the infectious arm below.
  biological_processes:
  - preferred_term: establishment of blood-retinal barrier
    modifier: DECREASED
    term:
      id: GO:1990963
      label: establishment of blood-retinal barrier
  notes: >-
    GO:1990963 is a developmental-process term (establishment, not
    maintenance) but is the only blood-retinal-barrier term in GO — there is
    no maintenance analogue to GO:0035633 (maintenance of blood-brain
    barrier). Used deliberately with DECREASED to represent adult barrier
    breakdown; do not re-litigate this without a better term becoming
    available.
  downstream:
  - target: Autoreactive Th1/Th17 T Cell Priming and Uveal Infiltration
    description: >-
      Loss of ocular immune privilege permits systemic activation and
      intraocular entry of autoreactive T cells.
    causal_link_type: DIRECT
  evidence:
  - reference: PMID:41877771
    reference_title: "The Immunopathogenesis of uveitis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Layered mechanisms normally restrain inflammation: physical barriers (blood-aqueous and blood-retina), a locally immunosuppressive milieu, and systemic tolerance circuits such as anterior chamber-associated immune deviation."
    explanation: Describes the layered immune-privilege mechanisms whose failure is the entry point for autoimmune uveitis.
- name: Autoreactive Th1/Th17 T Cell Priming and Uveal Infiltration
  biological_scale: CELLULAR
  description: >-
    Genetic susceptibility (HLA class I/II alleles and peptide-trimming
    enzymes such as ERAP1) shapes antigen presentation and lowers the
    activation threshold for autoreactive T cells directed against ocular
    or cross-reactive antigens. These T cells are primed toward Th1/Th17
    phenotypes in draining lymphoid tissue, then infiltrate the eye where
    they are restimulated by resident microglia and recruited macrophages.
    This is the mechanism underlying HLA-B27-associated and juvenile
    idiopathic arthritis-associated anterior uveitis and contributes to
    Behcet's disease- and Vogt-Koyanagi-Harada disease-associated
    panuveitis. Experimental autoimmune uveitis (EAU) models in rodents are
    the primary source of mechanistic detail for this pathway.
  cell_types:
  - preferred_term: CD4-positive, alpha-beta T cell
    term:
      id: CL:0000624
      label: CD4-positive, alpha-beta T cell
  - preferred_term: T-helper 17 cell
    term:
      id: CL:0000899
      label: T-helper 17 cell
  - preferred_term: microglial cell
    term:
      id: CL:0000129
      label: microglial cell
  biological_processes:
  - preferred_term: T-helper 1 type immune response
    modifier: INCREASED
    term:
      id: GO:0042088
      label: T-helper 1 type immune response
  - preferred_term: T-helper 17 type immune response
    modifier: INCREASED
    term:
      id: GO:0072538
      label: T-helper 17 type immune response
  downstream:
  - target: Cytokine-Driven Leukocyte Recruitment and Barrier Disruption
    description: >-
      Restimulated effector T cells and resident myeloid cells drive
      cytokine cascades that recruit further leukocytes and damage ocular
      barriers.
    causal_link_type: DIRECT
  evidence:
  - reference: PMID:18317764
    reference_title: "New perspectives on effector mechanisms in uveitis."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Th17 cells elicit EAU, can be found in uveitic eyes along with Th1 cells, and are dominant in some types of EAU. In other types of EAU, Th1 cells have a dominant role."
    explanation: Rodent experimental autoimmune uveitis studies establish the dual Th1/Th17 effector basis of autoimmune uveitis.
  - reference: PMID:27245590
    reference_title: "HLA-B27 Anterior Uveitis: Immunology and Immunopathology."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Studies of patients with AAU and animal models of disease indicate a role for innate immunity, the IL-23 cytokine pathway and exogenous factors, in the pathogenesis of both SpA and acute anterior uveitis."
    explanation: Supports genetic-pathway (IL-23/Th17 axis) involvement in human HLA-B27-associated anterior uveitis.
- name: Cytokine-Driven Leukocyte Recruitment and Barrier Disruption
  biological_scale: TISSUE
  description: >-
    Effector T cell and myeloid cytokine production amplifies leukocyte
    recruitment into the aqueous, vitreous, retina, and choroid while
    further disrupting the blood-retinal barrier, producing the clinical
    signs and sight-threatening complications common to non-infectious
    uveitis of any anatomic class.
  biological_processes:
  - preferred_term: leukocyte migration
    modifier: INCREASED
    term:
      id: GO:0050900
      label: leukocyte migration
  - preferred_term: inflammatory response
    modifier: INCREASED
    term:
      id: GO:0006954
      label: inflammatory response
  downstream:
  - target: Ocular pain
    description: Intraocular inflammation and elevated intraocular pressure produce pain.
    causal_link_type: DIRECT
  - target: Photophobia
    description: Anterior chamber and ciliary inflammation causes light sensitivity.
    causal_link_type: DIRECT
  - target: Blurred vision
    description: Vitreous haze and macular edema reduce visual clarity.
    causal_link_type: DIRECT
  - target: Macular edema
    description: Leukocyte infiltration and cytokine-driven vascular permeability promote macular edema.
    causal_link_type: DIRECT
  evidence:
  - reference: PMID:41877771
    reference_title: "The Immunopathogenesis of uveitis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "effector T-cells are restimulated by resident microglia and recruited macrophages, driving cytokine cascades that disrupt the blood-retina barrier and amplify leukocyte recruitment"
    explanation: Directly supports the cytokine-driven leukocyte recruitment and barrier disruption mechanism of autoimmune uveitis.
- name: Ocular Pathogen Invasion or Reactivation
  biological_scale: TISSUE
  description: >-
    Infectious uveitis is triggered by direct invasion or reactivation of
    an infectious agent within the eye, mechanistically distinct from the
    autoimmune arm above. The responsible organism differs by anatomic
    class: herpesviruses (herpes simplex virus, varicella zoster virus)
    predominate in infectious anterior uveitis; Toxoplasma gondii,
    cytomegalovirus, and Mycobacterium tuberculosis predominate in
    infectious posterior uveitis and panuveitis. This node begins the
    infectious arm of uveitis pathogenesis and is modeled as a separate
    causal chain rather than merged with the autoimmune arm.
  downstream:
  - target: Pathogen Antigen-Driven Uveal Inflammatory Damage
    description: >-
      Ongoing pathogen replication or antigen persistence drives a
      destructive local inflammatory response.
    causal_link_type: DIRECT
  evidence:
  - reference: PMID:40456390
    reference_title: "Infectious uveitis: Epidemiology, etiology, diagnostic test performance and treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Infectious uveitis is an inflammation of the uveal tract, corresponding to the middle layer of the eye, triggered by a response against an infectious agent."
    explanation: Establishes the direct infectious-trigger mechanism that distinguishes this arm from autoimmune uveitis.
  - reference: PMID:41877771
    reference_title: "The Immunopathogenesis of uveitis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Infectious uveitis reflects direct intraocular infection or reactivation."
    explanation: Confirms direct infection or pathogen reactivation, rather than autoimmunity, as the trigger for this arm.
- name: Pathogen Antigen-Driven Uveal Inflammatory Damage
  biological_scale: TISSUE
  description: >-
    Persistent pathogen replication or retained antigen drives ocular
    infiltration by T cells and B/plasma cells and local production of
    proinflammatory cytokines and chemokines, causing necrotizing or
    granulomatous tissue damage and the same downstream clinical
    complications seen in the autoimmune arm, despite the distinct upstream
    trigger.
  cell_types:
  - preferred_term: lymphocyte
    term:
      id: CL:0000542
      label: lymphocyte
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  biological_processes:
  - preferred_term: inflammatory response
    modifier: INCREASED
    term:
      id: GO:0006954
      label: inflammatory response
  - preferred_term: defense response
    modifier: INCREASED
    term:
      id: GO:0006952
      label: defense response
  downstream:
  - target: Ocular pain
    description: Active infectious inflammation produces pain and redness.
    causal_link_type: DIRECT
  - target: Floaters
    description: Vitreous inflammatory infiltrate produces floaters.
    causal_link_type: DIRECT
  - target: Blurred vision
    description: Retinochoroiditis and vitreous haze reduce visual clarity.
    causal_link_type: DIRECT
  - target: Retinal detachment
    description: Necrotizing retinochoroiditis can lead to retinal detachment.
    causal_link_type: DIRECT
  evidence:
  - reference: PMID:29543540
    reference_title: "Immunopathology of Virus-Induced Anterior Uveitis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "These viral infections are commonly associated with ocular infiltration of T cells and B/plasma cells, and expression of cytokines and chemokines typical of a proinflammatory immune response."
    explanation: Directly supports pathogen-driven lymphocyte infiltration and proinflammatory cytokine expression as the tissue-damage mechanism of infectious uveitis.
phenotypes:
- category: Ophthalmologic
  name: Uveitis
  description: Intraocular inflammation affecting one or more layers of the uveal tract.
  phenotype_term:
    preferred_term: Uveitis
    term:
      id: HP:0000554
      label: Uveitis
  evidence:
  - reference: PMID:36164924
    reference_title: "The standardisation of uveitis nomenclature (SUN) project."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The uveitides are a collection of over 30 diseases characterised by intraocular inflammation."
    explanation: SUN establishes uveitis as intraocular inflammation spanning a large, anatomically classified group of diseases.
- category: Ophthalmologic
  name: Ocular pain
  description: Eye pain may accompany active intraocular inflammation.
  phenotype_term:
    preferred_term: Ocular pain
    term:
      id: HP:0200026
      label: Ocular pain
  evidence:
  - reference: PMID:40434762
    reference_title: "Uveitis in Adults: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "eye redness, pain, photophobia, floaters, and blurred vision"
    explanation: This review lists pain among common presenting symptoms of uveitis.
- category: Ophthalmologic
  name: Photophobia
  description: Light sensitivity commonly accompanies active anterior segment inflammation.
  phenotype_term:
    preferred_term: Photophobia
    term:
      id: HP:0000613
      label: Photophobia
  evidence:
  - reference: PMID:40434762
    reference_title: "Uveitis in Adults: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "eye redness, pain, photophobia, floaters, and blurred vision"
    explanation: This review lists photophobia among common presenting symptoms of uveitis.
- category: Ophthalmologic
  name: Floaters
  description: Vitreous floaters can occur during active intraocular inflammation.
  phenotype_term:
    preferred_term: Floaters
    term:
      id: HP:0100832
      label: Vitreous floaters
  evidence:
  - reference: PMID:40434762
    reference_title: "Uveitis in Adults: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "eye redness, pain, photophobia, floaters, and blurred vision"
    explanation: This review lists floaters among common presenting symptoms of uveitis.
- category: Ophthalmologic
  name: Blurred vision
  description: Vitreous haze, macular edema, or posterior segment inflammation can reduce visual clarity.
  phenotype_term:
    preferred_term: Blurred vision
    term:
      id: HP:0000622
      label: Blurred vision
  evidence:
  - reference: PMID:40434762
    reference_title: "Uveitis in Adults: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "eye redness, pain, photophobia, floaters, and blurred vision"
    explanation: This review lists blurred vision among common presenting symptoms of uveitis.
- category: Ophthalmologic
  name: Macular edema
  description: Macular edema is a common sight-threatening inflammatory complication of uveitis.
  phenotype_term:
    preferred_term: Macular edema
    term:
      id: HP:0040049
      label: Macular edema
  evidence:
  - reference: PMID:40434762
    reference_title: "Uveitis in Adults: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "cataracts, glaucoma, macular edema, retinal detachment, optic nerve damage, and vision loss"
    explanation: This review lists macular edema among major complications of untreated uveitis.
- category: Ophthalmologic
  name: Retinal detachment
  description: Retinal detachment can occur as a severe structural complication of uncontrolled uveitis.
  phenotype_term:
    preferred_term: Retinal detachment
    term:
      id: HP:0000541
      label: Retinal detachment
  evidence:
  - reference: PMID:40434762
    reference_title: "Uveitis in Adults: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "cataracts, glaucoma, macular edema, retinal detachment, optic nerve damage, and vision loss"
    explanation: This review lists retinal detachment among major complications of untreated uveitis.
- category: Ophthalmologic
  name: Cataract
  description: Cataract is a common vision-threatening complication of uveitis and its corticosteroid treatment.
  phenotype_term:
    preferred_term: Cataract
    term:
      id: HP:0000518
      label: Cataract
  evidence:
  - reference: PMID:40434762
    reference_title: "Uveitis in Adults: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "cataracts, glaucoma, macular edema, retinal detachment, optic nerve damage, and vision loss"
    explanation: This review lists cataracts among major complications of untreated uveitis.
- category: Ophthalmologic
  name: Glaucoma
  description: Glaucoma can complicate uveitis through inflammatory and corticosteroid-related mechanisms.
  phenotype_term:
    preferred_term: Glaucoma
    term:
      id: HP:0000501
      label: Glaucoma
  evidence:
  - reference: PMID:40434762
    reference_title: "Uveitis in Adults: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "cataracts, glaucoma, macular edema, retinal detachment, optic nerve damage, and vision loss"
    explanation: This review lists glaucoma among major complications of untreated uveitis.
- category: Ophthalmologic
  name: Visual impairment
  description: Uveitis is a leading cause of preventable vision loss, ranging from mild acuity reduction to blindness.
  phenotype_term:
    preferred_term: Visual impairment
    term:
      id: HP:0000505
      label: Visual impairment
  evidence:
  - reference: PMID:40434762
    reference_title: "Uveitis in Adults: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "cataracts, glaucoma, macular edema, retinal detachment, optic nerve damage, and vision loss"
    explanation: This review lists vision loss among major complications of untreated uveitis.
- category: Ophthalmologic
  name: Eye redness
  description: Conjunctival/ciliary injection commonly accompanies active anterior segment inflammation.
  phenotype_term:
    preferred_term: Conjunctival hyperemia
    term:
      id: HP:0030953
      label: Conjunctival hyperemia
  evidence:
  - reference: PMID:40434762
    reference_title: "Uveitis in Adults: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "eye redness, pain, photophobia, floaters, and blurred vision"
    explanation: This review lists eye redness among common presenting symptoms of uveitis.
genetic:
- name: HLA-B27
  gene_term:
    preferred_term: HLA-B
    term:
      id: hgnc:4932
      label: HLA-B
  association: Strong Risk Factor
  relationship_type: RISK_FACTOR
  notes: >-
    HLA-B27 is the single most frequently identified genetic risk factor for
    acute anterior uveitis, acting principally through HLA-B27-associated
    spondyloarthropathy, and is also a recognized genetic influence on
    uveitis incidence and prevalence more broadly.
  evidence:
  - reference: PMID:19027424
    reference_title: "Incidence and prevalence of uveitis in Veterans Affairs Medical Centers of the Pacific Northwest."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "human leukocyte antigen-B27-related diseases being the most common identified cause"
    explanation: A population-based cohort identifies HLA-B27-related disease as the leading identified cause of anterior uveitis.
  - reference: PMID:40434762
    reference_title: "Uveitis in Adults: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Incidence and prevalence of uveitis are influenced by genetic factors (eg, human leukocyte antigen–B27)"
    explanation: Identifies HLA-B27 as a genetic factor influencing uveitis incidence and prevalence broadly.
- name: ERAP1
  gene_term:
    preferred_term: ERAP1
    term:
      id: hgnc:18173
      label: ERAP1
  association: Risk Factor
  relationship_type: SUSCEPTIBILITY
  notes: >-
    ERAP1 encodes an endoplasmic-reticulum aminopeptidase that trims
    peptides for MHC class I presentation; ERAP1 variants show gene-gene
    interaction with HLA-B27 and shape susceptibility to acute anterior
    uveitis in the context of HLA-B27-associated spondyloarthropathy.
  evidence:
  - reference: PMID:27245590
    reference_title: "HLA-B27 Anterior Uveitis: Immunology and Immunopathology."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Patients with ankylosing spondylitis (AS) and AAU share other genetic markers, such as ERAP-1, which show strong evidence of gene-gene interaction and point to new mechanisms of disease pathogenesis."
    explanation: Directly supports ERAP1 as a shared genetic modifier contributing to HLA-B27-associated acute anterior uveitis via gene-gene interaction.
diagnosis:
- name: SUN Anatomic Classification
  description: >-
    Diagnosis begins with ophthalmic examination establishing the SUN
    anatomic class (anterior, intermediate, posterior, panuveitis), followed
    by directed evaluation to distinguish infectious from non-infectious
    (autoimmune) etiology.
  diagnosis_term:
    preferred_term: clinical assessment
    term:
      id: NCIT:C124351
      label: Clinical Evaluation
  results: >-
    Anatomic classification narrows the differential; systemic and
    infectious workup then determines the causal arm and specific etiology.
  evidence:
  - reference: PMID:36164924
    reference_title: "The standardisation of uveitis nomenclature (SUN) project."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The SUN \"Developing Classification Criteria for the Uveitides\" project used a rigorous, multi-phase approach to develop classification criteria for 25 of the most common uveitic diseases."
    explanation: Describes the SUN classification project that underlies anatomic and etiologic diagnosis of uveitis.
- name: Intraocular Fluid Pathogen PCR Testing
  description: >-
    Polymerase chain reaction testing of aqueous or vitreous fluid supports
    identification of the infectious arm when clinical features suggest a
    herpetic, toxoplasmic, or other infectious etiology.
  diagnosis_term:
    preferred_term: polymerase chain reaction testing
    term:
      id: NCIT:C17003
      label: Polymerase Chain Reaction
  results: >-
    A positive intraocular PCR result for a specific pathogen supports
    infectious rather than autoimmune uveitis and directs antimicrobial
    therapy.
  evidence:
  - reference: PMID:40456390
    reference_title: "Infectious uveitis: Epidemiology, etiology, diagnostic test performance and treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "polymerase chain reaction (PCR) on ocular specimens for Herpes simplex virus has a sensitivity of 91.3% and specificity of 98.8%, while for toxoplasmosis the sensitivity is 43.1% and specificity 98.5%"
    explanation: Reports the diagnostic performance of intraocular PCR testing used to confirm infectious etiologies of uveitis.
environmental:
- name: Immune checkpoint inhibitor therapy
  exposure_term:
    preferred_term: immune checkpoint inhibitor therapy
  notes: >-
    ECTO was searched (via OLS, ontology=ecto) for "immune checkpoint
    inhibitor" and "checkpoint inhibitor"; no suitable exposure term was
    found, so `term:` is intentionally left unbound.
  evidence:
  - reference: PMID:38264654
    reference_title: "Association between immune checkpoint inhibitor medication and uveitis: a population-based cohort study utilizing TriNetX database."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Associated Kaplan-Meier curves showed significantly increased uveitis risk among the ICI group for all follow-up years (p<0.001)."
    explanation: >-
      Establishes immune checkpoint inhibitor therapy as a documented uveitis
      exposure in its own right, with risk elevated across the whole follow-up
      period. This attests the exposure entry; the separate evidence on the
      influences_mechanisms link attests that it acts on ocular immune privilege.
  influences_mechanisms:
  - target: Breakdown of Ocular Immune Privilege
    environmental_effect: TRIGGERS
    causal_link_type: DIRECT
    description: >-
      Immune checkpoint inhibitor therapy releases the checkpoints that
      normally restrain autoreactive T cells, precipitating loss of ocular
      immune privilege and drug-induced uveitis.
    evidence:
    - reference: PMID:38264654
      reference_title: "Association between immune checkpoint inhibitor medication and uveitis: a population-based cohort study utilizing TriNetX database."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "The risk of uveitis was also higher among the ICI group during the 144-month follow-up period with a hazard ratio (HR) of 2.39 (95% CI: 2.07-2.75)."
      explanation: >-
        A matched TriNetX cohort study of 71,931 exposed and 71,931
        unexposed cancer patients found a significantly elevated hazard
        ratio for new-onset uveitis among immune checkpoint inhibitor
        recipients, supporting a direct causal trigger role.
prevalence:
- population: Northern California health maintenance organization members, USA
  measure_type: ANNUAL_INCIDENCE
  prevalence_class: BAND_1_5_PER_10000
  rate_per_100000: 52.4
  notes: Northern California Epidemiology of Uveitis Study.
  evidence:
  - reference: PMID:15019324
    reference_title: "Incidence and prevalence of uveitis in Northern California; the Northern California Epidemiology of Uveitis Study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "These data yielded an incidence of 52.4/100 000 person-years and a period prevalence of 115.3/100 000 persons."
    explanation: Reports incidence in the largest US population-based uveitis study to date.
- population: Northern California health maintenance organization members, USA
  measure_type: PERIOD_PREVALENCE
  prevalence_class: ABOVE_1_IN_1000
  rate_per_100000: 115.3
  notes: Northern California Epidemiology of Uveitis Study.
  evidence:
  - reference: PMID:15019324
    reference_title: "Incidence and prevalence of uveitis in Northern California; the Northern California Epidemiology of Uveitis Study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "These data yielded an incidence of 52.4/100 000 person-years and a period prevalence of 115.3/100 000 persons."
    explanation: Reports period prevalence in the largest US population-based uveitis study to date.
- population: Kaiser Permanente Hawaii health plan members, USA
  measure_type: ANNUAL_INCIDENCE
  prevalence_class: BAND_1_5_PER_10000
  rate_per_100000: 24.9
  notes: Pacific Ocular Inflammation Study.
  evidence:
  - reference: PMID:24008391
    reference_title: "Incidence and prevalence of uveitis: results from the Pacific Ocular Inflammation Study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The overall uveitis incidence rate was 24.9 cases per 100,000 person-years."
    explanation: Reports incidence in a Hawaiian managed-care population.
- population: Kaiser Permanente Hawaii health plan members, USA (2006)
  measure_type: PERIOD_PREVALENCE
  prevalence_class: BAND_1_5_PER_10000
  rate_per_100000: 57.5
  notes: Pacific Ocular Inflammation Study, annual (calendar-year) prevalence for 2006.
  evidence:
  - reference: PMID:24008391
    reference_title: "Incidence and prevalence of uveitis: results from the Pacific Ocular Inflammation Study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The annual prevalence rates for 2006 and 2007 were 57.5 and 58.0 per 100,000 persons, respectively."
    explanation: Reports annual (calendar-year) prevalence for 2006 in a Hawaiian managed-care population.
- population: Kaiser Permanente Hawaii health plan members, USA (2007)
  measure_type: PERIOD_PREVALENCE
  prevalence_class: BAND_1_5_PER_10000
  rate_per_100000: 58.0
  notes: Pacific Ocular Inflammation Study, annual (calendar-year) prevalence for 2007.
  evidence:
  - reference: PMID:24008391
    reference_title: "Incidence and prevalence of uveitis: results from the Pacific Ocular Inflammation Study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The annual prevalence rates for 2006 and 2007 were 57.5 and 58.0 per 100,000 persons, respectively."
    explanation: Reports annual (calendar-year) prevalence for 2007 in a Hawaiian managed-care population.
- population: Veterans Affairs Medical Centers, Oregon and Washington, USA
  measure_type: ANNUAL_INCIDENCE
  prevalence_class: BAND_1_5_PER_10000
  rate_per_100000: 25.6
  notes: VA Pacific Northwest study.
  evidence:
  - reference: PMID:19027424
    reference_title: "Incidence and prevalence of uveitis in Veterans Affairs Medical Centers of the Pacific Northwest."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "This study found a crude incidence of 25.6 cases/100,000 person-years and a crude prevalence of 69 cases/100,000 persons."
    explanation: Reports incidence in a VA Pacific Northwest population.
- population: Veterans Affairs Medical Centers, Oregon and Washington, USA
  measure_type: PERIOD_PREVALENCE
  prevalence_class: BAND_1_5_PER_10000
  rate_per_100000: 69
  notes: VA Pacific Northwest study.
  evidence:
  - reference: PMID:19027424
    reference_title: "Incidence and prevalence of uveitis in Veterans Affairs Medical Centers of the Pacific Northwest."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "This study found a crude incidence of 25.6 cases/100,000 person-years and a crude prevalence of 69 cases/100,000 persons."
    explanation: Reports crude prevalence in a VA Pacific Northwest population.
clinical_trials:
- name: NCT06431373
  phase: PHASE_III
  status: ACTIVE_NOT_RECRUITING
  description: >-
    Randomized, double-masked, placebo-controlled trial of oral brepocitinib
    in adults with active, non-infectious intermediate, posterior, or
    panuveitis.
  evidence:
  - reference: clinicaltrials:NCT06431373
    reference_title: "A Phase 3 Randomized, Double-Masked, Placebo-Controlled Study to Investigate the Safety and Efficacy of Oral Brepocitinib in Adults With Active, Non-Infectious Intermediate-, Posterior-, and Panuveitis"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The purpose of this study is to determine the safety and efficacy of brepocitinib in participants with active, non-anterior (intermediate, posterior, or pan) non-infectious uveitis (NIU)."
    explanation: ClinicalTrials.gov record establishes the trial's objective of testing oral brepocitinib in non-anterior non-infectious uveitis.
- name: NCT05384249
  phase: PHASE_II
  status: TERMINATED
  description: >-
    Trial of izokibep, a selective interleukin-17A inhibitor, in subjects
    with active non-infectious intermediate-, posterior-, or pan-uveitis
    requiring high-dose steroids.
  evidence:
  - reference: clinicaltrials:NCT05384249
    reference_title: "A Phase 2b Pivotal Study to Evaluate the Efficacy and Safety of Izokibep in Subjects with Non-infectious, Intermediate-, Posterior- or Pan-uveitis"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Izokibep is a small protein molecule that acts as a selective, potent inhibitor of interleukin-17A, to which it binds with high affinity."
    explanation: ClinicalTrials.gov record establishes izokibep's IL-17A-inhibitor mechanism as tested in non-infectious uveitis.
- name: NCT02595398
  phase: PHASE_III
  status: COMPLETED
  description: >-
    Randomized, masked, controlled trial of suprachoroidally administered
    triamcinolone acetonide injectable suspension (CLS-TA) for macular edema
    associated with non-infectious uveitis.
  target_phenotypes:
  - preferred_term: Macular edema
    term:
      id: HP:0040049
      label: Macular edema
  evidence:
  - reference: clinicaltrials:NCT02595398
    reference_title: "A Phase 3, Randomized, Masked, Controlled Clinical Trial to Study the Safety and Efficacy of Triamcinolone Acetonide Injectable Suspension (CLS-TA) for the Treatment of Subjects With Macular Edema Associated With Non-infectious Uveitis"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The study is designed to evaluate the safety and efficacy of suprachoroidally administered triamcinolone acetonide, CLS-TA, in subjects with macular edema associated with non-infectious uveitis."
    explanation: ClinicalTrials.gov record establishes the trial's evaluation of suprachoroidal CLS-TA for uveitic macular edema.
treatments:
- name: Etiology-Directed Antimicrobial Therapy
  description: >-
    Infectious uveitis requires treatment directed at the causative organism
    (antiviral, antiparasitic, or antimycobacterial therapy), typically
    combined with anti-inflammatory therapy once pathogen load is controlled.
  treatment_term:
    preferred_term: antimicrobial pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
  target_mechanisms:
  - target: Ocular Pathogen Invasion or Reactivation
    treatment_effect: INHIBITS
    description: Antimicrobial therapy directly targets the causative infectious agent underlying this arm of uveitis.
  evidence:
  - reference: PMID:40434762
    reference_title: "Uveitis in Adults: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Infectious uveitis requires systemic antimicrobial treatment."
    explanation: Directly supports organism-directed antimicrobial therapy as the mainstay treatment of infectious uveitis.
- name: Topical Corticosteroid Therapy
  description: >-
    Topical corticosteroid eye drops are first-line therapy for
    non-infectious anterior uveitis, delivering high local drug
    concentration to the anterior segment while limiting systemic exposure.
  treatment_term:
    preferred_term: topical corticosteroid therapy
    term:
      id: NCIT:C122078
      label: Topical Corticosteroid Therapy
  target_mechanisms:
  - target: Cytokine-Driven Leukocyte Recruitment and Barrier Disruption
    treatment_effect: INHIBITS
    description: Topical corticosteroids suppress the cytokine-driven leukocyte recruitment and inflammation that damages ocular tissue in non-infectious anterior uveitis.
  evidence:
  - reference: PMID:40434762
    reference_title: "Uveitis in Adults: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "corticosteroid eyedrops are first-line treatment"
    explanation: States that topical corticosteroid eye drops are first-line therapy for noninfectious anterior uveitis.
- name: Systemic Corticosteroid Therapy
  description: >-
    Systemic corticosteroids rapidly suppress non-infectious intraocular
    inflammation in patients with moderate-to-severe intermediate,
    posterior, or panuveitis who are at high risk of sight-threatening
    complications.
  treatment_term:
    preferred_term: systemic corticosteroid therapy
    term:
      id: NCIT:C122080
      label: Systemic Corticosteroid Therapy
  target_mechanisms:
  - target: Cytokine-Driven Leukocyte Recruitment and Barrier Disruption
    treatment_effect: INHIBITS
    description: Systemic corticosteroids suppress the cytokine-driven leukocyte recruitment and inflammation that damages ocular tissue in non-infectious uveitis.
  evidence:
  - reference: PMID:40434762
    reference_title: "Uveitis in Adults: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "require systemic and/or intravitreal corticosteroids and immunosuppressive agents"
    explanation: Directly supports systemic corticosteroids for moderate-to-severe non-infectious uveitis.
- name: Local (Intravitreal) Corticosteroid Therapy
  description: >-
    Locally delivered intravitreal corticosteroids are used, as an
    alternative or adjunct to systemic therapy, for moderate-to-severe
    non-infectious intermediate, posterior, or panuveitis, achieving high
    intraocular drug concentration while limiting systemic corticosteroid
    exposure. No NCIT clinical-action term specifically names the
    intravitreal route (the closest candidate, Localized Corticosteroid
    Therapy NCIT:C121367, is explicitly defined as intraarticular, topical,
    or inhaled only), so this treatment uses the generic Pharmacotherapy
    action term with a corticosteroid therapeutic agent instead of
    overclaiming a route-specific NCIT term.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: corticosteroid
      term:
        id: CHEBI:50858
        label: corticosteroid
  target_mechanisms:
  - target: Cytokine-Driven Leukocyte Recruitment and Barrier Disruption
    treatment_effect: INHIBITS
    description: Locally delivered intravitreal corticosteroids suppress the cytokine-driven leukocyte recruitment and inflammation that damages ocular tissue in non-infectious uveitis, without the systemic exposure of oral or intravenous therapy.
  evidence:
  - reference: PMID:40434762
    reference_title: "Uveitis in Adults: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "require systemic and/or intravitreal corticosteroids and immunosuppressive agents"
    explanation: Directly supports intravitreal corticosteroids as a local-delivery option for moderate-to-severe non-infectious uveitis.
- name: Steroid-Sparing Immunosuppressive Therapy
  description: >-
    Chronic, recurrent, bilateral, or vision-threatening non-infectious
    uveitis commonly requires steroid-sparing immunosuppression such as
    methotrexate or mycophenolate mofetil.
  treatment_term:
    preferred_term: immune suppressant agent therapy
    term:
      id: NCIT:C15261
      label: Immunosuppressive Therapy
  target_mechanisms:
  - target: Cytokine-Driven Leukocyte Recruitment and Barrier Disruption
    treatment_effect: INHIBITS
    description: Immunosuppressive therapy reduces recurrent autoimmune ocular inflammation while limiting corticosteroid exposure.
  evidence:
  - reference: PMID:40434762
    reference_title: "Uveitis in Adults: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "For posterior uveitis, first-line therapy with disease-modifying antirheumatic drugs such as methotrexate achieved remission of inflammation in 52.1% (95% CI, 38.6%-67.1%) of patients, and mycophenolate mofetil controlled inflammation in 70.9% (95% CI, 57.1%-83.5%)"
    explanation: Provides quantitative human clinical outcome data for steroid-sparing immunosuppressive therapy in non-infectious uveitis.
- name: Adalimumab
  description: >-
    Adalimumab is a steroid-sparing anti-TNF biologic for active or inactive
    non-infectious intermediate, posterior, or panuveitis when inflammation
    is not adequately controlled with corticosteroid-based therapy.
  treatment_term:
    preferred_term: anti-TNF biologic therapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: Adalimumab
      term:
        id: NCIT:C65216
        label: Adalimumab
  therapeutic_modality: MONOCLONAL_ANTIBODY
  target_mechanisms:
  - target: Cytokine-Driven Leukocyte Recruitment and Barrier Disruption
    treatment_effect: INHIBITS
    description: Anti-TNF therapy inhibits the cytokine cascade that drives leukocyte recruitment and barrier disruption in non-infectious uveitis.
  evidence:
  - reference: PMID:27602665
    reference_title: "Adalimumab in Patients with Active Noninfectious Uveitis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "median time to treatment failure was 24 weeks in the adalimumab group and 13 weeks in the placebo group"
    explanation: The VISUAL I trial supports adalimumab efficacy in active non-infectious intermediate, posterior, or panuveitis.
  - reference: PMID:39157460
    reference_title: "Update on non-infectious uveitis treatment: anti-TNF-alpha and beyond."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "TNF-α inhibitors, anti-CD20 therapy and alkylating agents have shown considerable efficacy"
    explanation: This review confirms TNF-alpha inhibitors as an effective biologic option for non-infectious uveitis refractory to corticosteroids.
📚

References & Deep Research

Deep Research

1
Falcon ▸
Disease Characteristics Research Template
Edison Scientific Literature 46 citations 2026-08-26T22:20:20.095600

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Disease Characteristics Research Template

Target Disease

  • Disease Name: Uveitis
  • MONDO ID: (if available)
  • Category: Complex

Research Objectives

Please provide a comprehensive research report on Uveitis covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.

For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.

1. Disease Information

Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed

  • What is the disease? Provide a concise overview.
  • What are the key identifiers? (OMIM, Orphanet, ICD-10/ICD-11, MeSH, Mondo)
  • What are the common synonyms and alternative names?
  • Is the information derived from individual patients (e.g., EHR) or aggregated disease-level resources?

2. Etiology

  • Disease Causal Factors: What are the primary causes? (genetic, environmental, infectious, mechanistic)
  • Risk Factors:

    Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases

  • Genetic risk factors (causal variants, susceptibility loci, modifier genes)
  • Environmental risk factors (toxins, lifestyle, occupational exposures, age, sex, family history)
  • Protective Factors:

    Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases

  • Genetic protective factors (protective variants, modifier alleles)
  • Environmental protective factors (diet, lifestyle, exposures that reduce risk)
  • Gene-Environment Interactions: How do genetic and environmental factors interact to influence disease?

    Search first: CTD, PubMed, PheGenI, GxE databases

3. Phenotypes

Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC

For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities

For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype

4. Genetic/Molecular Information

  • Causal Genes: Gene mutations or chromosomal abnormalities responsible for disease (gene symbols, OMIM IDs)

    Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene

  • Pathogenic Variants:
  • Affected genes (gene symbols, HGNC IDs) > Search first: OMIM, NCBI Gene, Ensembl, HGNC, UniProt, GeneCards
  • Variant classification (pathogenic, likely pathogenic, VUS per ACMG/AMP guidelines) > Search first: ClinVar, ClinGen, ACMG/AMP guidelines, VarSome
  • Variant type/class (missense, frameshift, nonsense, splice-site, structural)
  • Allele frequency in population databases > Search first: gnomAD, 1000 Genomes, ExAC, TOPMed, dbSNP
  • Somatic vs germline origin > Search first: COSMIC (somatic), ClinVar, ICGC, TCGA
  • Functional consequences (loss of function, gain of function, dominant negative)
  • Modifier Genes: Genes that modify disease severity or expression
  • Epigenetic Information: DNA methylation, histone modifications, chromatin changes affecting disease

    Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth

  • Chromosomal Abnormalities: Large-scale genetic changes (aneuploidy, translocations, inversions)

    Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser

5. Environmental Information

  • Environmental Factors: Non-genetic contributing factors (toxins, radiation, pollution, occupational exposure)

    Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases

  • Lifestyle Factors: Behavioral factors (smoking, diet, exercise, alcohol consumption)

    Search first: CDC databases, WHO, PubMed, NHANES

  • Infectious Agents: If applicable, pathogens causing or triggering disease (bacteria, viruses, fungi, parasites)

    Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON

6. Mechanism / Pathophysiology

  • Molecular Pathways: Specific signaling cascades or biochemical pathways involved (Wnt, MAPK, mTOR, PI3K-AKT, etc.)

    Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc

  • Cellular Processes: Cell-level mechanisms (apoptosis, autophagy, cell cycle dysregulation, inflammation, etc.)

    Search first: Gene Ontology (GO), Reactome, KEGG, PubMed

  • Protein Dysfunction: How protein structure or function is altered (misfolding, aggregation, loss of function, gain of function)

    Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold

  • Metabolic Changes: Alterations in metabolic processes (energy metabolism, lipid metabolism, amino acid metabolism)

    Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA

  • Immune System Involvement: Role of immune response (autoimmunity, immunodeficiency, chronic inflammation)

    Search first: ImmPort, Immunome Database, IEDB, Gene Ontology

  • Tissue Damage Mechanisms: How tissues/ are injured (oxidative stress, ischemia, fibrosis, necrosis)

    Search first: PubMed, Gene Ontology, Reactome

  • Biochemical Abnormalities: Specific molecular defects (enzyme deficiencies, receptor dysfunction, ion channel defects)

    Search first: BRENDA, UniProt, KEGG, OMIM, PubMed

  • Epigenetic Changes: DNA methylation, histone modifications affecting gene expression in disease

    Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth

  • Molecular Profiling (if available):
  • Transcriptomics/gene expression changes > Search first: GEO (Gene Expression Omnibus), ArrayExpress, GTEx, Human Cell Atlas, SRA
  • Proteomics findings > Search first: PRIDE, ProteomeXchange, Human Protein Atlas, STRING, BioGRID
  • Metabolomics signatures > Search first: MetaboLights, Metabolomics Workbench, HMDB, METLIN
  • Lipidomics alterations > Search first: LIPID MAPS, SwissLipids, LipidHome, Metabolomics Workbench
  • Genomic structural features > Search first: UCSC Genome Browser, Ensembl, NCBI, dbVar, DGV
  • Advanced Technologies (if applicable):
  • Single-cell analysis findings (cell-type specific mechanisms, cellular heterogeneity) > Search first: Human Cell Atlas, Single Cell Portal, GEO, CELLxGENE
  • Spatial transcriptomics findings > Search first: GEO, Spatial Research, Vizgen, 10x Genomics data
  • Multi-omics integration results > Search first: TCGA, ICGC, cBioPortal, LinkedOmics, PubMed
  • Functional genomics screens (CRISPR, RNAi) > Search first: DepMap, GenomeRNAi, PubMed, BioGRID ORCS

For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types

7. Anatomical Structures Affected

  • Organ Level:
  • Primary organs directly affected
  • Secondary organ involvement (complications, secondary effects)
  • Body systems involved (cardiovascular, nervous, digestive, respiratory, endocrine, etc.)

    Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT

  • Tissue and Cell Level:
  • Specific tissue types affected (epithelial, connective, muscle, nervous)
  • Specific cell populations targeted (with Cell Ontology terms)

    Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB

  • Subcellular Level:
  • Cellular compartments involved (mitochondria, nucleus, ER, lysosomes) (with GO Cellular Component terms)

    Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas

  • Localization:
  • Specific anatomical sites (with UBERON terms) > Search first: FMA, Uberon, NeuroNames (for brain), SNOMED CT
  • Lateralization (unilateral, bilateral, asymmetric) > Search first: HPO, clinical literature, imaging databases

8. Temporal Development

  • Onset:
  • Typical age of onset (congenital, pediatric, adult, geriatric)
  • Onset pattern (acute, subacute, chronic, insidious)

    Search first: OMIM, Orphanet, HPO, PubMed

  • Progression:
  • Disease stages (early, intermediate, advanced, end-stage) > Search first: Cancer Staging Manual (AJCC), WHO classifications, PubMed
  • Progression rate (rapid, slow, variable)
  • Disease course pattern (episodic, relapsing-remitting, progressive, stable)
  • Disease duration (self-limited, chronic lifelong)

    Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM

  • Patterns:
  • Remission patterns (spontaneous, treatment-induced) > Search first: Clinical trial databases, disease registries, PubMed
  • Critical periods (time windows of vulnerability or opportunity for intervention) > Search first: PubMed, developmental biology databases, clinical guidelines

9. Inheritance and Population

  • Epidemiology:
  • Prevalence (cases per 100,000 at given time)
  • Incidence (new cases per 100,000 per year)

    Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries

  • For Genetic Etiology:
  • Inheritance pattern (AD, AR, X-linked, mitochondrial, multifactorial, polygenic) > Search first: OMIM, Orphanet, ClinVar, GTR (Genetic Testing Registry)
  • Penetrance (complete, incomplete, age-dependent) > Search first: ClinVar, OMIM, PubMed, ClinGen
  • Expressivity (variable, consistent) > Search first: OMIM, ClinVar, PubMed
  • Genetic anticipation (increasing severity in successive generations) > Search first: OMIM, PubMed (especially for repeat expansion disorders)
  • Germline mosaicism > Search first: ClinVar, OMIM, genetic counseling literature, PubMed
  • Founder effects (population-specific mutations) > Search first: gnomAD, population genetics databases, PubMed
  • Consanguinity role > Search first: OMIM, population studies, genetic counseling resources
  • Carrier frequency > Search first: gnomAD, carrier screening databases, GeneReviews, GTR
  • Population Demographics:
  • Affected populations (ethnic or demographic groups with higher prevalence) > Search first: gnomAD, 1000 Genomes, PAGE Study, PubMed, population registries
  • Geographic distribution (endemic areas, regional variation) > Search first: WHO, CDC, GBD, Orphanet, geographic epidemiology databases
  • Geographic distribution of specific variants
  • Sex ratio (male:female) > Search first: Disease registries, OMIM, PubMed, epidemiological databases
  • Age distribution of affected individuals > Search first: CDC, disease registries, SEER, Orphanet

10. Diagnostics

  • Clinical Tests:
  • Laboratory tests (blood, urine, tissue chemistry, specific enzyme assays) > Search first: LOINC, LabTests Online, PubMed
  • Biomarkers (proteins, metabolites, genetic markers, circulating biomarkers) > Search first: FDA Biomarker List, BEST (Biomarkers, EndpointS, and other Tools), PubMed
  • Imaging studies (X-ray, CT, MRI, PET, ultrasound) > Search first: RadLex, DICOM, Radiopaedia, imaging databases
  • Functional tests (pulmonary function, cardiac stress tests) > Search first: LOINC, clinical guidelines, PubMed
  • Electrophysiology (EEG, EMG, ECG, nerve conduction studies) > Search first: LOINC, clinical neurophysiology databases, PubMed
  • Biopsy findings (histopathology, immunohistochemistry) > Search first: SNOMED CT, College of American Pathologists resources, PubMed
  • Pathology findings (microscopic examination) > Search first: SNOMED CT, Digital Pathology databases, PubMed
  • Genetic Testing:

    Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen

  • Overview of recommended genetic testing approach
  • Whole genome sequencing (WGS) utility > Search first: GTR, ClinVar, GEL (Genomics England), gnomAD
  • Whole exome sequencing (WES) utility > Search first: GTR, ClinVar, OMIM, GeneMatcher
  • Gene panels (which panels, which genes) > Search first: GTR, ClinVar, laboratory-specific databases
  • Single gene testing > Search first: GTR, ClinVar, OMIM, GeneReviews
  • Chromosomal microarray (CMA) > Search first: DECIPHER, ClinVar, dbVar, ECARUCA
  • Karyotyping > Search first: Chromosome Abnormality Database, ClinVar, cytogenetics resources
  • FISH > Search first: ClinVar, cytogenetics databases, PubMed
  • Mitochondrial DNA testing > Search first: MITOMAP, MSeqDR, ClinVar, GTR
  • Repeat expansion testing > Search first: GTR, ClinVar, repeat expansion databases, PubMed
  • Omics-Based Diagnostics (if applicable):
  • RNA sequencing / transcriptomics > Search first: GEO, ArrayExpress, GTEx, RNA-seq databases
  • Proteomics > Search first: PRIDE, ProteomeXchange, FDA Biomarker database
  • Metabolomics > Search first: MetaboLights, Metabolomics Workbench, HMDB
  • Epigenomics > Search first: GEO, ENCODE, Roadmap Epigenomics, MethBase
  • Liquid biopsy > Search first: COSMIC, ClinVar, liquid biopsy databases, PubMed
  • Clinical Criteria:
  • Standardized diagnostic criteria (DSM, ICD, society guidelines) > Search first: DSM-5, ICD-11, clinical society guidelines, UpToDate
  • Differential diagnosis (other conditions to rule out, with distinguishing features) > Search first: DynaMed, UpToDate, clinical decision support systems
  • Screening:
  • Screening methods for asymptomatic individuals (newborn screening, carrier screening, cascade screening) > Search first: ACMG recommendations, CDC newborn screening, GTR

11. Outcome/Prognosis

  • Survival and Mortality:
  • Survival rate (5-year, 10-year, overall) > Search first: SEER, cancer registries, disease-specific registries, PubMed
  • Life expectancy (with and without treatment if applicable) > Search first: Orphanet, disease registries, actuarial databases, PubMed
  • Mortality rate > Search first: CDC, WHO, GBD, national mortality databases
  • Disease-specific mortality (deaths directly attributable to disease) > Search first: Disease registries, CDC Wonder, GBD, PubMed
  • Morbidity and Function:
  • Morbidity (disease-related disability and health impacts) > Search first: GBD, WHO, disability databases, PubMed
  • Disability outcomes (long-term functional impairments) > Search first: ICF (International Classification of Functioning), disability registries
  • Quality of life measures (EQ-5D, SF-36, PROMIS, disease-specific tools) > Search first: EQ-5D database, SF-36, PROMIS, PubMed
  • Disease Course:
  • Complications (secondary problems: infections, organ failure, etc.) > Search first: ICD codes, disease registries, clinical databases, PubMed
  • Recovery potential (likelihood and extent of recovery, with vs without treatment) > Search first: Natural history studies, rehabilitation databases, PubMed
  • Prediction:
  • Prognostic factors (age, disease severity, biomarkers, treatment response) > Search first: Prognostic models databases, clinical calculators, PubMed
  • Prognostic biomarkers (molecular markers predicting disease course) > Search first: FDA Biomarker database, PubMed, cancer prognostic databases

12. Treatment

  • Pharmacotherapy:
  • Pharmacological treatments (drug names, drug classes, mechanisms of action) > Search first: DrugBank, RxNorm, ATC classification, DailyMed, FDA databases
  • Pharmacogenomics (how genetic variants affect drug metabolism, efficacy, toxicity) > Search first: PharmGKB, CPIC (Clinical Pharmacogenetics), FDA Table of PGx Biomarkers
  • Advanced Therapeutics:
  • Gene therapy (viral vectors, CRISPR, gene replacement, gene editing) > Search first: ClinicalTrials.gov, FDA gene therapy database, ASGCT resources
  • Cell therapy (stem cell transplant, CAR-T, cellular therapeutics) > Search first: ClinicalTrials.gov, FDA cell therapy database, FACT standards
  • RNA-based therapies (ASOs, siRNA, mRNA therapies) > Search first: ClinicalTrials.gov, FDA approvals, PubMed
  • Targeted therapies (treatments directed at specific molecular targets) > Search first: My Cancer Genome, OncoKB, ClinicalTrials.gov, FDA approvals
  • Immunotherapies (checkpoint inhibitors, monoclonal antibodies) > Search first: Cancer Immunotherapy Database, FDA approvals, ClinicalTrials.gov
  • Surgical and Interventional:
  • Surgical interventions (types of surgery, timing, outcomes) > Search first: CPT codes, surgical registries, clinical guidelines, PubMed
  • Supportive and Rehabilitative:
  • Supportive care (symptom management, pain control, nutrition) > Search first: Clinical guidelines, Cochrane Library, PubMed
  • Rehabilitation (physical therapy, occupational therapy, speech therapy) > Search first: Rehabilitation medicine databases, clinical guidelines, PubMed
  • Experimental:
  • Experimental treatments in clinical trials (with NCT identifiers if available) > Search first: ClinicalTrials.gov, EU Clinical Trials Register, WHO ICTRP
  • Treatment Outcomes:
  • Treatment response rates > Search first: Clinical trial databases, FDA reviews, systematic reviews, PubMed
  • Side effects and adverse events > Search first: FDA Adverse Event Reporting System (FAERS), MedWatch, PubMed
  • Treatment Strategy:
  • Treatment algorithms (clinical pathways, decision trees) > Search first: Clinical practice guidelines, NCCN Guidelines, UpToDate
  • Combination therapies > Search first: ClinicalTrials.gov, treatment guidelines, PubMed
  • Personalized medicine approaches (genotype-guided treatment) > Search first: My Cancer Genome, CIViC, PharmGKB, precision medicine databases

For each treatment, suggest NCIT (NCI Thesaurus) clinical-intervention terms where applicable.

13. Prevention

  • Prevention Levels:
  • Primary prevention (preventing disease occurrence: vaccination, risk factor modification) > Search first: CDC, WHO, USPSTF recommendations, Cochrane Library
  • Secondary prevention (early detection and treatment: screening programs, early intervention) > Search first: USPSTF, CDC screening guidelines, WHO
  • Tertiary prevention (preventing complications in those with disease) > Search first: Clinical guidelines, disease management protocols, PubMed
  • Immunization: Vaccine strategies (if applicable)

    Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database

  • Screening and Early Detection:
  • Screening programs (population-based: newborn screening, cancer screening) > Search first: CDC screening programs, USPSTF, cancer screening databases
  • Genetic screening (carrier screening, preimplantation genetic diagnosis, prenatal testing) > Search first: ACMG recommendations, ACOG guidelines, GTR
  • Risk stratification (identifying high-risk individuals for targeted prevention) > Search first: Risk prediction models, clinical calculators, PubMed
  • Behavioral Interventions: Lifestyle modifications to reduce risk

    Search first: CDC, WHO, behavioral intervention databases, Cochrane Library

  • Counseling: Genetic counseling (risk assessment, family planning guidance)

    Search first: NSGC resources, ACMG guidelines, GeneReviews

  • Public Health:
  • Public health interventions (sanitation, vector control, health education) > Search first: CDC, WHO, public health databases, PubMed
  • Environmental interventions (reducing environmental risk factors) > Search first: EPA databases, WHO environmental health, PubMed
  • Prophylaxis: Preventive medications or procedures

    Search first: Clinical guidelines, FDA approvals, PubMed

14. Other Species / Natural Disease

  • Taxonomy: Species affected (with NCBI Taxon identifiers)

    Search first: NCBI Taxonomy

  • Breed: Specific breeds affected (with VBO identifiers if applicable)

    Search first: VBO (Vertebrate Breed Ontology)

  • Gene: Orthologous genes in other species (with NCBI Gene IDs)

    Search first: NCBI Gene

  • Natural Disease:
  • Naturally occurring disease in other species (companion animals, wildlife) > Search first: OMIA (Online Mendelian Inheritance in Animals), VetCompass, PubMed
  • Veterinary relevance and importance in animal health > Search first: OMIA, veterinary databases, PubMed
  • Comparative Biology:
  • Comparative pathology (similarities and differences across species) > Search first: OMIA, comparative pathology databases, PubMed
  • Evolutionary conservation of disease mechanisms > Search first: HomoloGene, OrthoMCL, Alliance of Genome Resources
  • Transmission (if applicable):
  • Zoonotic potential > Search first: CDC zoonotic diseases, WHO zoonoses, GIDEON
  • Cross-species susceptibility > Search first: NCBI Taxonomy, veterinary databases, PubMed

15. Model Organisms

  • Model Types:
  • Model organism type (mammalian, invertebrate, cellular, in vitro) > Search first: Alliance of Genome Resources, model organism databases
  • Specific model systems (mouse, rat, zebrafish, Drosophila, C. elegans, yeast, cell lines, organoids, iPSCs) > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, SGD, ATCC, Cellosaurus
  • Induced models (drug treatment, surgical intervention, environmental manipulation) > Search first: MGI, model organism databases, PubMed
  • Genetic Models:
  • Types available (knockout, knock-in, transgenic, conditional, humanized) > Search first: MGI, IMPC, KOMP, EuMMCR, IMSR
  • Model Characteristics:
  • Phenotype recapitulation (how well model reproduces human disease features) > Search first: Model organism databases, comparative studies, PubMed
  • Model limitations (aspects of human disease not captured) > Search first: Model organism databases, PubMed, review articles
  • Applications:
  • Research applications (what aspects of disease can be studied) > Search first: Model organism databases, PubMed
  • Resources:
  • Model databases > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, IMSR, EMMA, MMRRC

Citation Requirements

  • Cite primary literature (PMID preferred) for all mechanistic and clinical claims
  • Prioritize recent reviews and landmark papers
  • Include direct quotes from abstracts where possible to support key statements
  • Distinguish evidence source types: human clinical, model organism, in vitro, computational

Output Format

Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, NCIT, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease

This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (NCIT terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details

Uveitis: comprehensive disease-characteristics report

Executive summary

Uveitis is not one molecular disease but a heterogeneous group of more than 25 intraocular inflammatory disorders. It is classified anatomically as anterior, intermediate, posterior, or panuveitis and etiologically as infectious, noninfectious immune-mediated, idiopathic, drug/trauma/surgery-associated, or masquerade disease. The umbrella concept is therefore complex and usually multifactorial, not a single-gene Mendelian condition. Uveitis disproportionately affects working-age people, can recur for decades, and causes vision loss through both direct inflammatory injury and complications such as macular edema, cataract, glaucoma, retinal ischemia, and retinal detachment. Reported prevalence is approximately 36.2–730 per 100,000 and incidence 17–52.4 per 100,000 person-years, with large geographic and methodological variation. (asghar2024“infectiousuveitisa pages 1-2, trivedi2019theuseof pages 3-5, rosenbaum2018theeyeshave pages 1-3, delatorre2024epidemiologyclinicalfeatures pages 1-2)

The most important 2023–2024 advances are: evidence connecting HLA-B27 uveitis to enteric antigen exposure and mucosally differentiated CD8 T cells; single-cell resolution of Th17/Treg and PIM1–CXCR4 biology; aqueous and tear proteomic biomarker discovery; highly accurate deep-learning detection of acute retinal necrosis; quantification of immune-checkpoint-inhibitor-associated risk; and late-stage trials of oral pathway-directed therapy and optimized local corticosteroid delivery. These findings remain heterogeneous in readiness: imaging AI has human external validation, proteomic panels require larger validation, and TIGIT, dimethyl fumarate, progesterone, and CD28/ICOS blockade remain preclinical for uveitis. (wu2024comprehensiveproteomicprofiling pages 1-2, peters2024tigitstimulationsuppresses pages 1-2, kuo2024associationbetweenimmune pages 1-2, rodriguezmartinez2024potentialprognosticprotein pages 1-2, liu2023progesteroneattenuatesth17cell pages 1-2, zhu2024beneficialmechanismsof pages 1-2, paley2024mucosalsignaturesof pages 1-2, wang2024automatedearlydetection pages 1-2, NCT06431373 chunk 1, wilson2023systemicadministrationof pages 1-2)

The following table provides a compact ontology-ready representation; the narrative below adds qualification and evidence interpretation.

Domain Core finding Suggested ontology terms/identifiers Evidence type
Definition / disease entity Uveitis is intraocular inflammation affecting the uveal tract and adjacent ocular structures; major anatomic classes are anterior, intermediate, posterior, and panuveitis (rosenbaum2018theeyeshave pages 1-3, rosenbaum2018theeyeshave pages 10-14, delatorre2024epidemiologyclinicalfeatures pages 1-2) MONDO:0020283 uveitis; label-only: anterior uveitis, intermediate uveitis, posterior uveitis, panuveitis; MeSH/ICD/SUN classification labels Human review + multicenter clinical cohort
Classification / disease-level resource SUN criteria are used for uveitis definition and anterior chamber grading; National Eye Institute system used for vitreous haze grading (delatorre2024epidemiologyclinicalfeatures pages 1-2, wang2024automatedearlydetection pages 1-2) label-only: SUN Working Group criteria; NEI vitreous haze scale Human clinical standards
Epidemiology Reported prevalence ranges about 36.2–730 per 100,000 and incidence 17–52.4 per 100,000; uveitis causes substantial visual impairment and often affects working-age adults (delatorre2024epidemiologyclinicalfeatures pages 1-2, trivedi2019theuseof pages 3-5, rosenbaum2018theeyeshave pages 1-3) label-only: epidemiologic measure, visual impairment Human epidemiology / reviews
Demographics / regional pattern In a Colombian multicenter cohort of 3,404 patients, mean age at diagnosis was 41.1 years, 54.2% were female, 66.7% unilateral, 48.3% acute, and 83% non-granulomatous (delatorre2024epidemiologyclinicalfeatures pages 1-2) label-only: unilateral disease, acute onset, non-granulomatous inflammation Human multicenter cohort
Major phenotype / ocular symptoms-signs Common phenotype spectrum includes anterior chamber cells/flare, vitreous haze, retinal vasculitis, chorioretinal inflammation, optic disc edema, and reduced visual acuity; anatomy-specific manifestations differ by subtype (rosenbaum2018theeyeshave pages 10-14, wang2024automatedearlydetection pages 1-2, delatorre2024epidemiologyclinicalfeatures pages 1-2) HPO label-only: decreased visual acuity, photophobia, ocular pain, eye redness, floaters, vitreous haze, retinal vasculitis, macular edema Human clinical + imaging
Major phenotype / pediatric disease Pediatric uveitis can be asymptomatic, especially JIA-associated chronic anterior uveitis; childhood incidence ~4.3/100,000 and prevalence ~27.9/100,000 (chang2021uveitisinchildren pages 1-3) HPO label-only: asymptomatic anterior uveitis, cataract, glaucoma Human pediatric review
Quality-of-life / functional burden Uveitis is sight-threatening and associated with physical, economic, and visual-function burden; VFQ-25 is used as an outcome in current trials (zhu2024beneficialmechanismsof pages 1-2, NCT06310837 chunk 1) label-only: NEI VFQ-25; visual function impairment Human review + interventional trial design
Anatomy affected / organ level Primary structures include iris, ciliary body, choroid, retina, vitreous, anterior chamber, and posterior segment (rosenbaum2018theeyeshave pages 10-14, wu2024comprehensiveproteomicprofiling pages 1-2, wang2024automatedearlydetection pages 1-2) UBERON label-only: iris, ciliary body, choroid, retina, vitreous humor, anterior chamber of eyeball, posterior segment of eyeball Human review + proteomics
Cell types involved Pathogenic and regulatory immune cells implicated include Th17 cells, Th1 cells, Treg cells, CD8+ T cells, dendritic cells, granulocytes/neutrophils, plasma cells/B cells, NK cells, and retinal/endothelial cells (peters2024tigitstimulationsuppresses pages 1-2, liu2023progesteroneattenuatesth17cell pages 1-2, zhu2024beneficialmechanismsof pages 1-2, paley2024mucosalsignaturesof pages 1-2, hoffmann2022preactivatedgranulocytesfrom pages 1-3, chang2021uveitisinchildren pages 1-3) CL label-only: T helper 17 cell, T-helper 1 cell, regulatory T cell, CD8-positive alpha-beta T cell, dendritic cell, neutrophil, plasma cell, natural killer cell, endothelial cell Human + animal + in vitro
Molecular pathways Recurrently implicated pathways include cytokine-cytokine receptor interaction, JAK-STAT signaling, IL-23/Th17/GM-CSF signaling, PIM1-AKT-FOXO1, CXCR4-mediated trafficking, complement activation, ROS/TXNIP/HIF-1α, NF-κB, and STAT3 (asghar2024“infectiousuveitisa pages 1-2, liu2023progesteroneattenuatesth17cell pages 1-2, zhu2024beneficialmechanismsof pages 1-2, wu2024comprehensiveproteomicprofiling pages 1-2, hoffmann2022preactivatedgranulocytesfrom pages 1-3) GO/Reactome label-only: inflammatory response, T cell activation, leukocyte migration, cytokine-mediated signaling pathway, complement activation, oxidative stress response Human omics + animal mechanistic + in vitro
Etiology / broad categories Uveitis can be infectious, noninfectious immune-mediated, drug-induced, traumatic, post-surgical, idiopathic, or masquerade syndrome (delatorre2024epidemiologyclinicalfeatures pages 1-2, trivedi2019theuseof pages 1-3, kuo2024associationbetweenimmune pages 1-2) MONDO:0020283; label-only: infectious uveitis, noninfectious uveitis, drug-induced uveitis, masquerade syndrome Human cohort + reviews
Etiology / infectious Infectious uveitis is caused by viruses, bacteria, fungi, and parasites; a 2024 review found viruses 39% and bacteria 17% among infectious etiologies reviewed, and Colombian data identified toxoplasmosis as a leading cause (25.3%) (asghar2024“infectiousuveitisa pages 1-2, delatorre2024epidemiologyclinicalfeatures pages 1-2) label-only: ocular toxoplasmosis, viral uveitis, tuberculous uveitis, herpetic uveitis Human systematic review + cohort
Etiology / immune-mediated systemic associations Important associated systemic diseases include spondyloarthritis/HLA-B27 disease, juvenile idiopathic arthritis, Behçet disease, sarcoidosis, Vogt–Koyanagi–Harada syndrome, inflammatory bowel disease, and TINU syndrome (trivedi2019theuseof pages 1-3, rosenbaum2018theeyeshave pages 1-3, chang2021uveitisinchildren pages 1-3) label-only: HLA-B27-associated acute anterior uveitis, JIA-associated uveitis, Behçet uveitis, ocular sarcoidosis, VKH, TINU syndrome Human reviews
Genetic risk HLA-B27 is a major risk allele for acute anterior uveitis; Open Targets links uveitis/anterior uveitis to ERAP1, IL23R, TNF, IL17A, and IL1B, supporting polygenic immune susceptibility (paley2024mucosalsignaturesof pages 1-2, OpenTargets Search: uveitis, chang2021uveitisinchildren pages 1-3) label-only: HLA-B27, ERAP1, IL23R, TNF, IL17A, IL1B Human genetic + database evidence
Gene-environment / microbiome HLA-B27-associated disease may involve enteric antigen exposure and molecular mimicry; YeiH-specific CD8+ T cells in B27-associated anterior uveitis show mucosal signatures (CD161, integrin α4β7, CCR6), supporting a gut-eye axis (paley2024mucosalsignaturesof pages 1-2) GO label-only: antigen processing and presentation, mucosal immune response; CL label-only: CD8+ T cell Human translational immunology
Environmental / drug trigger Immune checkpoint inhibitors are a clinically important trigger of drug-induced uveitis; in TriNetX, ICI exposure was associated with HR 2.39 for incident uveitis over 144 months (kuo2024associationbetweenimmune pages 1-2) NCIT label-only: immune checkpoint inhibitor therapy; HPO label-only: uveitis adverse event Human population-based EHR cohort
Diagnostics / clinical workup Standard workup includes ophthalmic examination by slit lamp, intraocular pressure measurement, dilated fundus examination, visual acuity, and evaluation for systemic/infectious disease in multidisciplinary care (delatorre2024epidemiologyclinicalfeatures pages 1-2, rodriguezmartinez2024potentialprognosticprotein pages 1-2) LOINC/SNOMED label-only: visual acuity testing, slit lamp exam, tonometry, dilated fundus exam Human clinical practice
Diagnostics / imaging Imaging and grading include OCT, fluorescein angiography, ultra-widefield color fundus photography, and OCT/OCTA in trials and biomarker workups (wang2024automatedearlydetection pages 1-2, NCT06310837 chunk 1, NCT02595398 chunk 1) label-only: optical coherence tomography, fluorescein angiography, OCT angiography, ultra-widefield fundus photography Human imaging studies + trials
Diagnostics / biomarkers Aqueous humor proteomics in idiopathic uveitis/VKH identified complement activation and suggested transferrin plus complement factor B as a biomarker panel; tear proteomics in anti-TNF nonresponders highlighted DEF-1,3, biotinidase, ABCA1, neutrophil effector functions, and redox imbalance (wu2024comprehensiveproteomicprofiling pages 1-2, rodriguezmartinez2024potentialprognosticprotein pages 1-2) label-only: transferrin, complement factor B, defensin-1/3, biotinidase, ABCA1, S100 proteins, cytokines/chemokines Human proteomics
Diagnostics / AI implementation Deep learning on ultra-widefield fundus images achieved AUROC 0.996 internal and 0.973 external for uveitis screening, and AUROC 0.960/0.971 for ARN discrimination, with performance comparable to ophthalmologists (wang2024automatedearlydetection pages 1-2) NCIT label-only: artificial intelligence-assisted diagnosis; label-only: acute retinal necrosis Human computational / imaging validation
Complications Important complications include cataract, glaucoma/ocular hypertension, cystoid macular edema, retinal detachment, epiretinal membrane, vitreous hemorrhage, retinal neovascularization, ischemia, and blindness/vision loss (trivedi2019theuseof pages 3-5, delatorre2024epidemiologyclinicalfeatures pages 1-2, wang2024automatedearlydetection pages 1-2, chang2021uveitisinchildren pages 1-3) HPO label-only: cataract, glaucoma, cystoid macular edema, retinal detachment, vitreous hemorrhage, blindness Human cohort + reviews
Prognosis / disease course Disease course may be acute, chronic, recurrent, unilateral or bilateral; recurrent or undertreated inflammation leads to structural damage and visual loss; ARN treatment delay is linked to worse vision outcomes (delatorre2024epidemiologyclinicalfeatures pages 1-2, wang2024automatedearlydetection pages 1-2, chang2021uveitisinchildren pages 1-3) HPO label-only: recurrent uveitis, chronic inflammation, severe visual loss Human cohort + disease-specific study
Established treatment / corticosteroids Corticosteroids remain mainstay therapy (topical, local, systemic); glucocorticoid target association is reflected by NR3C1 linkage in Open Targets (trivedi2019theuseof pages 1-3, OpenTargets Search: uveitis) NCIT label-only: corticosteroid therapy, triamcinolone acetonide, fluocinolone acetonide implant Human reviews + database
Established treatment / conventional immunomodulators Steroid-sparing systemic agents include methotrexate, azathioprine, mycophenolate mofetil, and cyclosporine (trivedi2019theuseof pages 1-3) NCIT label-only: methotrexate, azathioprine, mycophenolate mofetil, cyclosporine Human review
Established treatment / biologics Adalimumab is the only systemic biologic specifically noted as FDA/EMA approved for noninfectious intermediate, posterior, and panuveitis; nonresponse may occur in up to 40% (rodriguezmartinez2024potentialprognosticprotein pages 1-2, trivedi2019theuseof pages 1-3) NCIT label-only: adalimumab, TNF inhibitor Human review + clinical proteomics cohort
Local interventional therapy Intravitreal/suprachoroidal corticosteroid delivery is established in practice and trials; PEACHTREE tested suprachoroidal triamcinolone acetonide for uveitic macular edema, and TYNI is evaluating two YUTIQ implants versus sham (NCT02595398 chunk 1, NCT05486468 chunk 1) NCIT label-only: suprachoroidal injection, intravitreal implant, triamcinolone acetonide, fluocinolone acetonide Human phase 3 trials
Emerging systemic therapy / current trials Active 2024-era trials include brepocitinib phase 3 CLARITY in active noninfectious non-anterior uveitis and a randomized trial of adalimumab biosimilar + mycophenolate versus corticosteroids + mycophenolate; izokibep phase 2b was terminated after endpoints were not met (NCT06431373 chunk 1, NCT06310837 chunk 1, NCT05384249 chunk 1) NCIT label-only: brepocitinib, adalimumab biosimilar, mycophenolate mofetil, izokibep, JAK/TYK2 pathway inhibition, IL-17A inhibition Human clinical trials
Emerging therapeutic targets Candidate targets/mechanisms from recent work include TIGIT agonism, PIM1/CXCR4 inhibition, IL-6/JAK/complement targeting in anti-TNF-refractory disease, and dual CD28/ICOS blockade with acazicolcept (peters2024tigitstimulationsuppresses pages 1-2, zhu2024beneficialmechanismsof pages 1-2, rodriguezmartinez2024potentialprognosticprotein pages 1-2, wilson2023systemicadministrationof pages 1-2) NCIT label-only: TIGIT agonist, acazicolcept, IL-6 inhibitor, JAK inhibitor, complement inhibitor, CXCR4 inhibitor, PIM1 inhibitor Animal mechanistic + human proteomics + preclinical translational
Prevention / secondary-tertiary Practical prevention centers on early detection, prompt treatment, multidisciplinary screening in at-risk groups such as JIA, and avoidance/exclusion of infectious etiologies before immunosuppression (chang2021uveitisinchildren pages 1-3, delatorre2024epidemiologyclinicalfeatures pages 1-2, NCT06431373 chunk 1) label-only: ophthalmic screening, tertiary prevention, tuberculosis screening before biologics Human guidelines/review + trial eligibility
Natural disease in other species Equine recurrent uveitis is a spontaneous remitting-relapsing autoimmune uveitis and a leading cause of blindness in horses; it shares clinical and immunopathologic features with human recurrent panuveitis (hoffmann2022preactivatedgranulocytesfrom pages 1-3) label-only: equine recurrent uveitis; NCBI Taxon label-only: Equus caballus Veterinary natural disease + comparative pathology
Model organisms / experimental models Experimental autoimmune uveitis (EAU) in mice and rats is the principal model for autoimmune/noninfectious uveitis; useful for studying Th1/Th17 disease, Treg biology, ocular infiltration, and testing therapies, but does not fully capture all human subtypes (peters2024tigitstimulationsuppresses pages 1-2, liu2023progesteroneattenuatesth17cell pages 1-2, zhu2024beneficialmechanismsof pages 1-2, wilson2023systemicadministrationof pages 1-2, chang2021uveitisinchildren pages 1-3) label-only: experimental autoimmune uveitis, Lewis rat model, C57BL/6 mouse model Animal model review + mechanistic studies

Table: This table summarizes ontology-ready disease facts for uveitis across clinical, mechanistic, diagnostic, therapeutic, and translational domains. It is designed to support structured knowledge-base curation using only evidence already gathered.

1. Disease information

Definition and classification. Uveitis means intraocular inflammation involving the uveal tract—iris, ciliary body, and choroid—and often adjacent retina, vitreous, retinal vessels, and optic nerve. Under Standardization of Uveitis Nomenclature (SUN), anterior uveitis has anterior-chamber inflammation as the principal site; intermediate uveitis predominantly affects vitreous; posterior uveitis affects retina and/or choroid; and panuveitis involves anterior chamber, vitreous, and retina/choroid without one predominant site. Descriptors also include onset, duration, course, laterality, granulomatous morphology, activity, and structural damage. (asghar2024“infectiousuveitisa pages 1-2, rosenbaum2018theeyeshave pages 10-14, rosenbaum2018theeyeshave pages 1-3, delatorre2024epidemiologyclinicalfeatures pages 1-2)

Identifiers and synonyms. The current umbrella identifier retrieved from Open Targets/MONDO is MONDO:0020283. More specific entities include anterior uveitis MONDO:0006651, posterior uveitis MONDO:0006918, and autoimmune uveitis MONDO:0031012. Common terms include intraocular inflammation, iritis, iridocyclitis, choroiditis, chorioretinitis/retinochoroiditis, pars planitis, and panuveitis, although these are not fully interchangeable. ICD-10-CM distributes disease across H20–H22 and H30–H32 rather than providing one etiologically precise umbrella code; subtype coding should be preferred. No single OMIM or Orphanet entry appropriately represents all uveitis because the umbrella is not a unitary Mendelian or rare disease. (OpenTargets Search: uveitis, rosenbaum2018theeyeshave pages 10-14, rosenbaum2018theeyeshave pages 1-3)

Data provenance. Most facts here are aggregated disease-level evidence from reviews, cohorts, databases, and trials. The 2024 Colombian study aggregated clinical records from 3,404 patients; the immune-checkpoint study used propensity-matched EHR data; aqueous/tear studies used patient biospecimens; and experimental autoimmune uveitis (EAU) findings come from animals rather than individual-patient EHRs. (wu2024comprehensiveproteomicprofiling pages 1-2, kuo2024associationbetweenimmune pages 1-2, rodriguezmartinez2024potentialprognosticprotein pages 1-2, delatorre2024epidemiologyclinicalfeatures pages 1-2)

2. Etiology, risk, protection, and gene–environment interaction

Causal categories

  1. Infectious: herpesviruses including HSV/VZV/CMV, Toxoplasma gondii, Mycobacterium tuberculosis, Treponema pallidum, and regionally important bacterial, fungal, and parasitic infections. A 2024 systematic review of 97 studies reported viruses in 39% and bacteria in 17% of its infectious-uveitis etiologic distribution, emphasizing that proportions vary geographically. In Colombia, toxoplasmosis accounted for 25.3% of all cases and virus-associated disease for 6.4%. (asghar2024“infectiousuveitisa pages 1-2, asghar2024“infectiousuveitisa pages 14-15, delatorre2024epidemiologyclinicalfeatures pages 1-2)
  2. Noninfectious immune-mediated: isolated idiopathic uveitis or ocular manifestations of HLA-B27 spondyloarthritis, JIA, Behçet disease, sarcoidosis, inflammatory bowel disease, Vogt–Koyanagi–Harada disease, and tubulointerstitial nephritis–uveitis. (trivedi2019theuseof pages 1-3, rosenbaum2018theeyeshave pages 1-3, chang2021uveitisinchildren pages 1-3)
  3. Other: trauma, surgery, lens-related inflammation, drugs, and masquerade syndromes such as intraocular lymphoma. The Colombian investigators explicitly included autoimmune, autoinflammatory, traumatic, postsurgical, drug-induced, and idiopathic categories. (kuo2024associationbetweenimmune pages 1-2, delatorre2024epidemiologyclinicalfeatures pages 1-2)

Genetic susceptibility

Uveitis overall has multifactorial/polygenic inheritance. HLA-B27 is the strongest established risk factor for acute anterior uveitis; approximately 50% of acute anterior uveitis patients in a recent translational report were HLA-B27-positive. HLA-DR2/DR15 has been associated with pars planitis, and syndrome-specific associations include HLA-B51 in Behçet disease and melanocyte-directed HLA backgrounds in VKH. Open Targets supports associations involving ERAP1, IL23R, TNF, IL17A, IL1B, and other loci, but these are susceptibility/therapeutic associations, not deterministic “causal genes” for umbrella uveitis. (OpenTargets Search: uveitis, trivedi2019theuseof pages 3-5, paley2024mucosalsignaturesof pages 1-2, chang2021uveitisinchildren pages 1-3)

Accordingly, routine claims about pathogenic variants, penetrance, carrier frequency, anticipation, germline mosaicism, or founder variants are not applicable to nonsyndromic umbrella uveitis. Germline panel/WES/WGS testing is not routine; it is reserved for unusual pediatric, familial, syndromic, autoinflammatory, immunodeficiency, or retinal-dystrophy phenotypes. No recurrent somatic mutation or chromosomal abnormality defines ordinary uveitis.

Environmental and iatrogenic factors

Geography, pathogen prevalence, sanitation, food exposure, immune status, migration, and access to molecular diagnostics shape infectious disease. Smoking and microbiome alterations are plausible modifiers in associated systemic disease, but no universal lifestyle exposure has a sufficiently consistent effect to be considered causal across all uveitis. Drug triggers include immune checkpoint inhibitors. In a 2024 matched TriNetX cohort of 71,931 exposed and 71,931 unexposed cancer patients, ICI use was associated with uveitis HR 2.39 (95% CI 2.07–2.75); anti-PD-1 monotherapy HR was 1.98, anti-CTLA-4 5.86, and combined anti-PD-1/CTLA-4 5.04. The article’s conclusion states: “A significantly increased risk for uveitis diseases was found among the ICI group from the first year of follow-up.” (kuo2024associationbetweenimmune pages 1-2)

Protective factors and gene–environment interaction

No genetic or dietary factor is validated for primary prevention of all uveitis. Immune tolerance, intact blood–ocular barriers, regulatory T-cell activity, prompt infection control, and—in JIA—regular asymptomatic screening are practically protective against onset or damage. Hormonal observations, including pregnancy-associated remission, are hypothesis-generating rather than preventive recommendations. (liu2023progesteroneattenuatesth17cell pages 1-2, chang2021uveitisinchildren pages 1-3)

The clearest recent gene–environment model concerns HLA-B27. A 2024 human study found that YeiH-specific CD8 T cells in HLA-B27 acute anterior uveitis and axial spondyloarthritis expressed CD161, integrin α4β7, and CCR6, compatible with intestinal differentiation. Because YeiH occurs in enteric microbes and can be presented by HLA-B27 to ocular/joint-enriched public T-cell receptors, the proposed chain is: HLA-B27 antigen presentation + enteric microbial exposure → cross-reactive mucosal CD8 T-cell expansion → trafficking to eye → acute anterior inflammation. The authors cautiously conclude that early antigen exposure and differentiation “may occur in enteric organs”; this is strong translational evidence but not proof that one organism causes disease. Published July 18, 2024; DOI: https://doi.org/10.1172/jci.insight.174776. (paley2024mucosalsignaturesof pages 1-2)

3. Phenotypes

Anterior disease commonly produces acute pain, redness, photophobia, tearing, blurred vision, ciliary injection, keratic precipitates, anterior-chamber cells/flare, and sometimes posterior synechiae. HLA-B27 disease is typically sudden, unilateral, symptomatic, and recurrent. JIA-associated anterior uveitis is often bilateral, chronic, relapsing, and initially asymptomatic, making screening essential. Suggested HPO labels: ocular pain, photophobia, red eye, decreased visual acuity, anterior uveitis, posterior synechiae. (paley2024mucosalsignaturesof pages 1-2, chang2021uveitisinchildren pages 1-3)

Intermediate disease often causes floaters and blurred vision with vitreous cells/haze, snowballs/snowbanking, peripheral vasculitis, and macular edema. Pars planitis has a reported pediatric mean onset near 7.8 years. Suggested HPO labels: vitreous floaters, vitreous haze, retinal vasculitis, cystoid macular edema. (rosenbaum2018theeyeshave pages 10-14, chang2021uveitisinchildren pages 1-3)

Posterior/panuveitis causes floaters, visual-field defects, metamorphopsia or reduced acuity; signs include retinitis/choroiditis, retinal vasculitis, hemorrhage, optic-disc edema, macular edema, necrosis, and exudative or rhegmatogenous detachment. Severity ranges from mild self-limited episodes to rapidly blinding disease. Acute retinal necrosis is a particularly destructive herpetic phenotype. (asghar2024“infectiousuveitisa pages 1-2, wang2024automatedearlydetection pages 1-2)

Frequency and laterality vary by setting. In the 3,404-patient Colombian cohort, anterior uveitis was 49.5%, posterior 22.9%, panuveitis 22.3%, and intermediate 5.2%; 66.7% were unilateral, 48.3% acute, and 83% nongranulomatous. Mean diagnostic age was 41.1 years, 54.2% were female, and ages 30–50 were most frequent. These are referral-cohort—not universal population—frequencies. Published March 6, 2024; DOI: https://doi.org/10.1007/s00417-024-06422-z. (delatorre2024epidemiologyclinicalfeatures pages 1-2)

Pediatric phenotype. Estimated childhood incidence is 4.3/100,000 and prevalence 27.9/100,000. Approximate diagnostic proportions reported in a pediatric review were idiopathic anterior uveitis 29%, JIA-associated 21%, pars planitis 17%, and infectious 6%. Up to 45% of children with JIA-associated uveitis already have complications such as cataract or glaucoma at first ophthalmology assessment. (chang2021uveitisinchildren pages 1-3)

Quality of life. Pain and photophobia impair work/school during active anterior episodes; floaters, contrast loss, macular edema, field loss, treatment burden, and fear of recurrence impair daily function in chronic disease. NEI VFQ-25 is used in contemporary trials, but phenotype-specific utility/frequency values are not standardized across the heterogeneous umbrella. (zhu2024beneficialmechanismsof pages 1-2, NCT06310837 chunk 1, NCT05384249 chunk 1)

4. Genetic, molecular, and epigenetic information

There is no single causal gene for generic uveitis. Relevant molecular categories are: antigen presentation (HLA-B27, HLA-B51, ERAP1); Th17 biology (IL23R, IL17A, STAT3, RORC); inflammatory effectors (TNF, IL1B, IL6, IFNG); trafficking (CXCR4, integrins); and regulation (FOXP3/Treg, TIGIT, PIM1). Open Targets also highlights glucocorticoid receptor NR3C1 and DHFR, reflecting therapeutic biology. These should be annotated as susceptibility genes/targets rather than pathogenic monogenic variants. (OpenTargets Search: uveitis, asghar2024“infectiousuveitisa pages 1-2, liu2023progesteroneattenuatesth17cell pages 1-2, zhu2024beneficialmechanismsof pages 1-2)

Human pediatric literature reports uveitis-associated DNA methylation and microRNA differences, but no epigenetic signature is yet clinically validated. Likewise, current evidence does not support routine variant-level ClinVar interpretation, population allele-frequency reporting, CMA, karyotype, FISH, mtDNA, or repeat-expansion testing for typical uveitis. (chang2021uveitisinchildren pages 1-3)

5. Environmental and infectious information

The principal non-genetic determinants are infection exposure, immune status, regional endemicity, drugs, surgery/trauma, and systemic inflammatory disease activity. Infectious uveitis can be viral, bacterial, fungal, or parasitic and frequently differs by geography; developing/high-TB/HIV settings carry larger infectious fractions than many high-income settings. Targeted history should cover travel/residence, animal and undercooked-meat exposure, TB and syphilis risk, immunosuppression, recent ocular surgery/trauma, and medications. (asghar2024“infectiousuveitisa pages 1-2, trivedi2019theuseof pages 3-5, asghar2024“infectiousuveitisa pages 14-15)

No robust evidence supports alcohol, exercise, or a specific diet as universal risk/protective factors. Microbiome associations are an active research area, but clinical manipulation cannot yet be recommended. ICI-associated uveitis is the strongest quantified recent iatrogenic signal. (kuo2024associationbetweenimmune pages 1-2, paley2024mucosalsignaturesof pages 1-2)

6. Mechanism and pathophysiology

Integrated causal chain

Upstream events are ocular infection or immune recognition of retinal/uveal antigens in a genetically susceptible host. Pathogen-derived danger signals or antigen-presenting dendritic cells activate innate immunity and prime Th1, Th17, and cytotoxic T cells in draining lymphoid/mucosal compartments. Loss of Treg-mediated tolerance and molecular mimicry can sustain autoreactivity. Intermediate events include cytokine amplification through IL-23/IL-17/GM-CSF, IFN-γ, TNF, IL-6 and JAK–STAT; CXCR4/integrin-mediated leukocyte trafficking; complement activation; endothelial activation; and disruption of blood–aqueous/blood–retinal barriers. Downstream events are leukocyte entry, microglial/innate-cell activation, oxidative stress, edema, vasculitis, ECM disruption and photoreceptor/retinal injury, producing pain, floaters, reduced acuity, ischemia and irreversible scarring. (asghar2024“infectiousuveitisa pages 1-2, wu2024comprehensiveproteomicprofiling pages 1-2, liu2023progesteroneattenuatesth17cell pages 1-2, zhu2024beneficialmechanismsof pages 1-2, chang2021uveitisinchildren pages 1-3, hoffmann2022preactivatedgranulocytesfrom pages 1-3)

Suggested GO processes include inflammatory response, adaptive immune response, antigen processing and presentation, T-cell activation/differentiation, leukocyte migration, cytokine-mediated signaling, complement activation, response to oxidative stress, regulation of vascular permeability, and apoptotic cell death. Suggested CL terms include Th1 cell, Th17 cell, regulatory T cell, CD8-positive alpha-beta T cell, dendritic cell, neutrophil, monocyte/macrophage, plasma cell, NK cell, microglial cell, vascular endothelial cell, retinal pigment epithelial cell, and photoreceptor cell.

Recent molecular profiling

  • Human aqueous proteomics (2024): 44 samples—12 idiopathic uveitis, 16 VKH, 16 controls—yielded 557 proteins. IU and VKH shared ECM disruption, reduced retinal-cell proteins, complement activation, and innate-cell-marker enrichment; transferrin plus complement factor B formed a machine-learning-selected candidate panel validated by targeted mass spectrometry. Quote: “innate immunity played an important role, as indicated by complement cascade activation.” Published April 15, 2024; DOI: https://doi.org/10.1021/acsomega.3c10257. Small sample size makes this discovery evidence, not a diagnostic standard. (wu2024comprehensiveproteomicprofiling pages 1-2)
  • Human tear proteomics (2024): adalimumab nonresponders had 29 differential proteins—14 upregulated, 15 downregulated—linked to neutrophil effectors and redox imbalance. DEF-1/3, biotinidase, and ABCA1 were candidate response biomarkers. Up to 40% may have primary/secondary adalimumab nonresponse. Published November 14, 2024; DOI: https://doi.org/10.1167/iovs.65.13.29. (rodriguezmartinez2024potentialprognosticprotein pages 1-2)
  • Mouse single-cell studies: progesterone reversed AP-1/S100/Cxcr4 inflammatory programs, Th17/Treg imbalance, Id2/Pim1 and IL-23/Th17/GM-CSF signaling. Dimethyl fumarate suppressed PIM1/CXCR4, restored Teff/Treg balance through PIM1–AKT–FOXO1, and reduced ocular Teff infiltration. These support mechanisms but not human efficacy. DOI: https://doi.org/10.1186/s12974-023-02829-3 and https://doi.org/10.1186/s12974-024-03096-6. (liu2023progesteroneattenuatesth17cell pages 1-2, zhu2024beneficialmechanismsof pages 1-2)
  • Animal TIGIT work (2024): agonism at symptom onset reduced EAU severity and Th17 infiltration; transferred Tregs suppressed disease in recipients. Quote: stimulation “allows for induction of regulatory immunity that provides resistance to uveitis.” DOI: https://doi.org/10.1093/jleuko/qiae116. (peters2024tigitstimulationsuppresses pages 1-2)

Spatial transcriptomics, validated human single-cell atlases, CRISPR screens, and integrated clinical multi-omics remain limited; no such assay is standard of care.

7. Anatomical structures

The primary organ is the eye. Sites include iris and anterior chamber, ciliary body, pars plana, vitreous, choroid/choriocapillaris, retina and retinal vessels, retinal pigment epithelium, macula, and optic disc/nerve head. Secondary involvement includes lens (cataract), trabecular meshwork/optic nerve (uveitic glaucoma), epiretinal interface, and sclera. Suggested UBERON labels: eye, uvea, iris, ciliary body, choroid, retina, vitreous body, anterior chamber, retinal blood vessel, and optic nerve. (rosenbaum2018theeyeshave pages 10-14, wu2024comprehensiveproteomicprofiling pages 1-2, delatorre2024epidemiologyclinicalfeatures pages 1-2, wang2024automatedearlydetection pages 1-2)

Relevant subcellular compartments depend on mechanism: nucleus/chromatin for transcriptional programs, plasma membrane for HLA/TCR/cytokine receptors and adhesion, ER for antigen processing, mitochondria for redox metabolism, and inflammasome/cytosolic signaling complexes. These are mechanistic annotations rather than diagnostic lesions.

Laterality is subtype-dependent: HLA-B27 attacks often alternate unilaterally; JIA/VKH/Behçet and other systemic entities are commonly bilateral or become bilateral. In Colombia, all-subtype disease was unilateral in 66.7%. (paley2024mucosalsignaturesof pages 1-2, delatorre2024epidemiologyclinicalfeatures pages 1-2, chang2021uveitisinchildren pages 1-3)

8. Temporal development

Onset can occur from childhood through late adulthood. Acute disease develops suddenly; insidious JIA-associated disease may be asymptomatic. SUN course descriptors include acute, recurrent, and chronic. In the Colombian cohort, 48.3% were acute. HLA-B27 episodes generally resolve over weeks but recur; chronic intermediate/posterior/panuveitis can persist or relapse for years. (paley2024mucosalsignaturesof pages 1-2, delatorre2024epidemiologyclinicalfeatures pages 1-2, chang2021uveitisinchildren pages 1-3)

There is no universal stage system. Clinically useful states are active inflammation, improvement/inactivity, remission off therapy, recurrence, and accumulated damage. Critical windows include immediate treatment of destructive infection and early control of posterior inflammation or macular edema. In ARN, a mean treatment delay of 5.2 days was associated with a 2.3-fold higher likelihood of severe visual loss than treatment within one day. (wang2024automatedearlydetection pages 1-2)

Remission may be spontaneous in self-limited anterior attacks or treatment-induced. Durable remission is less predictable in chronic NIU. Continued surveillance remains important because structural damage can progress independently of current symptom intensity.

9. Inheritance and population

Prevalence estimates span approximately 36.2–730/100,000 and incidence 17–52.4/100,000/year. Older reviews estimate prevalence near 1/1,000. Uveitis accounts for approximately 5–10% of global visual impairment; up to 35% of affected patients may experience significant vision loss. Differences reflect case definitions, referral patterns, geography and infection prevalence. (trivedi2019theuseof pages 1-3, trivedi2019theuseof pages 3-5, rosenbaum2018theeyeshave pages 1-3, delatorre2024epidemiologyclinicalfeatures pages 1-2)

Adults of working age carry a large burden. The Colombian cohort’s peak was age 30–50, with modest female predominance, but there is no universal sex ratio: HLA-B27/spondyloarthritis-associated disease often tracks male-enriched systemic disease, while JIA-associated patterns differ. Infectious disease predominates in some lower-resource/endemic regions; immune-mediated anterior disease is proportionally more common in many developed settings. (asghar2024“infectiousuveitisa pages 1-2, trivedi2019theuseof pages 3-5, delatorre2024epidemiologyclinicalfeatures pages 1-2, chang2021uveitisinchildren pages 1-3)

Inheritance is generally complex/polygenic with variable, incomplete penetrance. Anticipation, carrier frequency and germline mosaicism are not meaningful umbrella-disease attributes. Population-specific HLA frequencies contribute to geographic variation, but do not determine disease by themselves.

10. Diagnostics

Diagnosis is clinical and etiologic. Minimum examination includes history, best-corrected visual acuity, pupils, slit-lamp examination with SUN anterior-cell grading, intraocular pressure, and dilated fundus examination with vitreous-haze grading. OCT quantifies macular edema/retinal structure; fluorescein angiography detects vascular leakage, ischemia and inflammatory lesions; indocyanine-green angiography supports choroidal disease; fundus photography/ultra-widefield imaging documents peripheral lesions; ultrasonography is useful when media are opaque. (delatorre2024epidemiologyclinicalfeatures pages 1-2, wang2024automatedearlydetection pages 1-2, NCT06310837 chunk 1, NCT02595398 chunk 1)

Laboratory investigation should be phenotype- and exposure-directed, not an indiscriminate panel. Commonly considered tests include syphilis serology and TB testing/chest imaging; HLA-B27 for recurrent acute anterior disease; ACE/chest imaging where sarcoidosis is plausible; ANA-based JIA risk assessment in children; renal studies for TINU; and ocular-fluid PCR for HSV/VZV/CMV or toxoplasma in selected atypical/severe cases. Aqueous/vitreous culture, PCR, or metagenomic testing is especially important before escalating immunosuppression when infection remains plausible. Biopsy/cytology/flow studies are reserved for suspected lymphoma or other masquerades.

Differential diagnoses include conjunctivitis, keratitis, scleritis, acute angle closure, endophthalmitis, retinal vascular occlusion, retinal detachment, intraocular lymphoma/leukemia, pigment dispersion, postoperative inflammation, and retinal degeneration. Distinguishing infection from sterile inflammation is the highest-stakes decision.

Recent implementation: DeepDrARN used 11,508 ultra-widefield images from 1,112 participants. Uveitis-screening AUROC was 0.996 internally and 0.973 externally; ARN discrimination AUROC was 0.960 and 0.971. External sensitivity/specificity for three-way classification were 78.7%/89.1%. Performance exceeded the average accuracy of seven ophthalmologists by 6.57% for screening and 11.14% for ARN identification. This is impressive retrospective validation, not yet autonomous diagnosis. DOI: https://doi.org/10.1186/s40662-024-00396-z. (wang2024automatedearlydetection pages 1-2)

Genetic testing, RNA-seq, proteomics, metabolomics, epigenomics and “liquid biopsy” are not standard diagnostics for generic uveitis. Aqueous/tear proteomics and microRNAs remain investigational. (golubenco2024biomarkersofuveitis pages 1-3, golubenco2024biomarkersofuveitis pages 10-10, wu2024comprehensiveproteomicprofiling pages 1-2, rodriguezmartinez2024potentialprognosticprotein pages 1-2)

11. Outcomes and prognosis

Uveitis usually does not independently shorten life expectancy; mortality is driven by associated infection/systemic disease or treatment complications. Therefore, conventional 5- or 10-year survival rates are not useful umbrella outcomes.

The main morbidity is visual disability. Reported complications include cataract (24%), retinal neovascularization (16%) and cystoid macular edema (8.6%) in one summarized evidence base, alongside glaucoma, epiretinal membrane, vitreous hemorrhage, ischemia and retinal detachment. In ARN, 20–73% of treated eyes may still develop rhegmatogenous retinal detachment. Prognosis is better with prompt etiologic diagnosis and inflammation control, and worse with posterior involvement, macular/optic-nerve damage, chronicity, frequent relapse, delayed treatment, infection, glaucoma, or poor therapeutic response. (trivedi2019theuseof pages 3-5, rodriguezmartinez2024potentialprognosticprotein pages 1-2, wang2024automatedearlydetection pages 1-2, chang2021uveitisinchildren pages 1-3)

Visual recovery is possible when loss reflects reversible cells/haze or edema, but limited after photoreceptor loss, macular ischemia, optic atrophy, glaucoma or detachment. No molecular prognostic biomarker is currently validated for routine care; S100 proteins, complement factor B/transferrin, and tear DEF-1/3–biotinidase–ABCA1 panels are candidates. (golubenco2024biomarkersofuveitis pages 1-3, wu2024comprehensiveproteomicprofiling pages 1-2, rodriguezmartinez2024potentialprognosticprotein pages 1-2)

12. Treatment and current implementation

Treatment requires first deciding whether disease is infectious. Infectious uveitis receives pathogen-directed antimicrobial therapy—often with carefully timed adjunctive anti-inflammatory treatment. Immunosuppression without antimicrobial coverage can worsen infection. (asghar2024“infectiousuveitisa pages 1-2)

Noninfectious anterior uveitis: topical corticosteroid plus cycloplegic/mydriatic is typical initial care; periocular/systemic therapy is used when severe or refractory. Intermediate/posterior/panuveitis: local corticosteroid injection/implant or systemic corticosteroid may induce control, followed by steroid-sparing therapy for chronic, bilateral, sight-threatening or relapsing disease. Conventional agents include methotrexate, mycophenolate mofetil, azathioprine and cyclosporine. Major toxicities include cataract/glaucoma from ocular steroids and metabolic, bone, infection and organ toxicities from systemic therapy. (trivedi2019theuseof pages 1-3, wilson2023systemicadministrationof pages 1-2)

Biologics: adalimumab, a TNF inhibitor, is the established systemic biologic for noninfectious intermediate, posterior and panuveitis; infliximab is widely used off-label, particularly in severe Behçet disease. Etanercept is not considered equivalently effective for uveitis. Tocilizumab, rituximab, abatacept and other pathway agents are used selectively/off-label. Up to 40% of patients may fail adalimumab primarily or secondarily, underscoring the need for response biomarkers and alternatives. (trivedi2019theuseof pages 1-3, rodriguezmartinez2024potentialprognosticprotein pages 1-2)

Local therapy: fluocinolone implants and intravitreal dexamethasone/triamcinolone can reduce systemic exposure but increase ocular hypertension and cataract risk. PEACHTREE was a phase 3, 160-person, randomized quadruple-masked study of two 4-mg suprachoroidal triamcinolone injections for uveitic macular edema; the primary endpoint was a ≥15-letter BCVA gain at week 24. (NCT02595398 chunk 1)

Current/recent trials:

  • CLARITY, NCT06431373: phase 3, randomized quadruple-masked oral brepocitinib versus placebo in 371 adults with active noninfectious intermediate/posterior/panuveitis; primary endpoint is time to treatment failure through 48 weeks. Started September 11, 2024; active, not recruiting in the retrieved record. https://clinicaltrials.gov/study/NCT06431373 (NCT06431373 chunk 1)
  • NCT06310837: 128-person randomized comparison of adalimumab biosimilar + mycophenolate versus corticosteroid + mycophenolate; primary endpoint is 24-week ETDRS BCVA change, with VFQ-25, imaging and steroid-toxicity outcomes. https://clinicaltrials.gov/study/NCT06310837 (NCT06310837 chunk 1)
  • TYNI, NCT05486468: recruiting phase 3 trial of two 0.18-mg YUTIQ fluocinolone implants versus sham, target n=30, with six-month recurrence as primary endpoint. https://clinicaltrials.gov/study/NCT05486468 (NCT05486468 chunk 1)
  • Izokibep, NCT05384249: 96-person phase 2b IL-17A-inhibitor trial was terminated because primary and secondary endpoints did not reach statistical significance. This negative result warns against inferring clinical efficacy directly from Th17 biology. https://clinicaltrials.gov/study/NCT05384249 (NCT05384249 chunk 1)

Gene, RNA and approved cell therapies are not current standard treatments. Acazicolcept, TIGIT agonism, dimethyl fumarate and progesterone remain experimental. In 57 Lewis rats, systemic acazicolcept reduced clinical score, histology, ocular CD45 cells, and IL-17A/IFN-γ-expressing T cells, without steroid-associated weight loss; human studies are still required. (peters2024tigitstimulationsuppresses pages 1-2, liu2023progesteroneattenuatesth17cell pages 1-2, zhu2024beneficialmechanismsof pages 1-2, wilson2023systemicadministrationof pages 1-2)

Suggested NCIT intervention labels include corticosteroid therapy, cycloplegic therapy, antimicrobial therapy, methotrexate, mycophenolate mofetil, azathioprine, cyclosporine, adalimumab, infliximab, intravitreal injection, suprachoroidal injection and fluocinolone implant. No broadly accepted pharmacogenomic dosing guideline currently directs uveitis therapy.

13. Prevention

Primary prevention is etiology-specific rather than universal: vaccination and infection control where relevant; TB/syphilis/HIV prevention and treatment; food hygiene to reduce toxoplasmosis risk; vector control for endemic infections; and avoidance or surveillance of causative drugs when alternatives exist. No vaccine prevents autoimmune uveitis generally. (asghar2024“infectiousuveitisa pages 1-2, asghar2024“infectiousuveitisa pages 14-15)

Secondary prevention is early detection. Children with high-risk JIA—young onset, ANA-positive, oligoarticular/RF-negative polyarticular/psoriatic/undifferentiated categories—may require slit-lamp screening every three months because disease can be silent. Prompt specialist review is also warranted for recurrent painful red eye, new floaters, or visual loss and for ICI-treated patients with ocular symptoms. (kuo2024associationbetweenimmune pages 1-2, chang2021uveitisinchildren pages 1-3)

Tertiary prevention comprises rapid suppression of inflammation, steroid-sparing control of recurrence, OCT/pressure surveillance, antimicrobial prophylaxis where immunosuppression warrants it, vaccination before major immunosuppression, and timely cataract/glaucoma/macular-edema management. TB and infection screening before biologic/JAK-pathway therapy is integral. (NCT06431373 chunk 1, NCT06310837 chunk 1)

Genetic counseling is not ordinarily indicated for isolated uveitis, but may be appropriate where a defined inherited syndrome or autoinflammatory disorder is suspected.

14. Other species and natural disease

Naturally occurring uveitis affects companion and agricultural species, notably dogs, cats and horses; infectious etiologies vary by species. Equine recurrent uveitis (ERU) in Equus caballus (NCBI Taxonomy 9796) is a spontaneous painful remitting–relapsing disease and a major cause of equine blindness. Warmblood horses often develop posterior or panuveitis involving choroid, retina and vitreous. ERU shares retinal autoantigens including CRALBP, IRBP and S-antigen and T-cell/granulocyte biology with human recurrent NIU, making it a valuable comparative model. (hoffmann2022preactivatedgranulocytesfrom pages 1-3)

ERU granulocyte proteomics found 170 differentially abundant proteins after IL-8 stimulation, with PKA, PTEN and leukocyte-extravasation pathways and increased MMP25 implicated in blood–retinal-barrier dysfunction. This is veterinary/in-vitro evidence, not a validated human biomarker. Published August 23, 2022; DOI: https://doi.org/10.3390/ijms23179555; ProteomeXchange PXD013648. (hoffmann2022preactivatedgranulocytesfrom pages 1-3)

Uveitis itself is not zoonotically transmitted, but pathogens capable of causing it—such as Toxoplasma and some vector-borne organisms—can cross species or have animal reservoirs.

15. Model organisms

EAU in mouse and rat is the dominant induced model. Immunization with retinal antigens such as IRBP/S-antigen plus adjuvant breaks tolerance and produces T-cell-mediated chorioretinal inflammation. C57BL/6 reporter/knockout systems enable Th17/Treg tracking and genetic dissection; Lewis rats develop robust disease useful for pharmacology, OCT and histology. Readouts include fundus/clinical scores, OCT, histopathology, flow cytometry and aqueous cytokines. (peters2024tigitstimulationsuppresses pages 1-2, liu2023progesteroneattenuatesth17cell pages 1-2, zhu2024beneficialmechanismsof pages 1-2, wilson2023systemicadministrationof pages 1-2)

EAU recapitulates antigen-specific Th1/Th17 activation, leukocyte trafficking, blood–retinal-barrier failure, retinal inflammation and treatment response. It is useful for testing costimulation blockade, checkpoint agonism, cellular therapy and pathway inhibitors. Limitations are artificial antigen/adjuvant induction, strain dependence, compressed time course, predominantly posterior pathology, and incomplete modeling of human anterior, infectious, granulomatous, JIA-associated and spontaneous relapsing disease. Critically, no model has shown that B cells/autoantibodies alone reproduce human uveitis. (chang2021uveitisinchildren pages 1-3, wilson2023systemicadministrationof pages 1-2)

ERU complements EAU by providing spontaneous relapsing disease in a large eye, but cost, genetics, husbandry and species-specific immunology constrain experiments. Cell cultures, retinal explants, organoids and blood–retinal-barrier systems can isolate endothelial, RPE or immune mechanisms but cannot reproduce whole-organism immune trafficking.

Evidence assessment and knowledge gaps

The most authoritative clinical conclusions are that uveitis is a syndrome requiring anatomic and etiologic classification; infection must be excluded before immunosuppression; early control prevents much visual loss; and chronic NIU often needs steroid-sparing multidisciplinary care. Epidemiologic estimates should always retain geography and referral context. Recent human HLA-B27/mucosal and proteomic studies provide biologically coherent mechanisms but need replication in larger, diverse cohorts. Animal single-cell findings identify promising PIM1, CXCR4, TIGIT and costimulation targets, yet the terminated izokibep trial demonstrates why mechanistic plausibility cannot substitute for randomized human efficacy. (rodriguezmartinez2024potentialprognosticprotein pages 1-2, paley2024mucosalsignaturesof pages 1-2, NCT06431373 chunk 1, wilson2023systemicadministrationof pages 1-2, NCT05384249 chunk 1)

Major gaps are validated noninvasive biomarkers, head-to-head treatment algorithms after anti-TNF failure, representative global incidence/DALY estimates, longitudinal pediatric risk prediction, prospective validation and bias auditing of diagnostic AI, human single-cell/spatial atlases, and precision selection among local, conventional systemic and targeted therapies.

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  25. (golubenco2024biomarkersofuveitis pages 1-3): Elena GOLUBENCO, Elena DOLAPCIU, Olga GAIDARJI, Lucia MAZUR-NICORICI, and Ninel REVENCO. Biomarkers of uveitis in juvenile idiopathic arthritis: a systematic review. Archives of the Balkan Medical Union, 59(4):415-424, Dec 2024. URL: https://doi.org/10.31688/abmu.2024.59.4.12, doi:10.31688/abmu.2024.59.4.12. This article has 1 citations.

  26. (golubenco2024biomarkersofuveitis pages 10-10): Elena GOLUBENCO, Elena DOLAPCIU, Olga GAIDARJI, Lucia MAZUR-NICORICI, and Ninel REVENCO. Biomarkers of uveitis in juvenile idiopathic arthritis: a systematic review. Archives of the Balkan Medical Union, 59(4):415-424, Dec 2024. URL: https://doi.org/10.31688/abmu.2024.59.4.12, doi:10.31688/abmu.2024.59.4.12. This article has 1 citations.

Artifacts

Reference Validation

Checked with linkml-reference-validator 0.2.1.

Outcome Count
References checked 16
Resolved 16
Unresolved (possible confabulation) 0
Unverifiable 0
References weighed for topical relevance 16
On topic 6
Off topic 0

All extracted references resolved successfully.