Glaucomatous Optic Neuropathies

name: Glaucomatous Optic Neuropathies
display_name: Glaucomatous Optic Neuropathies
creation_date: "2026-06-18T00:00:00Z"
description: >-
  Glaucomatous optic neuropathies are disorders whose pathophysiology converges
  on progressive retinal ganglion cell apoptosis, optic nerve degeneration, and
  visual field loss. Upstream causes of outflow dysfunction and intraocular
  pressure elevation differ across members, but the conserved endpoint is the
  glaucomatous optic neuropathy module.
grouping_basis:
- SHARED_MECHANISM
- SHARED_PHENOTYPE
grouping_rationale: >-
  Grouped on the shared glaucoma_optic_neuropathy module: each member includes
  retinal ganglion cell apoptosis and progressive optic nerve degeneration as
  the final common pathway. The broad Glaucoma entry is kept separate from
  Juvenile Open Angle Glaucoma because the latter is an early-onset, genetically
  enriched open-angle subset with explicit trabecular meshwork outflow
  dysfunction and MYOC/CYP1B1 involvement.
membership_criteria:
- description: >-
    A disorder belongs to this grouping if and only if it conforms to the
    glaucomatous optic neuropathy module, linking aqueous outflow or pressure
    stress to retinal ganglion cell apoptosis and optic nerve degeneration.
  criteria_semantics: NECESSARY_AND_SUFFICIENT
  logic:
    criterion_predicate: CONFORMS_TO_MODULE
    module: glaucoma_optic_neuropathy#Retinal Ganglion Cell Apoptosis
    description: >-
      Conforms to the glaucomatous optic neuropathy module at the retinal
      ganglion cell apoptosis node.
members:
- member: Glaucoma
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Broad glaucoma mechanism entry covering the common optic neuropathy
      endpoint, with visual field defect, optic atrophy, abnormal intraocular
      pressure, and visual impairment represented without restricting the entry
      to one genetic or angle-based subtype.
    phenotype_term:
      preferred_term: Visual field defect
      term:
        id: HP:0001123
        label: Visual field defect
- member: Juvenile Open Angle Glaucoma
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Early-onset open-angle glaucoma with grossly open drainage angle, high
      intraocular pressure, and genetically enriched trabecular meshwork
      dysfunction, especially MYOC and CYP1B1-associated disease.
    gene:
      preferred_term: MYOC
      term:
        id: hgnc:7610
        label: MYOC
    biological_processes:
    - preferred_term: trabecular meshwork development
      term:
        id: GO:0002930
        label: trabecular meshwork development
      modifier: ABNORMAL
- member: OPTN-related Open Angle Glaucoma
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      The one member that reaches the shared retinal ganglion cell apoptosis
      node WITHOUT the module's trabecular-outflow and elevated-pressure arm.
      Adult-onset autosomal dominant open-angle glaucoma caused by OPTN
      missense variants (classically E50K), presenting as normal-tension
      glaucoma: mutant optineurin, an autophagy receptor, binds TBK1
      abnormally and blocks autophagic-lysosomal flux and mitophagy in the
      ganglion cell itself, so the lesion is cell-autonomous and proteostatic
      rather than located in the aqueous drainage apparatus.
    gene:
      preferred_term: OPTN
      term:
        id: hgnc:17142
        label: OPTN
    module: glaucoma_optic_neuropathy#Retinal Ganglion Cell Apoptosis
    biological_processes:
    - preferred_term: macroautophagy
      term:
        id: GO:0016236
        label: macroautophagy
      modifier: DECREASED
notes: >-
  Disease-like phenotype grouping over entries already conforming to the
  glaucoma final-common-pathway module.

  Note that the grouping's NECESSARY_AND_SUFFICIENT criterion is deliberately
  written against the retinal ganglion cell apoptosis node, not against the
  module's outflow or intraocular-pressure nodes. OPTN-related Open Angle
  Glaucoma is why that matters: it is a genuine glaucomatous optic neuropathy
  that never passes through elevated intraocular pressure, so a criterion
  anchored on the pressure arm would have excluded it.