Papillophlebitis

– Definition and Epidemiology:

  – Papillophlebitis is a rare condition resembling central retinal vein occlusion (CRVO) in young, healthy adults (mean age ~25 years).

  – Characterized by optic disc swelling, retinal venous congestion, and hemorrhages, often with an inflammatory component.

– Clinical Presentation:

  – Common symptoms: Decreased vision (most frequent), floaters, flashes, eye pain, or blurred vision.

  – Mean symptom onset to presentation: ~17 days.

  – Ocular findings: Diffuse vascular leakage, optic disc leakage, retinal hemorrhages, and cotton-wool spots.

  – Cystoid macular edema (CME) in ~57% (4/7 patients), associated with worse prognosis.

  – Visual acuity (VA): Presenting logMAR ~0.2, final ~0.06 (generally favorable).

– Etiology and Systemic Associations:

  – Often idiopathic, considered a diagnosis of exclusion.

  – Systemic workup may reveal:

    – Thrombophilia: E.g., homozygous MTHFR C677T mutation (hyperhomocysteinemia, treated with folic acid).

    – Inflammatory diseases: E.g., Behçet disease (orogenital ulcers, skin rash, arthralgias).

    – Other reported associations: Polyarteritis nodosa, Guillain-Barré syndrome, Buerger’s disease, psoriatic arthritis, ulcerative colitis, Eales’ disease.

  – Family history of vascular occlusive events in ~43% (3/7 patients), but thrombophilia uncommon in most.

– Imaging and Diagnosis:

  – Fundus Fluorescein Angiography (FFA):

    – Shows hyperfluorescence of retinal veins, progressing to late leakage, with optic disc and macular leakage.

    – Detects capillary non-perfusion (late complication in some).

  – Spectral-Domain OCT (SD-OCT):

    – Identifies CME (intraretinal ± subretinal fluid).

    – Monitors CME resolution (absence of fluid).

  – Color Fundus Photography:

    – Documents optic disc swelling, vascular tortuosity, hemorrhages, and cotton-wool spots.

  – Visual Field Testing:

    – May show cecocentral scotoma in severe cases.

– Management and Outcomes:

  – Without CME (3/7 patients):

    – Benign course: 1 resolved spontaneously, 2 resolved with short-course oral prednisone.

    – Rapid recovery (~7–12 months).

  – With CME (4/7 patients):

    – Initial treatment: Systemic corticosteroids + intravitreal anti-VEGF (bevacizumab).

      – 1 patient: CME resolved after 3 injections, prednisone tapered, folic acid for MTHFR mutation; remission at 10 years.

      – 3 patients: Refractory CME despite anti-VEGF, steroid-dependent.

    – Escalation:

      – Steroid-sparing agents (methotrexate/azathioprine) added.

      – Adalimumab (TNF-α inhibitor) introduced at 6–8 months for persistent CME/vascular leakage.

      – CME resolution at 3–32 months post-adalimumab; improved papillophlebitis (less hemorrhages, vascular engorgement).

    – Complications:

      – Peripheral capillary non-perfusion in 2/4 patients (12–14 months post-diagnosis), requiring panretinal photocoagulation (PRP).

      – 1 patient developed neovascularization elsewhere (NVE), needing additional PRP.

  – Visual Outcome:

    – All patients achieved VA ≥6/12 at last follow-up (mean 40.4 months).

    – Guarded prognosis in some reports (up to 40% with VA ≤20/200, risk of neovascular glaucoma, vitreous hemorrhage).

– Pathophysiology:

  – Multifactorial: Inflammatory (TNF-α mediated) and ischemic components.

  – TNF-α activates vascular endothelium, increasing VEGF/IL-6, enhancing vascular permeability.

  – CME severity may reflect underlying ischemia/inflammation (similar to CRVO).

  – Systemic immune-inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR) elevated in RVO, supporting inflammatory etiology.

– Complications:

  – Common: CME, peripheral non-perfusion.

  – Rare: Neovascularization (disc, retina, iris), macular hole, neovascular glaucoma, vitreous hemorrhage.

  – Late-onset ischemia (after 6 months) in ~18% of cases, necessitating long-term monitoring.

– Key Management Principles:

  – Mild cases: Observation or short-course steroids.

  – CME: Systemic steroids + anti-VEGF; escalate to steroid-sparing agents (methotrexate/azathioprine) if refractory.

  – Recalcitrant cases: Add TNF-α inhibitors (adalimumab) for persistent CME/leakage.

  – Ischemia/NVE: PRP to prevent neovascular complications.

  – Systemic workup: Collaborate with hematology/rheumatology to identify thrombophilia or inflammatory diseases.

– Prognostic Factors:

  – Presence of CME: Predicts prolonged course, need for aggressive therapy.

  – Early control of inflammation/ischemia: Improves outcomes.

  – Periodic monitoring: Essential for late-onset ischemia (up to 50% of neovascular cases occur >6 months).

– Board-Relevant Pearls:

  – Papillophlebitis mimics CRVO but occurs in younger patients with inflammatory features.

  – FFA is critical for assessing vascular leakage and ischemia.

  – Adalimumab is a novel therapy for refractory cases, targeting TNF-α-driven inflammation.

  – Long-term follow-up is crucial due to risk of late ischemia/neovascularization.

  – Negative systemic workup is common, but MTHFR mutation and Behçet disease are notable associations.

Citation

Abdel Jalil, S., & Amer, R. (2024). The Spectrum of Papillophlebitis. *Ocular Immunology and Inflammation*, 32(10), 2515–2520. https://doi.org/10.1080/09273948.2024.2359622