Posterior Uveitis & Panuveitis
Ophthalmology · Uvea · lean revision notes
Posterior Uveitis & Panuveitis
Posterior uveitis (retina, choroid, vitreous) and panuveitis (all three uveal segments) are sight-threatening inflammations where the pattern of involvement points to the cause. NEET PG loves the classic "fundus picture + systemic association" linkage — toxoplasma, VKH, sympathetic ophthalmia, sarcoid and Behçet are the recurring favourites.
Anatomical classification (SUN working group)
The Standardisation of Uveitis Nomenclature (SUN) classifies uveitis by the primary site of inflammation, not by severity. This is the single most testable framework.
| Type | Primary site | Classic examples |
|---|---|---|
| Anterior uveitis | Iris ± ciliary body (iritis/iridocyclitis) | HLA-B27, JIA, Fuchs |
| Intermediate uveitis | Vitreous (pars plana = pars planitis) | Sarcoid, MS, Lyme |
| Posterior uveitis | Retina &/or choroid (retinitis, choroiditis, chorioretinitis) | Toxoplasma, CMV, syphilis |
| Panuveitis | All three (anterior + intermediate + posterior) | VKH, Behçet, sympathetic ophthalmia, sarcoid |
High-yield: SUN grades anterior chamber cells (the marker of activity) and flare (the marker of chronicity/protein leak) separately on a 0–4+ scale. Cells reflect active inflammation; flare alone does not warrant treatment escalation.
Course descriptors: acute (sudden, ≤3 months), recurrent (relapses with ≥3 months inactivity off treatment), chronic (relapse <3 months after stopping therapy). "Limited" = ≤3 months, "persistent" = >3 months.
General etiology & pathophysiology
Posterior uveitis is broadly infectious or non-infectious (immune-mediated) — distinguishing the two governs whether you give steroids with an anti-microbial or steroids/immunosuppression alone.
- Infectious: Toxoplasma (commonest infectious posterior uveitis worldwide), CMV (HIV/immunosuppressed), syphilis ("the great mimic"), TB, herpetic ARN, fungal/endogenous endophthalmitis.
- Non-infectious / autoimmune: VKH, sympathetic ophthalmia, Behçet, sarcoidosis, Birdshot chorioretinopathy, serpiginous choroiditis.
Immune-mediated disease is driven by a T-cell (Th1/Th17) response against ocular autoantigens — retinal S-antigen (arrestin), interphotoreceptor retinoid-binding protein (IRBP), tyrosinase (melanocyte antigen, central to VKH and sympathetic ophthalmia). Breakdown of the blood–retinal barrier allows leukocyte trafficking and granuloma formation in granulomatous types.
High-yield: Granulomatous uveitis (mutton-fat keratic precipitates, Koeppe/Busacca iris nodules, choroidal granulomas) → think VKH, sympathetic ophthalmia, sarcoid, TB, syphilis. Non-granulomatous (fine KPs) → HLA-B27, Behçet.
Toxoplasma chorioretinitis
The prototype necrotising retinochoroiditis. Caused by Toxoplasma gondii (cat = definitive host). Most ocular disease in India/developing world is post-natally acquired reactivation, though congenital disease classically gives bilateral macular scars.
Clinical features
- Unilateral painless floaters + blurring; new active lesion typically arises adjacent to an old pigmented chorioretinal scar (satellite lesion).
- "Headlight in the fog" appearance — a focal yellow-white retinitis lesion seen hazily through dense overlying vitritis. This is the signature exam phrase.
- Associated vasculitis (Kyrieleis arteriolitis = segmental periarterial plaques), papillitis.
Diagnosis
- Clinical (fundus appearance) is sufficient in classic cases.
- Serology (IgG/IgM) confirms exposure but does not prove activity; aqueous PCR and Goldmann–Witmer coefficient (intraocular vs serum antibody ratio) for atypical cases.
Management
High-yield: Classic triple/"triple therapy" = pyrimethamine + sulfadiazine + folinic acid (leucovorin), with systemic corticosteroid added 24–48 h after starting antimicrobials (never steroid alone — it worsens infection). Folinic acid prevents pyrimethamine marrow toxicity.
- Alternatives: clindamycin, co-trimoxazole (TMP-SMX) — widely used in India as monotherapy or with steroid. Intravitreal clindamycin + dexamethasone for refractory cases.
- Treat if: lesion threatens macula/optic nerve, dense vitritis, or immunocompromised host. Small peripheral lesions in the immunocompetent may be observed.
Vogt–Koyanagi–Harada (VKH) syndrome
A bilateral granulomatous panuveitis with extra-ocular features, from a T-cell autoimmune reaction against melanocyte antigens (tyrosinase). Strongly associated with HLA-DR4 / HLA-DRB1*04:05; commoner in pigmented races (Asians, Hispanics).
Phases & features
- Prodromal → flu-like illness, meningismus, tinnitus, CSF lymphocytic pleocytosis, dysacusis.
- Acute uveitic → bilateral serous (exudative) retinal detachments, disc hyperaemia, choroidal thickening.
- Convalescent → "sunset glow fundus" (depigmented orange-red choroid), perilimbal vitiligo = Sugiura sign, poliosis, alopecia, vitiligo.
- Chronic/recurrent → recurrent anterior granulomatous uveitis.
High-yield: Sunset glow fundus + bilateral exudative RD + auditory/CNS signs + integumentary changes = VKH. Sugiura sign (perilimbal vitiligo) is the earliest depigmentation sign.
Investigations
- FFA: multiple pinpoint leaks at RPE level → "starry sky" with subretinal pooling.
- ICG: hypofluorescent dark dots (choroidal granulomas).
- OCT: serous neurosensory detachment with septae.
- B-scan: diffuse choroidal thickening.
Management
- Early high-dose systemic corticosteroids (IV methylprednisolone pulse → oral taper over ≥6 months) prevent progression to sunset glow.
- Early steroid-sparing immunosuppression (mycophenolate, azathioprine, cyclosporine) reduces recurrence and improves long-term visual prognosis.
Sympathetic ophthalmia (SO)
A bilateral granulomatous panuveitis following penetrating trauma or intraocular surgery to one eye — the injured eye = "exciting eye", the fellow eye = "sympathising eye". A delayed (T-cell) hypersensitivity to exposed uveal/retinal antigens.
- Onset usually 2 weeks to 3 months post-injury (90% within 1 year; rarely decades later).
- Fundus shows Dalen–Fuchs nodules (yellow-white sub-RPE granulomas), mutton-fat KPs, disc oedema — histologically identical/similar to VKH but with trauma history and without choroidocapillaris sparing (SO classically spares the choriocapillaris; VKH does not — a fine exam distinction).
High-yield: Prophylactic enucleation of a blind, irreparably injured eye within 10–14 days of injury prevents SO. Once SO develops in the sympathising eye, do NOT enucleate the exciting eye if it retains useful vision (it may end up the better-seeing eye). Treat with aggressive systemic steroids + immunosuppression.
Mnemonic — VKH vs SO: both granulomatous, bilateral, Dalen–Fuchs nodules, treated the same. VKH has the "outside" features (skin/hair/ear/CNS); SO has the "inside" history (trauma/surgery).
Behçet disease (hypopyon uveitis & occlusive vasculitis)
A systemic vasculitis of all vessel sizes; ocular involvement is a major morbidity. Linked to HLA-B51; classic along the "Silk Route" (Turkey, Middle East, Japan). This is the most integrated/high-yield topic here.
Diagnostic criteria (ISG 1990)
Recurrent oral ulcers (≥3×/year) — mandatory — plus ≥2 of:
- Recurrent genital ulcers
- Eye lesions (anterior/posterior uveitis, retinal vasculitis)
- Skin lesions (erythema nodosum, pseudofolliculitis, acneiform nodules)
- Positive pathergy test (sterile pustule 24–48 h after needle prick).
Ocular features
- Relapsing, explosive, bilateral non-granulomatous panuveitis.
- Hypopyon that is mobile and shifts with head position, often without ciliary congestion ("cold hypopyon") — pathognomonic exam clue.
- Occlusive retinal vasculitis affecting both arteries and veins (most other uveitic vasculitides are venous) → ischaemia, neovascularisation, "ghost vessels"; leading cause of blindness.
High-yield: Behçet = HLA-B51, recurrent oral + genital ulcers, shifting hypopyon, occlusive retinal vasculitis, positive pathergy. The combination of arterial + venous occlusion distinguishes it.
Management
High-yield: Behçet uveitis responds poorly to steroids alone. First-line steroid-sparing agents are azathioprine and cyclosporine; biologics — infliximab/adalimumab (anti-TNF-α) and interferon-α — are now front-line for sight-threatening posterior involvement. Steroids control acute flares but do not alter long-term prognosis.
Sarcoid uveitis / panuveitis
Ocular sarcoidosis is a bilateral granulomatous uveitis; the eye is involved in ~25–50% of systemic sarcoid and may be the presenting feature.
Features (any segment — hence panuveitis)
- Anterior: mutton-fat KPs, Koeppe (pupillary margin) and Busacca (iris stroma) nodules, posterior synechiae.
- Intermediate: snowballs/"string of pearls" vitreous opacities.
- Posterior: periphlebitis with "candle-wax drippings" (taches de bougie) along veins, choroidal granulomas, optic nerve granuloma.
- Lacrimal gland enlargement, conjunctival granulomas.
High-yield: Heerfordt syndrome (uveoparotid fever) = uveitis + parotid enlargement + facial nerve palsy + fever. Löfgren syndrome = bilateral hilar lymphadenopathy + erythema nodosum + arthralgia (acute, good prognosis).
Investigations
- Serum ACE (raised; sensitivity limited), serum lysozyme, calcium (hypercalcaemia/hypercalciuria).
- Chest X-ray/HRCT — bilateral hilar lymphadenopathy.
- Conjunctival/biopsy → non-caseating granuloma (confirmatory).
- FFA, OCT for posterior activity.
- Management: corticosteroids first-line; methotrexate/anti-TNF if steroid-dependent.
Acute retinal necrosis (ARN) — a key infectious panuveitis
Fulminant herpetic (VZV > HSV) necrotising retinitis. Triad: (1) peripheral confluent full-thickness retinal necrosis, (2) occlusive arteritis, (3) prominent vitritis/anterior inflammation.
High-yield: ARN = peripheral necrosis spreading circumferentially + arteritis. High risk of rhegmatogenous retinal detachment (50–75%) as necrotic retina breaks down. Treat with IV aciclovir (then oral valaciclovir) ± intravitreal foscarnet/ganciclovir, plus steroid after antiviral cover and prophylactic laser barrage.
CMV retinitis (CD4 <50) contrasts: indolent, "pizza/cheese-and-tomato/brushfire" appearance, minimal vitritis — treat with ganciclovir/valganciclovir, intravitreal ganciclovir, and restore immunity (ART).
Diagnostic approach to posterior uveitis
A structured "name + tame + frame" workup:
1. History (trauma → SO; sexual/HIV → syphilis, CMV; travel/TB contact; oral/genital ulcers → Behçet; auditory/skin → VKH) → 2. Examine both eyes (granulomatous vs non-granulomatous, lesion pattern, vitritis density) → 3. Pattern recognition on fundus (satellite lesion, sunset glow, candle-wax drippings, shifting hypopyon) → 4. Targeted investigations (FFA/ICG/OCT + serology/PCR/aqueous tap + chest imaging + HLA typing) → 5. Rule out masquerade syndromes (intraocular lymphoma in elderly, retinoblastoma in children) → 6. Treat cause-specifically (antimicrobial first if infective; steroid + immunosuppression if autoimmune).
High-yield: In any uveitis, screen for syphilis (VDRL/TPHA) and TB (Mantoux/IGRA) before starting steroids/immunosuppression — they are treatable mimics and steroids alone worsen them. Syphilis can produce "acute syphilitic posterior placoid chorioretinitis (ASPPC)."
| Disease | Laterality | Granulomatous? | Signature sign | First-line treatment |
|---|---|---|---|---|
| Toxoplasma | Unilateral | Non-granul. | Headlight in fog, satellite lesion | Pyrimethamine + sulfadiazine + folinic acid + steroid |
| VKH | Bilateral | Granulomatous | Sunset glow, exudative RD, Sugiura | High-dose steroid + immunosuppression |
| Sympathetic ophthalmia | Bilateral | Granulomatous | Dalen–Fuchs nodules, trauma history | Steroid + immunosuppression (± enucleate blind eye) |
| Behçet | Bilateral | Non-granul. | Shifting hypopyon, occlusive vasculitis | Azathioprine/cyclosporine, anti-TNF, IFN-α |
| Sarcoid | Bilateral | Granulomatous | Candle-wax drippings, snowballs | Steroid, methotrexate |
| ARN | Uni→bilateral | — | Peripheral necrosis + arteritis | IV aciclovir + steroid + laser |
Management principles (autoimmune posterior/panuveitis)
The classic "step-ladder" of immunomodulation:
- Corticosteroids — topical (anterior only), periocular/intravitreal (sub-Tenon triamcinolone, dexamethasone/fluocinolone implants), or systemic (oral/IV pulse) for bilateral or posterior disease.
- Antimetabolites — methotrexate, mycophenolate mofetil, azathioprine.
- Calcineurin inhibitors — cyclosporine, tacrolimus.
- Biologics — anti-TNF (infliximab, adalimumab) — adalimumab is FDA-approved for non-infectious intermediate/posterior/panuveitis; interferon-α for Behçet.
High-yield: Steroid-sparing immunosuppression is started early in chronic sight-threatening non-infectious uveitis to keep total steroid below the safe ceiling (prednisolone ≤7.5 mg/day long-term). Always exclude infection first — biologics/immunosuppression in undiagnosed TB or syphilis can be catastrophic.
Complications
- Cystoid macular oedema (CMO) — commonest cause of vision loss in uveitis overall; detect on OCT / FFA (petalloid leak).
- Cataract (inflammation- and steroid-induced).
- Secondary glaucoma (synechiae, trabeculitis, steroid response).
- Retinal detachment (exudative in VKH; rhegmatogenous/tractional in ARN, Behçet).
- Choroidal/retinal neovascularisation, optic atrophy, epiretinal membrane, hypotony and phthisis bulbi (end-stage).
Key differentials / masquerade syndromes
- Primary vitreoretinal lymphoma — elderly with steroid-resistant vitritis, "sub-RPE deposits"; vitreous biopsy shows malignant B-cells (high IL-10:IL-6 ratio). Always suspect in >60 y "chronic uveitis."
- Retinoblastoma / leukaemia — pseudo-uveitis in children.
- Intraocular foreign body / chronic RD / endophthalmitis — mimic chronic inflammation.
- Birdshot chorioretinopathy — multiple cream-coloured "birdshot" spots, strongly HLA-A29 positive.
- Serpiginous choroiditis — geographic, peripapillary, recurrent, treat with immunosuppression (rule out TB-related serpiginous-like choroiditis first).
Recently asked / exam angle
- "Headlight in the fog" → Toxoplasma chorioretinitis (and the satellite-lesion-near-old-scar pattern). The triple drug regimen + why folinic acid is a recurring stem.
- Sunset glow fundus + bilateral exudative RD + tinnitus/poliosis → VKH; FFA "starry sky"; HLA-DR4.
- Shifting hypopyon + recurrent oral/genital ulcers + occlusive vasculitis → Behçet; HLA-B51; pathergy; treatment with anti-TNF/IFN-α not steroids alone.
- Trauma to one eye → inflammation in fellow eye after weeks–months → Sympathetic ophthalmia; Dalen–Fuchs nodules; prophylactic enucleation within 2 weeks.
- Candle-wax drippings / snowballs / bilateral hilar lymphadenopathy / raised ACE → Sarcoid; Heerfordt & Löfgren syndromes are direct one-liners.
- Peripheral necrotising retinitis + arteritis + vitritis → ARN (VZV/HSV), high RD risk, IV aciclovir.
- CD4 <50 + "pizza-pie" retinitis → CMV; valganciclovir + ART.
- Mutton-fat KPs / Koeppe vs Busacca nodules → granulomatous; Busacca = iris stroma, Koeppe = pupillary border.
- Concept questions: SUN classification (cells vs flare), why steroid is delayed in toxoplasma, and screen syphilis/TB before immunosuppression.
Rapid revision
- Cells = activity, flare = chronicity (SUN grading).
- Granulomatous uveitis → VKH, sympathetic ophthalmia, sarcoid, TB, syphilis.
- Toxoplasma = headlight in fog; new lesion adjacent to old scar; pyrimethamine + sulfadiazine + folinic acid + delayed steroid.
- Never give steroid alone in toxoplasma (or undiagnosed TB/syphilis).
- VKH = sunset glow fundus, exudative RD, Sugiura sign, HLA-DR4; treat with early high-dose steroids + immunosuppression.
- Sympathetic ophthalmia = post-trauma bilateral granulomatous panuveitis, Dalen–Fuchs nodules; prophylactic enucleation of blind eye within 2 weeks.
- Behçet = HLA-B51, shifting hypopyon, occlusive arterial + venous vasculitis; anti-TNF/IFN-α, not steroids alone.
- ISG criterion for Behçet: recurrent oral ulcers mandatory + 2 others (genital, eye, skin, pathergy).
- Sarcoid = candle-wax drippings, snowballs, raised serum ACE, non-caseating granuloma; Heerfordt (uveoparotid fever) & Löfgren.
- ARN = VZV/HSV peripheral necrosis + arteritis → high RD risk → IV aciclovir + laser barrage.
- CMO is the commonest cause of visual loss in uveitis — image with OCT.
- Vitreoretinal lymphoma masquerades as steroid-resistant uveitis in the elderly (IL-10:IL-6 >1).