Anterior Uveitis (Iritis)

Anterior uveitis (AU) is inflammation of the uveal tract confined to the anterior segment. When the inflammation primarily affects the iris it is termed iritis; involvement of both the iris and ciliary body is termed iridocyclitis. Anterior uveitis accounts for approximately 50–90% of all uveitis cases and is the most prevalent form encountered in general and specialist optometric practice.

The condition may be classified as acute (sudden onset, <3 months duration, typically self-limiting with treatment) or chronic (insidious onset, persisting ≥3 months, often requiring long-term immunosuppression). Non-granulomatous anterior uveitis — characterised by fine stellate keratic precipitates, no iris nodules, and a strong HLA-B27 association — is the most common subtype. Granulomatous anterior uveitis — with large mutton-fat KPs and Koeppe or Busacca nodules — implies sarcoidosis, tuberculosis, herpetic infection, Vogt-Koyanagi-Harada (VKH) syndrome, or sympathetic ophthalmia.

Urgent slit-lamp examination is essential for diagnosis and grading. Untreated or inadequately treated uveitis leads to posterior synechiae, cataract (from inflammation and corticosteroids), secondary glaucoma, cystoid macular oedema, and permanent visual loss. Identification of an underlying systemic cause guides targeted therapy and prevents recurrence.

• Idiopathic (~50%): No underlying systemic or infectious cause identified despite full workup; typically acute, unilateral, non-granulomatous. May represent undetected HLA-B27 spondyloarthropathy.
• HLA-B27 associated (~25–40%): Ankylosing spondylitis, reactive arthritis (Reiter syndrome), psoriatic arthritis, inflammatory bowel disease (Crohn disease, ulcerative colitis), undifferentiated spondyloarthropathy. Classically acute, unilateral, recurrent, non-granulomatous, with intense anterior chamber reaction.
• Infectious — viral: Herpes zoster ophthalmicus (HZO) — sectoral iris atrophy, elevated IOP (hypertensive uveitis); Herpes simplex virus (HSV); Cytomegalovirus (CMV) — Posner-Schlossman syndrome, very high IOP spikes, minimal cells in immunocompetent hosts; Varicella.
• Infectious — other: Toxoplasma gondii (anterior spillover from posterior focus); Mycobacterium tuberculosis (granulomatous, bilateral, systemic TB symptoms); Treponema pallidum — syphilitic uveitis (may mimic any form, must exclude); Lyme disease (Borrelia burgdorferi).
• Granulomatous non-infectious: Sarcoidosis (bilateral, mutton-fat KPs, iris nodules, hilar lymphadenopathy); Vogt-Koyanagi-Harada (VKH) syndrome (bilateral, Japanese/South American/Middle Eastern patients, associated with poliosis, vitiligo, meningism); Sympathetic ophthalmia (bilateral granulomatous uveitis after penetrating ocular injury or surgery).
• Juvenile idiopathic arthritis (JIA): The most important paediatric cause. Oligoarticular JIA (ANA-positive girls) carries the highest uveitis risk. The classic presentation is asymptomatic "white eye uveitis" — active inflammation without redness or pain, discovered only on screening slit-lamp examination.
• Fuchs heterochromic iridocyclitis (FHI): Chronic, low-grade, typically unilateral; stellate fine KPs distributed across the entire corneal endothelium (not just inferior); heterochromia; no posterior synechiae; vitreous cells; associated cataract and glaucoma. CMV now implicated in pathogenesis.
• Post-traumatic and post-surgical: Mechanical disruption of blood-aqueous barrier; lens-induced uveitis (phacoanaphylaxis); endophthalmitis must be excluded.

The fundamental mechanism of anterior uveitis involves a T-cell mediated immune response within the anterior uveal tissue. In HLA-B27-associated uveitis, molecular mimicry between bacterial antigens (particularly Gram-negative organisms such as Klebsiella in ankylosing spondylitis) and HLA-B27-derived peptides triggers autoreactive CD8+ T-cell activation. These autoreactive T cells infiltrate the iris and ciliary body, releasing pro-inflammatory cytokines including TNF-α, IL-1β, IL-6, and VEGF.

This cytokine cascade produces breakdown of the blood-aqueous barrier — the tight junctions between non-pigmented ciliary epithelial cells — resulting in protein extravasation into the anterior chamber (aqueous flare) and cellular migration of leucocytes into the anterior chamber (anterior chamber cells). Keratic precipitates form as inflammatory cells (macrophages, lymphocytes, fibrin) deposit on the inferior corneal endothelium, facilitated by convective aqueous currents (Ehrlich-Türk line).

Posterior synechiae develop when fibrin bridges form between the posterior iris surface and the anterior lens capsule, progressively occluding the pupillary aperture. Complete posterior synechiae produces iris bombé — forward bowing of the iris from trapped aqueous behind it — leading to acute pupillary block angle-closure glaucoma. Peripheral anterior synechiae (PAS) further compromise trabecular outflow, compounding IOP elevation.

In the chronic phase, VEGF release drives cystoid macular oedema — the principal cause of vision loss in chronic anterior uveitis. Corticosteroid use introduces its own complications: posterior subcapsular cataract and steroid-induced IOP elevation from trabecular dysfunction.

SUN (Standardisation of Uveitis Nomenclature) Working Group Classification

• HLA-B27 positivity: Present in ~8% of the Caucasian population but in ~50% of patients with acute non-granulomatous anterior uveitis. Confers a 25–30× increased relative risk of acute anterior uveitis.
• Spondyloarthropathy: Ankylosing spondylitis (25–40% lifetime risk of AU), reactive arthritis (20–50%), psoriatic arthritis (7–20%), IBD-associated arthropathy.
• Prior uveitis episodes: The most reliable predictor of recurrence, particularly in HLA-B27-positive patients.
• Immunosuppression: HIV, transplant immunosuppression, and anti-TNF biologics predispose to CMV uveitis and opportunistic infections.
• Childhood oligoarticular JIA: ANA-positive, female sex, young age at arthritis onset — highest risk group for chronic insidious uveitis.
• Herpesvirus exposure: Prior HSV or HZO episodes predispose to recurrent herpetic anterior uveitis.
• TB exposure: Residence in or travel to TB-endemic regions; household contact; immunosuppression.

Ciliary flush: Perilimbal conjunctival injection (deep episcleral/scleral vessel injection forming a ring around the limbus); distinguishes uveitis from conjunctivitis (diffuse injection).

Anterior chamber cells: White blood cells suspended in the aqueous, seen as bright specks in the slit-lamp beam; graded 0 to 4+ by SUN criteria. Cells distinguish active uveitis from quiescent flare.

Aqueous flare: Protein-rich aqueous from blood-aqueous barrier breakdown creates the Tyndall effect — scattering of the slit-lamp beam through the anterior chamber like a searchlight beam in fog. Graded 0 to 4+.

Keratic precipitates (KPs): Cellular deposits on the corneal endothelium. Fine/stellate KPs in inferior triangle (Arlt triangle) in non-granulomatous uveitis; large, greasy mutton-fat KPs distributed across the entire inferior cornea in granulomatous uveitis. In FHI, stellate KPs are distributed across the entire endothelial surface.

Posterior synechiae: Fibrinous adhesions between the posterior iris and the anterior lens capsule. Cause an irregular, poorly dilating pupil; visible as irregular pupil margin or persistent iris adhesion after cycloplegia. Total posterior synechiae produce iris bombé (forward bowing of iris).

Iris nodules: Koeppe nodules (grey-white nodules at pupil margin) and Busacca nodules (iris stroma nodules) — pathognomonic of granulomatous uveitis.

Sectoral iris atrophy: Sector-shaped iris transillumination defects; highly characteristic of herpetic (HSV or HZO) anterior uveitis; associated with elevated IOP (hypertensive uveitis).

Hypopyon: Layering of white cells (pus) in the inferior anterior chamber; seen in severe HLA-B27 uveitis, Behçet disease, and must be distinguished from endophthalmitis.

IOP changes: Usually low (ciliary body shutdown in severe anterior uveitis). May be acutely elevated in herpetic/CMV hypertensive uveitis or with pupillary block. Steroid-induced IOP elevation occurs in susceptible individuals.

Acute non-granulomatous anterior uveitis (HLA-B27): The classic triad is photophobia, pain (dull ache, periorbital or brow ache), and redness (ciliary flush). Decreased vision from cells and flare obscuring optical clarity. Tearing (reflex lacrimation from photophobia). Sudden onset; often unilateral.

Chronic anterior uveitis (JIA, FHI): Patients may be entirely asymptomatic or have only mild visual blurring. The absence of symptoms despite significant inflammation — the "white eye uveitis" of JIA — makes screening slit-lamp examinations mandatory in all children with oligoarticular JIA.

Herpetic hypertensive uveitis: Moderate symptoms, with notable IOP elevation (headache, haloes, nausea) in addition to photophobia and redness.

Chronic or recurrent episodes: Patients recognise their own pattern — episodic photophobia and aching — and may self-manage or present early with experience of the condition.

• Posterior synechiae: Lead to irregular pupil, difficulty with dilation, pupillary block glaucoma, and restricted lens-iris contact causing cataract acceleration. Require aggressive cycloplegia and may need laser synechiolysis or surgical pupil dilation.
• Cataract: Posterior subcapsular cataract develops from both chronic inflammation and corticosteroid use. Common in chronic anterior uveitis. Cataract surgery in uveitis carries higher complication rates (synechiae, fibrin, CMO) and requires pre-operative quiescence.
• Secondary glaucoma (~10–20%): Multiple mechanisms — trabeculitis (inflammatory cells clogging TM), pupillary block from total synechiae, PAS formation, and steroid-induced elevation. Requires careful balance of anti-inflammatory and IOP-lowering therapy.
• Cystoid macular oedema (CMO): The most common cause of irreversible visual loss in chronic anterior uveitis. Detected by OCT or FFA. Treat with anti-inflammatory intensification, periocular steroids, intravitreal anti-VEGF, or systemic immunosuppression.
• Band keratopathy: Interpalpebral calcium deposition in Bowman layer (grey horizontal band); associated with long-standing JIA uveitis and chronic hypotony. Treated with EDTA chelation.
• Hypotony: Ciliary body shut-down in severe chronic uveitis reduces aqueous production; may lead to hypotony maculopathy.
• Amblyopia: In children with cataract, sustained low VA, or corneal band keratopathy; requires aggressive treatment with optical correction and patching.

• Ankylosing spondylitis (AS): HLA-B27-positive males <40 years; inflammatory low back pain, sacroiliitis, bamboo spine on X-ray; ESR/CRP elevated; rheumatology co-management essential.
• Reactive arthritis (formerly Reiter syndrome): Triad of urethritis (or cervicitis), asymmetric oligoarthritis, and uveitis following bacterial GI or GU infection (Chlamydia, Salmonella, Shigella, Yersinia, Campylobacter). HLA-B27-positive in 80%.
• Psoriatic arthritis: Psoriatic skin and nail changes; asymmetric oligoarthritis or DIP involvement; uveitis in 7–20%.
• Inflammatory bowel disease (IBD): Crohn disease and ulcerative colitis; uveitis activity may be independent of bowel disease activity.
• Juvenile idiopathic arthritis (JIA): Oligoarticular subtype, ANA-positive, girls aged 1–8; asymptomatic uveitis requires regular slit-lamp screening (every 3–6 months) regardless of symptoms; risk of amblyopia from cataract and band keratopathy.
• Sarcoidosis: Bilateral granulomatous uveitis; bilateral hilar lymphadenopathy on chest X-ray; elevated serum ACE and LDH; skin nodules, erythema nodosum; parotid gland enlargement.
• Behçet disease: Recurrent oral and genital ulcers, skin lesions (erythema nodosum, pathergy), and hypopyon uveitis; bilateral; young Middle Eastern/Asian males; HLA-B51; severe visual prognosis without treatment.
• Syphilis (Treponema pallidum): Uveitis may occur in secondary or tertiary syphilis; serology (FTA-ABS, RPR/VDRL) must be obtained in all new cases of uveitis, as syphilis can mimic virtually any uveitis pattern.
• Tuberculosis: Granulomatous bilateral uveitis; IGRA (QuantiFERON) or Mantoux testing; chest X-ray; particularly important in Singapore given regional TB prevalence.
• VKH syndrome: Bilateral granulomatous panuveitis with bilateral serous retinal detachments acutely; followed by Dalen-Fuchs nodules and sunset glow fundus; extra-ocular features — poliosis (premature whitening of lashes/brows), vitiligo, dysacusis, aseptic meningism.

Slit-lamp examination (essential): Grade AC cells and flare by SUN criteria; characterise KP morphology (fine/stellate vs mutton-fat); document posterior synechiae, iris nodules, pupil morphology, lens changes, and any hypopyon. Retroillumination to assess iris TIDs and atrophy.

IOP measurement: Elevated IOP (herpetic/CMV uveitis) vs low IOP (ciliary body shutdown); baseline value is essential. Monitor at every visit — steroid-induced elevation typically occurs within 2–4 weeks of starting topical steroids.

Dilated fundus examination: To exclude posterior involvement, CMO (OCT), vitreous cells, and disc swelling. OCT macula should be performed in all chronic or recurrent anterior uveitis cases.

Blood investigations for workup: HLA-B27 typing; FBC, ESR, CRP; serum ACE and LDH (sarcoidosis); syphilis serology (FTA-ABS and RPR/VDRL — mandatory); IGRA/QuantiFERON or Mantoux (TB); ANA (JIA in children); ANCA (vasculitis); chest X-ray (sarcoidosis, TB). HLA-B51 if Behçet disease suspected.

Aqueous PCR: Anterior chamber paracentesis with PCR for HSV, HZV, CMV, and Toxoplasma if viral/infectious uveitis is suspected, especially when clinical features are atypical or response to empirical treatment is poor.

Fluorescein angiography (FFA) and OCT: Detect CMO and posterior segment involvement in chronic cases.

Acute idiopathic and HLA-B27-associated anterior uveitis carries an excellent prognosis when treated promptly — the majority of acute episodes resolve fully within 6–8 weeks with topical steroids and cycloplegia. However, 50–75% of patients with HLA-B27-associated AU will experience recurrent episodes, requiring patient education about early recognition and rapid treatment initiation.

Chronic anterior uveitis (JIA, FHI) requires prolonged therapy and carries a more guarded prognosis. Biologic therapy (adalimumab) has transformed outcomes in JIA uveitis, reducing cataract, band keratopathy, and glaucoma rates. FHI has a generally mild course with good long-term visual acuity despite persistent low-grade activity; cataract surgery in FHI carries excellent outcomes without postoperative fibrin or synechiae formation.

Complications — secondary glaucoma, CMO, and corticosteroid-induced cataract — are the principal determinants of final visual outcome. Identification of the underlying systemic aetiology allows targeted therapy and reduces the recurrence burden. Rheumatology co-management for HLA-B27 spondyloarthropathies and biologics for refractory cases have significantly improved long-term prognosis.

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