How is uveitis classified?
The International Uveitis Study Group (IUSG) and the Standardization of Uveitis Nomenclature (SUN) Working Group classify uveitis anatomically by the primary site of inflammation. The site is not changed by structural complications such as cystoid macular oedema.
| Type | Site of inflammation |
|---|---|
| Anterior uveitis | Iris and ciliary body (anterior chamber): iritis, iridocyclitis, anterior cyclitis |
| Intermediate uveitis | Vitreous and pars plana |
| Posterior uveitis | Retina and choroid |
| Panuveitis | Anterior, intermediate and posterior segments together |
Iritis is inflammation of the iris, anterior cyclitis involves the anterior part of the ciliary body, and when both are involved it is iridocyclitis. Anterior uveitis is the most common form of uveitis, and its commonest presentation is acute anterior uveitis (AAU).
| Basis | Categories |
|---|---|
| Aetiology (IUSG) | Infectious, non-infectious (idiopathic or systemic disease), masquerade (neoplastic and non-neoplastic) |
| Onset (SUN) | Sudden or insidious |
| Duration (SUN) | Limited (3 months or less) or persistent |
| Course (SUN) | Acute; chronic (relapse within 3 months of stopping treatment); recurrent (episodes separated by inactive periods); remission (no activity for 3 months or more) |
| Histology (Wood) | Suppurative, or non-suppurative divided into granulomatous and non-granulomatous |
What causes anterior uveitis?
Most cases of iritis are idiopathic, and about 20 percent follow blunt trauma. After idiopathic, HLA-B27-associated disease is the second commonest cause, responsible for 40 to 70 percent of anterior uveitis in different regions, and it is more common in males.
| Group | Examples |
|---|---|
| Seronegative spondyloarthropathies | Ankylosing spondylitis, inflammatory bowel disease (ulcerative colitis), psoriatic arthritis, reactive arthritis (Reiter syndrome) |
| Other systemic disease | Juvenile idiopathic arthritis, sarcoidosis, Behcet disease, SLE, multiple sclerosis, TINU |
| Infections | Tuberculosis, syphilis, herpes simplex, varicella-zoster (herpes zoster ophthalmicus), Lyme disease, chlamydia, toxoplasmosis |
| Others | Drug-induced uveitis, lens-related inflammation, masquerade syndromes (lymphoma, leukaemia, melanoma), juvenile xanthogranuloma |
In tertiary-centre series the most common form of uveitis was anterior, and the most common aetiology was idiopathic followed by seronegative arthropathy, JIA, herpes, sarcoidosis and SLE. Common causes of posterior uveitis were toxoplasmosis, idiopathic disease, CMV, SLE and sarcoidosis. Systemic links are reviewed in connective tissue disease autoantibodies and syphilis stages and serology.
What are the symptoms and pathophysiology of anterior uveitis?
Acute anterior uveitis causes pain, redness, photophobia, tearing and reduced vision that develop over hours to days (except after trauma). Chronic anterior uveitis gives blurred vision and mild redness with little pain or photophobia except during flares; it is usually bilateral and often linked to an underlying systemic disease.
- Pain is attributed to irritation of the ciliary nerves and ciliary muscle spasm; photophobia to trigeminal irritation from the spasm.
- Increased vascular permeability lets protein (flare) and white cells (cells) enter the aqueous: the hallmark 'flare and cells' of the slit lamp.
- Non-granulomatous uveitis: diffuse inflammation, dilated leaky vessels, iris oedema, small sluggish pupil, cells and flare, fine KPs.
- Granulomatous uveitis: lymphocytes, plasma cells, epithelioid and giant cells forming nodules, such as Koeppe nodules at the pupil margin and mutton-fat KPs on the endothelium.
| Feature | Acute (AAU) | Chronic (CAU) |
|---|---|---|
| Symptoms | Pain, redness, photophobia, tearing, reduced vision over hours or days | Blurred vision, mild redness; little pain or photophobia except during flares |
| Laterality | Commonly unilateral in the first episode | Usually bilateral, with an underlying systemic disease |
| Circumciliary congestion | Typically present (purple hue) | May be absent |
| Typical associations | HLA-B27 disease, idiopathic, trauma | Underlying systemic disease such as juvenile idiopathic arthritis |
What are the slit-lamp signs of anterior uveitis?
- Circumciliary (circumcorneal) congestion: purple-hued injection from deep vessels; typical of AAU, may be absent in chronic disease.
- Miosis: from sphincter spasm and iridoplegia; leads to posterior synechiae.
- Anterior chamber cells: graded with a 1 x 1 mm slit beam. Assess cells and flare before dilating the pupil, since dilatation releases pigment into the aqueous.
- Flare: turbid aqueous from protein after breakdown of the blood-aqueous barrier. In JIA-associated chronic anterior uveitis, flare marks long-term risk of complications.
Hypopyon is a gravity-dependent horizontal level of inflammatory cells (leucocytes) in the anterior chamber. It is common in HLA-B27-associated uveitis, where it is immobile because of high fibrin content; in Behcet disease the hypopyon is characteristically mobile because of low fibrin content.
What are keratic precipitates, iris nodules and synechiae?
Keratic precipitates (KPs) are inflammatory cell deposits (lymphocytes, plasma cells, macrophages; epithelioid and giant cells in granulomatous disease) on the corneal endothelium. In ordinary anterior uveitis they lie in the inferior third of the cornea in a triangle with its apex up (Arlt's triangle), because of aqueous convection currents and gravity. They are diffuse in Fuchs heterochromic iridocyclitis and stellate in viral uveitis.
| Nodule | Site / association |
|---|---|
| Koeppe | Pupillary margin (or at a synechia); seen in both granulomatous and non-granulomatous uveitis |
| Busacca | Iris stroma; mainly granulomatous uveitis |
| Roseolae | Yellow nodules from dilated iris vessels in syphilis |
| Berlin | In the angle in sarcoidosis |
| Iris pearls | Lepromatous uveitis |
| Russell bodies (iris crystals) | Fuchs heterochromic iridocyclitis and chronic uveitis; thought to be immunoglobulin deposits |
Posterior synechiae are adhesions of the pupil margin to the anterior lens capsule from uncontrolled inflammation; all patients should receive a cycloplegic (atropine or homatropine) to prevent them. Types: segmental, annular (ring, 360 degrees), total; broad synechiae are seen in tubercular uveitis and filiform in non-tubercular. Seclusio pupillae is 360-degree synechiae blocking aqueous flow; occlusio pupillae is a membrane over the lens surface; a festooned pupil has irregular shape on dilatation. Heterochromia occurs in Fuchs heterochromic iridocyclitis; diffuse iris atrophy is typical of Fuchs and sectoral atrophy of herpetic uveitis.
When should uveitis be investigated and which tests help?
In most uveitis, investigations are normal and no cause is found. Investigations are not mandatory after a first episode of mild unilateral non-granulomatous AAU with no previous ocular or systemic history, when the signs point to a specific diagnosis (such as Fuchs heterochromic iridocyclitis), or when systemic features already suggest a cause. They are helpful in bilateral, severe, recurrent, chronic treatment-resistant or granulomatous anterior uveitis, and when anterior uveitis coexists with intermediate, posterior or panuveitis.
| HLA type | Association |
|---|---|
| HLA-B27 | Recurrent acute anterior uveitis |
| HLA-B51 / B5 | Behcet disease |
| HLA-A29 | Birdshot retinochoroidopathy |
| HLA-DR4 | Sympathetic ophthalmia and Vogt-Koyanagi-Harada disease |
- Serum ACE is raised in about 80 percent of sarcoidosis patients and falls in remission; non-specific (also tuberculosis, leprosy). Serum lysozyme is less sensitive and specific.
- Syphilis serology: treponemal tests (such as ELISA) and non-treponemal VDRL/RPR.
- Chest X-ray for sarcoidosis or tuberculosis; sacroiliac joint X-ray for ankylosing spondylitis.
- Ocular imaging: B-scan if the fundus cannot be seen, OCT for cystoid macular oedema, fluorescein angiography for chronic uveitis and vasculitis, ICG for choroidal disease, UBM for ciliary body pathology.
- Fundus examination is mandatory to exclude masquerades and posterior segment complications.
How is anterior uveitis treated?
Treatment aims to reduce inflammation and pain and prevent complications. First-line: topical cycloplegic plus topical corticosteroid. The patient should see an ophthalmologist within 24 to 48 hours. Steroids should be started only with ophthalmologist input because uveitis is a diagnosis of exclusion and steroids can worsen herpetic disease.
| Step | Drug / procedure | Notes |
|---|---|---|
| Topical steroid | Prednisolone 1 percent or dexamethasone 0.1 percent (potent); difluprednate, loteprednol, fluorometholone, rimexolone milder | Often hourly then tapered over weeks; usually stopped after 6 to 8 weeks; risks: raised IOP, cataract, steroid glaucoma, herpes keratitis |
| Cycloplegic | Homatropine is the agent of choice; cyclopentolate; atropine acts 7 to 10 days | Relieves ciliary spasm and pain, breaks recent synechiae and prevents new ones; give at bedtime |
| Mydricaine | Subconjunctival adrenaline, atropine, procaine | Breaks posterior synechiae; transient tachycardia |
| Severe fibrin | Intracameral tissue plasminogen activator | Dissolves fibrin membrane |
| Periocular steroid | Subconjunctival betamethasone; posterior sub-Tenon methylprednisolone or triamcinolone | Severe disease, poor compliance, cystoid macular oedema |
| Systemic | Oral prednisolone for severe disease; NSAIDs (naproxen, tolmetin) long term in chronic AU | Taper steroids |
| Immunosuppression | Methotrexate for JIA-associated chronic AU; infliximab or adalimumab as second line for vision-threatening spondyloarthropathy uveitis | About half need treatment beyond corticosteroids |
What are the complications and differential diagnosis?
- Anterior segment: posterior synechiae, seclusio and occlusio pupillae, festooned pupil, iris atrophy, band keratopathy, corneal scar, non-resolving hypopyon, complicated cataract (inflammatory or steroid-induced), secondary glaucoma (pupillary block, trabeculitis, steroid).
- Posterior segment: cystoid macular oedema, macular scar, optic neuropathy, vitreous haemorrhage, retinal detachment, hypotony.
- Severe: endophthalmitis, panophthalmitis, permanent blindness.
- Intraocular pressure: may be low from ciliary shutdown or raised from angle closure, trabeculitis or steroids; see primary glaucoma and cataract types and surgery.
The differential of a red painful eye includes acute angle-closure glaucoma, conjunctivitis, subconjunctival haemorrhage, trauma, episcleritis and scleritis. Pupil size, circumciliary congestion, cells and flare and a fundus examination separate them.