Choroidal Vasculitis and Indocyanine Green Angiography (ICGA)

– Definition and Importance of Choroidal Vasculitis:

  – Choroidal vasculitis is a hallmark of choroidal inflammation, often underdiagnosed without ICGA.

  – ICGA is the gold standard for diagnosing and monitoring choroidal vasculitis, providing precise visualization of choriocapillaris and stromal involvement.

  – Divided into two main types: choriocapillaritis (occlusive) and stromal choroidal vasculitis (leaky).

– Indocyanine Green Angiography (ICGA) Principles:

  – Utilizes indocyanine green (ICG) molecule, which fluoresces at ~830 nm, penetrating retinal pigment epithelium (RPE) for choroidal visualization.

  – ICG binds to blood proteins (98%), forming large complexes (60,000–80,000 Daltons), preventing leakage from retinal or large choroidal vessels but egressing physiologically from fenestrated choriocapillaris.

  – Key ICGA patterns:

    – Choriocapillaritis: Hypofluorescent areas indicating non-perfusion (dots to geographic areas).

    – Stromal choroiditis: Hyperfluorescent leaky vessels, fuzzy vessels, and late diffuse hyperfluorescence.

– Choroidal Anatomy and Blood Flow:

  – Choroid is the most vascularized ocular tissue with high blood flow per gram.

  – Arterial supply via ophthalmic artery → ciliary arteries → choriocapillaris (fenestrated endothelium).

  – Venous drainage through vortex veins (3–8 per eye, typically 4–5).

  – Choriocapillaris is a lobular mesh with central arteriolar feeders and peripheral draining venules.

– Choriocapillaritis (Primary and Secondary):

  – Multiple Evanescent White Dot Syndrome (MEWDS):

    – Mildest form, affects end-capillary choriocapillaris.

    – ICGA: Small, non-confluent hypofluorescent dots, more visible in late phases.

    – Usually unilateral, self-resolving, no scarring.

    – OCT-A often normal due to insensitivity to low-flow vessels.

  – Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE):

    – Involves larger choriocapillaris vessels, causing confluent hypofluorescent areas on ICGA.

    – Bilateral, may require corticosteroids for macular involvement.

    – Associated with cerebral vasculitis in some cases.

  – Idiopathic Multifocal Choroiditis (MFC):

    – Recurrent, bilateral, leads to chorioretinal scars and choroidal neovascularization (CNV) in ~30% of cases.

    – ICGA findings similar to MEWDS initially but progressive with scarring.

    – Requires aggressive immunosuppression.

  – Serpiginous Choroiditis (SC):

    – Most severe, involves larger choriocapillaris/pre-capillary arterioles, causing creeping hypofluorescent patterns.

    – Idiopathic or tuberculosis-related (requires IGRA testing).

    – Needs dual/triple immunosuppression to halt progression.

  – Secondary Causes:

    – Acute Syphilitic Posterior Placoid Chorioretinitis (ASPPC): Immunologic reaction causing choriocapillaris non-perfusion, treatable with antibiotics and corticosteroids.

    – Tuberculosis-related SC: Extensive non-perfusion, responsive to anti-tuberculous therapy and immunosuppression.

– Stromal Choroidal Vasculitis:

  – Characterized by hyperfluorescent signs on ICGA:

    – Early hyperfluorescent vessels.

    – Fuzzy/indistinct vessels in intermediate phase.

    – Late diffuse choroidal hyperfluorescence, often obscuring hypofluorescent dark dots (HDDs).

  – Primary Conditions:

    – Vogt-Koyanagi-Harada (VKH) Disease:

      – Autoimmune stromal inflammation, evenly distributed HDDs on ICGA.

      – Additional signs: disc hyperfluorescence, pinpoint leaks causing serous retinal detachments.

      – Severe, requires high-dose corticosteroids.

    – Sympathetic Ophthalmia (SO): Similar to VKH but triggered by ocular trauma/surgery, less severe.

    – HLA-A29 Birdshot Retinochoroiditis (BRC):

      – Involves both retina and choroid, less severe than VKH.

      – ICGA shows HDDs, minimal early vessel hyperfluorescence, and fading HDDs in late phases.

  – Secondary Conditions:

    – Ocular sarcoidosis: Variable severity, uneven HDDs, may include macroaneurysms.

    – Systemic lupus erythematosus (SLE): Occlusive vasculitis of large choroidal vessels, Amalric’s triangular sign on ICGA.

    – Giant Cell Arteritis (GCA):

      – Occlusion of posterior ciliary arteries (PCA), causing triangular choroidal non-perfusion (Amalric’s sign).

      – Associated with anterior ischemic optic neuropathy (AION).

      – Ophthalmic emergency requiring immediate corticosteroids.

    – Scleritis-related: Choroidal vasculitis in 57% of posterior scleritis cases.

– ICGA Semiology:

  – Normal ICGA:

    – Intermediate phase (8–11 min): Vessels fluorescent (dye intravascular).

    – Late phase (>20 min): Vessels dark (dye in stroma), faint background fluorescence from physiological ICG leakage.

  – Pathologic Signs:

    – Choriocapillaritis: Hypofluorescent dots (MEWDS) or geographic areas (APMPPE, MFC, SC).

    – Stromal vasculitis: Fuzzy vessels, hyperfluorescent vessels, late diffuse hyperfluorescence, HDDs (space-occupying lesions blocking ICG diffusion).

  – HDDs in stromal choroiditis:

    – Evenly distributed in VKH/BRC (primary).

    – Uneven, irregular in sarcoidosis (secondary).

– Complementary Imaging Modalities:  

– Fluorescein Angiography (FA):

    – Limited to retinal vasculature, glimpses choriocapillaris in first 60 seconds.

    – Useful for APMPPE (early hypofluorescence) and retinal vasculitis in BRC.

  

– Spectral Domain OCT (SD-OCT) and Enhanced Depth Imaging (EDI-OCT):

    – Detects outer retinal damage in choriocapillaritis (photoreceptor loss).

    – EDI-OCT visualizes choroidal thickening (VKH) and granulomas (sarcoidosis).

 

 – OCT Angiography (OCT-A):

    – Non-invasive, detects flow in larger choriocapillaris vessels (APMPPE, MFC, SC).

    – Limited for end-capillary flow (MEWDS) and stromal choroiditis.

  

– Fundus Autofluorescence (FAF):

    – Hyperautofluorescence in choriocapillaritis due to RPE/photoreceptor damage.

    – Less useful in early stromal choroiditis.

– Therapeutic Implications:

  – Choriocapillaritis:

    – MEWDS: Often no treatment needed.

    – APMPPE: Corticosteroids for severe cases.

    – MFC/SC: Aggressive immunosuppression to prevent scarring/CNV.

 

 – Stromal Choroiditis:

    – VKH/SO: High-dose corticosteroids, often intravenous.

    – BRC: Immunosuppression tailored to severity.

    – GCA: Immediate high-dose corticosteroids to prevent bilateral vision loss.

  – Secondary causes (e.g., TB, syphilis): Treat underlying infection alongside inflammation.

– Historical Context and Misnomers:

  – Terms like “white dot syndromes” are outdated, grouping unrelated diseases by fundus appearance.

  – ICGA clarified pathophysiology (e.g., APMPPE as choriocapillaritis, not RPE disease).

  – Deutman’s term “Acute Multifocal Ischaemic Choriocapillaritis (AMIC)” for APMPPE was prescient, later validated by ICGA.

– Diagnostic Pitfalls:

  – Overreliance on OCT-A: Misses end-capillary non-perfusion (e.g., MEWDS).

  – Neglecting ICGA: Leads to missed choroidal vasculitis, especially in stromal choroiditis.

  – Misinterpreting FA: Limited to retinal/choriocapillaris glimpse, inadequate for stromal assessment.

Citation

Papasawvas, I., Tucker, W. R., Mantovani, A., Fabozzi, L., & Herbort, C. P. Jr. (2024). Choroidal vasculitis as a biomarker of inflammation of the choroid. Indocyanine Green Angiography (ICGA) spearheading for diagnosis and follow-up, an imaging tutorial. *Journal of Ophthalmic Inflammation and Infection*, 14(63). https://doi.org/10.1186/s12348-024-00442-w