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Subtypes

10

etiologic infectious

Ocular toxoplasmosis (Toxoplasma retinochoroiditis) MONDO:0005879

Necrotising retinochoroiditis caused by Toxoplasma gondii, the leading infectious cause of posterior uveitis worldwide. Classically presents as a focal white retinal lesion with overlying vitritis, frequently recurring at the border of a pre-existing pigmented chorioretinal scar as tissue cysts reactivate. Requires antiparasitic therapy; corticosteroid must never be given without antiparasitic cover.

Show evidence (1 reference)

PMID:36095008 SUPPORT Human Clinical

"Ocular toxoplasmosis is the leading cause of posterior uveitis worldwide"

Establishes ocular toxoplasmosis as the dominant infectious subtype of posterior uveitis/choroiditis.

Tubercular choroiditis and serpiginous-like choroiditis MONDO:0006876

Choroidal inflammation attributable to Mycobacterium tuberculosis, presenting as choroidal tubercles/tuberculoma, multifocal choroiditis, or — most treacherously — a diffuse serpiginous-like choroiditis that phenocopies idiopathic serpiginous choroiditis. Because the idiopathic phenocopy is conventionally treated with immunosuppression, misclassification here is the canonical harm scenario of the infectious/non-infectious fork.

Show evidence (1 reference)

PMID:33845014 SUPPORT Human Clinical

"Key criteria for tubercular uveitis were a compatible uveitic syndrome, including (1) anterior uveitis with iris nodules, (2) serpiginous-like tubercular choroiditis, (3) choroidal nodule (tuberculoma)"

SUN consensus criteria enumerate serpiginous-like choroiditis and choroidal tuberculoma as defining tubercular uveitic presentations.

Syphilitic chorioretinitis, including acute syphilitic posterior placoid chorioretinitis

Ocular involvement by Treponema pallidum, "the great masquerader". It can imitate almost any uveitic phenotype, and its one relatively distinctive form is acute syphilitic posterior placoid chorioretinitis (ASPPC), a large yellowish placoid outer-retinal lesion at the posterior pole. Serologic exclusion of syphilis is mandatory before immunosuppressing any choroiditis. No MONDO term for ocular/syphilitic chorioretinitis exists at time of curation, so this subtype carries no subtype_term.

Show evidence (2 references)

PMID:33831337 SUPPORT Human Clinical

"With the exception of syphilitic posterior placoid chorioretinitis, the diverse manifestations of ocular syphilis have few distinct features that can be used to assist in clinical diagnosis."

Documents both the masquerading breadth of ocular syphilis and ASPPC as its one distinctive chorioretinal form.

PMID:22863970 SUPPORT Human Clinical

"In all patients, posterior segment examination in the involved eyes revealed a large, yellowish, placoid, outer retinal lesion."

Defines the characteristic ASPPC lesion morphology in a 16-patient series.

Presumed ocular histoplasmosis syndrome (POHS) MONDO:0001263

A chorioretinal disorder of Histoplasma capsulatum-endemic regions (in the United States, the Mississippi and Ohio river valleys), characterised by punched-out "histo spots", peripapillary atrophy and absent vitritis. Vision loss is driven almost entirely by secondary choroidal neovascularization rather than by active inflammation, so management is anti-VEGF-led rather than immunosuppression-led.

Show evidence (1 reference)

PMID:25841248 SUPPORT Human Clinical

"Ocular histoplasmosis syndrome (OHS) is a chorioretinal disorder with a distinct fundus appearance that is commonly found in regions endemic for Histoplasma capsulatum."

Defines POHS as an endemic-region chorioretinal disorder attributed to Histoplasma capsulatum.

etiologic noninfectious

Birdshot chorioretinopathy (HLA-A29-associated) MONDO:0011599

A bilateral chronic posterior uveitis of middle-aged people of European descent with no extraocular manifestations, defined by scattered cream-coloured hypopigmented choroidal lesions with retinal vasculitis and vitritis. Its association with HLA-A29 is among the strongest HLA-disease associations documented in humans, and ERAP1/ERAP2 haplotypes modify risk within HLA-A29 carriers. Requires long-term immunosuppressive or biologic therapy.

Show evidence (1 reference)

PMID:25434765 SUPPORT Human Clinical

"BSCR is characterized by distinctive multiple choroidal hypopigmented lesions in combination with retinal vasculitis and vitritis, and the extraordinary feature that virtually all patients are HLA-A29 positive."

Defines the birdshot phenotype and its near-obligate HLA-A29 positivity.

Multifocal choroiditis with panuveitis (MFCPU) MONDO:0023833

Idiopathic chronic bilateral chorioretinopathy of predominantly young myopic women, with multiple punched-out chorioretinal lesions plus anterior-chamber and vitreous inflammation. Distinguished from PIC largely by the presence of overt intraocular inflammation and larger lesions; carries a high rate of choroidal neovascularization and of structural complications.

Show evidence (1 reference)

PMID:27994812 SUPPORT Human Clinical

"MFCPU is a variant of idiopathic MFC that has been described in association with anterior uveitis and/or vitritis, multiple punched-out atrophic chorioretinal lesions of variable size"

Defines MFCPU as the inflammatory variant of idiopathic multifocal choroiditis.

Punctate inner choroidopathy (PIC) MONDO:0035584

An uncommon idiopathic inflammatory chorioretinopathy of young myopic women, with small yellow-white lesions of the inner choroid and outer retina and characteristically absent vitritis. Choroidal neovascularization is exceptionally common and is the principal threat to sight, so management must distinguish new inflammatory lesions from new neovascular membranes.

Show evidence (1 reference)

PMID:38181975 SUPPORT Human Clinical

"Punctate inner choroidopathy (PIC) is an uncommon idiopathic inflammatory condition characterized by multifocal chorioretinopathy that primarily affects young adults, with a predilection for myopic females."

Defines PIC and its demographic predilection.

Serpiginous choroiditis (idiopathic) MONDO:0018152

A rare, usually bilateral, chronic and relentlessly recurrent inflammation of choroid, RPE and choriocapillaris that spreads in a geographic (serpentine) pattern, classically peripapillary, macular or ampiginous. Idiopathic serpiginous choroiditis must be separated from tubercular serpiginous-like choroiditis before immunosuppression is started.

Show evidence (1 reference)

PMID:15850812 SUPPORT Human Clinical

"Serpiginous choroiditis is a rare, usually bilateral, chronic, progressive, recurrent inflammation of the choroid, retinal pigment epithelium, and choriocapillaris of unknown etiology."

Defines idiopathic serpiginous choroiditis and its target tissues.

Sarcoidosis-associated choroiditis

Choroidal involvement in systemic sarcoidosis, part of a granulomatous uveitis that may include vitritis, retinal vasculitis and choroidal granulomas. The systemic granulomatous mechanism is curated in the Sarcoidosis and Neurosarcoidosis entries; this subtype scopes only the ocular/choroidal arm. No MONDO term for ocular sarcoidosis exists at time of curation, so this subtype carries no subtype_term.

Show evidence (1 reference)

PMID:37176633 SUPPORT Human Clinical

"Posterior involvement includes vitritis, vasculitis and choroidal lesions."

Documents choroidal involvement as part of posterior sarcoid uveitis.

Sympathetic ophthalmia MONDO:0019198

A rare bilateral granulomatous panuveitis following penetrating trauma or surgery to one eye, in which autoimmunity to sequestered uveal/retinal antigen released by the injured eye attacks the fellow ("sympathising") eye. Choroidal involvement takes the form of yellowish-white lesions or Dalen-Fuchs nodules.

Show evidence (1 reference)

PMID:35647958 SUPPORT Human Clinical

"Sympathetic ophthalmia is a rare, bilateral, granulomatous, panuveitis following penetrating trauma or surgery to one eye."

Defines sympathetic ophthalmia as post-traumatic bilateral granulomatous panuveitis.

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Pathophysiology

12

Aetiologic Fork - Infectious versus Non-Infectious Choroidal Inflammation

The root branch point of the entry. Choroidal inflammation may be driven by a replicating pathogen within ocular tissue or by an antigen-driven autoimmune/autoinflammatory process against ocular self-antigen. Both arms produce clinically overlapping choroiditis, and both converge on the same downstream tissue-injury cascade, but they diverge completely at the level of management: the infectious arm requires antimicrobial eradication and is made worse by unopposed immunosuppression, whereas the non-infectious arm requires exactly that immunosuppression. Distinguishing the arms is therefore the single most consequential diagnostic act in choroiditis.

choroid UBERON:0001776

Downstream

Pathogen Invasion and Persistence in the Choroid and Outer Retina Aetiologic assignment to the infectious arm.

Autoimmune Recognition of Ocular Self-Antigen Aetiologic assignment to the non-infectious arm.

Show evidence (2 references)

PMID:37589912 SUPPORT Human Clinical

"The spectrum of etiologies for uveitis is very broad and includes infectious and auto-immune diseases."

States the infectious/autoimmune aetiologic dichotomy that structures this entry.

PMID:37428299 SUPPORT Human Clinical

"Out of 6191 cases with uveitis, 1925 were infectious, 4125 were non-infectious"

Quantifies the infectious/non-infectious split in a 30-year tertiary uveitis cohort, showing both arms are numerically substantial.

Pathogen Invasion and Persistence in the Choroid and Outer Retina

In the infectious arm, an organism reaches and persists in the choroid, RPE or outer retina: Toxoplasma gondii as encysted bradyzoites in retinal scars, Mycobacterium tuberculosis within choroidal macrophages, Treponema pallidum disseminated haematogenously to the highly vascular choroid, or Histoplasma capsulatum presumed to have seeded the choroid during earlier fungaemia. The choroid's exceptionally high blood flow makes it a preferential site of haematogenous seeding. Organism persistence, not merely acute invasion, is what makes the infectious arm relapsing and what makes unopposed immunosuppression dangerous.

macrophage CL:0000235 retinal pigment epithelial cell CL:0002586

choroid UBERON:0001776

Downstream

Choroidal Inflammatory Cell Infiltration Pathogen antigen drives recruitment of leukocytes into the choroidal stroma.

Toxoplasma Cyst Reactivation and Recurrent Retinochoroiditis Persisting tissue cysts provide the reservoir for later reactivation.

Unopposed Immunosuppression of Unrecognised Infectious Choroiditis Persisting organism is the substrate on which immunosuppression given without antimicrobial cover acts.

Show evidence (3 references)

PMID:36095008 SUPPORT Human Clinical

"Ocular toxoplasmosis is the leading cause of posterior uveitis worldwide"

Establishes an infectious organism as the single commonest driver of posterior uveitis/choroiditis.

PMID:33831337 SUPPORT Human Clinical

"Ocular involvement can occur at any stage of syphilis and any part of the eye can be affected."

Documents haematogenous ocular seeding by Treponema pallidum at any disease stage.

PMID:33845014 SUPPORT Human Clinical

"evidence of tuberculosis, including histologically or microbiologically confirmed infection, positive interferon-γ release assay test, or positive tuberculin skin test"

Consensus criteria require demonstrable mycobacterial infection, supporting organism presence as the driver of the tubercular arm.

Toxoplasma Cyst Reactivation and Recurrent Retinochoroiditis

The signature relapsing behaviour of ocular toxoplasmosis. Bradyzoites encysted in the retina at the edge of an old pigmented chorioretinal scar convert back to proliferating tachyzoites, producing a new satellite focus of necrotising retinochoroiditis at the scar border. Each reactivation enlarges the area of destroyed outer retina, so cumulative visual loss is driven by recurrence count and lesion location rather than by any single episode. Immunocompromise markedly worsens lesion size and visual outcome.

photoreceptor cell CL:0000287

choroid UBERON:0001776

Downstream

Outer Retinal and Retinal Pigment Epithelial Damage Each reactivation episode destroys a further patch of outer retina.

Chorioretinal scar Healed reactivation foci leave pigmented atrophic scars.

Show evidence (3 references)

PMID:38843299 SUPPORT Human Clinical

"The cumulative incidence of recurrent OT at three years was 33.9%"

Quantifies the recurrent nature of ocular toxoplasmosis in a treated tertiary cohort.

PMID:38843299 SUPPORT Human Clinical

"OT reactivation, owing to the persistence of tissue cysts in retinal tissues, can increase the probability of VA loss."

Directly states the tissue-cyst-persistence mechanism of reactivation and its link to cumulative visual loss.

PMID:38843299 SUPPORT Human Clinical

"Immunocompromised patients showed a significantly larger size of retinitis than immunocompetent patients."

Shows host immune control constrains lesion size, consistent with reactivation being restrained by immunity.

Unopposed Immunosuppression of Unrecognised Infectious Choroiditis

The harm arm of the aetiologic fork, and the reason the fork must be modelled mechanistically rather than as a list. When infectious choroiditis is misclassified as an idiopathic non-infectious entity, it receives the correct treatment for the wrong diagnosis — corticosteroid and/or steroid-sparing immunosuppression without antimicrobial cover. The expected consequence is loss of host immune restraint on a replicating organism; note that the documented evidence here is for the misclassification hazard and for the superiority of adding antimicrobial therapy, rather than a trial measuring harm from unopposed immunosuppression directly. Tubercular serpiginous-like choroiditis is the canonical case, because its idiopathic phenocopy is conventionally immunosuppressed; syphilis is the second, because it can imitate essentially any uveitic phenotype. This is why serologic and mycobacterial exclusion precede immunosuppression in all choroiditis.

choroid UBERON:0001776

Downstream

Outer Retinal and Retinal Pigment Epithelial Damage Uncontrolled pathogen replication extends the zone of outer-retinal destruction.

Show evidence (3 references)

PMID:22675097 PARTIAL Human Clinical

"Choroidal tuberculosis (TB) infection may present itself as a diffuse choroiditis that resembles serpiginous choroiditis, usually treated with immunossupressants."

States the misclassification hazard directly - a TB choroiditis that phenocopies an entity conventionally treated with immunosuppressants. Marked PARTIAL because the source documents the risk of misdirected treatment rather than measuring harm from immunosuppression. (The spelling "immunossupressants" is as printed in the source.)

PMID:22675097 SUPPORT Human Clinical

"Recent studies have demonstrated that patients with serpiginous-like choroiditis and evidence of systemic or latent TB are best treated with antituberculosis treatment (ATT) in addition to the corticosteroid therapy."

Establishes that corticosteroid is appropriate in the infectious arm only when combined with antimicrobial therapy - the operational content of the management fork.

PMID:33831337 SUPPORT Human Clinical

"ocular syphilis should always be a part of the differential diagnosis of most, if not all, ocular infectious and inflammatory presentations"

Supports mandatory syphilis exclusion in any inflammatory ocular presentation before immunosuppression.

Autoimmune Recognition of Ocular Self-Antigen

In the non-infectious arm, T cells recognise peptide derived from ocular self-antigen presented on MHC molecules, breaking the eye's immune privilege. Loss of sequestration is explicit in sympathetic ophthalmia, where penetrating trauma exposes previously sequestered uveal antigen and provokes bilateral granulomatous disease. In birdshot chorioretinopathy the presenting molecule itself is the dominant genetic risk factor.

CD8-positive, alpha-beta T cell CL:0000625

antigen processing and presentation of peptide antigen via MHC class I GO:0002474 ⚠ ABNORMAL T cell mediated immunity GO:0002456 ↑ INCREASED

Downstream

HLA-A29-Restricted Antigen Presentation in Birdshot Chorioretinopathy The birdshot-specific instantiation of self-antigen presentation.

Choroidal Inflammatory Cell Infiltration Autoreactive T cells recruit and sustain a choroidal infiltrate.

Show evidence (2 references)

PMID:25434765 SUPPORT Human Clinical

"the association with HLA-A29 suggests that it is directly involved in the presentation of peptide antigens to T cells"

Frames the non-infectious arm as MHC-restricted peptide presentation to T cells.

PMID:35647958 SUPPORT Human Clinical

"Sympathetic ophthalmia is a rare, bilateral, granulomatous, panuveitis following penetrating trauma or surgery to one eye."

Sympathetic ophthalmia is the clearest human demonstration that breach of ocular antigen sequestration triggers bilateral autoimmune uveitis.

HLA-A29-Restricted Antigen Presentation in Birdshot Chorioretinopathy

Birdshot chorioretinopathy carries one of the strongest HLA-disease associations documented in human medicine: essentially all patients are HLA-A29 positive. In a classic series 47 of 49 birdshot patients (95.9%) carried HLA-A29, and the linked HLA-B12(B44) association is explained by linkage disequilibrium with HLA-A29 rather than by independent effect. Mechanistically the association is not merely a marker - genetic modifiers act on the peptide-loading pathway that supplies HLA-A29. ERAP1 and ERAP2 haplotypes that increase ERAP2 expression and decrease ERAP1 expression raise risk in HLA-A29 carriers, while a haplotype disrupting ERAP2 expression is protective, and homozygosity for HLA-A29 further increases susceptibility. Together these implicate a peptide-presentation threshold model in which excess presentation of ERAP2-shaped peptides on HLA-A29 activates the immune response in the choroid.

CD8-positive, alpha-beta T cell CL:0000625

HLA-A29 hgnc:4931 ERAP1 hgnc:18173 ERAP2 hgnc:29499

antigen processing and presentation of peptide antigen via MHC class I GO:0002474 ↑ INCREASED

choroid UBERON:0001776

Downstream

Choroidal Inflammatory Cell Infiltration Peptide presentation on HLA-A29 above a threshold activates the choroidal immune response.

Show evidence (5 references)

PMID:25434765 SUPPORT Human Clinical

"BSCR is the strongest documented association between HLA and disease in humans"

Direct statement that birdshot-HLA-A29 is the strongest known human HLA-disease association.

PMID:3341436 SUPPORT Human Clinical

"Of these 49 patients, 47 (95.9%) had the HLA-A29 antigen."

Quantifies HLA-A29 carriage at 95.9% in a birdshot series.

PMID:3341436 SUPPORT Human Clinical

"The HLA-B12 (B44) antigen was also significantly associated with the disease, but this antigen is known to be in linkage disequilibrium with the antigen HLA-A29."

Supports the statement that the secondary HLA-B12(B44) signal reflects linkage disequilibrium rather than independent effect.

+ 2 more references

Choroidal Inflammatory Cell Infiltration

The convergence node of both aetiologic arms. Leukocytes - lymphocytes, macrophages and, in granulomatous forms, epithelioid and giant cells - are recruited across the choroidal vasculature into the choroidal stroma, with spillover into the vitreous (vitritis) and retinal vessels (retinal vasculitis). Histologically, serpiginous lesions show moderate diffuse lymphocytic infiltrates throughout the choroid. Because both an infectious and an autoimmune trigger produce a broadly similar infiltrate, the pattern of inflammation narrows but does not settle aetiology - some morphologies are informative (caseation favours tuberculosis; a serpiginous-like or tuberculoma pattern is a SUN criterion for tubercular uveitis) but microbiologic and serologic confirmation is what actually decides treatment.

lymphocyte CL:0000542 macrophage CL:0000235 T cell CL:0000084

inflammatory response GO:0006954 ↑ INCREASED leukocyte migration involved in inflammatory response GO:0002523 ↑ INCREASED

choroid UBERON:0001776

Downstream

Granulomatous Choroidal Inflammation In sarcoidosis, tuberculosis and sympathetic ophthalmia the infiltrate organises into granulomas.

Choriocapillaris Hypoperfusion and Non-Perfusion Inflammation of and around the choriocapillaris obstructs its lobular perfusion.

Vitritis Spillover of inflammatory cells into the vitreous cavity.

Retinal vasculitis Extension of inflammation to retinal vessels.

Macular edema Inflammatory breakdown of the blood-retinal barrier causes fluid accumulation in the macula.

Posterior uveitis Choroidal infiltration is the anatomic substrate of the posterior uveitis phenotype.

Vitreous floaters Inflammatory cells and debris in the vitreous are perceived as floaters.

Ocular hypertension Intraocular inflammation (and its corticosteroid treatment) raises intraocular pressure.

Epiretinal membrane Chronic intraocular inflammation drives fibrocellular proliferation on the inner retinal surface.

Cataract Chronic intraocular inflammation and its corticosteroid treatment opacify the lens.

Show evidence (2 references)

PMID:15850812 SUPPORT Human Clinical

"moderate diffuse lymphocytic infiltrates throughout the choroid"

Histologic confirmation of diffuse lymphocytic infiltration of the choroid in serpiginous choroiditis.

PMID:37176633 SUPPORT Human Clinical

"Posterior involvement includes vitritis, vasculitis and choroidal lesions."

Documents the co-occurrence of choroidal inflammation with vitritis and retinal vasculitis.

Granulomatous Choroidal Inflammation

In sarcoidosis, tuberculosis and sympathetic ophthalmia the choroidal infiltrate organises into granulomas. Sarcoid granulomas are non-caseating epithelioid granulomas; tubercular disease produces choroidal tubercles and tuberculoma; sympathetic ophthalmia produces Dalen-Fuchs nodules, focal aggregates of epithelioid cells between Bruch's membrane and the RPE. That both an infectious (TB) and a sterile (sarcoid) trigger yield broadly overlapping granulomatous choroiditis is a second, tissue-level restatement of why the aetiologic fork is not reliably settled on morphology alone - tuberculosis is the standing differential for ocular sarcoidosis, and caseation, while suggestive of tuberculosis, is often unavailable because ocular biopsy is rarely performed.

macrophage CL:0000235

granuloma formation GO:0002432 ↑ INCREASED

choroid UBERON:0001776 Bruch's membrane UBERON:0003957

Downstream

Outer Retinal and Retinal Pigment Epithelial Damage Granulomatous destruction of the outer retinal/RPE complex.

Show evidence (3 references)

PMID:37176633 SUPPORT Human Clinical

"The diagnosis is based on histology with the presence of non-caseating epithelioid granulomas."

Defines the sarcoid granuloma as the histologic substrate.

PMID:37176633 SUPPORT Human Clinical

"Tuberculosis is a classic differential diagnosis to be wary of, especially in people who have spent time in endemic areas."

Confirms that infectious (TB) and sterile (sarcoid) granulomatous choroiditis are not separable on morphology alone.

PMID:35647958 SUPPORT Human Clinical

"It manifests as acute/chronic granulomatous uveitis with yellowish-white choroidal lesions or Dalen-Fuchs nodules."

Documents Dalen-Fuchs nodules as the granulomatous choroidal lesion of sympathetic ophthalmia.

Choriocapillaris Hypoperfusion and Non-Perfusion

The shared final common pathway of several white-dot entities. Inflammation of the choriocapillaris and its precapillary supply produces hypo- or non-perfusion of choroidal lobules, which is the defining clinicopathological mechanism of the primary inflammatory choriocapillaropathies. The calibre of vessel affected grades disease severity: involvement of only terminal choriocapillaries gives the benign end of the spectrum (MEWDS), whereas involvement of larger choriocapillaris or precapillary vessels gives the severe forms - APMPPE, idiopathic multifocal choroiditis and serpiginous choroiditis. Because the choriocapillaris is the sole blood supply of the outer retina and RPE, its non-perfusion is directly ischaemic to the photoreceptor/RPE complex, and it is imaged as patchy lobular hypofluorescence on indocyanine green angiography.

endothelial cell CL:0000115

cellular response to hypoxia GO:0071456 ↑ INCREASED

choriocapillaris UBERON:0005336

Downstream

Outer Retinal and Retinal Pigment Epithelial Damage Loss of the sole vascular supply of the outer retina causes ischaemic photoreceptor and RPE injury.

Inflammatory Choroidal Neovascularization Inflammation-driven hypoperfusion generates a retinal-choroidal hypoxia gradient that promotes neovascularization.

Show evidence (3 references)

PMID:35208488 SUPPORT Human Clinical

"PICCPs are resulting from one common clinicopathological mechanism, inflammatory choriocapillaris hypo- or non-perfusion."

States choriocapillaris non-perfusion as the single shared mechanism of this disease group.

PMID:35208488 SUPPORT Human Clinical

"ICGA shows the typical pattern of patchy lobular hypofluorescence reflecting hypo- or non-perfusion of the choriocapillaris"

Links the mechanism to its imaging signature on indocyanine green angiography.

PMID:35208488 SUPPORT Human Clinical

"Choriocapillaris non-perfusion can affect the end-choriocappilaries, at the benign end of the PICCP spectrum (MEWDS), to larger choriocapillaris vessels or precapillary vessels at the origin of more severe forms such as acute posterior multifocal placoid pigment epitheliopathy (APMPPE),..."

Supports the vessel-calibre severity gradient asserted in this node. (The spelling "end-choriocappilaries" is as printed in the source.)

Outer Retinal and Retinal Pigment Epithelial Damage

The route from choroidal inflammation to actual vision loss. Because the choroid supplies the avascular outer retina, choroidal inflammation and choriocapillaris non-perfusion injure the photoreceptor/RPE complex rather than the choroid alone. Histology of serpiginous lesions shows atrophy of the choriocapillaris, RPE and photoreceptor cells together, and on OCT active lesions show disruption of the ellipsoid zone and RPE. Photoreceptor loss is irreversible, which is why choroiditis causes permanent scotomata and why the therapeutic goal is preventing new lesions rather than recovering old ones.

photoreceptor cell CL:0000210 retinal pigment epithelial cell CL:0002586

apoptotic process GO:0006915 ↑ INCREASED

retinal pigment epithelium UBERON:0001782 outer nuclear layer of retina UBERON:0001789

Downstream

Chorioretinal Scarring and Bruch Membrane Disruption Destroyed outer retina heals as an atrophic pigmented scar.

Chorioretinal atrophy Confluent outer-retinal and RPE loss appears as chorioretinal atrophy.

Scotoma Focal photoreceptor loss produces a corresponding permanent field defect.

Photopsia Irritated or dysfunctional photoreceptors generate positive visual phenomena.

Reduced visual acuity Outer-retinal damage involving the macula reduces central acuity.

Blindness Extensive or macula-involving outer-retinal destruction causes severe visual loss.

Show evidence (2 references)

PMID:15850812 SUPPORT Human Clinical

"The histological findings of the lesions are atrophy of the choriocapillaris, retinal pigment epithelium and photoreceptor cells"

Direct histologic evidence that choroiditis destroys the RPE/photoreceptor complex, not just the choroid.

PMID:15850812 SUPPORT Human Clinical

"Visual outcome is directly related to the involvement of the para-fovea and fovea by the lesions or secondary choroidal neovascularization."

Links outer-retinal lesion location to the visual outcome.

Chorioretinal Scarring and Bruch Membrane Disruption

Healed choroiditis lesions become punched-out atrophic, often pigmented, chorioretinal scars with disruption of the RPE-Bruch's membrane complex. The scar is not inert: a breached RPE-Bruch's membrane barrier is the anatomical precondition for ingrowth of new choroidal vessels into the subretinal space, and in ocular toxoplasmosis the scar border is the reservoir from which recurrent disease arises. Scars are therefore simultaneously the record of past disease and the substrate of future sight-threatening complications.

Bruch's membrane UBERON:0003957 retinal pigment epithelium UBERON:0001782

Downstream

Inflammatory Choroidal Neovascularization Breach of the RPE-Bruch's membrane complex permits choroidal vessel ingrowth.

Chorioretinal scar The healed lesion is clinically observed as a chorioretinal scar.

Macular scar A healed lesion involving the macula leaves a macular scar, the commonest structural complication of ocular toxoplasmosis.

Show evidence (2 references)

PMID:38541191 SUPPORT Human Clinical

"Inflammatory CNV develops when inflammation or infection directly involves the retinal pigment epithelium (RPE)-Bruch's membrane complex."

Identifies RPE-Bruch's membrane involvement as the precondition for inflammatory CNV.

PMID:27994812 SUPPORT Human Clinical

"circumscribed areas of chorioretinal atrophy and subretinal pigmented fibrotic scars"

Documents atrophic and fibrotic chorioretinal scarring as the healed end-state of multifocal choroiditis.

Inflammatory Choroidal Neovascularization

A major sight-threatening complication of inflammatory chorioretinal scars, and in some entities the dominant cause of vision loss rather than the inflammation itself. Inflammation compromises choroidal perfusion, generating a retinal-choroidal hypoxia gradient; VEGF, SDF-1-alpha and other mediators are released; and with the RPE-Bruch's membrane barrier already breached, new choroidal vessels grow into the subretinal space, the majority appearing as a classic type 2 lesion. It is especially common in punctate inner choroidopathy, multifocal choroiditis, serpiginous choroiditis and presumed ocular histoplasmosis syndrome. Clinically it is hard to distinguish from an active inflammatory lesion, which matters because the treatments differ: anti-VEGF for the neovascular membrane versus anti-inflammatory therapy for active choroiditis.

endothelial cell CL:0000115

angiogenesis GO:0001525 ↑ INCREASED vascular endothelial growth factor signaling pathway GO:0038084 ↑ INCREASED

macula lutea UBERON:0000053

Downstream

Choroidal neovascularization The neovascular membrane is the observed clinical phenotype.

Metamorphopsia Subretinal fluid and elevation from the membrane distort central vision.

Reduced visual acuity Subfoveal or juxtafoveal neovascular membranes reduce central acuity.

Show evidence (3 references)

PMID:38541191 SUPPORT Human Clinical

"Inflammation itself can compromise perfusion, generating a gradient of retinal-choroidal hypoxia that additionally promotes the formation of choroidal neovascularization in the course of uveitis."

States the hypoxia-driven mechanism connecting choroidal inflammation to neovascularization.

PMID:38541191 SUPPORT Human Clinical

"The development of choroidal neovascularization may be a complication, especially in conditions such as punctate inner choroidopathy, multifocal choroiditis, serpiginous choroiditis, and presumed ocular histoplasmosis syndrome."

Identifies the choroiditis subtypes in which inflammatory CNV is most frequent.

PMID:30209691 SUPPORT Human Clinical

"A number of uveitic entities may be complicated by the development of choroidal neovascularization leading to a decrease in central visual acuity."

Confirms inflammatory CNV as a cause of central acuity loss across uveitic entities.

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Histopathology

3

Diffuse Lymphocytic Choroidal Infiltrate

Moderate diffuse lymphocytic infiltration throughout the choroid, accompanied by atrophy of the choriocapillaris, RPE and photoreceptors in established lesions.

Show evidence (1 reference)

PMID:15850812 SUPPORT Human Clinical

"The histological findings of the lesions are atrophy of the choriocapillaris, retinal pigment epithelium and photoreceptor cells, and moderate diffuse lymphocytic infiltrates throughout the choroid."

Direct histologic description of serpiginous choroiditis lesions.

Non-Caseating Epithelioid Granuloma

Compact aggregates of epithelioid macrophages without central caseation, the histologic hallmark of sarcoid choroiditis. Caseation instead favours tuberculosis, but biopsy yield in the eye is low and the diagnosis of ocular sarcoidosis is usually clinico-radiological.

Show evidence (1 reference)

PMID:37176633 SUPPORT Human Clinical

"The diagnosis is based on histology with the presence of non-caseating epithelioid granulomas."

Defines the non-caseating epithelioid granuloma as the diagnostic histologic finding of sarcoidosis.

Dalen-Fuchs Nodule

Focal aggregates of epithelioid cells lying between Bruch's membrane and the retinal pigment epithelium, seen as yellowish-white choroidal lesions in sympathetic ophthalmia.

Show evidence (1 reference)

PMID:35647958 SUPPORT Human Clinical

"It manifests as acute/chronic granulomatous uveitis with yellowish-white choroidal lesions or Dalen-Fuchs nodules."

Documents Dalen-Fuchs nodules as the characteristic choroidal lesion of sympathetic ophthalmia.

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Pathograph

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Phenotypes

17

Cardiovascular 1

Retinal vasculitis Retinal vasculitis HP:0025188

Show evidence (2 references)

PMID:25434765 SUPPORT Human Clinical

"BSCR is characterized by distinctive multiple choroidal hypopigmented lesions in combination with retinal vasculitis and vitritis"

Documents retinal vasculitis as a defining feature of birdshot chorioretinopathy.

PMID:33845014 SUPPORT Human Clinical

"(4) occlusive retinal vasculitis, and (5) in hosts with evidence of active systemic tuberculosis, multifocal choroiditis"

Lists occlusive retinal vasculitis among the SUN-defining presentations of tubercular uveitis.

Eye 6

Reduced visual acuity Reduced visual acuity HP:0007663

Show evidence (2 references)

PMID:27994812 SUPPORT Human Clinical

"patients may complain of a temporal scotoma, metamorphopsia, floaters, photopsias, photophobia, and decreased vision"

Lists decreased vision among the presenting symptoms of multifocal choroiditis.

PMID:38843299 SUPPORT Human Clinical

"At the final visit, 21% of all affected eyes suffered VA ≤ 20/200."

Quantifies severe residual acuity loss after treated ocular toxoplasmosis.

Macular edema Macular edema HP:0040049

Show evidence (1 reference)

PMID:27994812 SUPPORT Human Clinical

"higher frequency of structural complications such as cataract, cystoid macular edema (CME), and epiretinal membrane (ERM) related to intraocular inflammation"

Documents cystoid macular edema as an inflammation-related structural complication of MFCPU.

Photopsia Photopsia HP:0030786

Show evidence (1 reference)

PMID:27994812 SUPPORT Human Clinical

"patients may complain of a temporal scotoma, metamorphopsia, floaters, photopsias, photophobia, and decreased vision"

Lists photopsia among the presenting symptoms of multifocal choroiditis.

Blindness Blindness HP:0000618

Show evidence (1 reference)

PMID:39452769 SUPPORT Human Clinical

"Ocular toxoplasmosis (OT), a severe manifestation of T. gondii infection, can lead to potentially blinding complications."

Documents blindness as a potential outcome of the commonest infectious choroiditis.

Vitreous floaters Vitreous floaters HP:0100832

Show evidence (1 reference)

PMID:27994812 SUPPORT Human Clinical

"patients may complain of a temporal scotoma, metamorphopsia, floaters, photopsias, photophobia, and decreased vision"

Lists floaters among the presenting symptoms of multifocal choroiditis.

Cataract Cataract HP:0000518

Show evidence (1 reference)

PMID:27994812 SUPPORT Human Clinical

"higher frequency of structural complications such as cataract, cystoid macular edema (CME), and epiretinal membrane (ERM) related to intraocular inflammation"

Documents cataract as an inflammation-related structural complication of MFCPU.

Other 10

Posterior uveitis Posterior uveitis HP:0012123

Show evidence (1 reference)

PMID:37589912 SUPPORT Human Clinical

"Posterior uveitis is a common chorioretinal pathology affecting all ages worldwide and is a frequent reason for referral to the retina clinic."

Establishes posterior uveitis as the clinical presentation class of chorioretinal inflammation.

Chorioretinal atrophy Chorioretinal atrophy HP:0000533

Show evidence (1 reference)

PMID:27994812 SUPPORT Human Clinical

"circumscribed areas of chorioretinal atrophy and subretinal pigmented fibrotic scars"

Documents chorioretinal atrophy as a defining structural outcome of idiopathic multifocal choroiditis.

Chorioretinal scar Chorioretinal scar HP:0007777

Show evidence (2 references)

PMID:27994812 SUPPORT Human Clinical

"Affected eyes typically show multiple punched-out chorioretinal lesions ranging from 50 to 350 μm in size"

Documents punched-out chorioretinal lesions as the characteristic healed lesion morphology.

PMID:38843299 PARTIAL Human Clinical

"Patients mainly presented with primary retinitis without previous scar (62%)"

Marked PARTIAL because this is an argument from the complement: 62% had no previous scar, so the remaining ~38% presented in eyes carrying a pre-existing chorioretinal scar. The source reports the former directly, not the latter.

Choroidal neovascularization Choroidal neovascularization HP:0011506

Show evidence (2 references)

PMID:25841248 SUPPORT Human Clinical

"Choroidal neovascularization (CNV) secondary to OHS is considered one of the principal causes of central vision loss among young adults in endemic areas."

Documents CNV as the dominant vision-threatening complication in POHS.

PMID:38181975 SUPPORT Human Clinical

"New or worsening PIC lesions suggest active inflammation, while new neovascular membranes may indicate secondary neovascular processes."

Confirms neovascular membranes as a distinct, treatment-relevant complication of PIC.

Vitritis Vitritis HP:0011531

Show evidence (2 references)

PMID:37176633 SUPPORT Human Clinical

"Posterior involvement includes vitritis, vasculitis and choroidal lesions."

Documents vitritis accompanying choroidal involvement in posterior uveitis.

PMID:25434765 SUPPORT Human Clinical

"BSCR is characterized by distinctive multiple choroidal hypopigmented lesions in combination with retinal vasculitis and vitritis"

Documents vitritis as a defining feature of birdshot chorioretinopathy.

Scotoma Scotoma HP:0000575

Show evidence (1 reference)

PMID:27994812 SUPPORT Human Clinical

"patients may complain of a temporal scotoma, metamorphopsia, floaters, photopsias, photophobia, and decreased vision"

Lists scotoma among the presenting symptoms of multifocal choroiditis.

Metamorphopsia Metamorphopsia HP:0012508

Show evidence (1 reference)

PMID:27994812 SUPPORT Human Clinical

"patients may complain of a temporal scotoma, metamorphopsia, floaters, photopsias, photophobia, and decreased vision"

Lists metamorphopsia among the presenting symptoms of multifocal choroiditis.

Macular scar OCCASIONAL Macular scar HP:0200056

Show evidence (1 reference)

PMID:38843299 SUPPORT Human Clinical

"Macular scar 24 (24.7)"

Complications table reports macular scar in 24 of 97 patients (24.7%), supporting the OCCASIONAL (5-29%) frequency band.

Ocular hypertension OCCASIONAL Ocular hypertension HP:0007906

Show evidence (1 reference)

PMID:38843299 SUPPORT Human Clinical

"Ocular hypertension (IOP >21 mmHg) 20 (20.6)"

Complications table reports ocular hypertension in 20 of 97 patients (20.6%), supporting the OCCASIONAL (5-29%) frequency band.

Epiretinal membrane Epiretinal membrane HP:0100014

Show evidence (1 reference)

PMID:27994812 SUPPORT Human Clinical

"higher frequency of structural complications such as cataract, cystoid macular edema (CME), and epiretinal membrane (ERM) related to intraocular inflammation"

Documents epiretinal membrane as an inflammation-related structural complication of MFCPU.

🧬

Genetic Associations

3

HLA-A29

Gene: HLA-A29 hgnc:4931 relationship_type: SUSCEPTIBILITY

Show evidence (2 references)

PMID:25434765 SUPPORT Human Clinical

"BSCR is the strongest documented association between HLA and disease in humans"

Establishes the exceptional strength of the HLA-A29 association.

PMID:39570638 SUPPORT Human Clinical

"Homozygosity for HLA-A29 increased the risk of developing BSCR without affecting disease severity."

Demonstrates the allele-dosage effect on susceptibility.

ERAP1

Gene: ERAP1 hgnc:18173 relationship_type: MODIFIER

Show evidence (1 reference)

PMID:34727153 SUPPORT Human Clinical

"an expression quantitative trait locus (eQTL) decreasing ERAP1 expression"

Identifies the ERAP1 risk variant as an expression-lowering eQTL.

ERAP2

Gene: ERAP2 hgnc:29499 relationship_type: MODIFIER

Show evidence (1 reference)

PMID:34727153 SUPPORT Human Clinical

"an eQTL increasing ERAP2 expression. Furthermore, ERAP2-rs2248374 that disrupts ERAP2 expression is protective"

Documents both the risk-increasing and the protective ERAP2 expression variants.

💊

Medical Actions

7

Antiparasitic Therapy for Ocular Toxoplasmosis

Category: Therapeutic Action: Pharmacotherapy NCIT:C15986

Agent: pyrimethamine CHEBI:8673 sulfadiazine CHEBI:9328

Antimicrobial eradication of the active Toxoplasma focus, historically pyrimethamine plus sulfadiazine with corticosteroid ("classic therapy"), with trimethoprim-sulfamethoxazole a well-supported alternative in immunocompetent patients. Corticosteroid is added only under antiparasitic cover; it must never be given alone.

Mechanism Target:

INHIBITS Pathogen Invasion and Persistence in the Choroid and Outer Retina — Antiparasitic drugs suppress replicating tachyzoites in the retina and choroid.

Show evidence (1 reference)

PMID:29704469 SUPPORT Human Clinical

"Based on our network meta-analysis, therapy with TMP-SMX seems to be an alternative treatment of OT in immunocompetent patients."

Network meta-analysis supporting antiparasitic therapy directed at the organism.

Show evidence (2 references)

PMID:34370174 SUPPORT Human Clinical

"The current mainstay for the treatment, if necessary, is the use of oral antibiotic with systemic corticosteroids."

Establishes the combined antimicrobial-plus-corticosteroid regimen - the infectious arm's version of anti-inflammatory therapy, always paired with antimicrobial cover.

PMID:29704469 SUPPORT Human Clinical

"the combination of pyrimethamine, sulfadiazine, and corticosteroids"

Names the conventional antiparasitic-plus-corticosteroid regimen for ocular toxoplasmosis.

Antitubercular Therapy for Tubercular Choroiditis

Category: Therapeutic Action: Antibiotic Therapy NCIT:C15620

Agent: rifampicin CHEBI:28077 isoniazid CHEBI:6030

Multi-drug antitubercular therapy (ATT) added to corticosteroid in serpiginous-like choroiditis with evidence of systemic or latent tuberculosis. ATT reduces active inflammation and, critically, eliminates the recurrences that immunosuppression alone would not prevent. Trials are ongoing on optimal duration.

Mechanism Target:

INHIBITS Unopposed Immunosuppression of Unrecognised Infectious Choroiditis — Adding antimicrobial cover converts the harmful unopposed-immunosuppression scenario into safe combined therapy.

Show evidence (1 reference)

PMID:22675097 SUPPORT Human Clinical

"patients with serpiginous-like choroiditis and evidence of systemic or latent TB are best treated with antituberculosis treatment (ATT) in addition to the corticosteroid therapy"

Directly supports adding ATT to corticosteroid rather than immunosuppressing alone.

Show evidence (1 reference)

PMID:22675097 SUPPORT Human Clinical

"The use of ATT in these patients is likely to reduce active inflammation and eliminate future recurrences."

States the dual benefit of antitubercular therapy in serpiginous-like choroiditis.

Penicillin for Ocular Syphilis

Category: Therapeutic Action: Antibiotic Therapy NCIT:C15620

Agent: benzylpenicillin (penicillin G) CHEBI:18208

Ocular syphilis is managed as neurosyphilis, with parenteral aqueous crystalline penicillin G the drug of choice. Timely treatment is curative; delay produces long-term visual impairment. This is the clearest case in which the correct diagnosis converts an untreatable-looking uveitis into a curable infection.

Mechanism Target:

INHIBITS Pathogen Invasion and Persistence in the Choroid and Outer Retina — Penicillin eradicates Treponema pallidum from ocular and CNS compartments.

Show evidence (1 reference)

PMID:33831337 SUPPORT Human Clinical

"Centers for Disease Control and Prevention recommend that ocular syphilis be managed according to its treatment guidelines for neurosyphilis, with parenteral aqueous crystalline penicillin G the drug of choice."

Guideline-level support for penicillin G as the eradicating therapy.

Show evidence (1 reference)

PMID:33831337 SUPPORT Human Clinical

"With the timely diagnosis and appropriate treatment, ocular syphilis is curable. However, delayed diagnosis of ocular syphilis may result in long-term visual impairment."

Documents curability with timely antibiotic therapy and the cost of delay.

Corticosteroid Therapy

Category: Therapeutic Action: Pharmacotherapy NCIT:C15986

Agent: corticosteroid CHEBI:50858

First-line anti-inflammatory therapy for non-infectious choroiditis, given locally or systemically. It is the mainstay of the non-infectious arm and remains first-line in ocular sarcoidosis. In the infectious arm it is permissible only in combination with antimicrobial therapy; given alone to an unrecognised infectious choroiditis it removes immune restraint on the organism. Up to 30% of sarcoidosis patients require high doses, which is what drives the move to steroid-sparing agents.

Mechanism Target:

INHIBITS Choroidal Inflammatory Cell Infiltration — Corticosteroid suppresses the choroidal inflammatory infiltrate.

Show evidence (1 reference)

PMID:37176633 SUPPORT Human Clinical

"Corticosteroids remain the first-line treatment for sarcoidosis, but up to 30% of patients require high doses, justifying the use of corticosteroid-sparing treatments."

Establishes corticosteroid as first-line anti-inflammatory therapy and its dose-limiting problem.

Show evidence (2 references)

PMID:36013011 SUPPORT Human Clinical

"Local and systemic corticosteroids can be used for short periods, but immunosuppressive or biological therapies are usually needed for the long-term management of the disease."

Positions corticosteroid as short-term therapy in birdshot, with immunosuppression for maintenance.

PMID:22675097 PARTIAL Human Clinical

"Choroidal tuberculosis (TB) infection may present itself as a diffuse choroiditis that resembles serpiginous choroiditis, usually treated with immunossupressants."

Supports the safety caveat by documenting a TB choroiditis that phenocopies an entity conventionally treated with immunosuppression. Marked PARTIAL because the source states the misclassification risk rather than measuring corticosteroid harm directly.

Immunosuppressive and Biologic Therapy

Category: Therapeutic Action: Immunosuppressive Therapy NCIT:C15261

Corticosteroid-sparing immunomodulation - methotrexate, mycophenolate mofetil, and anti-TNF biologics - for chronic non-infectious choroiditis, especially birdshot chorioretinopathy, serpiginous choroiditis, MFCPU and sarcoid uveitis. This is the arm of the treatment fork that is actively dangerous if the aetiology is in fact infectious and untreated. Spans two platforms (small-molecule antimetabolites and monoclonal-antibody biologics), hence therapeutic_modality OTHER.

Mechanism Target:

INHIBITS Autoimmune Recognition of Ocular Self-Antigen — Immunomodulatory therapy suppresses the autoreactive T-cell response driving non-infectious choroiditis.

Show evidence (1 reference)

PMID:37176633 SUPPORT Human Clinical

"immunosuppressive treatments such as methotrexate may be introduced. More recent biotherapies such as anti-TNF are also very effective (as they are in other non-infectious uveitis etiologies)"

Supports methotrexate and anti-TNF for non-infectious uveitis broadly.

Show evidence (2 references)

PMID:36013011 SUPPORT Human Clinical

"immunosuppressive or biological therapies are usually needed for the long-term management of the disease"

Documents long-term immunomodulation as standard in birdshot chorioretinopathy.

PMID:15850812 PARTIAL Human Clinical

"treatment with immunosuppressive and alkylating agents have shown possible efficacy in small case series"

Supports immunosuppression in serpiginous choroiditis, marked PARTIAL because the evidence base is small uncontrolled case series.

Anti-VEGF Therapy for Inflammatory Choroidal Neovascularization

Category: Therapeutic Action: Pharmacotherapy NCIT:C15986

Agent: anti-VEGF agent NCIT:C1742

Intravitreal anti-VEGF injection for inflammatory choroidal neovascular membranes, with or without concomitant anti-inflammatory therapy. In POHS and PIC, where CNV rather than inflammation dominates vision loss, this is the principal sight-preserving intervention.

Mechanism Target:

INHIBITS Inflammatory Choroidal Neovascularization — VEGF blockade causes regression of the inflammatory neovascular membrane.

Show evidence (1 reference)

PMID:30209691 SUPPORT Human Clinical

"Management of these neovascular membranes consists of anti-vascular growth factor agents, with or without concomitant anti-inflammatory and/or corticosteroid therapy."

Establishes anti-VEGF as the management of inflammatory CNV.

Show evidence (1 reference)

PMID:25841248 SUPPORT Human Clinical

"Subfoveal and juxtafoveal CNVs are managed with anti-vascular endothelial growth factor therapy, photodynamic therapy, or a combination of both."

Documents anti-VEGF as standard management of CNV in POHS.

Laser Photocoagulation for Extrafoveal Choroidal Neovascularization

Category: Therapeutic Action: Laser Therapy NCIT:C15466

Thermal laser ablation of extrafoveal inflammatory choroidal neovascular membranes, where the membrane is far enough from the fovea that the resulting scotoma is acceptable. Largely superseded by anti-VEGF for subfoveal and juxtafoveal lesions.

Mechanism Target:

INHIBITS Inflammatory Choroidal Neovascularization — Photocoagulation ablates the extrafoveal neovascular membrane.

Show evidence (1 reference)

PMID:25841248 SUPPORT Human Clinical

"Extrafoveal CNVs are successfully treated with laser photocoagulation."

Supports laser photocoagulation for extrafoveal CNV.

Show evidence (1 reference)

PMID:25841248 SUPPORT Human Clinical

"Extrafoveal CNVs are successfully treated with laser photocoagulation."

Documents laser photocoagulation as effective for extrafoveal neovascular membranes.

🌍

Environmental Factors

3

Ocular penetrating trauma or intraocular surgery

Show evidence (1 reference)

PMID:35647958 SUPPORT Human Clinical

"Sympathetic ophthalmia is a rare, bilateral, granulomatous, panuveitis following penetrating trauma or surgery to one eye."

Ocular penetrating injury is the required environmental trigger of sympathetic ophthalmia.

Residence in a Histoplasma capsulatum-endemic region

Show evidence (1 reference)

PMID:32168355 SUPPORT Human Clinical

"Eleven of the 13 states with the highest POHS rates bordered the Mississippi and Ohio rivers."

Geographic clustering along the Mississippi/Ohio river valleys ties POHS risk to Histoplasma-endemic residence.

Immunocompromise

Show evidence (1 reference)

PMID:38843299 SUPPORT Human Clinical

"Immunocompromised patients showed a significantly larger size of retinitis than immunocompetent patients."

Impaired host immunity worsens infectious choroiditis, the biological basis of the immunosuppression hazard.

🔀

Differential Diagnoses

7

Conditions with similar clinical presentations that must be differentiated from Choroiditis:

Intraocular (vitreoretinal) lymphoma Not Yet Curated MONDO:0004351

Overlapping Features The most important masquerade syndrome of choroiditis. Lymphoma produces sub-RPE nodular deposits with autofluorescence and fluorescein angiographic findings closely resembling multifocal choroiditis, and it may transiently respond to corticosteroid, further delaying diagnosis.

Distinguishing Features

Older patients, typically over 50 years
Sub-RPE nodular elevations approximately 100 microns in diameter
Frequent CNS involvement
Vitreous or chorioretinal biopsy with cytology, IL-10/IL-6 ratio and MYD88 testing
Corticosteroid response is transient and incomplete

Show evidence (1 reference)

PMID:27994812 SUPPORT Human Clinical

"causes subretinal pigment epithelium (sub-RPE) nodular elevations about 100 μm in diameter which demostrate autofluorescence and fluorescein angiographic findings similar to those seen in MFC"

Documents the imaging overlap between vitreoretinal lymphoma and multifocal choroiditis. (The spelling "demostrate" is as printed in the source.)

Vogt-Koyanagi-Harada disease MONDO:0018092

Overlapping Features A bilateral granulomatous panuveitis with diffuse choroidal inflammation, exudative retinal detachment and extraocular (auditory, meningeal, integumentary) features. Curated as its own dismech entry; listed here as the principal non-infectious granulomatous mimic of diffuse choroiditis.

Distinguishing Features

Exudative/serous retinal detachments with diffuse choroidal thickening on EDI-OCT
Extraocular features (tinnitus, headache, meningismus, poliosis, vitiligo, alopecia)
Predilection for pigmented ethnicities
No antecedent ocular trauma, which would instead suggest sympathetic ophthalmia

Show evidence (2 references)

PMID:34145419 SUPPORT Human Clinical

"Vogt-Koyanagi-Harada (VKH) disease is a primary autoimmune stromal choroiditis."

Establishes VKH as itself a form of choroiditis - a stromal rather than choriocapillaris-based one - which is exactly why it must be distinguished from the entities modelled here.

PMID:34145419 SUPPORT Human Clinical

"the sine qua non presence of diffuse choroiditis, detected with indocyanine green angiography (ICGA) and/or Enhanced Depth Imaging OCT (EDI-OCT)"

Supports the distinguishing feature - diffuse choroidal involvement on ICGA/EDI-OCT - separating VKH from the focal/multifocal lesions of the white-dot entities.

Ocular tuberculosis Not Yet Curated MONDO:0006876

Overlapping Features Tubercular choroiditis is curated as a subtype of this entry, but it is simultaneously the standing differential for every non-infectious granulomatous choroiditis, above all ocular sarcoidosis and idiopathic serpiginous choroiditis, because misclassification leads to harmful unopposed immunosuppression.

Distinguishing Features

Positive interferon-gamma release assay or tuberculin skin test
Residence in or travel to a tuberculosis-endemic area
Choroidal tubercle or tuberculoma
Occlusive retinal vasculitis
Response to antitubercular therapy

Show evidence (1 reference)

PMID:37176633 SUPPORT Human Clinical

"Tuberculosis is a classic differential diagnosis to be wary of, especially in people who have spent time in endemic areas."

Names tuberculosis as the classic differential for sarcoid uveitis.

Ocular syphilis Not Yet Curated MONDO:0005976

Overlapping Features Syphilitic chorioretinitis is curated as a subtype here, but ocular syphilis is also the universal differential: it can imitate essentially any ocular inflammatory presentation, and serologic exclusion is mandatory before immunosuppression.

Distinguishing Features

Positive treponemal serology using the CDC reverse screening algorithm
Acute syphilitic posterior placoid chorioretinitis morphology with leopard-spot hypofluorescence
Frequent HIV co-infection and neurosyphilis
Rapid resolution on penicillin

Show evidence (1 reference)

PMID:33831337 SUPPORT Human Clinical

"ocular syphilis should always be a part of the differential diagnosis of most, if not all, ocular infectious and inflammatory presentations"

Directly states the universal differential status of ocular syphilis.

Sarcoidosis MONDO:0019338

Overlapping Features Systemic granulomatous disease involving the eye in a large minority of cases, sometimes without systemic involvement. The systemic mechanism is curated in the dismech Sarcoidosis and Neurosarcoidosis entries; the ocular arm is a subtype here.

Distinguishing Features

Granulomatous anterior uveitis with mutton-fat keratic precipitates and synechiae
Bilateral hilar lymphadenopathy on chest imaging
Raised serum angiotensin-converting enzyme
Non-caseating epithelioid granulomas on biopsy

Show evidence (1 reference)

PMID:37176633 SUPPORT Human Clinical

"Sarcoidosis is an inflammatory disease that involves the eyes in 10-55% of cases, sometimes without systemic involvement."

Quantifies ocular involvement in sarcoidosis and notes it may be isolated.

Behcet disease MONDO:0007191

Overlapping Features Systemic vasculitis producing occlusive retinal vasculitis and panuveitis. Curated as its own dismech entry; listed here because its posterior-segment inflammation overlaps with choroiditis and it is a recognised non-infectious uveitis aetiology in large cohorts.

Distinguishing Features

Recurrent oral and genital aphthous ulceration, skin lesions, pathergy
Explosive occlusive retinal vasculitis with retinal haemorrhage rather than primary choroidal lesions
HLA-B51 association
Silk Road geographic distribution

Show evidence (1 reference)

PMID:37428299 SUPPORT Human Clinical

"The most frequent causes of non-infectious uveitis included sarcoidosis, white dot syndromes, ankylosing spondylitis, lens-induced uveitis, Adamantiades-Behçet disease, and idiopathic juvenile arthritis."

Places Behcet disease among the leading non-infectious uveitis aetiologies to be distinguished.

Cytomegalovirus retinitis MONDO:0000878

Overlapping Features Viral necrotising retinitis of the profoundly immunocompromised, curated as its own dismech entry. A key infectious differential in any patient with posterior-segment inflammation and low CD4 count.

Distinguishing Features

Severe immunosuppression, typically CD4 below 50 cells per microlitre
Granular retinitis with haemorrhage along the vascular arcades
Minimal vitritis
Aqueous PCR positive for cytomegalovirus
Responds to antivirals, not to immunosuppression

Show evidence (2 references)

PMID:28012878 SUPPORT Human Clinical

"others, such as cytomegalovirus retinitis or acute retinal necrosis, may result in serious complications and profound vision loss"

Identifies CMV retinitis specifically as a sight-threatening viral posterior uveitis requiring differentiation.

PMID:28012878 SUPPORT Human Clinical

"Since some of these infections may respond well to antiviral therapy, it is important to work up all cases of posterior uveitis to rule out an infectious etiology."

Supports the management consequence of the distinction - antiviral therapy rather than immunosuppression.

🔬

Clinical Trials

2

NCT06613919 PHASE_IV COMPLETED

Randomised non-inferiority trial comparing 6 versus 9 months of antitubercular therapy for tubercular posterior uveitis and choroiditis. Directly addresses the treatment-duration question in the infectious arm of the aetiologic fork.

Target Phenotypes: Posterior uveitis HP:0012123

Show evidence (1 reference)

clinicaltrials:NCT06613919 SUPPORT Human Clinical

"The goal of this clinical trial is to learn if 6-months anti-TB therapy is not worse than 9-months therapy for the treatment of tubercular posterior uveitis."

Confirms the trial tests antitubercular therapy duration in tubercular posterior uveitis.

NCT01449877 PHASE_III COMPLETED

Randomised double-masked trial of trimethoprim-sulfamethoxazole prophylaxis versus placebo after acute treatment of Toxoplasma retinochoroiditis, with recurrence over long-term follow-up as the primary outcome. Tests whether continued antimicrobial suppression prevents cyst reactivation.

Target Phenotypes: Chorioretinal scar HP:0007777

Show evidence (1 reference)

clinicaltrials:NCT01449877 SUPPORT Human Clinical

"The investigators study aims to determine the effect of prophylactic therapy with Trimethoprim-sulfamethoxazole on the recurrences of toxoplasma retinochoroiditis gondii."

Confirms the trial tests antimicrobial prophylaxis against recurrence of ocular toxoplasmosis.

{ }

Source YAML

click to show

name: Choroiditis
creation_date: '2026-08-01T09:15:00Z'
description: >-
  Choroiditis is inflammation of the choroid, the high-flow vascular layer between
  the retina and the sclera that supplies the outer retina and retinal pigment
  epithelium (RPE). It is the principal anatomic substrate of posterior uveitis and
  a major cause of irreversible vision loss. Choroiditis is not a single disease but
  an umbrella over a heterogeneous set of entities that divide along one
  clinically decisive axis: infectious versus non-infectious aetiology. Infectious
  choroiditis includes ocular toxoplasmosis (the commonest infectious posterior
  uveitis worldwide), tubercular serpiginous-like choroiditis, syphilitic
  chorioretinitis, and presumed ocular histoplasmosis syndrome. Non-infectious
  choroiditis includes the white-dot syndromes (multifocal choroiditis with
  panuveitis, punctate inner choroidopathy, serpiginous choroiditis, birdshot
  chorioretinopathy) and granulomatous disease (sarcoidosis, sympathetic
  ophthalmia). The two arms converge on shared downstream mechanisms —
  choriocapillaris hypoperfusion, outer-retinal and RPE damage, chorioretinal
  scarring, and inflammatory choroidal neovascularization — but they demand
  opposed management: corticosteroids and immunosuppression are the mainstay of
  non-infectious disease and are actively harmful when given without antimicrobial
  cover in unrecognised infectious disease.
category: Immune
disease_term:
  preferred_term: choroiditis
  term:
    id: MONDO:0001280
    label: choroiditis
parents:
- Posterior uveitis
- Uveitis
- Eye disorder
synonyms:
- Choroiditides
- Chorioretinitis

has_subtypes:
- name: Ocular Toxoplasmosis
  display_name: Ocular toxoplasmosis (Toxoplasma retinochoroiditis)
  classification: etiologic_infectious
  subtype_term:
    preferred_term: ocular toxoplasmosis
    term:
      id: MONDO:0005879
      label: ocular toxoplasmosis
  description: >-
    Necrotising retinochoroiditis caused by Toxoplasma gondii, the leading
    infectious cause of posterior uveitis worldwide. Classically presents as a
    focal white retinal lesion with overlying vitritis, frequently recurring at
    the border of a pre-existing pigmented chorioretinal scar as tissue cysts
    reactivate. Requires antiparasitic therapy; corticosteroid must never be
    given without antiparasitic cover.
  evidence:
  - reference: PMID:36095008
    reference_title: Ocular Toxoplasmosis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Ocular toxoplasmosis is the leading cause of posterior uveitis worldwide"
    explanation: Establishes ocular toxoplasmosis as the dominant infectious subtype of posterior uveitis/choroiditis.

- name: Tubercular Choroiditis
  display_name: Tubercular choroiditis and serpiginous-like choroiditis
  classification: etiologic_infectious
  subtype_term:
    preferred_term: ocular tuberculosis
    term:
      id: MONDO:0006876
      label: ocular tuberculosis
  description: >-
    Choroidal inflammation attributable to Mycobacterium tuberculosis, presenting
    as choroidal tubercles/tuberculoma, multifocal choroiditis, or — most
    treacherously — a diffuse serpiginous-like choroiditis that phenocopies
    idiopathic serpiginous choroiditis. Because the idiopathic phenocopy is
    conventionally treated with immunosuppression, misclassification here is the
    canonical harm scenario of the infectious/non-infectious fork.
  evidence:
  - reference: PMID:33845014
    reference_title: Classification Criteria for Tubercular Uveitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Key criteria for tubercular uveitis were a compatible uveitic syndrome, including (1) anterior uveitis with iris nodules, (2) serpiginous-like tubercular choroiditis, (3) choroidal nodule (tuberculoma)"
    explanation: SUN consensus criteria enumerate serpiginous-like choroiditis and choroidal tuberculoma as defining tubercular uveitic presentations.

- name: Syphilitic Chorioretinitis
  display_name: Syphilitic chorioretinitis, including acute syphilitic posterior placoid chorioretinitis
  classification: etiologic_infectious
  description: >-
    Ocular involvement by Treponema pallidum, "the great masquerader". It can
    imitate almost any uveitic phenotype, and its one relatively distinctive form
    is acute syphilitic posterior placoid chorioretinitis (ASPPC), a large
    yellowish placoid outer-retinal lesion at the posterior pole. Serologic
    exclusion of syphilis is mandatory before immunosuppressing any choroiditis.
    No MONDO term for ocular/syphilitic chorioretinitis exists at time of
    curation, so this subtype carries no subtype_term.
  evidence:
  - reference: PMID:33831337
    reference_title: Ocular syphilis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "With the exception of syphilitic posterior placoid chorioretinitis, the diverse manifestations of ocular syphilis have few distinct features that can be used to assist in clinical diagnosis."
    explanation: Documents both the masquerading breadth of ocular syphilis and ASPPC as its one distinctive chorioretinal form.
  - reference: PMID:22863970
    reference_title: "Acute syphilitic posterior placoid chorioretinitis: report of a case series and comprehensive review of the literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In all patients, posterior segment examination in the involved eyes revealed a large, yellowish, placoid, outer retinal lesion."
    explanation: Defines the characteristic ASPPC lesion morphology in a 16-patient series.

- name: Presumed Ocular Histoplasmosis Syndrome
  display_name: Presumed ocular histoplasmosis syndrome (POHS)
  classification: etiologic_infectious
  subtype_term:
    preferred_term: histoplasmosis retinitis
    term:
      id: MONDO:0001263
      label: histoplasmosis retinitis
  description: >-
    A chorioretinal disorder of Histoplasma capsulatum-endemic regions (in the
    United States, the Mississippi and Ohio river valleys), characterised by
    punched-out "histo spots", peripapillary atrophy and absent vitritis. Vision
    loss is driven almost entirely by secondary choroidal neovascularization
    rather than by active inflammation, so management is anti-VEGF-led rather
    than immunosuppression-led.
  evidence:
  - reference: PMID:25841248
    reference_title: Ocular histoplasmosis syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Ocular histoplasmosis syndrome (OHS) is a chorioretinal disorder with a distinct fundus appearance that is commonly found in regions endemic for Histoplasma capsulatum."
    explanation: Defines POHS as an endemic-region chorioretinal disorder attributed to Histoplasma capsulatum.

- name: Birdshot Chorioretinopathy
  display_name: Birdshot chorioretinopathy (HLA-A29-associated)
  classification: etiologic_noninfectious
  subtype_term:
    preferred_term: birdshot chorioretinopathy
    term:
      id: MONDO:0011599
      label: birdshot chorioretinopathy
  description: >-
    A bilateral chronic posterior uveitis of middle-aged people of European
    descent with no extraocular manifestations, defined by scattered
    cream-coloured hypopigmented choroidal lesions with retinal vasculitis and
    vitritis. Its association with HLA-A29 is among the strongest HLA-disease
    associations documented in humans, and ERAP1/ERAP2 haplotypes modify risk
    within HLA-A29 carriers. Requires long-term immunosuppressive or biologic
    therapy.
  evidence:
  - reference: PMID:25434765
    reference_title: The immunopathogenesis of birdshot chorioretinopathy; a bird of many feathers.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "BSCR is characterized by distinctive multiple choroidal hypopigmented lesions in combination with retinal vasculitis and vitritis, and the extraordinary feature that virtually all patients are HLA-A29 positive."
    explanation: Defines the birdshot phenotype and its near-obligate HLA-A29 positivity.

- name: Multifocal Choroiditis with Panuveitis
  display_name: Multifocal choroiditis with panuveitis (MFCPU)
  classification: etiologic_noninfectious
  subtype_term:
    preferred_term: multifocal choroiditis
    term:
      id: MONDO:0023833
      label: multifocal choroiditis
  description: >-
    Idiopathic chronic bilateral chorioretinopathy of predominantly young myopic
    women, with multiple punched-out chorioretinal lesions plus anterior-chamber
    and vitreous inflammation. Distinguished from PIC largely by the presence of
    overt intraocular inflammation and larger lesions; carries a high rate of
    choroidal neovascularization and of structural complications.
  evidence:
  - reference: PMID:27994812
    reference_title: Idiopathic Multifocal Choroiditis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "MFCPU is a variant of idiopathic MFC that has been described in association with anterior uveitis and/or vitritis, multiple punched-out atrophic chorioretinal lesions of variable size"
    explanation: Defines MFCPU as the inflammatory variant of idiopathic multifocal choroiditis.

- name: Punctate Inner Choroidopathy
  display_name: Punctate inner choroidopathy (PIC)
  classification: etiologic_noninfectious
  subtype_term:
    preferred_term: punctate inner choroidopathy
    term:
      id: MONDO:0035584
      label: punctate inner choroidopathy
  description: >-
    An uncommon idiopathic inflammatory chorioretinopathy of young myopic women,
    with small yellow-white lesions of the inner choroid and outer retina and
    characteristically absent vitritis. Choroidal neovascularization is
    exceptionally common and is the principal threat to sight, so management must
    distinguish new inflammatory lesions from new neovascular membranes.
  evidence:
  - reference: PMID:38181975
    reference_title: "Punctate inner choroidopathy: A review of the current diagnostic and therapeutic approaches."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Punctate inner choroidopathy (PIC) is an uncommon idiopathic inflammatory condition characterized by multifocal chorioretinopathy that primarily affects young adults, with a predilection for myopic females."
    explanation: Defines PIC and its demographic predilection.

- name: Serpiginous Choroiditis
  display_name: Serpiginous choroiditis (idiopathic)
  classification: etiologic_noninfectious
  subtype_term:
    preferred_term: serpiginous choroiditis
    term:
      id: MONDO:0018152
      label: serpiginous choroiditis
  description: >-
    A rare, usually bilateral, chronic and relentlessly recurrent inflammation of
    choroid, RPE and choriocapillaris that spreads in a geographic
    (serpentine) pattern, classically peripapillary, macular or ampiginous.
    Idiopathic serpiginous choroiditis must be separated from tubercular
    serpiginous-like choroiditis before immunosuppression is started.
  evidence:
  - reference: PMID:15850812
    reference_title: Serpiginous choroiditis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Serpiginous choroiditis is a rare, usually bilateral, chronic, progressive, recurrent inflammation of the choroid, retinal pigment epithelium, and choriocapillaris of unknown etiology."
    explanation: Defines idiopathic serpiginous choroiditis and its target tissues.

- name: Sarcoid Choroiditis
  display_name: Sarcoidosis-associated choroiditis
  classification: etiologic_noninfectious
  description: >-
    Choroidal involvement in systemic sarcoidosis, part of a granulomatous
    uveitis that may include vitritis, retinal vasculitis and choroidal
    granulomas. The systemic granulomatous mechanism is curated in the
    Sarcoidosis and Neurosarcoidosis entries; this subtype scopes only the
    ocular/choroidal arm. No MONDO term for ocular sarcoidosis exists at time of
    curation, so this subtype carries no subtype_term.
  evidence:
  - reference: PMID:37176633
    reference_title: "Sarcoidosis-Related Uveitis: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Posterior involvement includes vitritis, vasculitis and choroidal lesions."
    explanation: Documents choroidal involvement as part of posterior sarcoid uveitis.

- name: Sympathetic Ophthalmia
  display_name: Sympathetic ophthalmia
  classification: etiologic_noninfectious
  subtype_term:
    preferred_term: sympathetic ophthalmia
    term:
      id: MONDO:0019198
      label: sympathetic ophthalmia
  description: >-
    A rare bilateral granulomatous panuveitis following penetrating trauma or
    surgery to one eye, in which autoimmunity to sequestered uveal/retinal
    antigen released by the injured eye attacks the fellow ("sympathising") eye.
    Choroidal involvement takes the form of yellowish-white lesions or
    Dalen-Fuchs nodules.
  evidence:
  - reference: PMID:35647958
    reference_title: "Sympathetic ophthalmia: A comprehensive update."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Sympathetic ophthalmia is a rare, bilateral, granulomatous, panuveitis following penetrating trauma or surgery to one eye."
    explanation: Defines sympathetic ophthalmia as post-traumatic bilateral granulomatous panuveitis.

pathophysiology:
- name: Aetiologic Fork - Infectious versus Non-Infectious Choroidal Inflammation
  biological_scale: ORGANISM
  role: trigger
  description: >-
    The root branch point of the entry. Choroidal inflammation may be driven by a
    replicating pathogen within ocular tissue or by an antigen-driven
    autoimmune/autoinflammatory process against ocular self-antigen. Both arms
    produce clinically overlapping choroiditis, and both converge on the same
    downstream tissue-injury cascade, but they diverge completely at the level of
    management: the infectious arm requires antimicrobial eradication and is made
    worse by unopposed immunosuppression, whereas the non-infectious arm requires
    exactly that immunosuppression. Distinguishing the arms is therefore the
    single most consequential diagnostic act in choroiditis.
  locations:
  - preferred_term: choroid
    term:
      id: UBERON:0001776
      label: optic choroid
  downstream:
  - target: Pathogen Invasion and Persistence in the Choroid and Outer Retina
    description: Aetiologic assignment to the infectious arm.
    causal_link_type: DIRECT
  - target: Autoimmune Recognition of Ocular Self-Antigen
    description: Aetiologic assignment to the non-infectious arm.
    causal_link_type: DIRECT
  evidence:
  - reference: PMID:37589912
    reference_title: Challenges in posterior uveitis-tips and tricks for the retina specialist.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The spectrum of etiologies for uveitis is very broad and includes infectious and auto-immune diseases."
    explanation: States the infectious/autoimmune aetiologic dichotomy that structures this entry.
  - reference: PMID:37428299
    reference_title: "The large Hellenic Study of Uveitis: epidemiology, etiologic factors and classification."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Out of 6191 cases with uveitis, 1925 were infectious, 4125 were non-infectious"
    explanation: Quantifies the infectious/non-infectious split in a 30-year tertiary uveitis cohort, showing both arms are numerically substantial.

- name: Pathogen Invasion and Persistence in the Choroid and Outer Retina
  biological_scale: CELLULAR
  role: trigger
  description: >-
    In the infectious arm, an organism reaches and persists in the choroid, RPE
    or outer retina: Toxoplasma gondii as encysted bradyzoites in retinal scars,
    Mycobacterium tuberculosis within choroidal macrophages, Treponema pallidum
    disseminated haematogenously to the highly vascular choroid, or Histoplasma
    capsulatum presumed to have seeded the choroid during earlier fungaemia. The
    choroid's exceptionally high blood flow makes it a preferential site of
    haematogenous seeding. Organism persistence, not merely acute invasion, is
    what makes the infectious arm relapsing and what makes unopposed
    immunosuppression dangerous.
  cell_types:
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  - preferred_term: retinal pigment epithelial cell
    term:
      id: CL:0002586
      label: retinal pigment epithelial cell
  locations:
  - preferred_term: choroid
    term:
      id: UBERON:0001776
      label: optic choroid
  downstream:
  - target: Choroidal Inflammatory Cell Infiltration
    description: Pathogen antigen drives recruitment of leukocytes into the choroidal stroma.
    causal_link_type: DIRECT
  - target: Toxoplasma Cyst Reactivation and Recurrent Retinochoroiditis
    description: Persisting tissue cysts provide the reservoir for later reactivation.
    causal_link_type: DIRECT
  - target: Unopposed Immunosuppression of Unrecognised Infectious Choroiditis
    description: >-
      Persisting organism is the substrate on which immunosuppression given
      without antimicrobial cover acts.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Misclassification of infectious choroiditis as an idiopathic non-infectious entity
    evidence:
    - reference: PMID:22675097
      reference_title: Tubercular serpiginous-like choroiditis.
      supports: PARTIAL
      evidence_source: HUMAN_CLINICAL
      snippet: "Choroidal tuberculosis (TB) infection may present itself as a diffuse choroiditis that resembles serpiginous choroiditis, usually treated with immunossupressants."
      explanation: >-
        Documents the specific route by which a persisting organism ends up
        receiving immunosuppression - phenocopy of an entity conventionally
        treated that way. Marked PARTIAL because the source establishes the
        misclassification risk, not a measured harm from immunosuppression.
  evidence:
  - reference: PMID:36095008
    reference_title: Ocular Toxoplasmosis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Ocular toxoplasmosis is the leading cause of posterior uveitis worldwide"
    explanation: Establishes an infectious organism as the single commonest driver of posterior uveitis/choroiditis.
  - reference: PMID:33831337
    reference_title: Ocular syphilis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Ocular involvement can occur at any stage of syphilis and any part of the eye can be affected."
    explanation: Documents haematogenous ocular seeding by Treponema pallidum at any disease stage.
  - reference: PMID:33845014
    reference_title: Classification Criteria for Tubercular Uveitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "evidence of tuberculosis, including histologically or microbiologically confirmed infection, positive interferon-γ release assay test, or positive tuberculin skin test"
    explanation: Consensus criteria require demonstrable mycobacterial infection, supporting organism presence as the driver of the tubercular arm.

- name: Toxoplasma Cyst Reactivation and Recurrent Retinochoroiditis
  biological_scale: TISSUE
  role: amplifier
  description: >-
    The signature relapsing behaviour of ocular toxoplasmosis. Bradyzoites
    encysted in the retina at the edge of an old pigmented chorioretinal scar
    convert back to proliferating tachyzoites, producing a new satellite focus of
    necrotising retinochoroiditis at the scar border. Each reactivation enlarges
    the area of destroyed outer retina, so cumulative visual loss is driven by
    recurrence count and lesion location rather than by any single episode.
    Immunocompromise markedly worsens lesion size and visual outcome.
  cell_types:
  - preferred_term: photoreceptor cell
    term:
      id: CL:0000287
      label: eye photoreceptor cell
  locations:
  - preferred_term: choroid
    term:
      id: UBERON:0001776
      label: optic choroid
  downstream:
  - target: Outer Retinal and Retinal Pigment Epithelial Damage
    description: Each reactivation episode destroys a further patch of outer retina.
    causal_link_type: DIRECT
  - target: Chorioretinal scar
    description: Healed reactivation foci leave pigmented atrophic scars.
    causal_link_type: DIRECT
  evidence:
  - reference: PMID:38843299
    reference_title: "Clinical characteristics, visual acuity outcomes, and factors associated with loss of vision among patients with active ocular toxoplasmosis: A retrospective study in a Thai tertiary center."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The cumulative incidence of recurrent OT at three years was 33.9%"
    explanation: Quantifies the recurrent nature of ocular toxoplasmosis in a treated tertiary cohort.
  - reference: PMID:38843299
    reference_title: "Clinical characteristics, visual acuity outcomes, and factors associated with loss of vision among patients with active ocular toxoplasmosis: A retrospective study in a Thai tertiary center."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "OT reactivation, owing to the persistence of tissue cysts in retinal tissues, can increase the probability of VA loss."
    explanation: >-
      Directly states the tissue-cyst-persistence mechanism of reactivation and
      its link to cumulative visual loss.
  - reference: PMID:38843299
    reference_title: "Clinical characteristics, visual acuity outcomes, and factors associated with loss of vision among patients with active ocular toxoplasmosis: A retrospective study in a Thai tertiary center."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Immunocompromised patients showed a significantly larger size of retinitis than immunocompetent patients."
    explanation: Shows host immune control constrains lesion size, consistent with reactivation being restrained by immunity.

- name: Unopposed Immunosuppression of Unrecognised Infectious Choroiditis
  biological_scale: ORGANISM
  role: amplifier
  description: >-
    The harm arm of the aetiologic fork, and the reason the fork must be modelled
    mechanistically rather than as a list. When infectious choroiditis is
    misclassified as an idiopathic non-infectious entity, it receives the correct
    treatment for the wrong diagnosis — corticosteroid and/or steroid-sparing
    immunosuppression without antimicrobial cover. The expected consequence is
    loss of host immune restraint on a replicating organism; note that the
    documented evidence here is for the misclassification hazard and for the
    superiority of adding antimicrobial therapy, rather than a trial measuring
    harm from unopposed immunosuppression directly. Tubercular
    serpiginous-like choroiditis is the canonical case, because its idiopathic
    phenocopy is conventionally immunosuppressed; syphilis is the second, because
    it can imitate essentially any uveitic phenotype. This is why serologic and
    mycobacterial exclusion precede immunosuppression in all choroiditis.
  locations:
  - preferred_term: choroid
    term:
      id: UBERON:0001776
      label: optic choroid
  downstream:
  - target: Outer Retinal and Retinal Pigment Epithelial Damage
    description: >-
      Uncontrolled pathogen replication extends the zone of outer-retinal
      destruction.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Unrestrained pathogen replication in choroid and outer retina
  evidence:
  - reference: PMID:22675097
    reference_title: Tubercular serpiginous-like choroiditis.
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "Choroidal tuberculosis (TB) infection may present itself as a diffuse choroiditis that resembles serpiginous choroiditis, usually treated with immunossupressants."
    explanation: >-
      States the misclassification hazard directly - a TB choroiditis that
      phenocopies an entity conventionally treated with immunosuppressants.
      Marked PARTIAL because the source documents the risk of misdirected
      treatment rather than measuring harm from immunosuppression.
      (The spelling "immunossupressants" is as printed in the source.)
  - reference: PMID:22675097
    reference_title: Tubercular serpiginous-like choroiditis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Recent studies have demonstrated that patients with serpiginous-like choroiditis and evidence of systemic or latent TB are best treated with antituberculosis treatment (ATT) in addition to the corticosteroid therapy."
    explanation: >-
      Establishes that corticosteroid is appropriate in the infectious arm only
      when combined with antimicrobial therapy - the operational content of the
      management fork.
  - reference: PMID:33831337
    reference_title: Ocular syphilis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "ocular syphilis should always be a part of the differential diagnosis of most, if not all, ocular infectious and inflammatory presentations"
    explanation: Supports mandatory syphilis exclusion in any inflammatory ocular presentation before immunosuppression.

- name: Autoimmune Recognition of Ocular Self-Antigen
  biological_scale: MOLECULAR
  role: trigger
  description: >-
    In the non-infectious arm, T cells recognise peptide derived from ocular
    self-antigen presented on MHC molecules, breaking the eye's immune
    privilege. Loss of sequestration is explicit in
    sympathetic ophthalmia, where penetrating trauma exposes previously
    sequestered uveal antigen and provokes bilateral granulomatous disease. In
    birdshot chorioretinopathy the presenting molecule itself is the dominant
    genetic risk factor.
  cell_types:
  - preferred_term: CD8-positive, alpha-beta T cell
    term:
      id: CL:0000625
      label: CD8-positive, alpha-beta T cell
  biological_processes:
  - preferred_term: antigen processing and presentation of peptide antigen via MHC class I
    modifier: ABNORMAL
    term:
      id: GO:0002474
      label: antigen processing and presentation of peptide antigen via MHC class I
  - preferred_term: T cell mediated immunity
    modifier: INCREASED
    term:
      id: GO:0002456
      label: T cell mediated immunity
  downstream:
  - target: HLA-A29-Restricted Antigen Presentation in Birdshot Chorioretinopathy
    description: The birdshot-specific instantiation of self-antigen presentation.
    causal_link_type: DIRECT
  - target: Choroidal Inflammatory Cell Infiltration
    description: Autoreactive T cells recruit and sustain a choroidal infiltrate.
    causal_link_type: DIRECT
  evidence:
  - reference: PMID:25434765
    reference_title: The immunopathogenesis of birdshot chorioretinopathy; a bird of many feathers.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the association with HLA-A29 suggests that it is directly involved in the presentation of peptide antigens to T cells"
    explanation: Frames the non-infectious arm as MHC-restricted peptide presentation to T cells.
  - reference: PMID:35647958
    reference_title: "Sympathetic ophthalmia: A comprehensive update."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Sympathetic ophthalmia is a rare, bilateral, granulomatous, panuveitis following penetrating trauma or surgery to one eye."
    explanation: >-
      Sympathetic ophthalmia is the clearest human demonstration that breach of
      ocular antigen sequestration triggers bilateral autoimmune uveitis.

- name: HLA-A29-Restricted Antigen Presentation in Birdshot Chorioretinopathy
  biological_scale: MOLECULAR
  role: driver
  description: >-
    Birdshot chorioretinopathy carries one of the strongest HLA-disease
    associations documented in human medicine: essentially all patients are
    HLA-A29 positive. In a classic series 47 of 49 birdshot patients (95.9%)
    carried HLA-A29, and the linked HLA-B12(B44) association is explained by
    linkage disequilibrium with HLA-A29 rather than by independent effect.
    Mechanistically the association is not merely a marker - genetic modifiers
    act on the peptide-loading pathway that supplies HLA-A29. ERAP1 and ERAP2
    haplotypes that increase ERAP2 expression and decrease ERAP1 expression raise
    risk in HLA-A29 carriers, while a haplotype disrupting ERAP2 expression is
    protective, and homozygosity for HLA-A29 further increases susceptibility.
    Together these implicate a peptide-presentation threshold model in which
    excess presentation of ERAP2-shaped peptides on HLA-A29 activates the immune
    response in the choroid.
  cell_types:
  - preferred_term: CD8-positive, alpha-beta T cell
    term:
      id: CL:0000625
      label: CD8-positive, alpha-beta T cell
  biological_processes:
  - preferred_term: antigen processing and presentation of peptide antigen via MHC class I
    modifier: INCREASED
    term:
      id: GO:0002474
      label: antigen processing and presentation of peptide antigen via MHC class I
  genes:
  - preferred_term: HLA-A29
    term:
      id: hgnc:4931
      label: HLA-A
  - preferred_term: ERAP1
    term:
      id: hgnc:18173
      label: ERAP1
  - preferred_term: ERAP2
    term:
      id: hgnc:29499
      label: ERAP2
  locations:
  - preferred_term: choroid
    term:
      id: UBERON:0001776
      label: optic choroid
  downstream:
  - target: Choroidal Inflammatory Cell Infiltration
    description: >-
      Peptide presentation on HLA-A29 above a threshold activates the choroidal
      immune response.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:34727153
      reference_title: ERAP1, ERAP2, and Two Copies of HLA-Aw19 Alleles Increase the Risk for Birdshot Chorioretinopathy in HLA-A29 Carriers.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "This suggests a mechanism in which exceeding a peptide presentation threshold activates the immune response in choroids of A29 carriers."
      explanation: States the peptide-threshold mechanism linking HLA-A29 presentation to choroidal inflammation.
  evidence:
  - reference: PMID:25434765
    reference_title: The immunopathogenesis of birdshot chorioretinopathy; a bird of many feathers.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "BSCR is the strongest documented association between HLA and disease in humans"
    explanation: Direct statement that birdshot-HLA-A29 is the strongest known human HLA-disease association.
  - reference: PMID:3341436
    reference_title: HLA typing in birdshot chorioretinopathy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Of these 49 patients, 47 (95.9%) had the HLA-A29 antigen."
    explanation: Quantifies HLA-A29 carriage at 95.9% in a birdshot series.
  - reference: PMID:3341436
    reference_title: HLA typing in birdshot chorioretinopathy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The HLA-B12 (B44) antigen was also significantly associated with the disease, but this antigen is known to be in linkage disequilibrium with the antigen HLA-A29."
    explanation: Supports the statement that the secondary HLA-B12(B44) signal reflects linkage disequilibrium rather than independent effect.
  - reference: PMID:34727153
    reference_title: ERAP1, ERAP2, and Two Copies of HLA-Aw19 Alleles Increase the Risk for Birdshot Chorioretinopathy in HLA-A29 Carriers.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We also confirm that ERAP1 and ERAP2 haplotypes modulate disease risk."
    explanation: Establishes the antigen-processing genes as risk modifiers within HLA-A29 carriers.
  - reference: PMID:39570638
    reference_title: The Impact of HLA-A29 Homozygosity and of the Second HLA-A Allele on Susceptibility and Severity of Birdshot Chorioretinitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Homozygosity for HLA-A29 increased the risk of developing BSCR without affecting disease severity."
    explanation: Demonstrates an allele-dosage effect of HLA-A29 on susceptibility.

- name: Choroidal Inflammatory Cell Infiltration
  biological_scale: TISSUE
  role: central_effector
  description: >-
    The convergence node of both aetiologic arms. Leukocytes - lymphocytes,
    macrophages and, in granulomatous forms, epithelioid and giant cells - are
    recruited across the choroidal vasculature into the choroidal stroma, with
    spillover into the vitreous (vitritis) and retinal vessels (retinal
    vasculitis). Histologically, serpiginous lesions show moderate diffuse
    lymphocytic infiltrates throughout the choroid. Because both an infectious
    and an autoimmune trigger produce a broadly similar infiltrate, the pattern
    of inflammation narrows but does not settle aetiology - some morphologies
    are informative (caseation favours tuberculosis; a serpiginous-like or
    tuberculoma pattern is a SUN criterion for tubercular uveitis) but
    microbiologic and serologic confirmation is what actually decides treatment.
  cell_types:
  - preferred_term: lymphocyte
    term:
      id: CL:0000542
      label: lymphocyte
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  - preferred_term: T cell
    term:
      id: CL:0000084
      label: T cell
  biological_processes:
  - preferred_term: inflammatory response
    modifier: INCREASED
    term:
      id: GO:0006954
      label: inflammatory response
  - preferred_term: leukocyte migration involved in inflammatory response
    modifier: INCREASED
    term:
      id: GO:0002523
      label: leukocyte migration involved in inflammatory response
  locations:
  - preferred_term: choroid
    term:
      id: UBERON:0001776
      label: optic choroid
  downstream:
  - target: Granulomatous Choroidal Inflammation
    description: >-
      In sarcoidosis, tuberculosis and sympathetic ophthalmia the infiltrate
      organises into granulomas.
    causal_link_type: DIRECT
  - target: Choriocapillaris Hypoperfusion and Non-Perfusion
    description: >-
      Inflammation of and around the choriocapillaris obstructs its lobular
      perfusion.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:35208488
      reference_title: "Diagnosis and Treatment of Primary Inflammatory Choriocapillaropathies (PICCPs): A Comprehensive Overview."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "PICCPs are resulting from one common clinicopathological mechanism, inflammatory choriocapillaris hypo- or non-perfusion."
      explanation: Establishes inflammation as the cause of choriocapillaris hypo/non-perfusion.
  - target: Vitritis
    description: Spillover of inflammatory cells into the vitreous cavity.
    causal_link_type: DIRECT
  - target: Retinal vasculitis
    description: Extension of inflammation to retinal vessels.
    causal_link_type: DIRECT
  - target: Macular edema
    description: >-
      Inflammatory breakdown of the blood-retinal barrier causes fluid
      accumulation in the macula.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Cytokine-mediated breakdown of the blood-retinal barrier
  - target: Posterior uveitis
    description: >-
      Choroidal infiltration is the anatomic substrate of the posterior uveitis
      phenotype.
    causal_link_type: DIRECT
  - target: Vitreous floaters
    description: >-
      Inflammatory cells and debris in the vitreous are perceived as floaters.
    causal_link_type: DIRECT
  - target: Ocular hypertension
    description: >-
      Intraocular inflammation (and its corticosteroid treatment) raises
      intraocular pressure.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Inflammatory trabecular meshwork dysfunction and corticosteroid response
  - target: Epiretinal membrane
    description: >-
      Chronic intraocular inflammation drives fibrocellular proliferation on the
      inner retinal surface.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Inflammation-driven glial and fibrocellular proliferation at the vitreoretinal interface
  - target: Cataract
    description: >-
      Chronic intraocular inflammation and its corticosteroid treatment opacify
      the lens.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Chronic inflammatory and corticosteroid-induced lens epithelial injury
  evidence:
  - reference: PMID:15850812
    reference_title: Serpiginous choroiditis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "moderate diffuse lymphocytic infiltrates throughout the choroid"
    explanation: Histologic confirmation of diffuse lymphocytic infiltration of the choroid in serpiginous choroiditis.
  - reference: PMID:37176633
    reference_title: "Sarcoidosis-Related Uveitis: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Posterior involvement includes vitritis, vasculitis and choroidal lesions."
    explanation: Documents the co-occurrence of choroidal inflammation with vitritis and retinal vasculitis.

- name: Granulomatous Choroidal Inflammation
  biological_scale: TISSUE
  role: effector
  description: >-
    In sarcoidosis, tuberculosis and sympathetic ophthalmia the choroidal
    infiltrate organises into granulomas. Sarcoid granulomas are non-caseating
    epithelioid granulomas; tubercular disease produces choroidal tubercles and
    tuberculoma; sympathetic ophthalmia produces Dalen-Fuchs nodules, focal
    aggregates of epithelioid cells between Bruch's membrane and the RPE. That
    both an infectious (TB) and a sterile (sarcoid) trigger yield broadly
    overlapping granulomatous choroiditis is a second, tissue-level restatement
    of why the aetiologic fork is not reliably settled on morphology alone -
    tuberculosis is the standing differential for ocular sarcoidosis, and
    caseation, while suggestive of tuberculosis, is often unavailable because
    ocular biopsy is rarely performed.
  cell_types:
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  biological_processes:
  - preferred_term: granuloma formation
    modifier: INCREASED
    term:
      id: GO:0002432
      label: granuloma formation
  locations:
  - preferred_term: choroid
    term:
      id: UBERON:0001776
      label: optic choroid
  - preferred_term: Bruch's membrane
    term:
      id: UBERON:0003957
      label: Bruch's membrane
  downstream:
  - target: Outer Retinal and Retinal Pigment Epithelial Damage
    description: Granulomatous destruction of the outer retinal/RPE complex.
    causal_link_type: DIRECT
  evidence:
  - reference: PMID:37176633
    reference_title: "Sarcoidosis-Related Uveitis: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The diagnosis is based on histology with the presence of non-caseating epithelioid granulomas."
    explanation: Defines the sarcoid granuloma as the histologic substrate.
  - reference: PMID:37176633
    reference_title: "Sarcoidosis-Related Uveitis: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Tuberculosis is a classic differential diagnosis to be wary of, especially in people who have spent time in endemic areas."
    explanation: >-
      Confirms that infectious (TB) and sterile (sarcoid) granulomatous
      choroiditis are not separable on morphology alone.
  - reference: PMID:35647958
    reference_title: "Sympathetic ophthalmia: A comprehensive update."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "It manifests as acute/chronic granulomatous uveitis with yellowish-white choroidal lesions or Dalen-Fuchs nodules."
    explanation: Documents Dalen-Fuchs nodules as the granulomatous choroidal lesion of sympathetic ophthalmia.

- name: Choriocapillaris Hypoperfusion and Non-Perfusion
  biological_scale: TISSUE
  role: central_effector
  description: >-
    The shared final common pathway of several white-dot entities. Inflammation
    of the choriocapillaris and its precapillary supply produces hypo- or
    non-perfusion of choroidal lobules, which is the defining clinicopathological
    mechanism of the primary inflammatory choriocapillaropathies. The calibre of
    vessel affected grades disease severity: involvement of only terminal
    choriocapillaries gives the benign end of the spectrum (MEWDS), whereas
    involvement of larger choriocapillaris or precapillary vessels gives the
    severe forms - APMPPE, idiopathic multifocal choroiditis and serpiginous
    choroiditis. Because the choriocapillaris is the sole blood supply of the
    outer retina and RPE, its non-perfusion is directly ischaemic to the
    photoreceptor/RPE complex, and it is imaged as patchy lobular
    hypofluorescence on indocyanine green angiography.
  cell_types:
  - preferred_term: endothelial cell
    term:
      id: CL:0000115
      label: endothelial cell
  biological_processes:
  - preferred_term: cellular response to hypoxia
    modifier: INCREASED
    term:
      id: GO:0071456
      label: cellular response to hypoxia
  locations:
  - preferred_term: choriocapillaris
    term:
      id: UBERON:0005336
      label: capillary layer of choroid
  downstream:
  - target: Outer Retinal and Retinal Pigment Epithelial Damage
    description: >-
      Loss of the sole vascular supply of the outer retina causes ischaemic
      photoreceptor and RPE injury.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:15850812
      reference_title: Serpiginous choroiditis.
      supports: PARTIAL
      evidence_source: HUMAN_CLINICAL
      snippet: "The histological findings of the lesions are atrophy of the choriocapillaris, retinal pigment epithelium and photoreceptor cells"
      explanation: >-
        Shows choriocapillaris atrophy co-localising with RPE and photoreceptor
        atrophy in the same lesion. Marked PARTIAL because the histology
        establishes co-occurrence rather than proving the direction of causation.
  - target: Inflammatory Choroidal Neovascularization
    description: >-
      Inflammation-driven hypoperfusion generates a retinal-choroidal hypoxia
      gradient that promotes neovascularization.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:38541191
      reference_title: Diagnostic Challenges in Inflammatory Choroidal Neovascularization.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Inflammation itself can compromise perfusion, generating a gradient of retinal-choroidal hypoxia that additionally promotes the formation of choroidal neovascularization in the course of uveitis."
      explanation: States the perfusion-to-hypoxia-to-neovascularization causal chain explicitly.
  evidence:
  - reference: PMID:35208488
    reference_title: "Diagnosis and Treatment of Primary Inflammatory Choriocapillaropathies (PICCPs): A Comprehensive Overview."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "PICCPs are resulting from one common clinicopathological mechanism, inflammatory choriocapillaris hypo- or non-perfusion."
    explanation: States choriocapillaris non-perfusion as the single shared mechanism of this disease group.
  - reference: PMID:35208488
    reference_title: "Diagnosis and Treatment of Primary Inflammatory Choriocapillaropathies (PICCPs): A Comprehensive Overview."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "ICGA shows the typical pattern of patchy lobular hypofluorescence reflecting hypo- or non-perfusion of the choriocapillaris"
    explanation: Links the mechanism to its imaging signature on indocyanine green angiography.
  - reference: PMID:35208488
    reference_title: "Diagnosis and Treatment of Primary Inflammatory Choriocapillaropathies (PICCPs): A Comprehensive Overview."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Choriocapillaris non-perfusion can affect the end-choriocappilaries, at the benign end of the PICCP spectrum (MEWDS), to larger choriocapillaris vessels or precapillary vessels at the origin of more severe forms such as acute posterior multifocal placoid pigment epitheliopathy (APMPPE), idiopathic multifocal choroiditis (MFC) and Serpiginous Choroiditis (SC)."
    explanation: >-
      Supports the vessel-calibre severity gradient asserted in this node.
      (The spelling "end-choriocappilaries" is as printed in the source.)

- name: Outer Retinal and Retinal Pigment Epithelial Damage
  biological_scale: TISSUE
  role: effector
  description: >-
    The route from choroidal inflammation to actual vision loss. Because the
    choroid supplies the avascular outer retina, choroidal inflammation and
    choriocapillaris non-perfusion injure the photoreceptor/RPE complex rather
    than the choroid alone. Histology of serpiginous lesions shows atrophy of the
    choriocapillaris, RPE and photoreceptor cells together, and on OCT active
    lesions show disruption of the ellipsoid zone and RPE. Photoreceptor loss is
    irreversible, which is why choroiditis causes permanent scotomata and why the
    therapeutic goal is preventing new lesions rather than recovering old ones.
  cell_types:
  - preferred_term: photoreceptor cell
    term:
      id: CL:0000210
      label: photoreceptor cell
  - preferred_term: retinal pigment epithelial cell
    term:
      id: CL:0002586
      label: retinal pigment epithelial cell
  biological_processes:
  - preferred_term: apoptotic process
    modifier: INCREASED
    term:
      id: GO:0006915
      label: apoptotic process
  locations:
  - preferred_term: retinal pigment epithelium
    term:
      id: UBERON:0001782
      label: pigmented layer of retina
  - preferred_term: outer nuclear layer of retina
    term:
      id: UBERON:0001789
      label: outer nuclear layer of retina
  downstream:
  - target: Chorioretinal Scarring and Bruch Membrane Disruption
    description: Destroyed outer retina heals as an atrophic pigmented scar.
    causal_link_type: DIRECT
  - target: Chorioretinal atrophy
    description: Confluent outer-retinal and RPE loss appears as chorioretinal atrophy.
    causal_link_type: DIRECT
  - target: Scotoma
    description: Focal photoreceptor loss produces a corresponding permanent field defect.
    causal_link_type: DIRECT
  - target: Photopsia
    description: Irritated or dysfunctional photoreceptors generate positive visual phenomena.
    causal_link_type: DIRECT
  - target: Reduced visual acuity
    description: Outer-retinal damage involving the macula reduces central acuity.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:15850812
      reference_title: Serpiginous choroiditis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Visual outcome is directly related to the involvement of the para-fovea and fovea by the lesions or secondary choroidal neovascularization."
      explanation: Ties visual outcome directly to whether outer-retinal lesions involve the fovea.
  - target: Blindness
    description: Extensive or macula-involving outer-retinal destruction causes severe visual loss.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Cumulative macular photoreceptor and RPE loss across recurrent episodes
  evidence:
  - reference: PMID:15850812
    reference_title: Serpiginous choroiditis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The histological findings of the lesions are atrophy of the choriocapillaris, retinal pigment epithelium and photoreceptor cells"
    explanation: Direct histologic evidence that choroiditis destroys the RPE/photoreceptor complex, not just the choroid.
  - reference: PMID:15850812
    reference_title: Serpiginous choroiditis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Visual outcome is directly related to the involvement of the para-fovea and fovea by the lesions or secondary choroidal neovascularization."
    explanation: Links outer-retinal lesion location to the visual outcome.

- name: Chorioretinal Scarring and Bruch Membrane Disruption
  biological_scale: TISSUE
  role: consequence
  description: >-
    Healed choroiditis lesions become punched-out atrophic, often pigmented,
    chorioretinal scars with disruption of the RPE-Bruch's membrane complex. The
    scar is not inert: a breached RPE-Bruch's membrane barrier is the anatomical
    precondition for ingrowth of new choroidal vessels into the subretinal space,
    and in ocular toxoplasmosis the scar border is the reservoir from which
    recurrent disease arises. Scars are therefore simultaneously the record of
    past disease and the substrate of future sight-threatening complications.
  locations:
  - preferred_term: Bruch's membrane
    term:
      id: UBERON:0003957
      label: Bruch's membrane
  - preferred_term: retinal pigment epithelium
    term:
      id: UBERON:0001782
      label: pigmented layer of retina
  downstream:
  - target: Inflammatory Choroidal Neovascularization
    description: >-
      Breach of the RPE-Bruch's membrane complex permits choroidal vessel
      ingrowth.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:38541191
      reference_title: Diagnostic Challenges in Inflammatory Choroidal Neovascularization.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Inflammatory CNV develops when inflammation or infection directly involves the retinal pigment epithelium (RPE)-Bruch's membrane complex."
      explanation: Identifies RPE-Bruch's membrane disruption as the precondition for inflammatory CNV.
  - target: Chorioretinal scar
    description: The healed lesion is clinically observed as a chorioretinal scar.
    causal_link_type: DIRECT
  - target: Macular scar
    description: >-
      A healed lesion involving the macula leaves a macular scar, the commonest
      structural complication of ocular toxoplasmosis.
    causal_link_type: DIRECT
  evidence:
  - reference: PMID:38541191
    reference_title: Diagnostic Challenges in Inflammatory Choroidal Neovascularization.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Inflammatory CNV develops when inflammation or infection directly involves the retinal pigment epithelium (RPE)-Bruch's membrane complex."
    explanation: Identifies RPE-Bruch's membrane involvement as the precondition for inflammatory CNV.
  - reference: PMID:27994812
    reference_title: Idiopathic Multifocal Choroiditis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "circumscribed areas of chorioretinal atrophy and subretinal pigmented fibrotic scars"
    explanation: Documents atrophic and fibrotic chorioretinal scarring as the healed end-state of multifocal choroiditis.

- name: Inflammatory Choroidal Neovascularization
  biological_scale: TISSUE
  role: consequence
  description: >-
    A major sight-threatening complication of inflammatory chorioretinal scars,
    and in some entities the dominant cause of vision loss rather than the
    inflammation itself. Inflammation compromises choroidal perfusion, generating
    a retinal-choroidal hypoxia gradient; VEGF, SDF-1-alpha and other mediators
    are released; and with the RPE-Bruch's membrane barrier already breached, new
    choroidal vessels grow into the subretinal space, the majority appearing as
    a classic type 2 lesion.
    It is especially common in punctate inner choroidopathy, multifocal
    choroiditis, serpiginous choroiditis and presumed ocular histoplasmosis
    syndrome. Clinically it is hard to distinguish from an active inflammatory
    lesion, which matters because the treatments differ: anti-VEGF for the
    neovascular membrane versus anti-inflammatory therapy for active choroiditis.
  cell_types:
  - preferred_term: endothelial cell
    term:
      id: CL:0000115
      label: endothelial cell
  biological_processes:
  - preferred_term: angiogenesis
    modifier: INCREASED
    term:
      id: GO:0001525
      label: angiogenesis
  - preferred_term: vascular endothelial growth factor signaling pathway
    modifier: INCREASED
    term:
      id: GO:0038084
      label: vascular endothelial growth factor signaling pathway
  locations:
  - preferred_term: macula lutea
    term:
      id: UBERON:0000053
      label: macula lutea
  downstream:
  - target: Choroidal neovascularization
    description: The neovascular membrane is the observed clinical phenotype.
    causal_link_type: DIRECT
  - target: Metamorphopsia
    description: Subretinal fluid and elevation from the membrane distort central vision.
    causal_link_type: DIRECT
  - target: Reduced visual acuity
    description: Subfoveal or juxtafoveal neovascular membranes reduce central acuity.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:30209691
      reference_title: "An update on inflammatory choroidal neovascularization: epidemiology, multimodal imaging, and management."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "A number of uveitic entities may be complicated by the development of choroidal neovascularization leading to a decrease in central visual acuity."
      explanation: Directly links inflammatory CNV to loss of central visual acuity.
  evidence:
  - reference: PMID:38541191
    reference_title: Diagnostic Challenges in Inflammatory Choroidal Neovascularization.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Inflammation itself can compromise perfusion, generating a gradient of retinal-choroidal hypoxia that additionally promotes the formation of choroidal neovascularization in the course of uveitis."
    explanation: States the hypoxia-driven mechanism connecting choroidal inflammation to neovascularization.
  - reference: PMID:38541191
    reference_title: Diagnostic Challenges in Inflammatory Choroidal Neovascularization.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The development of choroidal neovascularization may be a complication, especially in conditions such as punctate inner choroidopathy, multifocal choroiditis, serpiginous choroiditis, and presumed ocular histoplasmosis syndrome."
    explanation: Identifies the choroiditis subtypes in which inflammatory CNV is most frequent.
  - reference: PMID:30209691
    reference_title: "An update on inflammatory choroidal neovascularization: epidemiology, multimodal imaging, and management."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A number of uveitic entities may be complicated by the development of choroidal neovascularization leading to a decrease in central visual acuity."
    explanation: Confirms inflammatory CNV as a cause of central acuity loss across uveitic entities.

phenotypes:
- category: Ocular
  name: Posterior uveitis
  description: >-
    Inflammation localised to the posterior segment involving the choroid and
    retina, the defining anatomic class of choroiditis.
  phenotype_term:
    preferred_term: Posterior uveitis
    term:
      id: HP:0012123
      label: Posterior uveitis
  diagnostic: true
  evidence:
  - reference: PMID:37589912
    reference_title: Challenges in posterior uveitis-tips and tricks for the retina specialist.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Posterior uveitis is a common chorioretinal pathology affecting all ages worldwide and is a frequent reason for referral to the retina clinic."
    explanation: Establishes posterior uveitis as the clinical presentation class of chorioretinal inflammation.

- category: Ocular
  name: Reduced visual acuity
  description: >-
    Loss of central visual acuity, the principal functional consequence of
    choroiditis. In a treated ocular toxoplasmosis cohort one-fifth of affected
    eyes ended with acuity of 20/200 or worse.
  phenotype_term:
    preferred_term: Reduced visual acuity
    term:
      id: HP:0007663
      label: Reduced visual acuity
  evidence:
  - reference: PMID:27994812
    reference_title: Idiopathic Multifocal Choroiditis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "patients may complain of a temporal scotoma, metamorphopsia, floaters, photopsias, photophobia, and decreased vision"
    explanation: Lists decreased vision among the presenting symptoms of multifocal choroiditis.
  - reference: PMID:38843299
    reference_title: "Clinical characteristics, visual acuity outcomes, and factors associated with loss of vision among patients with active ocular toxoplasmosis: A retrospective study in a Thai tertiary center."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "At the final visit, 21% of all affected eyes suffered VA ≤ 20/200."
    explanation: Quantifies severe residual acuity loss after treated ocular toxoplasmosis.

- category: Ocular
  name: Chorioretinal atrophy
  description: >-
    Confluent loss of choriocapillaris, RPE and outer retina producing
    well-demarcated atrophic chorioretinal zones, the structural end-state of
    repeated or extensive choroiditis.
  phenotype_term:
    preferred_term: Chorioretinal atrophy
    term:
      id: HP:0000533
      label: Chorioretinal atrophy
  evidence:
  - reference: PMID:27994812
    reference_title: Idiopathic Multifocal Choroiditis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "circumscribed areas of chorioretinal atrophy and subretinal pigmented fibrotic scars"
    explanation: Documents chorioretinal atrophy as a defining structural outcome of idiopathic multifocal choroiditis.

- category: Ocular
  name: Chorioretinal scar
  description: >-
    Punched-out, often pigmented healed chorioretinal lesions. In ocular
    toxoplasmosis a pre-existing scar marks the site from which recurrent
    retinochoroiditis characteristically arises at the lesion border.
  phenotype_term:
    preferred_term: Chorioretinal scar
    term:
      id: HP:0007777
      label: Chorioretinal scar
  evidence:
  - reference: PMID:27994812
    reference_title: Idiopathic Multifocal Choroiditis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Affected eyes typically show multiple punched-out chorioretinal lesions ranging from 50 to 350 μm in size"
    explanation: Documents punched-out chorioretinal lesions as the characteristic healed lesion morphology.
  - reference: PMID:38843299
    reference_title: "Clinical characteristics, visual acuity outcomes, and factors associated with loss of vision among patients with active ocular toxoplasmosis: A retrospective study in a Thai tertiary center."
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "Patients mainly presented with primary retinitis without previous scar (62%)"
    explanation: >-
      Marked PARTIAL because this is an argument from the complement: 62% had no
      previous scar, so the remaining ~38% presented in eyes carrying a
      pre-existing chorioretinal scar. The source reports the former directly,
      not the latter.

- category: Ocular
  name: Choroidal neovascularization
  description: >-
    Ingrowth of new choroidal vessels through a breached RPE-Bruch's membrane
    complex into the subretinal space. A major sight-threatening complication and
    in POHS and PIC the dominant cause of vision loss.
  phenotype_term:
    preferred_term: Choroidal neovascularization
    term:
      id: HP:0011506
      label: Choroidal neovascularization
  evidence:
  - reference: PMID:25841248
    reference_title: Ocular histoplasmosis syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Choroidal neovascularization (CNV) secondary to OHS is considered one of the principal causes of central vision loss among young adults in endemic areas."
    explanation: Documents CNV as the dominant vision-threatening complication in POHS.
  - reference: PMID:38181975
    reference_title: "Punctate inner choroidopathy: A review of the current diagnostic and therapeutic approaches."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "New or worsening PIC lesions suggest active inflammation, while new neovascular membranes may indicate secondary neovascular processes."
    explanation: Confirms neovascular membranes as a distinct, treatment-relevant complication of PIC.

- category: Ocular
  name: Vitritis
  description: >-
    Inflammatory cells in the vitreous cavity, reflecting spillover from
    choroidal and retinal inflammation. Characteristically present in ocular
    toxoplasmosis, birdshot chorioretinopathy and MFCPU, and characteristically
    absent in punctate inner choroidopathy - a discriminating sign.
  phenotype_term:
    preferred_term: Vitritis
    term:
      id: HP:0011531
      label: Vitritis
  evidence:
  - reference: PMID:37176633
    reference_title: "Sarcoidosis-Related Uveitis: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Posterior involvement includes vitritis, vasculitis and choroidal lesions."
    explanation: Documents vitritis accompanying choroidal involvement in posterior uveitis.
  - reference: PMID:25434765
    reference_title: The immunopathogenesis of birdshot chorioretinopathy; a bird of many feathers.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "BSCR is characterized by distinctive multiple choroidal hypopigmented lesions in combination with retinal vasculitis and vitritis"
    explanation: Documents vitritis as a defining feature of birdshot chorioretinopathy.

- category: Ocular
  name: Retinal vasculitis
  description: >-
    Inflammation of retinal vessels accompanying choroidal inflammation. A
    defining component of birdshot chorioretinopathy and a recognised feature of
    sarcoid and tubercular posterior uveitis (where it may be occlusive).
  phenotype_term:
    preferred_term: Retinal vasculitis
    term:
      id: HP:0025188
      label: Retinal vasculitis
  evidence:
  - reference: PMID:25434765
    reference_title: The immunopathogenesis of birdshot chorioretinopathy; a bird of many feathers.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "BSCR is characterized by distinctive multiple choroidal hypopigmented lesions in combination with retinal vasculitis and vitritis"
    explanation: Documents retinal vasculitis as a defining feature of birdshot chorioretinopathy.
  - reference: PMID:33845014
    reference_title: Classification Criteria for Tubercular Uveitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "(4) occlusive retinal vasculitis, and (5) in hosts with evidence of active systemic tuberculosis, multifocal choroiditis"
    explanation: Lists occlusive retinal vasculitis among the SUN-defining presentations of tubercular uveitis.

- category: Ocular
  name: Macular edema
  description: >-
    Accumulation of intraretinal fluid at the macula from inflammatory breakdown
    of the blood-retinal barrier. A leading reversible cause of vision loss in
    choroiditis and the primary endpoint of several uveitis trials.
  phenotype_term:
    preferred_term: Macular edema
    term:
      id: HP:0040049
      label: Macular edema
  evidence:
  - reference: PMID:27994812
    reference_title: Idiopathic Multifocal Choroiditis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "higher frequency of structural complications such as cataract, cystoid macular edema (CME), and epiretinal membrane (ERM) related to intraocular inflammation"
    explanation: Documents cystoid macular edema as an inflammation-related structural complication of MFCPU.

- category: Ocular
  name: Scotoma
  description: >-
    A localised blind spot in the visual field corresponding to a zone of
    destroyed outer retina. Because photoreceptor loss is irreversible, scotomata
    from healed choroiditis lesions are permanent.
  phenotype_term:
    preferred_term: Scotoma
    term:
      id: HP:0000575
      label: Scotoma
  evidence:
  - reference: PMID:27994812
    reference_title: Idiopathic Multifocal Choroiditis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "patients may complain of a temporal scotoma, metamorphopsia, floaters, photopsias, photophobia, and decreased vision"
    explanation: Lists scotoma among the presenting symptoms of multifocal choroiditis.

- category: Ocular
  name: Metamorphopsia
  description: >-
    Distortion of straight lines, typically signalling macular involvement by
    subretinal fluid or a choroidal neovascular membrane.
  phenotype_term:
    preferred_term: Metamorphopsia
    term:
      id: HP:0012508
      label: Metamorphopsia
  evidence:
  - reference: PMID:27994812
    reference_title: Idiopathic Multifocal Choroiditis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "patients may complain of a temporal scotoma, metamorphopsia, floaters, photopsias, photophobia, and decreased vision"
    explanation: Lists metamorphopsia among the presenting symptoms of multifocal choroiditis.

- category: Ocular
  name: Photopsia
  description: >-
    Perceived flashes or shimmering of light arising from dysfunctional or
    irritated photoreceptors overlying active outer-retinal inflammation.
  phenotype_term:
    preferred_term: Photopsia
    term:
      id: HP:0030786
      label: Photopsia
  evidence:
  - reference: PMID:27994812
    reference_title: Idiopathic Multifocal Choroiditis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "patients may complain of a temporal scotoma, metamorphopsia, floaters, photopsias, photophobia, and decreased vision"
    explanation: Lists photopsia among the presenting symptoms of multifocal choroiditis.

- category: Ocular
  name: Blindness
  description: >-
    Severe irreversible visual loss, the feared endpoint of macula-involving or
    repeatedly recurrent choroiditis.
  phenotype_term:
    preferred_term: Blindness
    term:
      id: HP:0000618
      label: Blindness
  evidence:
  - reference: PMID:39452769
    reference_title: "Ocular Toxoplasmosis: Advances in Toxoplasma gondii Biology, Clinical Manifestations, Diagnostics, and Therapy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Ocular toxoplasmosis (OT), a severe manifestation of T. gondii infection, can lead to potentially blinding complications."
    explanation: Documents blindness as a potential outcome of the commonest infectious choroiditis.

- category: Ocular
  name: Vitreous floaters
  description: >-
    Perceived mobile opacities from inflammatory cells and debris in the
    vitreous, a common presenting symptom of active choroiditis.
  phenotype_term:
    preferred_term: Vitreous floaters
    term:
      id: HP:0100832
      label: Vitreous floaters
  evidence:
  - reference: PMID:27994812
    reference_title: Idiopathic Multifocal Choroiditis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "patients may complain of a temporal scotoma, metamorphopsia, floaters, photopsias, photophobia, and decreased vision"
    explanation: Lists floaters among the presenting symptoms of multifocal choroiditis.

- category: Ocular
  name: Macular scar
  description: >-
    A healed, often pigmented chorioretinal scar involving the macula. The
    commonest structural complication in an ocular toxoplasmosis cohort, present
    in 24.7% of patients, and a direct cause of permanent central visual loss.
  phenotype_term:
    preferred_term: Macular scar
    term:
      id: HP:0200056
      label: Macular scar
  frequency: OCCASIONAL
  evidence:
  - reference: PMID:38843299
    reference_title: "Clinical characteristics, visual acuity outcomes, and factors associated with loss of vision among patients with active ocular toxoplasmosis: A retrospective study in a Thai tertiary center."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Macular scar 24 (24.7)"
    explanation: >-
      Complications table reports macular scar in 24 of 97 patients (24.7%),
      supporting the OCCASIONAL (5-29%) frequency band.

- category: Ocular
  name: Ocular hypertension
  description: >-
    Raised intraocular pressure (above 21 mmHg) complicating intraocular
    inflammation and its corticosteroid treatment, recorded in 20.6% of an
    ocular toxoplasmosis cohort.
  phenotype_term:
    preferred_term: Ocular hypertension
    term:
      id: HP:0007906
      label: Ocular hypertension
  frequency: OCCASIONAL
  evidence:
  - reference: PMID:38843299
    reference_title: "Clinical characteristics, visual acuity outcomes, and factors associated with loss of vision among patients with active ocular toxoplasmosis: A retrospective study in a Thai tertiary center."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Ocular hypertension (IOP >21 mmHg) 20 (20.6)"
    explanation: >-
      Complications table reports ocular hypertension in 20 of 97 patients
      (20.6%), supporting the OCCASIONAL (5-29%) frequency band.

- category: Ocular
  name: Epiretinal membrane
  description: >-
    A fibrocellular membrane on the inner retinal surface, a structural
    complication of chronic intraocular inflammation that can distort the macula
    and reduce acuity. Reported in 12.6% of an ocular toxoplasmosis cohort.
  phenotype_term:
    preferred_term: Epiretinal membrane
    term:
      id: HP:0100014
      label: Epiretinal membrane
  evidence:
  - reference: PMID:27994812
    reference_title: Idiopathic Multifocal Choroiditis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "higher frequency of structural complications such as cataract, cystoid macular edema (CME), and epiretinal membrane (ERM) related to intraocular inflammation"
    explanation: Documents epiretinal membrane as an inflammation-related structural complication of MFCPU.

- category: Ocular
  name: Cataract
  description: >-
    Lens opacification arising from chronic intraocular inflammation and from
    the corticosteroid therapy used to treat it - a complication of both the
    disease and its management.
  phenotype_term:
    preferred_term: Cataract
    term:
      id: HP:0000518
      label: Cataract
  evidence:
  - reference: PMID:27994812
    reference_title: Idiopathic Multifocal Choroiditis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "higher frequency of structural complications such as cataract, cystoid macular edema (CME), and epiretinal membrane (ERM) related to intraocular inflammation"
    explanation: Documents cataract as an inflammation-related structural complication of MFCPU.

histopathology:
- name: Diffuse Lymphocytic Choroidal Infiltrate
  description: >-
    Moderate diffuse lymphocytic infiltration throughout the choroid, accompanied
    by atrophy of the choriocapillaris, RPE and photoreceptors in established
    lesions.
  evidence:
  - reference: PMID:15850812
    reference_title: Serpiginous choroiditis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The histological findings of the lesions are atrophy of the choriocapillaris, retinal pigment epithelium and photoreceptor cells, and moderate diffuse lymphocytic infiltrates throughout the choroid."
    explanation: Direct histologic description of serpiginous choroiditis lesions.

- name: Non-Caseating Epithelioid Granuloma
  description: >-
    Compact aggregates of epithelioid macrophages without central caseation, the
    histologic hallmark of sarcoid choroiditis. Caseation instead favours
    tuberculosis, but biopsy yield in the eye is low and the diagnosis of ocular
    sarcoidosis is usually clinico-radiological.
  diagnostic: true
  evidence:
  - reference: PMID:37176633
    reference_title: "Sarcoidosis-Related Uveitis: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The diagnosis is based on histology with the presence of non-caseating epithelioid granulomas."
    explanation: Defines the non-caseating epithelioid granuloma as the diagnostic histologic finding of sarcoidosis.

- name: Dalen-Fuchs Nodule
  description: >-
    Focal aggregates of epithelioid cells lying between Bruch's membrane and the
    retinal pigment epithelium, seen as yellowish-white choroidal lesions in
    sympathetic ophthalmia.
  evidence:
  - reference: PMID:35647958
    reference_title: "Sympathetic ophthalmia: A comprehensive update."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "It manifests as acute/chronic granulomatous uveitis with yellowish-white choroidal lesions or Dalen-Fuchs nodules."
    explanation: Documents Dalen-Fuchs nodules as the characteristic choroidal lesion of sympathetic ophthalmia.

diagnosis:
- name: Optical Coherence Tomography (including EDI-OCT)
  description: >-
    The preferred modality for detecting active choroiditis lesions and for
    monitoring recurrence. OCT resolves the RPE elevations, ellipsoid-zone
    disruption and subretinal material of active lesions, and enhanced-depth
    imaging (EDI-OCT) visualises the choroid itself. SUN classification criteria
    for MFCPU and PIC now incorporate OCT findings for assessment of activity.
  diagnosis_term:
    preferred_term: Optical Coherence Tomography
    term:
      id: NCIT:C20828
      label: Optical Coherence Tomography
  evidence:
  - reference: PMID:40288596
    reference_title: Evidence and Consensus-Based Imaging Guidelines in Multifocal Choroiditis With Panuveitis and Punctate Inner Choroiditis-Multimodal Imaging in Uveitis (MUV) Taskforce Report 5.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "OCT is the preferred modality for detecting active lesions."
    explanation: Expert-consensus statement designating OCT as first-line for detecting activity.
  - reference: PMID:40288596
    reference_title: Evidence and Consensus-Based Imaging Guidelines in Multifocal Choroiditis With Panuveitis and Punctate Inner Choroiditis-Multimodal Imaging in Uveitis (MUV) Taskforce Report 5.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Incorporating imaging findings, particularly OCT, into the Standardization of Uveitis Nomenclature (SUN) classification criteria for MFCPU and PIC enables more precise assessment of disease activity."
    explanation: Documents integration of OCT into formal classification criteria.

- name: Fundus Autofluorescence
  description: >-
    A non-invasive map of RPE health. Hypoautofluorescence marks RPE loss in
    healed lesions and hyperautofluorescence can mark active or recent disease.
    Consensus places FAF alongside OCT as an effective modality for monitoring
    disease recurrence in MFCPU and PIC.
  diagnosis_term:
    preferred_term: Fundus Autofluorescence Imaging
    term:
      id: NCIT:C162465
      label: Fundus Autofluorescence Imaging
  evidence:
  - reference: PMID:40288596
    reference_title: Evidence and Consensus-Based Imaging Guidelines in Multifocal Choroiditis With Panuveitis and Punctate Inner Choroiditis-Multimodal Imaging in Uveitis (MUV) Taskforce Report 5.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Both FAF and OCT are effective for monitoring disease recurrence."
    explanation: Consensus designation of fundus autofluorescence as a recurrence-monitoring modality.

- name: Indocyanine Green Angiography
  description: >-
    The modality that images the choroidal circulation directly and therefore the
    one that reveals choriocapillaris hypo- and non-perfusion, seen as patchy
    lobular hypofluorescence. Late-phase ICGA is most valuable in recurrent
    disease when lesions are invisible on fundus autofluorescence and colour
    fundus photography.
  diagnosis_term:
    preferred_term: Indocyanine Green Fluorescence Angiography
    term:
      id: NCIT:C175030
      label: Indocyanine Green Fluorescence Angiography
  evidence:
  - reference: PMID:35208488
    reference_title: "Diagnosis and Treatment of Primary Inflammatory Choriocapillaropathies (PICCPs): A Comprehensive Overview."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "ICGA shows the typical pattern of patchy lobular hypofluorescence reflecting hypo- or non-perfusion of the choriocapillaris"
    explanation: Establishes ICGA as the modality that visualises the choriocapillaris non-perfusion mechanism.
  - reference: PMID:40288596
    reference_title: Evidence and Consensus-Based Imaging Guidelines in Multifocal Choroiditis With Panuveitis and Punctate Inner Choroiditis-Multimodal Imaging in Uveitis (MUV) Taskforce Report 5.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Late-phase ICGA is most valuable in recurrent disease when the lesions are not visible on FAF and CFP."
    explanation: Defines the specific clinical niche of ICGA in choroiditis follow-up.

- name: Fluorescein Angiography
  description: >-
    Images the retinal circulation and the RPE window, delineating active
    inflammatory lesions and choroidal neovascular membranes. In acute syphilitic
    posterior placoid chorioretinitis it shows progressive hyperfluorescence with
    scattered focal hypofluorescence ("leopard spotting").
  diagnosis_term:
    preferred_term: Fluorescein Angiography
    term:
      id: NCIT:C190541
      label: Fluorescein Angiography
  evidence:
  - reference: PMID:22863970
    reference_title: "Acute syphilitic posterior placoid chorioretinitis: report of a case series and comprehensive review of the literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Fluorescein angiography showed progressive hyperfluorescence in the area of the lesion, often with scattered focal hypofluorescence, or leopard spotting."
    explanation: Documents the characteristic fluorescein angiographic signature of ASPPC.

- name: Treponemal and Non-Treponemal Serology for Syphilis
  description: >-
    Mandatory exclusion test in any choroiditis before immunosuppression, given
    that ocular syphilis mimics nearly every uveitic phenotype. SUN criteria for
    syphilitic uveitis require a positive treponemal test alongside a compatible
    uveitic presentation, using the CDC reverse screening algorithm. Every
    patient with ocular syphilis also needs CSF testing for neurosyphilis and HIV
    serology.
  notes: >-
    Left without a diagnosis_term deliberately: NCIT has no term for the
    combined treponemal-plus-non-treponemal syphilis serology algorithm this
    entry describes. NCIT:C132388 Treponema pallidum Antibody Measurement
    covers only the treponemal half and would misrepresent the recommended
    two-test CDC reverse screening sequence.
  evidence:
  - reference: PMID:33845020
    reference_title: Classification Criteria for Syphilitic Uveitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Key criteria for syphilitic uveitis included a compatible uveitic presentation (anterior uveitis; intermediate uveitis; or posterior or panuveitis with retinal, retinal pigment epithelial, or retinal vascular inflammation) and evidence of syphilis infection with a positive treponemal test."
    explanation: SUN consensus criteria requiring treponemal serology for the syphilitic subtype.
  - reference: PMID:33831337
    reference_title: Ocular syphilis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "All patients with ocular syphilis should have their cerebrospinal fluids tested for the co-existence of neurosyphilis and their blood tested for human immunodeficiency virus co-infection."
    explanation: Documents the mandatory neurosyphilis and HIV co-testing that follows a positive ocular syphilis diagnosis.

- name: Interferon-Gamma Release Assay and Tuberculin Skin Testing
  description: >-
    Evidence of mycobacterial infection is required to classify a choroiditis as
    tubercular, and hence to redirect management from immunosuppression alone to
    antitubercular therapy. SUN criteria accept histologic or microbiologic
    confirmation, a positive interferon-gamma release assay, or a positive
    tuberculin skin test.
  diagnosis_term:
    preferred_term: Interferon Gamma Release Assay
    term:
      id: NCIT:C128363
      label: Interferon Gamma Release Assay
  evidence:
  - reference: PMID:33845014
    reference_title: Classification Criteria for Tubercular Uveitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "evidence of tuberculosis, including histologically or microbiologically confirmed infection, positive interferon-γ release assay test, or positive tuberculin skin test"
    explanation: SUN consensus criteria for demonstrating the mycobacterial aetiology.

- name: Intraocular Fluid PCR
  description: >-
    Detection of pathogen DNA in aqueous or vitreous humour provides definitive
    aetiologic proof in infectious choroiditis when serology and clinical
    appearance are equivocal - most usefully for Toxoplasma gondii.
  diagnosis_term:
    preferred_term: Polymerase Chain Reaction
    term:
      id: NCIT:C17003
      label: Polymerase Chain Reaction
  evidence:
  - reference: PMID:34370174
    reference_title: "Ocular toxoplasmosis: a review of the current diagnostic and therapeutic approaches."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The detection of the parasite DNA in the aqueous or vitreous humor can provide evidence for a definitive diagnosis."
    explanation: Establishes intraocular PCR as the definitive aetiologic test in ocular toxoplasmosis.

- name: HLA-A29 Typing
  description: >-
    HLA typing supports the diagnosis of birdshot chorioretinopathy, in which
    virtually all patients carry HLA-A29. A negative HLA-A29 result should prompt
    reconsideration of the diagnosis.
  diagnosis_term:
    preferred_term: HLA Typing
    term:
      id: NCIT:C71329
      label: HLA Typing
  evidence:
  - reference: PMID:3341436
    reference_title: HLA typing in birdshot chorioretinopathy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Of these 49 patients, 47 (95.9%) had the HLA-A29 antigen."
    explanation: Quantifies the near-universal HLA-A29 carriage that gives the test its diagnostic value.

genetic:
- name: HLA-A29
  gene_term:
    preferred_term: HLA-A29
    term:
      id: hgnc:4931
      label: HLA-A
  notes: >-
    The dominant genetic risk factor for birdshot chorioretinopathy and the
    strongest documented HLA-disease association in humans. Virtually all
    patients carry HLA-A29, and homozygosity increases susceptibility further
    without altering severity. This is a susceptibility allele in an
    HLA-restricted autoimmune disease, not a Mendelian causal gene.
  relationship_type: SUSCEPTIBILITY
  subtype: Birdshot Chorioretinopathy
  evidence:
  - reference: PMID:25434765
    reference_title: The immunopathogenesis of birdshot chorioretinopathy; a bird of many feathers.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "BSCR is the strongest documented association between HLA and disease in humans"
    explanation: Establishes the exceptional strength of the HLA-A29 association.
  - reference: PMID:39570638
    reference_title: The Impact of HLA-A29 Homozygosity and of the Second HLA-A Allele on Susceptibility and Severity of Birdshot Chorioretinitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Homozygosity for HLA-A29 increased the risk of developing BSCR without affecting disease severity."
    explanation: Demonstrates the allele-dosage effect on susceptibility.

- name: ERAP1
  gene_term:
    preferred_term: ERAP1
    term:
      id: hgnc:18173
      label: ERAP1
  notes: >-
    Endoplasmic reticulum aminopeptidase 1 trims peptides for MHC class I
    loading. An expression quantitative trait locus decreasing ERAP1 expression
    (rs27432) raises birdshot risk within HLA-A29 carriers, consistent with a
    model in which altered peptide processing changes the HLA-A29 peptidome.
  relationship_type: MODIFIER
  subtype: Birdshot Chorioretinopathy
  evidence:
  - reference: PMID:34727153
    reference_title: ERAP1, ERAP2, and Two Copies of HLA-Aw19 Alleles Increase the Risk for Birdshot Chorioretinopathy in HLA-A29 Carriers.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "an expression quantitative trait locus (eQTL) decreasing ERAP1 expression"
    explanation: Identifies the ERAP1 risk variant as an expression-lowering eQTL.

- name: ERAP2
  gene_term:
    preferred_term: ERAP2
    term:
      id: hgnc:29499
      label: ERAP2
  notes: >-
    Endoplasmic reticulum aminopeptidase 2, whose increased expression raises
    birdshot risk while a haplotype disrupting its expression is protective. The
    opposing directions of the two ERAP2 variants make the antigen-processing
    mechanism unusually well supported.
  relationship_type: MODIFIER
  subtype: Birdshot Chorioretinopathy
  evidence:
  - reference: PMID:34727153
    reference_title: ERAP1, ERAP2, and Two Copies of HLA-Aw19 Alleles Increase the Risk for Birdshot Chorioretinopathy in HLA-A29 Carriers.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "an eQTL increasing ERAP2 expression. Furthermore, ERAP2-rs2248374 that disrupts ERAP2 expression is protective"
    explanation: Documents both the risk-increasing and the protective ERAP2 expression variants.

environmental:
- name: Ocular penetrating trauma or intraocular surgery
  presence: PRESENT
  evidence:
  - reference: PMID:35647958
    reference_title: "Sympathetic ophthalmia: A comprehensive update."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Sympathetic ophthalmia is a rare, bilateral, granulomatous, panuveitis following penetrating trauma or surgery to one eye."
    explanation: Ocular penetrating injury is the required environmental trigger of sympathetic ophthalmia.

- name: Residence in a Histoplasma capsulatum-endemic region
  presence: PRESENT
  evidence:
  - reference: PMID:32168355
    reference_title: "Presumed ocular histoplasmosis syndrome in a commercially insured population, United States."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Eleven of the 13 states with the highest POHS rates bordered the Mississippi and Ohio rivers."
    explanation: Geographic clustering along the Mississippi/Ohio river valleys ties POHS risk to Histoplasma-endemic residence.

- name: Immunocompromise
  presence: PRESENT
  evidence:
  - reference: PMID:38843299
    reference_title: "Clinical characteristics, visual acuity outcomes, and factors associated with loss of vision among patients with active ocular toxoplasmosis: A retrospective study in a Thai tertiary center."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Immunocompromised patients showed a significantly larger size of retinitis than immunocompetent patients."
    explanation: Impaired host immunity worsens infectious choroiditis, the biological basis of the immunosuppression hazard.

infectious_agent:
- name: Toxoplasma gondii
  description: >-
    An obligate intracellular apicomplexan protozoan, the commonest infectious
    cause of posterior uveitis worldwide. Persists lifelong as encysted
    bradyzoites in retinal tissue, providing the reservoir for recurrent
    retinochoroiditis.
  evidence:
  - reference: PMID:29704469
    reference_title: "Current treatment of ocular toxoplasmosis in immunocompetent patients: a network meta-analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Ocular toxoplasmosis (OT) is the most frequent form of infectious posterior uveitis caused by the protozoan parasite Toxoplasma gondii."
    explanation: Identifies T. gondii as the agent of the commonest infectious posterior uveitis.

- name: Treponema pallidum
  description: >-
    The spirochaete of syphilis. Disseminates haematogenously and can involve any
    ocular structure at any disease stage, producing chorioretinitis that mimics
    nearly all other uveitic entities.
  evidence:
  - reference: PMID:33831337
    reference_title: Ocular syphilis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Syphilis is a sexually transmitted, systemic, inflammatory disease caused by the spirochaete, Treponema pallidum."
    explanation: Identifies the causative spirochaete of the syphilitic subtype.

- name: Human herpesviruses and other neurotropic viruses
  description: >-
    Herpesviruses (CMV, HSV, VZV) and other viruses are collectively the
    commonest infectious cause of uveitis in some referral cohorts, producing
    necrotising retinitis with secondary choroidal involvement rather than
    primary choroiditis. Many remain latent with reactivation gated by host
    immunity. Included here because they sit on the infectious side of the
    aetiologic fork and respond to antivirals, not immunosuppression; the
    dedicated ocular entity is curated in Cytomegalovirus_Retinitis.
  evidence:
  - reference: PMID:28012878
    reference_title: Viral posterior uveitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Many viruses remain latent in the infected host with a risk of reactivation that depends on various factors, including virulence and host immunity, age, and comorbidities."
    explanation: >-
      Documents latency-plus-reactivation gated by host immunity, the same
      immunosuppression-hazard logic as the toxoplasmosis and tuberculosis arms.
  - reference: PMID:37428299
    reference_title: "The large Hellenic Study of Uveitis: epidemiology, etiologic factors and classification."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Herpetic uveitis (HSV-1 and VZV/HZV) was the most common cause of infectious uveitis (14.87%)"
    explanation: Quantifies herpetic infection as the leading infectious uveitis aetiology in a large tertiary cohort.

- name: Mycobacterium tuberculosis
  description: >-
    Causes choroidal tubercles, tuberculoma and serpiginous-like choroiditis.
    Ocular disease may occur without demonstrable active systemic tuberculosis,
    so exclusion depends on immunologic evidence of infection.
  evidence:
  - reference: PMID:33845014
    reference_title: Classification Criteria for Tubercular Uveitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "evidence of tuberculosis, including histologically or microbiologically confirmed infection, positive interferon-γ release assay test, or positive tuberculin skin test"
    explanation: Defines how mycobacterial aetiology is established for tubercular choroiditis.

treatments:
- name: Antiparasitic Therapy for Ocular Toxoplasmosis
  description: >-
    Antimicrobial eradication of the active Toxoplasma focus, historically
    pyrimethamine plus sulfadiazine with corticosteroid ("classic therapy"), with
    trimethoprim-sulfamethoxazole a well-supported alternative in immunocompetent
    patients. Corticosteroid is added only under antiparasitic cover; it must
    never be given alone.
  action_category: THERAPEUTIC
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: pyrimethamine
      term:
        id: CHEBI:8673
        label: pyrimethamine
    - preferred_term: sulfadiazine
      term:
        id: CHEBI:9328
        label: sulfadiazine
  notes: >-
    treatment_term is Pharmacotherapy rather than NCIT:C15620 Antibiotic
    Therapy because Toxoplasma gondii is a protozoan, not a bacterium, and that
    term is defined as treatment of bacterial infections.
  target_mechanisms:
  - target: Pathogen Invasion and Persistence in the Choroid and Outer Retina
    treatment_effect: INHIBITS
    description: Antiparasitic drugs suppress replicating tachyzoites in the retina and choroid.
    evidence:
    - reference: PMID:29704469
      reference_title: "Current treatment of ocular toxoplasmosis in immunocompetent patients: a network meta-analysis."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Based on our network meta-analysis, therapy with TMP-SMX seems to be an alternative treatment of OT in immunocompetent patients."
      explanation: Network meta-analysis supporting antiparasitic therapy directed at the organism.
  evidence:
  - reference: PMID:34370174
    reference_title: "Ocular toxoplasmosis: a review of the current diagnostic and therapeutic approaches."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The current mainstay for the treatment, if necessary, is the use of oral antibiotic with systemic corticosteroids."
    explanation: >-
      Establishes the combined antimicrobial-plus-corticosteroid regimen - the
      infectious arm's version of anti-inflammatory therapy, always paired with
      antimicrobial cover.
  - reference: PMID:29704469
    reference_title: "Current treatment of ocular toxoplasmosis in immunocompetent patients: a network meta-analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the combination of pyrimethamine, sulfadiazine, and corticosteroids"
    explanation: Names the conventional antiparasitic-plus-corticosteroid regimen for ocular toxoplasmosis.

- name: Antitubercular Therapy for Tubercular Choroiditis
  description: >-
    Multi-drug antitubercular therapy (ATT) added to corticosteroid in
    serpiginous-like choroiditis with evidence of systemic or latent
    tuberculosis. ATT reduces active inflammation and, critically, eliminates the
    recurrences that immunosuppression alone would not prevent. Trials are
    ongoing on optimal duration.
  action_category: THERAPEUTIC
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Antibiotic Therapy
    term:
      id: NCIT:C15620
      label: Antibiotic Therapy
    therapeutic_agent:
    - preferred_term: rifampicin
      term:
        id: CHEBI:28077
        label: rifampicin
    - preferred_term: isoniazid
      term:
        id: CHEBI:6030
        label: isoniazide
  target_mechanisms:
  - target: Unopposed Immunosuppression of Unrecognised Infectious Choroiditis
    treatment_effect: INHIBITS
    description: >-
      Adding antimicrobial cover converts the harmful unopposed-immunosuppression
      scenario into safe combined therapy.
    evidence:
    - reference: PMID:22675097
      reference_title: Tubercular serpiginous-like choroiditis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "patients with serpiginous-like choroiditis and evidence of systemic or latent TB are best treated with antituberculosis treatment (ATT) in addition to the corticosteroid therapy"
      explanation: Directly supports adding ATT to corticosteroid rather than immunosuppressing alone.
  evidence:
  - reference: PMID:22675097
    reference_title: Tubercular serpiginous-like choroiditis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The use of ATT in these patients is likely to reduce active inflammation and eliminate future recurrences."
    explanation: States the dual benefit of antitubercular therapy in serpiginous-like choroiditis.

- name: Penicillin for Ocular Syphilis
  description: >-
    Ocular syphilis is managed as neurosyphilis, with parenteral aqueous
    crystalline penicillin G the drug of choice. Timely treatment is curative;
    delay produces long-term visual impairment. This is the clearest case in
    which the correct diagnosis converts an untreatable-looking uveitis into a
    curable infection.
  action_category: THERAPEUTIC
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Antibiotic Therapy
    term:
      id: NCIT:C15620
      label: Antibiotic Therapy
    therapeutic_agent:
    - preferred_term: benzylpenicillin (penicillin G)
      term:
        id: CHEBI:18208
        label: benzylpenicillin
  target_mechanisms:
  - target: Pathogen Invasion and Persistence in the Choroid and Outer Retina
    treatment_effect: INHIBITS
    description: Penicillin eradicates Treponema pallidum from ocular and CNS compartments.
    evidence:
    - reference: PMID:33831337
      reference_title: Ocular syphilis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Centers for Disease Control and Prevention recommend that ocular syphilis be managed according to its treatment guidelines for neurosyphilis, with parenteral aqueous crystalline penicillin G the drug of choice."
      explanation: Guideline-level support for penicillin G as the eradicating therapy.
  evidence:
  - reference: PMID:33831337
    reference_title: Ocular syphilis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "With the timely diagnosis and appropriate treatment, ocular syphilis is curable. However, delayed diagnosis of ocular syphilis may result in long-term visual impairment."
    explanation: Documents curability with timely antibiotic therapy and the cost of delay.

- name: Corticosteroid Therapy
  description: >-
    First-line anti-inflammatory therapy for non-infectious choroiditis, given
    locally or systemically. It is the mainstay of the non-infectious arm and
    remains first-line in ocular sarcoidosis. In the infectious arm it is
    permissible only in combination with antimicrobial therapy; given alone to an
    unrecognised infectious choroiditis it removes immune restraint on the
    organism. Up to 30% of sarcoidosis patients require high doses, which is what
    drives the move to steroid-sparing agents.
  action_category: THERAPEUTIC
  therapeutic_modality: SMALL_MOLECULE
  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: Choroidal Inflammatory Cell Infiltration
    treatment_effect: INHIBITS
    description: Corticosteroid suppresses the choroidal inflammatory infiltrate.
    evidence:
    - reference: PMID:37176633
      reference_title: "Sarcoidosis-Related Uveitis: A Review."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Corticosteroids remain the first-line treatment for sarcoidosis, but up to 30% of patients require high doses, justifying the use of corticosteroid-sparing treatments."
      explanation: Establishes corticosteroid as first-line anti-inflammatory therapy and its dose-limiting problem.
  notes: >-
    Safety caveat central to this entry - corticosteroid monotherapy is
    contraindicated until infectious causes (toxoplasmosis, tuberculosis,
    syphilis) have been excluded or are being concurrently treated.
  evidence:
  - reference: PMID:36013011
    reference_title: "Birdshot Chorioretinopathy: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Local and systemic corticosteroids can be used for short periods, but immunosuppressive or biological therapies are usually needed for the long-term management of the disease."
    explanation: Positions corticosteroid as short-term therapy in birdshot, with immunosuppression for maintenance.
  - reference: PMID:22675097
    reference_title: Tubercular serpiginous-like choroiditis.
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "Choroidal tuberculosis (TB) infection may present itself as a diffuse choroiditis that resembles serpiginous choroiditis, usually treated with immunossupressants."
    explanation: >-
      Supports the safety caveat by documenting a TB choroiditis that phenocopies
      an entity conventionally treated with immunosuppression. Marked PARTIAL
      because the source states the misclassification risk rather than measuring
      corticosteroid harm directly.

- name: Immunosuppressive and Biologic Therapy
  description: >-
    Corticosteroid-sparing immunomodulation - methotrexate, mycophenolate
    mofetil, and anti-TNF biologics - for chronic non-infectious choroiditis,
    especially birdshot chorioretinopathy, serpiginous choroiditis, MFCPU and
    sarcoid uveitis. This is the arm of the treatment fork that is actively
    dangerous if the aetiology is in fact infectious and untreated. Spans two
    platforms (small-molecule antimetabolites and monoclonal-antibody
    biologics), hence therapeutic_modality OTHER.
  action_category: THERAPEUTIC
  therapeutic_modality: OTHER
  treatment_term:
    preferred_term: Immunosuppressive Therapy
    term:
      id: NCIT:C15261
      label: Immunosuppressive Therapy
  target_mechanisms:
  - target: Autoimmune Recognition of Ocular Self-Antigen
    treatment_effect: INHIBITS
    description: >-
      Immunomodulatory therapy suppresses the autoreactive T-cell response
      driving non-infectious choroiditis.
    evidence:
    - reference: PMID:37176633
      reference_title: "Sarcoidosis-Related Uveitis: A Review."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "immunosuppressive treatments such as methotrexate may be introduced. More recent biotherapies such as anti-TNF are also very effective (as they are in other non-infectious uveitis etiologies)"
      explanation: Supports methotrexate and anti-TNF for non-infectious uveitis broadly.
  evidence:
  - reference: PMID:36013011
    reference_title: "Birdshot Chorioretinopathy: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "immunosuppressive or biological therapies are usually needed for the long-term management of the disease"
    explanation: Documents long-term immunomodulation as standard in birdshot chorioretinopathy.
  - reference: PMID:15850812
    reference_title: Serpiginous choroiditis.
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "treatment with immunosuppressive and alkylating agents have shown possible efficacy in small case series"
    explanation: >-
      Supports immunosuppression in serpiginous choroiditis, marked PARTIAL
      because the evidence base is small uncontrolled case series.

- name: Anti-VEGF Therapy for Inflammatory Choroidal Neovascularization
  description: >-
    Intravitreal anti-VEGF injection for inflammatory choroidal neovascular
    membranes, with or without concomitant anti-inflammatory therapy. In POHS and
    PIC, where CNV rather than inflammation dominates vision loss, this is the
    principal sight-preserving intervention.
  action_category: THERAPEUTIC
  therapeutic_modality: MONOCLONAL_ANTIBODY
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: anti-VEGF agent
      term:
        id: NCIT:C1742
        label: Angiogenesis Inhibitor
  target_mechanisms:
  - target: Inflammatory Choroidal Neovascularization
    treatment_effect: INHIBITS
    description: VEGF blockade causes regression of the inflammatory neovascular membrane.
    evidence:
    - reference: PMID:30209691
      reference_title: "An update on inflammatory choroidal neovascularization: epidemiology, multimodal imaging, and management."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Management of these neovascular membranes consists of anti-vascular growth factor agents, with or without concomitant anti-inflammatory and/or corticosteroid therapy."
      explanation: Establishes anti-VEGF as the management of inflammatory CNV.
  evidence:
  - reference: PMID:25841248
    reference_title: Ocular histoplasmosis syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Subfoveal and juxtafoveal CNVs are managed with anti-vascular endothelial growth factor therapy, photodynamic therapy, or a combination of both."
    explanation: Documents anti-VEGF as standard management of CNV in POHS.

- name: Laser Photocoagulation for Extrafoveal Choroidal Neovascularization
  description: >-
    Thermal laser ablation of extrafoveal inflammatory choroidal neovascular
    membranes, where the membrane is far enough from the fovea that the resulting
    scotoma is acceptable. Largely superseded by anti-VEGF for subfoveal and
    juxtafoveal lesions.
  action_category: THERAPEUTIC
  therapeutic_modality: DEVICE
  treatment_term:
    preferred_term: Laser Therapy
    term:
      id: NCIT:C15466
      label: Laser Therapy
  target_mechanisms:
  - target: Inflammatory Choroidal Neovascularization
    treatment_effect: INHIBITS
    description: Photocoagulation ablates the extrafoveal neovascular membrane.
    evidence:
    - reference: PMID:25841248
      reference_title: Ocular histoplasmosis syndrome.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Extrafoveal CNVs are successfully treated with laser photocoagulation."
      explanation: Supports laser photocoagulation for extrafoveal CNV.
  evidence:
  - reference: PMID:25841248
    reference_title: Ocular histoplasmosis syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Extrafoveal CNVs are successfully treated with laser photocoagulation."
    explanation: Documents laser photocoagulation as effective for extrafoveal neovascular membranes.

differential_diagnoses:
- name: Intraocular (vitreoretinal) lymphoma
  description: >-
    The most important masquerade syndrome of choroiditis. Lymphoma produces
    sub-RPE nodular deposits with autofluorescence and fluorescein angiographic
    findings closely resembling multifocal choroiditis, and it may transiently
    respond to corticosteroid, further delaying diagnosis.
  distinguishing_features:
  - Older patients, typically over 50 years
  - Sub-RPE nodular elevations approximately 100 microns in diameter
  - Frequent CNS involvement
  - Vitreous or chorioretinal biopsy with cytology, IL-10/IL-6 ratio and MYD88 testing
  - Corticosteroid response is transient and incomplete
  disease_term:
    preferred_term: intraocular lymphoma
    term:
      id: MONDO:0004351
      label: intraocular lymphoma
  evidence:
  - reference: PMID:27994812
    reference_title: Idiopathic Multifocal Choroiditis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "causes subretinal pigment epithelium (sub-RPE) nodular elevations about 100 μm in diameter which demostrate autofluorescence and fluorescein angiographic findings similar to those seen in MFC"
    explanation: >-
      Documents the imaging overlap between vitreoretinal lymphoma and multifocal
      choroiditis. (The spelling "demostrate" is as printed in the source.)

- name: Vogt-Koyanagi-Harada disease
  description: >-
    A bilateral granulomatous panuveitis with diffuse choroidal inflammation,
    exudative retinal detachment and extraocular (auditory, meningeal,
    integumentary) features. Curated as its own dismech entry; listed here as the
    principal non-infectious granulomatous mimic of diffuse choroiditis.
  distinguishing_features:
  - Exudative/serous retinal detachments with diffuse choroidal thickening on EDI-OCT
  - Extraocular features (tinnitus, headache, meningismus, poliosis, vitiligo, alopecia)
  - Predilection for pigmented ethnicities
  - No antecedent ocular trauma, which would instead suggest sympathetic ophthalmia
  disease_term:
    preferred_term: Vogt-Koyanagi-Harada disease
    term:
      id: MONDO:0018092
      label: Vogt-Koyanagi-Harada disease
  evidence:
  - reference: PMID:34145419
    reference_title: "Precise, simplified diagnostic criteria and optimised management of initial-onset Vogt-Koyanagi-Harada disease: an updated review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Vogt-Koyanagi-Harada (VKH) disease is a primary autoimmune stromal choroiditis."
    explanation: >-
      Establishes VKH as itself a form of choroiditis - a stromal rather than
      choriocapillaris-based one - which is exactly why it must be
      distinguished from the entities modelled here.
  - reference: PMID:34145419
    reference_title: "Precise, simplified diagnostic criteria and optimised management of initial-onset Vogt-Koyanagi-Harada disease: an updated review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the sine qua non presence of diffuse choroiditis, detected with indocyanine green angiography (ICGA) and/or Enhanced Depth Imaging OCT (EDI-OCT)"
    explanation: >-
      Supports the distinguishing feature - diffuse choroidal involvement on
      ICGA/EDI-OCT - separating VKH from the focal/multifocal lesions of the
      white-dot entities.

- name: Ocular tuberculosis
  description: >-
    Tubercular choroiditis is curated as a subtype of this entry, but it is
    simultaneously the standing differential for every non-infectious
    granulomatous choroiditis, above all ocular sarcoidosis and idiopathic
    serpiginous choroiditis, because misclassification leads to harmful
    unopposed immunosuppression.
  distinguishing_features:
  - Positive interferon-gamma release assay or tuberculin skin test
  - Residence in or travel to a tuberculosis-endemic area
  - Choroidal tubercle or tuberculoma
  - Occlusive retinal vasculitis
  - Response to antitubercular therapy
  disease_term:
    preferred_term: ocular tuberculosis
    term:
      id: MONDO:0006876
      label: ocular tuberculosis
  evidence:
  - reference: PMID:37176633
    reference_title: "Sarcoidosis-Related Uveitis: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Tuberculosis is a classic differential diagnosis to be wary of, especially in people who have spent time in endemic areas."
    explanation: Names tuberculosis as the classic differential for sarcoid uveitis.

- name: Ocular syphilis
  description: >-
    Syphilitic chorioretinitis is curated as a subtype here, but ocular syphilis
    is also the universal differential: it can imitate essentially any ocular
    inflammatory presentation, and serologic exclusion is mandatory before
    immunosuppression.
  distinguishing_features:
  - Positive treponemal serology using the CDC reverse screening algorithm
  - Acute syphilitic posterior placoid chorioretinitis morphology with leopard-spot hypofluorescence
  - Frequent HIV co-infection and neurosyphilis
  - Rapid resolution on penicillin
  disease_term:
    preferred_term: syphilis
    term:
      id: MONDO:0005976
      label: syphilis
  notes: >-
    No MONDO term for ocular syphilis exists at time of curation, so the parent
    term syphilis is bound rather than a stage-specific term - ocular
    involvement can occur at any stage, so binding to secondary syphilis would
    contradict this entry's own cited evidence.
  evidence:
  - reference: PMID:33831337
    reference_title: Ocular syphilis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "ocular syphilis should always be a part of the differential diagnosis of most, if not all, ocular infectious and inflammatory presentations"
    explanation: Directly states the universal differential status of ocular syphilis.

- name: Sarcoidosis
  description: >-
    Systemic granulomatous disease involving the eye in a large minority of
    cases, sometimes without systemic involvement. The systemic mechanism is
    curated in the dismech Sarcoidosis and Neurosarcoidosis entries; the ocular
    arm is a subtype here.
  distinguishing_features:
  - Granulomatous anterior uveitis with mutton-fat keratic precipitates and synechiae
  - Bilateral hilar lymphadenopathy on chest imaging
  - Raised serum angiotensin-converting enzyme
  - Non-caseating epithelioid granulomas on biopsy
  disease_term:
    preferred_term: sarcoidosis
    term:
      id: MONDO:0019338
      label: sarcoidosis
  evidence:
  - reference: PMID:37176633
    reference_title: "Sarcoidosis-Related Uveitis: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Sarcoidosis is an inflammatory disease that involves the eyes in 10-55% of cases, sometimes without systemic involvement."
    explanation: Quantifies ocular involvement in sarcoidosis and notes it may be isolated.

- name: Behcet disease
  description: >-
    Systemic vasculitis producing occlusive retinal vasculitis and panuveitis.
    Curated as its own dismech entry; listed here because its posterior-segment
    inflammation overlaps with choroiditis and it is a recognised non-infectious
    uveitis aetiology in large cohorts.
  distinguishing_features:
  - Recurrent oral and genital aphthous ulceration, skin lesions, pathergy
  - Explosive occlusive retinal vasculitis with retinal haemorrhage rather than primary choroidal lesions
  - HLA-B51 association
  - Silk Road geographic distribution
  disease_term:
    preferred_term: Behcet disease
    term:
      id: MONDO:0007191
      label: Behcet disease
  evidence:
  - reference: PMID:37428299
    reference_title: "The large Hellenic Study of Uveitis: epidemiology, etiologic factors and classification."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The most frequent causes of non-infectious uveitis included sarcoidosis, white dot syndromes, ankylosing spondylitis, lens-induced uveitis, Adamantiades-Behçet disease, and idiopathic juvenile arthritis."
    explanation: Places Behcet disease among the leading non-infectious uveitis aetiologies to be distinguished.

- name: Cytomegalovirus retinitis
  description: >-
    Viral necrotising retinitis of the profoundly immunocompromised, curated as
    its own dismech entry. A key infectious differential in any patient with
    posterior-segment inflammation and low CD4 count.
  distinguishing_features:
  - Severe immunosuppression, typically CD4 below 50 cells per microlitre
  - Granular retinitis with haemorrhage along the vascular arcades
  - Minimal vitritis
  - Aqueous PCR positive for cytomegalovirus
  - Responds to antivirals, not to immunosuppression
  disease_term:
    preferred_term: cytomegalovirus retinitis
    term:
      id: MONDO:0000878
      label: cytomegalovirus retinitis
  evidence:
  - reference: PMID:28012878
    reference_title: Viral posterior uveitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "others, such as cytomegalovirus retinitis or acute retinal necrosis, may result in serious complications and profound vision loss"
    explanation: >-
      Identifies CMV retinitis specifically as a sight-threatening viral
      posterior uveitis requiring differentiation.
  - reference: PMID:28012878
    reference_title: Viral posterior uveitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Since some of these infections may respond well to antiviral therapy, it is important to work up all cases of posterior uveitis to rule out an infectious etiology."
    explanation: >-
      Supports the management consequence of the distinction - antiviral therapy
      rather than immunosuppression.

prevalence:
- subtype: Presumed Ocular Histoplasmosis Syndrome
  population: United States commercially insured enrollees
  measure_type: POINT_PREVALENCE
  prevalence_class: BAND_1_5_PER_10000
  rate_per_100000: 13.0
  notes: >-
    Claims-based diagnosis-code prevalence among more than 50 million MarketScan
    enrollees. Geographically concentrated in the Mississippi and Ohio river
    valleys.
  evidence:
  - reference: PMID:32168355
    reference_title: "Presumed ocular histoplasmosis syndrome in a commercially insured population, United States."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Among >50 million total MarketScan enrollees, 6,678 (13 per 100,000) had a POHS diagnosis code."
    explanation: Directly reports POHS prevalence as 13 per 100,000 insured enrollees.

epidemiology:
- name: Infectious versus non-infectious share of uveitis
  description: >-
    In a 30-year Greek tertiary referral cohort of 6,191 uveitis cases, 1,925
    were infectious and 4,125 non-infectious, with 141 masquerade syndromes.
    Both arms of the aetiologic fork are therefore numerically substantial in
    referral practice, and masquerades are a small but non-trivial third
    category.
  evidence:
  - reference: PMID:37428299
    reference_title: "The large Hellenic Study of Uveitis: epidemiology, etiologic factors and classification."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Out of 6191 cases with uveitis, 1925 were infectious, 4125 were non-infectious, and an overall of 141 masquerade syndromes were recorded."
    explanation: Quantifies the aetiologic composition of a large tertiary uveitis cohort.

- name: Leading infectious causes in a tertiary uveitis cohort
  description: >-
    Herpetic uveitis was the commonest infectious cause (14.87% of all cases),
    followed by toxoplasmosis (6.6%) and tuberculosis (2.74%). Note this is a
    case-mix fraction within a referral cohort, not a population rate, and is
    strongly geography-dependent.
  evidence:
  - reference: PMID:37428299
    reference_title: "The large Hellenic Study of Uveitis: epidemiology, etiologic factors and classification."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Herpetic uveitis (HSV-1 and VZV/HZV) was the most common cause of infectious uveitis (14.87%), followed by toxoplasmosis (6.6%) and tuberculosis (2.74%)."
    explanation: Quantifies the relative contribution of infectious aetiologies in a tertiary cohort.

- name: Geographic variation in infectious share
  description: >-
    Infectious causes account for 30-60% of uveitis in developing countries,
    while non-infectious uveitis predominates in the developed world - though
    tuberculosis and syphilis have been increasing in developed countries. The
    prior probability on the aetiologic fork therefore depends heavily on where
    the patient is seen.
  evidence:
  - reference: PMID:27467180
    reference_title: A Focus on the Epidemiology of Uveitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Infectious causes are common (30-60%) in the developing countries."
    explanation: Quantifies the infectious share of uveitis in developing countries.
  - reference: PMID:27467180
    reference_title: A Focus on the Epidemiology of Uveitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Non-infectious uveitic conditions are generally more common in the developed world."
    explanation: Documents the complementary predominance of non-infectious uveitis in the developed world.
  - reference: PMID:27467180
    reference_title: A Focus on the Epidemiology of Uveitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "An increase in the prevalence of infectious etiologies, including tuberculosis and syphilis, has been seen in developed countries."
    explanation: Supports the caveat that the two key immunosuppression-hazard infections are rising in developed settings.

progression:
- phase: Acute active choroiditis
  notes: >-
    Active inflammatory lesions with overlying vitritis and, depending on
    aetiology, retinal necrosis or placoid outer-retinal whitening. Symptoms
    include blurred vision, floaters, photopsia and scotoma.
  evidence:
  - reference: PMID:27994812
    reference_title: Idiopathic Multifocal Choroiditis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "patients may complain of a temporal scotoma, metamorphopsia, floaters, photopsias, photophobia, and decreased vision"
    explanation: Describes the symptom complex of active choroiditis.

- phase: Healed atrophic and scarred phase
  notes: >-
    Resolution of active inflammation leaves punched-out atrophic chorioretinal
    lesions and pigmented fibrotic scars, with permanent corresponding field
    defects. In toxoplasmosis the scar border is the site of future reactivation.
  evidence:
  - reference: PMID:27994812
    reference_title: Idiopathic Multifocal Choroiditis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "circumscribed areas of chorioretinal atrophy and subretinal pigmented fibrotic scars"
    explanation: Describes the healed structural end-state.

- phase: Chronic recurrent and complication phase
  notes: >-
    Many entities are chronically recurrent, with cumulative lesion accrual and
    the late development of choroidal neovascularization, macular edema,
    cataract, epiretinal membrane and progressive chorioretinal atrophy.
    Recurrence rather than the index episode governs long-term visual outcome.
  evidence:
  - reference: PMID:27994812
    reference_title: Idiopathic Multifocal Choroiditis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The rate of increase in the size and number of lesions and development of new or recurrent CME and/or CNV is also high despite the relative absence of anterior uveitis or vitritis."
    explanation: Documents ongoing lesion accrual and complication development in the chronic phase.
  - reference: PMID:38843299
    reference_title: "Clinical characteristics, visual acuity outcomes, and factors associated with loss of vision among patients with active ocular toxoplasmosis: A retrospective study in a Thai tertiary center."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The cumulative incidence of recurrent OT at three years was 33.9%"
    explanation: Quantifies recurrence risk over three years in ocular toxoplasmosis.

clinical_burden:
  burden_level: HIGH
  rationale: >-
    Choroiditis is a leading cause of irreversible vision loss from posterior
    uveitis. Photoreceptor and RPE loss is permanent, one-fifth of eyes in a
    treated ocular toxoplasmosis cohort ended with acuity of 20/200 or worse, and
    recurrent disease plus choroidal neovascularization accrue further deficit
    over decades. Many patients require indefinite immunosuppression with its own
    morbidity, and the disease typically affects working-age adults.
  evidence:
  - reference: PMID:38843299
    reference_title: "Clinical characteristics, visual acuity outcomes, and factors associated with loss of vision among patients with active ocular toxoplasmosis: A retrospective study in a Thai tertiary center."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "At the final visit, 21% of all affected eyes suffered VA ≤ 20/200."
    explanation: Quantifies severe residual visual impairment after treated disease.

clinical_trials:
- name: NCT06613919
  phase: PHASE_IV
  status: COMPLETED
  description: >-
    Randomised non-inferiority trial comparing 6 versus 9 months of antitubercular
    therapy for tubercular posterior uveitis and choroiditis. Directly addresses
    the treatment-duration question in the infectious arm of the aetiologic fork.
  target_phenotypes:
  - preferred_term: Posterior uveitis
    term:
      id: HP:0012123
      label: Posterior uveitis
  evidence:
  - reference: clinicaltrials:NCT06613919
    reference_title: Prospective Randomised Trial for 6-Months Versus 9-Months Anti-TB Therapy for Tubercular Posterior Uveitis
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The goal of this clinical trial is to learn if 6-months anti-TB therapy is not worse than 9-months therapy for the treatment of tubercular posterior uveitis."
    explanation: Confirms the trial tests antitubercular therapy duration in tubercular posterior uveitis.

- name: NCT01449877
  phase: PHASE_III
  status: COMPLETED
  description: >-
    Randomised double-masked trial of trimethoprim-sulfamethoxazole prophylaxis
    versus placebo after acute treatment of Toxoplasma retinochoroiditis, with
    recurrence over long-term follow-up as the primary outcome. Tests whether
    continued antimicrobial suppression prevents cyst reactivation.
  target_phenotypes:
  - preferred_term: Chorioretinal scar
    term:
      id: HP:0007777
      label: Chorioretinal scar
  evidence:
  - reference: clinicaltrials:NCT01449877
    reference_title: Influence of Trimethoprim-sulfamethoxazole for the Recurrence of Retinochoroiditis Toxoplasma Gondii
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The investigators study aims to determine the effect of prophylactic therapy with Trimethoprim-sulfamethoxazole on the recurrences of toxoplasma retinochoroiditis gondii."
    explanation: Confirms the trial tests antimicrobial prophylaxis against recurrence of ocular toxoplasmosis.

notes: >-
  Boundary handling against existing dismech entries. This entry is deliberately
  scoped to the ocular/choroidal arm and cross-references rather than duplicates
  systemic disease mechanisms curated elsewhere: Sarcoidosis and Neurosarcoidosis
  (systemic granulomatous mechanism), Tuberculosis (systemic mycobacterial
  mechanism), Behcets_Disease, Vogt-Koyanagi-Harada_Disease, Panuveitis (the
  anatomic-class sibling covering all-uveal-layer involvement), and
  Cytomegalovirus_Retinitis. No standalone ocular toxoplasmosis, ocular syphilis,
  histoplasmosis, birdshot, serpiginous, MFC or PIC entry existed in
  kb/disorders/ at time of curation, so those are modelled here as subtypes.
  Choroiditis is distinct from choroideremia (an X-linked chorioretinal
  degeneration) and from choroid plexus disease; MONDO:0001280 is anchored to
  UBERON:0001776 optic choroid.

  Ontology gaps encountered: MONDO has no term for ocular syphilis or for ocular
  sarcoidosis, so the syphilis differential is bound to the parent
  MONDO:0005976 syphilis and the sarcoid choroiditis subtype carries no
  subtype_term. (The choriocapillaris is covered by UBERON:0005336 capillary
  layer of choroid, whose "choriocapillaris" is a RELATED synonym - findable by
  synonym search, not by label search.)

  Open nosological question for a human curator: MONDO:0001280 carries
  subset: disease_grouping and subset: ordo_group_of_disorders, and this entry
  is explicitly modelled as an umbrella over ten aetiologically heterogeneous
  entities. It may belong in kb/groupings/ as a Grouping rather than as a
  Disease. It is curated here as a Disease because the entry's substantive
  content is the shared downstream mechanism (choriocapillaris hypoperfusion →
  outer-retinal/RPE damage → scarring → inflammatory CNV) plus the
  infectious/non-infectious management fork, which is genuine pathophysiology
  rather than a taxonomy. Flagging for review rather than deciding unilaterally.

references:
- reference: PMID:35208488
  title: "Diagnosis and Treatment of Primary Inflammatory Choriocapillaropathies (PICCPs): A Comprehensive Overview."
- reference: PMID:25434765
  title: The immunopathogenesis of birdshot chorioretinopathy; a bird of many feathers.
- reference: PMID:38541191
  title: Diagnostic Challenges in Inflammatory Choroidal Neovascularization.

📚

References & Deep Research

References

3

PMID:35208488

Diagnosis and Treatment of Primary Inflammatory Choriocapillaropathies (PICCPs): A Comprehensive Overview.

No top-level findings curated for this source.

PMID:25434765

The immunopathogenesis of birdshot chorioretinopathy; a bird of many feathers.

No top-level findings curated for this source.

PMID:38541191

Diagnostic Challenges in Inflammatory Choroidal Neovascularization.

No top-level findings curated for this source.

Deep Research

1

Falcon ▸

Disease Characteristics Research Template

Edison Scientific Literature 28 citations 2026-08-01T08:48:31.396231

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: Choroiditis
MONDO ID: (if available)
Category: Immune

Research Objectives

Please provide a comprehensive research report on Choroiditis 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

Choroiditis: disease-characteristics research report

Executive interpretation

Choroiditis is not one etiologically uniform disease. It is an anatomic/pathologic term for inflammation centered in the choroid, usually classified clinically under posterior uveitis and often accompanied by retinal inflammation, hence chorioretinitis or retinochoroiditis. Named entities include infectious toxoplasma or tubercular choroiditis and immune-mediated birdshot chorioretinopathy, multifocal choroiditis, punctate inner choroidopathy (PIC), serpiginous choroiditis, and Vogt–Koyanagi–Harada (VKH) disease. Etiology, genetics, laterality, course, treatment, and prognosis must therefore be represented at subtype level rather than assigned indiscriminately to “choroiditis.” A 2023 expert review similarly describes posterior uveitis as a broad spectrum of infectious, autoimmune, drug-related, systemic, and masquerading diseases (paezescamilla2023challengesinposterior pages 1-2).

Domain/subtype	Strongest quantitative finding	Evidence type and year	Source DOI or NCT
Choroiditis umbrella / posterior uveitis context	Posterior/infectious inflammatory disorders are vision-threatening and epidemiologically heterogeneous; in a 30-year Greek tertiary cohort, 6,191 uveitis cases included 1,925 infectious, 4,125 non-infectious, and 141 masquerade syndromes (kalogeropoulos2023thelargehellenic pages 1-2)	Observational cohort, 2023	https://doi.org/10.1007/s10792-023-02772-5
Birdshot chorioretinopathy (epidemiology)	Accounts for 0.6–1.5% of uveitis cases at tertiary centers, 5–8% of posterior uveitis, with estimated prevalence 0.1–0.6/100,000; mean onset ~53 years (bousquet2022birdshotchorioretinopathya pages 1-2)	Review of clinical literature, 2022	https://doi.org/10.3390/jcm11164772
Birdshot chorioretinopathy (core HLA association)	>95% of patients carry HLA-A29; reported OR 157.5 for HLA-A29 association (gelfman2021erap1erap2and pages 1-2)	Human genetic association study, 2021	https://doi.org/10.1167/iovs.62.14.3
Birdshot chorioretinopathy (ERAP/HLA modifiers)	ERAP1-rs27432 OR 2.46 (95% CI 1.85–3.26), ERAP2-rs10044354 OR 1.95 (1.55–2.44), protective ERAP2-rs2248374 OR 0.56 (0.45–0.70); combined ERAP1/2 risk genotypes + two HLA-Aw19 alleles OR 13.53 (3.79–54.77) (gelfman2021erap1erap2and pages 1-2)	Human genetic association/meta-analysis, 2021	https://doi.org/10.1167/iovs.62.14.3
Birdshot chorioretinopathy (2024 HLA-A29 homozygosity/protection)	Second HLA-A29 allele overrepresented in cases vs HLA-A29-positive controls: OR 1.57 (95% CI 1.01–2.44); HLA-A32 under-represented/protective: OR 0.40 (0.19–0.85); no severity effect detected (loeliger2024theimpactof pages 1-2)	Human genetic association study, 2024	https://doi.org/10.1167/iovs.65.13.47
Ocular toxoplasmosis / toxoplasma retinochoroiditis	In 92 patients (95 eyes), 21% had VA ≤20/200 at final visit; 3-year recurrence 33.9% (95% CI 19.7–54.2%); poor 6-month VA ≤20/50 associated with immunocompromise aOR 4.9, macular lesion aOR 5.4, initial VA ≤20/200 aOR 9.1 (sittivarakul2024clinicalcharacteristicsvisual pages 1-2, sittivarakul2024clinicalcharacteristicsvisual pages 13-14)	Retrospective clinical cohort, 2024	https://doi.org/10.1371/journal.pntd.0012232
Ocular toxoplasmosis (recurrence biology/clinical risk)	Contralateral-eye recurrence reported as 40% when bilateral retinal scars are present versus 4% in unaffected eyes; pregnancy-related recurrence estimates vary (IRR 0.54–0.75 in some studies, 7.4-fold increase in another) (miyagaki2024oculartoxoplasmosisadvances pages 14-15)	Review, 2024	https://doi.org/10.3390/pathogens13100898
Hellenic uveitis etiologies relevant to choroiditis differential	Of all 6,191 cases, 24.2% were linked to 4 microorganisms; most common infectious causes were herpetic uveitis 14.87%, toxoplasmosis 6.6%, tuberculosis 2.74%; 49.2% of non-infectious cases had no systemic correlation (kalogeropoulos2023thelargehellenic pages 1-2)	Observational cohort, 2023	https://doi.org/10.1007/s10792-023-02772-5
Human intraocular immune mechanisms	In aqueous fluid, 6 chemokines were elevated and enriched in active uveitis; CCL2 and CXCL10 were consistently enriched across patients, and single-cell RNA-seq implicated macrophages as a key source (lin2024aqueousmacrophagescontribute pages 1-2)	Single-cell + protein profiling study, 2024	https://doi.org/10.1016/j.xops.2023.100453
Systems proteomics / biomarker discovery	3,668 proteins identified and >3,000 quantified from 278 samples; EV proteomes correlated with disease better than plasma, with disease-specific biomarker panels validated (wu2023comprehensiveprofilingof pages 1-2)	Proteomics biomarker study, 2023	https://doi.org/10.1186/s12967-023-04228-x
Trial: Birdshot treatment	Randomized phase 2 BIRDFERON trial in birdshot chorioretinopathy with macular edema; enrollment 58; compared interferon alfa-2a vs prednisone; primary endpoint: decrease in OCT macular-center thickness over 4 months (NCT00508040 chunk 1)	Interventional trial record, 2007–2013	NCT00508040
Trial: Ocular toxoplasmosis recurrence prevention	Randomized triple-masked phase 3 ISROT trial; enrollment 141; after acute TMP-SMX treatment, prophylaxis used TMP-SMX every other day for 311 days vs placebo, with recurrence followed to 120 months (NCT01449877 chunk 1)	Interventional trial record, 2011–2016	NCT01449877
Trial: Tubercular posterior uveitis/choroiditis	Randomized phase 4 non-inferiority trial; enrollment 58; compared 6 vs 9 months anti-TB therapy for tubercular posterior uveitis/choroiditis; primary endpoint: non-recurrence of inflammation 1 year after ATT completion (NCT06613919 chunk 1)	Interventional trial record, 2024 posting	NCT06613919

Table: This table summarizes key quantitative evidence for choroiditis as a heterogeneous umbrella syndrome, spanning immune and infectious subtypes, mechanisms, and clinical trials. It is useful for quickly identifying the strongest current numbers and the exact source records behind them.

1. Disease information

Definition and classification

The choroid is the vascular, pigmented posterior component of the uveal tract. Choroiditis denotes inflammatory infiltration or injury of this tissue; adjacent retinal, retinal-pigment-epithelial (RPE), vitreous, retinal vascular, and optic-disc involvement is common. In the Standardization of Uveitis Nomenclature framework, lesions centered primarily in the retina/choroid constitute posterior uveitis; simultaneous anterior, intermediate, and posterior inflammation is panuveitis.

Common names: choroiditis; posterior uveitis with choroidal involvement; chorioretinitis; retinochoroiditis; disseminated/multifocal choroiditis. “Central serous chorioretinopathy” is not ordinarily an inflammatory choroiditis and should not be merged with this entity.

Identifiers and coding:

MeSH: Choroiditis, D002833; related terms include Posterior Uveitis and Chorioretinitis. The MeSH identifier is explicitly present in ClinicalTrials.gov-derived indexing (NCT00508040 chunk 1, NCT06613919 chunk 1).
ICD-10-CM: principally H30.-, Chorioretinal inflammation, with subtype and laterality extensions; coding should use the most specific clinical diagnosis.
MONDO/OMIM/Orphanet: no single disease-level record should be assumed for the umbrella term. Named subtypes may have individual ontology entries. No OMIM disease or Mendelian inheritance model is appropriate for nonspecific choroiditis. A MONDO identifier was not verified in the retrieved evidence.
Data provenance: the present entry synthesizes aggregated literature, tertiary cohorts, human biospecimens, and clinical-trial records—not individual EHR-level data.

2. Etiology

Causal factors

Infectious: Toxoplasma gondii; Mycobacterium tuberculosis; Treponema pallidum; herpesviruses; fungi, especially in immunocompromised hosts; and less commonly other bacterial, viral, or parasitic agents. In a 6,191-case Greek tertiary uveitis cohort, 1,925 cases were infectious; herpetic disease accounted for 14.87% of all cases, toxoplasmosis 6.6%, and tuberculosis 2.74%. These are overall uveitis—not choroiditis-specific—frequencies and reflect referral and geography (kalogeropoulos2023thelargehellenic pages 1-2).
Immune-mediated/idiopathic: birdshot chorioretinopathy, multifocal choroiditis/PIC, serpiginous choroiditis, VKH, sarcoidosis, Behçet disease, and other systemic inflammatory disorders. In the same cohort, 4,125 cases were noninfectious and 49.2% of those lacked an identified systemic association (kalogeropoulos2023thelargehellenic pages 1-2).
Drug or iatrogenic triggers: immune-checkpoint inhibitors, MEK inhibitors, paradoxical anti-TNF inflammation, intraocular drugs, and occasionally temporally associated vaccination have been reported; causality requires careful pharmacovigilance assessment (paezescamilla2023challengesinposterior pages 1-2).
Masqueraders: primary vitreoretinal lymphoma, leukemia/lymphoma, inherited retinal degeneration, vascular/ischemic disease, amyloidosis, and central serous chorioretinopathy can mimic inflammatory choroiditis. Masquerade syndromes represented 141/6,191 cases in the Greek tertiary cohort (kalogeropoulos2023thelargehellenic pages 1-2).

Risk and protective factors

Birdshot: HLA-A29 is the dominant susceptibility factor; European ancestry and middle age characterize the typical population. It is necessary or nearly necessary in conventional classification but is not sufficient because HLA-A29 is far more common than birdshot disease (bousquet2022birdshotchorioretinopathya pages 1-2, gelfman2021erap1erap2and pages 1-2).
Ocular toxoplasmosis: undercooked meat, contaminated soil/water or food, cat-feces exposure, congenital transmission, and immunosuppression are biologically relevant exposure routes. Immunocompromise is associated with larger lesions and poor vision. In a 2024 Thai cohort, the adjusted odds ratio for 6-month VA ≤20/50 was 4.9 in immunocompromised patients (sittivarakul2024clinicalcharacteristicsvisual pages 1-2, sittivarakul2024clinicalcharacteristicsvisual pages 13-14).
Tubercular disease: residence or exposure in TB-endemic settings and evidence of latent/systemic infection increase diagnostic probability, although active pulmonary TB and ocular-fluid microbiological confirmation are often absent (NCT06613919 chunk 1).
Broad noninfectious uveitis observations: smoking and vitamin-D deficiency have been associated with risk, but these should not be encoded as proven causal factors for every choroiditis subtype.
Potential protection in birdshot: HLA-A32 was underrepresented among cases in a 2024 French study, OR 0.40 (95% CI 0.19–0.85), suggesting—not proving—a protective effect. ERAP2 rs2248374, which disrupts full-length ERAP2 expression, was also protective, OR 0.56 (95% CI 0.45–0.70) (gelfman2021erap1erap2and pages 1-2, loeliger2024theimpactof pages 1-2).

Gene–environment interaction

The clearest model is birdshot: HLA-A29-dependent antigen presentation is modified by ERAP1/ERAP2 peptide trimming, but the low penetrance among HLA-A29 carriers implies additional environmental or stochastic immune triggers. No specific exposure has yet been established as the necessary trigger. In infection-associated disease, pathogen exposure interacts with host immunity, pregnancy, age, strain biology, and immunosuppression; these are multifactorial rather than Mendelian interactions.

3. Phenotypes

Phenotype	Character and course	Suggested HPO term
Blurred or reduced vision	Common, variable; acute in infection, episodic or progressive in immune disease	Visual impairment (HP:0000505)
Floaters	Vitreous inflammatory cells/debris; often acute or fluctuating	Vitreous floaters (use current HPO label/ID validation)
Photopsia	Prominent in white-dot syndromes/PIC/MFC	Photopsia (validate current HPO ID)
Scotoma/field loss	Focal lesions or diffuse retinal dysfunction; progressive in birdshot	Visual field defect (HP:0001123)
Photophobia/ocular discomfort	Variable; posterior disease may be relatively painless	Photophobia (HP:0000613)
Chorioretinal inflammatory lesions	Cream-colored, punctate, placoid, serpiginous, granulomatous, or necrotizing depending on subtype	Chorioretinal abnormality; chorioretinal scar (validate subtype-specific HPO IDs)
Vitritis	Clinical sign accompanying many posterior uveitides	Vitreous inflammation/opacity
Retinal vasculitis	Leakage/occlusion on fluorescein angiography	Retinal vasculitis
Macular edema	Major cause of reduced acuity in birdshot and other immune subtypes	Cystoid macular edema (HP:0011510)
Choroidal neovascularization	Important complication of PIC/MFC and healed inflammatory lesions	Choroidal neovascularization (HP:0011506)
Chorioretinal atrophy/scarring	Downstream structural damage causing permanent scotoma or central loss	Chorioretinal atrophy (HP:0000533)

Age and laterality are subtype dependent. Birdshot is a bilateral chronic disorder with mean onset around 53 years; ocular toxoplasmosis in the 2024 Thai cohort had median age 35.9 years and was unilateral in 92.4% (bousquet2022birdshotchorioretinopathya pages 1-2, sittivarakul2024clinicalcharacteristicsvisual pages 1-2). PIC/MFC generally affects young-to-middle-aged, often myopic women, whereas congenital infection can manifest in infancy or later through reactivation.

In active ocular toxoplasmosis, focal necrotizing retinitis, hyperpigmented scars, vitritis, and vasculitis are characteristic. In the Thai cohort, 62% had primary retinitis without an old scar, 56% had posterior-pole lesions, and 75% had lesions no larger than two disc areas; the source abstract’s exact summary was: “Ocular toxoplasmosis mainly presents as unilateral primary retinitis within the posterior pole.” (sittivarakul2024clinicalcharacteristicsvisual pages 1-2, sittivarakul2024clinicalcharacteristicsvisual pages 2-4).

Quality-of-life loss arises from impaired reading, driving, work, contrast sensitivity, visual fields, and recurrent-treatment burden. No reliable umbrella-level EQ-5D or SF-36 estimate was identified.

4. Genetic and molecular information

There is no established single causal gene, pathogenic variant, chromosomal abnormality, or inheritance pattern for choroiditis as an umbrella condition. Routine WES/WGS, karyotyping, CMA, FISH, repeat-expansion, or mitochondrial testing is therefore not indicated solely for acquired choroiditis.

Birdshot susceptibility architecture

More than 95% of conventional birdshot cases carry HLA-A29; one study reports an OR of approximately 157.5. HLA-A29 nevertheless has incomplete penetrance and is a susceptibility allele, not a deterministic pathogenic variant (gelfman2021erap1erap2and pages 1-2).
Human sequencing of 286 cases and 108 HLA-A29-positive controls found ERAP1 rs27432, OR 2.46 (95% CI 1.85–3.26), and ERAP2 rs10044354, OR 1.95 (1.55–2.44). A second HLA-Aw19-family allele gave OR 4.44, while combined ERAP1/ERAP2 risk genotypes plus two HLA-Aw19 alleles gave OR 13.53 (3.79–54.77) (gelfman2021erap1erap2and pages 1-2).
A 2024 study expanded the series by 120 cases and compared it with 151,997 French subjects. HLA-A29 homozygosity increased susceptibility, OR 1.57 (1.01–2.44), but did not measurably affect severity; HLA-A32 was potentially protective (loeliger2024theimpactof pages 1-2).
Functional interpretation: ERAP1/ERAP2 alter peptide trimming for HLA class-I presentation. The investigators’ exact conclusion was that the findings suggest “exceeding a peptide presentation threshold activates the immune response in choroids of A29 carriers.” (gelfman2021erap1erap2and pages 1-2).

These are germline common-variant associations; they are not ACMG “pathogenic variants,” and clinical population allele frequency is ancestry dependent. No validated modifier-gene panel or genotype-guided treatment is standard.

5. Environmental, lifestyle, and infectious information

Environmental determinants are mostly subtype-specific. Food/water hygiene and meat preparation affect toxoplasma acquisition; TB exposure, crowding, migration, and regional endemicity affect tubercular posterior uveitis; immunosuppressive therapy and HIV modify opportunistic disease. Infectious ocular disease is geographically heterogeneous and often unilateral or asymmetric, while climate, conflict, poverty, urbanization, and environmental degradation may influence future burdens (miyagaki2024oculartoxoplasmosisadvances pages 14-15).

Smoking cessation is prudent because smoking is associated with uveitis and may worsen inflammatory/vascular outcomes, but direct prevention data for nonspecific choroiditis are insufficient. No diet, exercise, alcohol, toxin, radiation, pollution, or occupational intervention has been proven to prevent all choroiditis.

6. Mechanism and pathophysiology

Causal chains

Infectious choroiditis: pathogen exposure/reactivation → invasion or persistence in retina/choroid/RPE → innate immune sensing and leukocyte recruitment → focal necrosis, granuloma, or vasculitis → edema and photoreceptor/RPE injury → scar/atrophy, field defect, or reduced acuity. In toxoplasmosis, currently available drugs suppress replicating tachyzoites but do not eradicate latent tissue cysts, explaining recurrence (miyagaki2024oculartoxoplasmosisadvances pages 14-15, NCT01449877 chunk 1).

Immune-mediated choroiditis: susceptibility plus an incompletely defined trigger → breakdown of ocular immune privilege and antigen presentation → activation of T-cell/macrophage pathways → chemokine-mediated recruitment across the blood–ocular barrier → choroidal stromal/RPE/retinal inflammation → vascular leakage, macular edema, photoreceptor injury, atrophy, fibrosis, or neovascularization.

Birdshot-specific upstream mechanism: HLA-A29 plus ERAP1/ERAP2-dependent immunopeptidome changes → aberrant class-I peptide presentation → CD8-associated and broader adaptive immune activation → independent but concurrent choroidal stromal and retinal inflammation (bousquet2022birdshotchorioretinopathya pages 14-15, gelfman2021erap1erap2and pages 1-2).

Recent human molecular profiling

A 2024 human aqueous-fluid study measured 31 inflammatory proteins and performed single-cell expression analysis. Six chemokines—CCL2, CXCL10, CXCL9, CXCL8, CCL3, and CCL14—were elevated in active uveitis and enriched in aqueous relative to plasma. CCL2 and CXCL10 were consistently enriched, and single-cell RNA sequencing implicated ocular macrophages as a source. The authors concluded: “ocular macrophages may play a central role, via CCL2 and CXCL10 production, in recruiting inflammatory cells to the eye.” This is pan-uveitis evidence, not proof that all choroiditis subtypes share identical signaling (lin2024aqueousmacrophagescontribute pages 1-2).

A 2023 SWATH-MS study analyzed 278 plasma/EV samples, identified 3,668 proteins, quantified more than 3,000, and found that small- and large-EV proteomes correlated with disease better than plasma. It validated candidate panels for AS-related uveitis, Behçet uveitis, VKH, and posterior scleritis; these remain research biomarkers rather than routine diagnostics (wu2023comprehensiveprofilingof pages 1-2).

Suggested GO biological processes: inflammatory response (GO:0006954), immune response (GO:0006955), leukocyte migration (GO:0050900), chemotaxis (GO:0006935), antigen processing and presentation of peptide antigen via MHC class I (GO:0002474), T-cell activation (GO:0042110), macrophage activation (GO:0042116), angiogenesis (GO:0001525), and apoptotic process (GO:0006915).

Suggested CL terms: macrophage (CL:0000235), CD8-positive alpha-beta T cell (CL:0000625), CD4-positive alpha-beta T cell (CL:0000624), retinal pigment epithelial cell (CL:0002586), vascular endothelial cell (CL:0000115), photoreceptor cell (CL:0000210), and choroidal melanocyte where an appropriate current CL identifier is available.

7. Anatomical structures affected

Primary organ: eye.
Primary site: choroid; suggested UBERON:0001776 (choroid).
Frequent contiguous structures: retina (UBERON:0000966), RPE, vitreous body (UBERON:0001797), optic disc/nerve, retinal and choroidal vessels, and macula.
Tissue/cell targets: choroidal stroma and vasculature, melanocytes, resident macrophages, RPE, photoreceptors, retinal vascular endothelium, and infiltrating lymphocytes.
Subcellular processes: ER peptide trimming and MHC-I loading are particularly relevant in birdshot; mitochondria, lysosomes, and apoptotic machinery participate downstream but no universal organelle defect is established.
Laterality: bilateral in birdshot and typically VKH; often unilateral in active toxoplasmosis; PIC/MFC may be unilateral, bilateral, or asymmetric.
Secondary organs: depend on cause—neurologic/auditory/integumentary involvement in VKH, pulmonary/lymphatic disease in sarcoidosis or TB, mucocutaneous/vascular disease in Behçet, and systemic infection in immunocompromised patients.

8. Temporal development

Onset ranges from congenital to geriatric. Infection may be acute or subacute; toxoplasma lesions resolve into scars but can reactivate. Immune subtypes are commonly episodic, relapsing-remitting, or chronic progressive. Birdshot is indolent but potentially severe and usually requires prolonged control; mean onset is approximately 53 years (bousquet2022birdshotchorioretinopathya pages 1-2, gelfman2021erap1erap2and pages 1-2).

In the 2024 toxoplasmosis cohort, cumulative recurrence at three years was 33.9% (95% CI 19.7–54.2%). A broader 2024 review reported greater recurrence risk in younger people and approximately 40% contralateral recurrence when bilateral scars were present versus 4% in previously unaffected contralateral eyes (miyagaki2024oculartoxoplasmosisadvances pages 14-15, sittivarakul2024clinicalcharacteristicsvisual pages 1-2).

The critical therapeutic window is active inflammation before irreversible macular/optic-nerve injury, vascular occlusion, or fibrosis. Delay in anti-TB therapy has been associated with chronic inflammation and prolonged visual impairment (NCT06613919 chunk 1).

9. Inheritance and population

Choroiditis is generally acquired and not inherited in Mendelian fashion. Penetrance, anticipation, mosaicism, founder effects, carrier frequency, and reproductive genetic screening are therefore not applicable at the umbrella level. Birdshot has polygenic immune susceptibility with markedly incomplete penetrance.

Reliable global incidence/prevalence is unavailable because “choroiditis” pools multiple disorders and coding practices. Overall uveitis estimates reported in the 2023 Greek study were incidence 20–50/100,000/year and prevalence 38–714/100,000, but these should not be entered as choroiditis-specific rates (kalogeropoulos2023thelargehellenic pages 1-2).

Birdshot is rare: approximately 0.6–1.5% of tertiary-center uveitis, 5–8% of posterior uveitis, and an estimated 0.1–0.6/100,000 population prevalence. It predominantly affects middle-aged people of European ancestry and has no consistent sex predominance (bousquet2022birdshotchorioretinopathya pages 1-2). Infectious subtype frequencies vary strongly with geography, sanitation, pathogen prevalence, migration, and immune status.

10. Diagnostics

Core clinical approach

Confirm intraocular inflammation by dilated slit-lamp and fundus examination.
Localize primary pathology using color/wide-field photography, OCT with enhanced-depth choroidal imaging, fluorescein angiography, indocyanine-green angiography, fundus autofluorescence, and OCT angiography. Multimodal imaging is now a real-world standard for lesion activity, macular edema, vasculitis, atrophy, and CNV (bousquet2022birdshotchorioretinopathya pages 14-15, paezescamilla2023challengesinposterior pages 1-2, miyagaki2024oculartoxoplasmosisadvances pages 14-15).
Use targeted rather than indiscriminate laboratory testing: syphilis serology; TB IGRA/TST and thoracic imaging where relevant; toxoplasma serology with ocular-fluid PCR or intraocular antibody testing in atypical cases; CBC/chemistry; and directed studies for sarcoidosis, HIV, or systemic autoimmunity.
Consider aqueous/vitreous PCR, cytology, flow cytometry, cytokine analysis, or biopsy when infection or lymphoma remains plausible.

Subtype-supportive tests

Birdshot: HLA-A29 testing, ICG angiography, fluorescein angiography, OCT, autofluorescence, visual fields, and electroretinography. HLA-A29 supports classification but is not a standalone diagnostic test (bousquet2022birdshotchorioretinopathya pages 14-15, bousquet2022birdshotchorioretinopathya pages 1-2).
Toxoplasmosis: classic focal necrotizing retinitis adjacent to a pigmented scar may be diagnosed clinically; multimodal imaging and laboratory confirmation are more important in atypical or immunocompromised disease (miyagaki2024oculartoxoplasmosisadvances pages 14-15, sittivarakul2024clinicalcharacteristicsvisual pages 2-4).
Tubercular posterior uveitis: characteristic lesions/vasculitis plus evidence of TB infection and exclusion of alternatives; ocular-fluid microbiology is often negative. The phase-4 trial used TST/IGRA, CBC, ESR, HIV and VDRL testing, and contrast-enhanced chest CT or radiography (NCT06613919 chunk 1).

Differential diagnosis

Infectious retinitis/choroiditis, white-dot syndromes, sarcoidosis, VKH, Behçet disease, posterior scleritis, retinal vasculitis, central serous chorioretinopathy, age-related or myopic CNV, intraocular lymphoma, leukemia, metastatic disease, inherited retinal degeneration, and drug toxicity must be distinguished before immunosuppression. Expert analysis emphasizes that overlapping phenotypes and masqueraders make history, medication review, imaging, and sometimes genetic or tissue testing essential (paezescamilla2023challengesinposterior pages 1-2).

No asymptomatic population screening or newborn screening program exists for choroiditis. Genetic testing is limited mainly to HLA-A29 as a diagnostic adjunct in suspected birdshot; WGS/WES and broad panels are not standard.

11. Outcome and prognosis

Choroiditis rarely affects life expectancy directly; survival statistics are not meaningful for the umbrella diagnosis. Morbidity is predominantly visual. Important complications are macular edema, chorioretinal atrophy/scarring, retinal vasculitis/occlusion, CNV, epiretinal membrane, cataract, glaucoma/ocular hypertension, retinal detachment, and treatment toxicity.

In the Thai toxoplasmosis cohort, 21% of affected eyes had final VA ≤20/200. Severe permanent loss occurred in 17% of immunocompetent and 50% of immunocompromised patients; macular scarring accounted for 24.7% of vision loss. Ocular hypertension occurred in 20.6%, epiretinal membrane in 12.6%, and cataract in 6.2%. Poor 6-month vision was predicted by immunocompromise (aOR 4.9), macular lesions (aOR 5.4), and initial VA ≤20/200 (aOR 9.1) (sittivarakul2024clinicalcharacteristicsvisual pages 1-2, sittivarakul2024clinicalcharacteristicsvisual pages 13-14).

A birdshot trial record cites legal blindness in 14% at five years and macular edema in 80%, but these historical estimates should be interpreted cautiously because they derive from older referred cohorts (NCT00508040 chunk 1). Early control, lesion location, baseline acuity, immunocompetence, recurrence, and development of macular edema/CNV are major prognostic determinants.

12. Treatment

Treatment must follow etiology; systemic corticosteroids must not be given as unopposed therapy until important infections have been excluded.

Infectious disease

Toxoplasmosis: commonly TMP–sulfamethoxazole, or pyrimethamine plus sulfadiazine and folinic acid; alternatives include clindamycin, azithromycin, atovaquone, and intravitreal clindamycin in selected cases. Corticosteroid is adjunctive only after effective antiparasitic therapy in vision-threatening inflammation. In the 2024 Thai cohort, 85% received oral TMP–sulfamethoxazole monotherapy (sittivarakul2024clinicalcharacteristicsvisual pages 1-2).
Tuberculosis: multidrug anti-tuberculosis treatment, frequently with adjunctive corticosteroid or immunomodulation after antimicrobial coverage. NCT06613919 compared six versus nine months (NCT06613919 chunk 1).
Syphilis: intravenous aqueous penicillin G according to neurosyphilis/ocular-syphilis protocols.
Herpetic disease: systemic acyclovir/valacyclovir or appropriate antiviral, with intravitreal therapy for severe necrotizing retinitis.
Fungal disease: systemic and/or intravitreal antifungal treatment plus source control.

Noninfectious disease

Corticosteroids—local, periocular, intravitreal, or systemic—provide rapid induction but are unsuitable as long-term monotherapy in chronic disease.
Steroid-sparing agents include methotrexate, mycophenolate mofetil, azathioprine, cyclosporine/tacrolimus, and other conventional immunomodulators.
Biologics, especially anti-TNF agents such as adalimumab or infliximab, are used for refractory noninfectious posterior uveitis; subtype and systemic comorbidity guide selection. Current cytokine-targeted therapies fail in an estimated 30–50% of heterogeneous uveitis patients, motivating chemokine-directed research (lin2024aqueousmacrophagescontribute pages 1-2).
Inflammatory CNV: intravitreal anti-VEGF, generally combined with control of underlying inflammation.
Surgery treats complications—cataract extraction when inflammation is controlled, vitrectomy for nonclearing opacity/traction or diagnostic sampling, and retinal-detachment repair.

Suggested NCIT intervention concepts include Corticosteroid Therapy, Immunosuppressive Therapy, Methotrexate, Mycophenolate Mofetil, Cyclosporine, Adalimumab, Infliximab, Interferon Alfa-2a, Anti-infective Therapy, Anti-VEGF Therapy, Intravitreal Injection, Vitrectomy, and Cataract Surgery; current NCIT codes should be validated at ingestion.

Trials and experimental applications

NCT00508040/BIRDFERON: completed randomized phase 2, 58 participants, interferon alfa-2a versus prednisone for HLA-A29-positive birdshot with macular edema; OCT central thickness was the primary endpoint (NCT00508040 chunk 1).
NCT01449877/ISROT: completed randomized triple-masked phase 3, 141 participants. After 45 days of acute TMP–sulfamethoxazole, prophylaxis every other day for 311 days was compared with placebo, with recurrence follow-up planned through ten years (NCT01449877 chunk 1).
NCT06613919: completed randomized phase 4 noninferiority study, 58 participants, comparing six and nine months of anti-TB therapy; endpoint was nonrecurrence one year after treatment (NCT06613919 chunk 1).

No approved gene, RNA, stem-cell, or CRISPR therapy exists for choroiditis. EV biomarker panels and CCL2/CXCL10-directed strategies remain investigational (lin2024aqueousmacrophagescontribute pages 1-2, wu2023comprehensiveprofilingof pages 1-2).

13. Prevention

Primary prevention: food and water hygiene, adequate cooking of meat, hand hygiene after soil/raw-meat exposure, prevention and treatment of maternal infection, TB control and contact management, HIV prevention/treatment, vaccination against relevant preventable systemic infections, and avoidance of unnecessary immunosuppression. There is no vaccine preventing all choroiditis and no licensed human toxoplasma vaccine.

Secondary prevention: rapid ophthalmic assessment for new floaters, photopsia, scotoma, or reduced vision; early etiologic testing and multimodal imaging; surveillance of the fellow eye and of high-risk immunocompromised patients.

Tertiary prevention: maintain inflammatory remission, monitor OCT/angiography and visual fields, minimize corticosteroid toxicity, promptly treat CNV and macular edema, and provide low-vision rehabilitation. TMP–sulfamethoxazole prophylaxis after recurrent toxoplasma retinochoroiditis is supported by randomized investigation, but it is subtype- and patient-specific rather than universal prophylaxis (NCT01449877 chunk 1).

Pregnancy and toxoplasmosis recurrence data are inconsistent: reported estimates range from lower recurrence during pregnancy (IRR 0.54–0.75) to a 7.4-fold increase in another population. This precludes a single universal risk estimate and supports specialist monitoring (miyagaki2024oculartoxoplasmosisadvances pages 14-15).

14. Other species and natural disease

T. gondii naturally infects many warm-blooded vertebrates; felids are definitive hosts and numerous mammals and birds are intermediate hosts. Ocular toxoplasmosis occurs naturally in companion and production animals, although species-specific lesion patterns and clinical importance vary. Equine recurrent uveitis, canine/feline uveitis, and infectious chorioretinitis are important comparative conditions but should not be treated as exact equivalents of human immune-mediated choroiditis.

Suggested taxa include Homo sapiens (NCBI Taxon 9606), Mus musculus (10090), Rattus norvegicus (10116), Canis lupus familiaris (9615), Felis catus (9685), and Toxoplasma gondii (5811). No breed-specific VBO association, orthologous monogenic disease, or zoonotic transmission from human choroiditis itself is established. Zoonotic relevance pertains to the causal pathogen, particularly T. gondii, not to ocular inflammation as a transmissible phenotype.

15. Model organisms

Experimental autoimmune uveitis (EAU): mice or rats immunized with retinal antigens such as interphotoreceptor retinoid-binding protein, usually with adjuvant, develop T-cell-driven retinal/choroidal inflammation. It is useful for immune recruitment, Th1/Th17 biology, blood–retinal barrier failure, and therapeutic screening, but does not reproduce the full etiologic or chronic heterogeneity of human choroiditis.
Unprimed mycobacterial uveitis: the 2024 chemokine study injected killed M. tuberculosis H37Ra antigen intravitreally into C57BL/6J mice. This models acute innate ocular inflammation and chemokine recruitment, not viable tubercular choroiditis (lin2024aqueousmacrophagescontribute pages 1-2).
Ocular toxoplasmosis: mouse infection models and retinal/RPE cell culture systems permit analysis of parasite invasion, cyst persistence, inflammation, and strain effects; differences in ocular anatomy, immunity, and parasite strains limit direct clinical translation.
VKH/birdshot: antigen-induced or humanized HLA models probe melanocyte/retinal antigen responses, but no model fully reproduces HLA-A29-restricted human birdshot.
In vitro systems: primary RPE, retinal organoids, choroidal endothelial cells, macrophage/T-cell coculture, and iPSC-derived ocular cells can dissect cell-specific injury and drug response. They lack complete vascular, neural, and systemic immunity.

Model resources include MGI, IMSR, MMRRC, RGD, ZFIN, Cellosaurus, GEO, and CELLxGENE. Animal-model findings should be labeled experimental and not used as direct evidence of human treatment efficacy.

Evidence limitations and knowledge-base recommendations

Encode choroiditis as a parent anatomic inflammatory concept, with infectious, immune-mediated, and masquerade children.
Do not attach birdshot HLA findings, toxoplasma recurrence, or TB treatment directly to every choroiditis case.
Mark HLA-A29/ERAP findings as susceptibility associations, not ACMG-pathogenic Mendelian variants.
Treat EV proteomics and aqueous single-cell signatures as research-stage biomarkers/mechanisms, not validated diagnostic tests.
Epidemiologic values are mostly uveitis-wide or subtype-specific; a defensible global prevalence or incidence for undifferentiated choroiditis is unavailable.
Retrieved records supplied DOI URLs consistently, but PMIDs were not available for most cited 2023–2024 articles; PMIDs should be resolved through PubMed during database ingestion rather than inferred.

References

(paezescamilla2023challengesinposterior pages 1-2): Manuel Paez-Escamilla, Sonny Caplash, Gagan Kalra, Jamie Odden, Danielle Price, Oscar C. Marroquin, Stephen Koscumb, Patrick Commiskey, Chad Indermill, Jerome Finkelstein, Anna G. Gushchin, Andreea Coca, Thomas R. Friberg, Andrew W. Eller, Denise S. Gallagher, Jean C. Harwick, Evan L. Waxman, Jay Chhablani, Gabrielle Bonhomme, Colin Prensky, Alexander J. Anetakis, Joseph N. Martel, Erika Massicotte, Raphaelle Ores, Jean-Francois Girmens, Thomas M Pearce, Jose-Alain Sahel, Kunal Dansingani, Mark Westcott, and Marie-Helene Errera. Challenges in posterior uveitis—tips and tricks for the retina specialist. Journal of Ophthalmic Inflammation and Infection, Aug 2023. URL: https://doi.org/10.1186/s12348-023-00342-5, doi:10.1186/s12348-023-00342-5. This article has 20 citations and is from a peer-reviewed journal.
(kalogeropoulos2023thelargehellenic pages 1-2): Dimitrios Kalogeropoulos, Ioannis Asproudis, Maria Stefaniotou, Marilita M. Moschos, Vassilios P. Kozobolis, Paraskevi V. Voulgari, Andreas Katsanos, Constantina Gartzonika, and Chris Kalogeropoulos. The large hellenic study of uveitis: epidemiology, etiologic factors and classification. International Ophthalmology, 43:3633-3650, Jul 2023. URL: https://doi.org/10.1007/s10792-023-02772-5, doi:10.1007/s10792-023-02772-5. This article has 43 citations and is from a peer-reviewed journal.
(bousquet2022birdshotchorioretinopathya pages 1-2): Elodie Bousquet, Pierre Duraffour, Louis Debillon, Swathi Somisetty, Dominique Monnet, and Antoine P. Brézin. Birdshot chorioretinopathy: a review. Journal of Clinical Medicine, 11:4772, Aug 2022. URL: https://doi.org/10.3390/jcm11164772, doi:10.3390/jcm11164772. This article has 45 citations.
(gelfman2021erap1erap2and pages 1-2): Sahar Gelfman, Dominique Monnet, Ann J. Ligocki, Thierry Tabary, Arden Moscati, Xiaodong Bai, Jan Freudenberg, Blerta Cooper, Jack A. Kosmicki, Sarah Wolf, Manuel A. R. Ferreira, John Overton, Jonathan Weyne, Eli A. Stahl, Aris Baras, Carmelo Romano, Jacques H. M. Cohen, Giovanni Coppola, and Antoine Brézin. Erap1, erap2, and two copies of hla-aw19 alleles increase the risk for birdshot chorioretinopathy in hla-a29 carriers. Nov 2021. URL: https://doi.org/10.1167/iovs.62.14.3, doi:10.1167/iovs.62.14.3. This article has 30 citations.
(loeliger2024theimpactof pages 1-2): Jordan Loeliger, Romain Lhotte, Sahar Gelfman, Eli A. Stahl, Dominique Monnet, Valentin Clichet, Linda Imikirene, Souhila Kecili, Jean-Luc Taupin, Thierry Tabary, Jacques H. M. Cohen, and Antoine P. Brézin. The impact of hla-a29 homozygosity and of the second hla-a allele on susceptibility and severity of birdshot chorioretinitis. Investigative Ophthalmology & Visual Science, 65:47, Nov 2024. URL: https://doi.org/10.1167/iovs.65.13.47, doi:10.1167/iovs.65.13.47. This article has 2 citations and is from a domain leading peer-reviewed journal.
(sittivarakul2024clinicalcharacteristicsvisual pages 1-2): Wantanee Sittivarakul, Wanitcha Treerutpun, and Usanee Tungsattayathitthan. Clinical characteristics, visual acuity outcomes, and factors associated with loss of vision among patients with active ocular toxoplasmosis: a retrospective study in a thai tertiary center. PLOS Neglected Tropical Diseases, 18:e0012232, Jun 2024. URL: https://doi.org/10.1371/journal.pntd.0012232, doi:10.1371/journal.pntd.0012232. This article has 7 citations and is from a domain leading peer-reviewed journal.
(sittivarakul2024clinicalcharacteristicsvisual pages 13-14): Wantanee Sittivarakul, Wanitcha Treerutpun, and Usanee Tungsattayathitthan. Clinical characteristics, visual acuity outcomes, and factors associated with loss of vision among patients with active ocular toxoplasmosis: a retrospective study in a thai tertiary center. PLOS Neglected Tropical Diseases, 18:e0012232, Jun 2024. URL: https://doi.org/10.1371/journal.pntd.0012232, doi:10.1371/journal.pntd.0012232. This article has 7 citations and is from a domain leading peer-reviewed journal.
(miyagaki2024oculartoxoplasmosisadvances pages 14-15): Miki Miyagaki, Yuan Zong, Mingming Yang, Jing Zhang, Yaru Zou, Kyoko Ohno-Matsui, and Koju Kamoi. Ocular toxoplasmosis: advances in toxoplasma gondii biology, clinical manifestations, diagnostics, and therapy. Pathogens, 13:898, Oct 2024. URL: https://doi.org/10.3390/pathogens13100898, doi:10.3390/pathogens13100898. This article has 35 citations.
(lin2024aqueousmacrophagescontribute pages 1-2): Joseph B. Lin, Kathryn L. Pepple, Christian Concepcion, Yulia Korshunova, Michael A. Paley, Grace L. Paley, Jennifer Laurent, Rajendra S. Apte, and Lynn M. Hassman. Aqueous macrophages contribute to conserved ccl2 and cxcl10 gradients in uveitis. Ophthalmology Science, 4:100453, Jul 2024. URL: https://doi.org/10.1016/j.xops.2023.100453, doi:10.1016/j.xops.2023.100453. This article has 15 citations.
(wu2023comprehensiveprofilingof pages 1-2): Lingzi Wu, Lei Zhou, Jinying An, Xianfeng Shao, Hui Zhang, Chunxi Wang, Guixia Zhao, Shuang Chen, Xuexue Cui, Xinyi Zhang, Fuhua Yang, Xiaorong Li, and Xiaomin Zhang. Comprehensive profiling of extracellular vesicles in uveitis and scleritis enables biomarker discovery and mechanism exploration. Journal of Translational Medicine, Jun 2023. URL: https://doi.org/10.1186/s12967-023-04228-x, doi:10.1186/s12967-023-04228-x. This article has 18 citations and is from a peer-reviewed journal.
(NCT00508040 chunk 1): Evaluation of Birdshot Retine Choroidopathy Treatment by Either Steroid or Interferon alpha2a. Assistance Publique - Hôpitaux de Paris. 2007. ClinicalTrials.gov Identifier: NCT00508040
(NCT01449877 chunk 1): Joao Paulo Felix. Influence of Trimethoprim-Sulfamethoxazole for the Recurrence of Ocular Toxoplasmosis. University of Campinas, Brazil. 2011. ClinicalTrials.gov Identifier: NCT01449877
(NCT06613919 chunk 1): HERF. Six-months Versus Nine-months ATT for Ocular TB. L.V. Prasad Eye Institute. 2020. ClinicalTrials.gov Identifier: NCT06613919
(sittivarakul2024clinicalcharacteristicsvisual pages 2-4): Wantanee Sittivarakul, Wanitcha Treerutpun, and Usanee Tungsattayathitthan. Clinical characteristics, visual acuity outcomes, and factors associated with loss of vision among patients with active ocular toxoplasmosis: a retrospective study in a thai tertiary center. PLOS Neglected Tropical Diseases, 18:e0012232, Jun 2024. URL: https://doi.org/10.1371/journal.pntd.0012232, doi:10.1371/journal.pntd.0012232. This article has 7 citations and is from a domain leading peer-reviewed journal.
(bousquet2022birdshotchorioretinopathya pages 14-15): Elodie Bousquet, Pierre Duraffour, Louis Debillon, Swathi Somisetty, Dominique Monnet, and Antoine P. Brézin. Birdshot chorioretinopathy: a review. Journal of Clinical Medicine, 11:4772, Aug 2022. URL: https://doi.org/10.3390/jcm11164772, doi:10.3390/jcm11164772. This article has 45 citations.

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Subtypes

Pathophysiology

Histopathology

Pathograph

Phenotypes

Genetic Associations

Medical Actions

Environmental Factors

Differential Diagnoses

Clinical Trials

Source YAML

References & Deep Research

References

Deep Research

Disease Characteristics Research Template

Target Disease

Research Objectives

1. Disease Information

2. Etiology

3. Phenotypes

4. Genetic/Molecular Information

5. Environmental Information

6. Mechanism / Pathophysiology

7. Anatomical Structures Affected

8. Temporal Development

9. Inheritance and Population

10. Diagnostics

11. Outcome/Prognosis

12. Treatment

13. Prevention

14. Other Species / Natural Disease

15. Model Organisms

Citation Requirements

Output Format

Choroiditis: disease-characteristics research report

Executive interpretation

1. Disease information

Definition and classification

2. Etiology

Causal factors

Risk and protective factors

Gene–environment interaction

3. Phenotypes

4. Genetic and molecular information

Birdshot susceptibility architecture

5. Environmental, lifestyle, and infectious information

6. Mechanism and pathophysiology

Causal chains

Recent human molecular profiling

7. Anatomical structures affected

8. Temporal development

9. Inheritance and population

10. Diagnostics

Core clinical approach

Subtype-supportive tests

Differential diagnosis

11. Outcome and prognosis

12. Treatment

Infectious disease

Noninfectious disease

Trials and experimental applications

13. Prevention

14. Other species and natural disease

15. Model organisms

Evidence limitations and knowledge-base recommendations

Artifacts