Ophthalmology – Non-Granulomatous Anterior Uveitis

Basics

Description

Non-granulomatous anterior uveitis (NGAU) is inflammation predominantly involving the anterior uveal tract:

• Iris → iritis
• Ciliary body → cyclitis
• Both → iridocyclitis

Typical symptoms include:

• Ocular pain
• Redness
• Photophobia
• Blurred vision

It may be:

• Infectious
• Immune-mediated
• Associated with systemic disease
• Limited to the eye
• Idiopathic

A classic slit-lamp feature is the presence of small, fine keratic precipitates (KPs) rather than the large “mutton-fat” KPs more typical of granulomatous inflammation.

Epidemiology

Reported incidence is approximately:

8–17 cases per 100,000 population

Important epidemiologic associations include:

• HLA-B27-associated uveitis – more common in younger adults, classically males with spondyloarthropathy
• Behçet disease – more common in populations from the Middle East and parts of Asia
• JIA-associated uveitis – more common in children, particularly girls with certain JIA phenotypes

Risk Factors

Important risk factors include:

• Ocular trauma
• HLA-B27 positivity
• HLA-B51 positivity
• Autoimmune disease
• Smoking
• Previous episodes of uveitis
• Certain infections
• Selected medications

Genetics

HLA-B27

Associated with:

• Ankylosing spondylitis
• Reactive arthritis
• Psoriatic arthritis
• Inflammatory bowel disease-associated arthritis

HLA-B27-associated anterior uveitis is typically:

• Acute
• Unilateral
• Recurrent
• Painful
• Often associated with marked anterior chamber inflammation

HLA-B51

Associated particularly with:

Behçet disease

which may cause:

• Recurrent anterior uveitis
• Hypopyon
• Retinal vasculitis
• Panuveitis

Etiology

Common causes include:

• Idiopathic
• HLA-B27-associated disease
• JIA
• Herpetic anterior uveitis
• Fuchs uveitis syndrome
• Posner-Schlossman syndrome
• Behçet disease
• TINU syndrome
• Trauma
• Lens-induced inflammation
• UGH syndrome
• Drug-induced uveitis

A substantial proportion of cases remain idiopathic.

Classification by Clinical Course

Using standard uveitis terminology:

Acute

• Sudden onset
• Limited duration

Recurrent

• Repeated episodes
• Separated by periods of inactivity without treatment

Chronic

• Persistent inflammation
• Relapse soon after treatment is stopped

History

A targeted history is essential.

Ask about:

• Onset
• Duration
• Laterality
• Previous episodes
• Trauma
• Previous ocular surgery
• Previous treatment
• Response to corticosteroids
• Medication use
• Infectious exposures
• Autoimmune disease
• STI risk
• Intravenous drug use

Review of Systems

Constitutional

Ask about:

• Fever
• Chills
• Night sweats
• Weight loss

These may suggest:

• Infection
• Tuberculosis
• Malignancy
• Systemic inflammatory disease

Skin and Mucosal Symptoms

Ask about:

• Oral ulcers
• Genital ulcers
• Psoriatic plaques
• Erythema nodosum
• Vitiligo
• Rash
• Herpetic lesions

Important associations include:

• Behçet disease
• Psoriasis
• Reactive arthritis
• Sarcoidosis
• Syphilis
• VKH

Musculoskeletal Symptoms

Ask about:

• Inflammatory back pain
• Sacroiliac pain
• Morning stiffness
• Peripheral arthritis
• Enthesitis
• Tendon pain

These suggest:

• Ankylosing spondylitis
• Reactive arthritis
• Psoriatic arthritis
• IBD-associated arthritis

Gastrointestinal Symptoms

Ask about:

• Chronic diarrhea
• Bloody stool
• Abdominal pain

These may suggest:

• Inflammatory bowel disease
• Reactive arthritis

Genitourinary Symptoms

Ask about:

• Urethritis
• Genital ulcers
• Dysuria
• Epididymitis

These may be relevant to:

• Reactive arthritis
• Behçet disease
• Syphilis
• HSV

Renal Symptoms

Consider:

• Abnormal urinalysis
• Elevated creatinine
• Systemic symptoms

in suspected:

Tubulointerstitial nephritis and uveitis (TINU)

Neurologic Symptoms

Ask about:

• Headache
• Meningitic symptoms
• Cranial nerve palsies
• Sensory or motor symptoms

Possible associations include:

• Sarcoidosis
• Behçet disease
• Lyme disease
• Multiple sclerosis
• VKH
• Lymphoma

Physical Examination

External Examination

Assess:

• Skin
• Joints
• Oral cavity
• Lymph nodes
• Neurologic findings

Pupils

Possible findings include:

• Miosis
• Irregular pupil
• Posterior synechiae
• Seclusio pupillae

A fixed irregular pupil may indicate extensive synechiae.

Intraocular Pressure

IOP may be:

• Low from ciliary body shutdown
• Normal
• Elevated from trabeculitis, inflammation, or steroid response

Elevated IOP is particularly associated with:

• Herpetic anterior uveitis
• Fuchs uveitis syndrome
• Posner-Schlossman syndrome

Gonioscopy

Gonioscopy may reveal:

• Peripheral anterior synechiae
• Angle KPs
• Secondary angle closure
• Abnormal angle vessels

In Fuchs uveitis syndrome, abnormal angle vessels may predispose to bleeding during surgery.

Conjunctiva and Sclera

Typical finding:

Ciliary flush

Associated episcleritis or scleritis may suggest systemic inflammatory disease.

Cornea

Important findings include:

• Small punctate KPs
• Fine stellate KPs
• Corneal edema
• Reduced corneal sensation in herpetic disease
• Band keratopathy in chronic uveitis, especially JIA

Keratic Precipitates

In NGAU, KPs are usually:

• Fine
• Small
• Punctate
• Stellate

Large greasy “mutton-fat” KPs suggest granulomatous inflammation, although overlap can occur.

Iris Findings

Look for:

• Posterior synechiae
• Iris atrophy
• Transillumination defects
• Heterochromia
• Iris nodules
• Pupillary membranes

Posterior Synechiae

Posterior synechiae occur when the iris adheres to the anterior lens capsule.

Complications include:

• Irregular pupil
• Seclusio pupillae
• Iris bombe
• Secondary angle closure

Cycloplegics help reduce this risk.

Hypopyon

Hypopyon may occur in:

• HLA-B27-associated uveitis
• Behçet disease
• Severe infectious uveitis
• Masquerade syndromes

A hypopyon should prompt careful consideration of infection before escalating immunosuppression.

Hyphema

Possible causes in an inflamed eye include:

• Herpetic disease
• Fuchs uveitis syndrome
• UGH syndrome
• Juvenile xanthogranuloma
• Neovascularization
• Leukemia

Anterior Chamber Cell Grading

Using SUN criteria with a 1 × 1 mm slit beam:

• 0: <1 cell
• 0.5+: 1–5 cells
• 1+: 6–15 cells
• 2+: 16–25 cells
• 3+: 26–50 cells
• 4+: >50 cells

Anterior Chamber Flare

Typical grading:

• 0: none
• 1+: faint
• 2+: moderate
• 3+: marked
• 4+: intense, often with fibrin

Lens and Anterior Vitreous

Look for:

• Posterior subcapsular cataract
• Lenticular precipitates
• Retained lens material
• IOL-related irritation
• Cyclitic membrane
• Anterior vitreous cells

Dilated Fundus Examination

A complete dilated examination is essential to exclude posterior disease.

Look for:

• Vitritis
• CME
• Retinal vasculitis
• Toxoplasmosis scars
• Retinal necrosis
• Choroidal lesions
• Snowballs/snowbanking
• Intraocular foreign body
• Retinal or choroidal infiltrates

Diagnostic Workup

A laboratory workup should be targeted, not indiscriminate.

Workup is particularly indicated when disease is:

• Bilateral
• Recurrent
• Severe
• Chronic
• Atypical
• Poorly responsive to treatment
• Associated with systemic symptoms

Common Initial Tests

Depending on presentation, consider:

• Syphilis serology
• TB testing
• HLA-B27
• Chest imaging for sarcoidosis/TB
• Lyme testing only when epidemiologically appropriate

HLA-B27 Testing

Useful particularly in:

• Recurrent acute unilateral anterior uveitis
• Young adults
• Inflammatory back pain
• Known spondyloarthropathy

JIA Evaluation

In a child with suspected JIA-associated uveitis, consider:

• ANA
• Rheumatologic assessment

JIA uveitis may be asymptomatic, making screening crucial.

TINU Evaluation

If TINU is suspected:

• Serum creatinine
• Urinalysis
• Urine β2-microglobulin

may be useful.

Renal consultation may be appropriate.

Vasculitis / Scleritis Workup

If uveitis is associated with:

• Scleritis
• Peripheral ulcerative keratitis
• Sinopulmonary disease
• Systemic vasculitic symptoms

consider targeted testing such as:

• ANCA
• ESR
• CRP

Imaging

OCT

OCT is useful for detecting and monitoring:

• Cystoid macular edema
• Epiretinal membrane
• Macular structural damage

Fluorescein Angiography

Useful when there is concern for:

• CME
• Retinal vasculitis
• Posterior segment inflammatory disease

B-Scan Ultrasonography

Useful when media opacity prevents visualization of the posterior segment.

Anterior Chamber or Vitreous Sampling

May be considered in selected cases for:

• HSV PCR
• VZV PCR
• CMV PCR
• Toxoplasma PCR
• Cytology for lymphoma or leukemia

This is particularly useful in atypical or treatment-resistant disease.

Differential Diagnosis

Important causes include:

• HLA-B27-associated anterior uveitis
• Ankylosing spondylitis
• Psoriatic arthritis
• IBD-associated uveitis
• Reactive arthritis
• JIA
• HSV
• VZV
• CMV
• Posner-Schlossman syndrome
• Fuchs uveitis syndrome
• Behçet disease
• TINU
• Traumatic iritis
• Lens-induced uveitis
• UGH syndrome
• Drug-induced uveitis
• Intraocular lymphoma
• Idiopathic anterior uveitis

Other infectious or granulomatous diseases such as syphilis, TB, and sarcoidosis can also present with anterior inflammation and should be considered when appropriate.

Treatment

First-Line – Topical Corticosteroids

The mainstay of treatment for noninfectious anterior uveitis is:

Topical corticosteroid therapy

Common choices include:

• Prednisolone acetate 1%
• Difluprednate 0.05%

Frequency depends on severity.

Severe inflammation may initially require very frequent dosing, then gradual tapering according to clinical response.

Important Treatment Principle

Do not taper corticosteroids based only on symptoms.

Taper according to:

• Anterior chamber cell count
• Flare
• Clinical course

Tapering too quickly may cause recurrence.

Cycloplegics

Cycloplegic or mydriatic agents are used to:

• Reduce ciliary spasm
• Relieve pain
• Prevent posterior synechiae
• Break fresh synechiae

Options include:

• Homatropine
• Cyclopentolate
• Atropine in severe disease

Herpetic Anterior Uveitis

If HSV or VZV is suspected, treatment generally includes:

• Systemic antiviral therapy
• Topical corticosteroid under antiviral cover
• IOP-lowering therapy when needed

Steroid monotherapy should be avoided when active herpetic disease is suspected.

Periocular Steroids

Sub-Tenon corticosteroid injection may be considered for:

• Chronic uveitis
• Significant CME
• Poor response to topical therapy
• Poor adherence

Monitor closely for:

• Steroid-induced ocular hypertension
• Cataract

Systemic Corticosteroids

Oral prednisone may be needed when inflammation is:

• Severe
• Bilateral
• Posteriorly extensive
• Refractory to topical/local therapy

Prolonged high-dose therapy should generally be avoided when steroid-sparing therapy is appropriate.

Steroid-Sparing Immunomodulatory Therapy

Consider when:

• Disease is chronic
• Relapses occur during steroid taper
• Long-term systemic corticosteroid is required
• Steroid toxicity develops

Options include:

• Methotrexate
• Mycophenolate mofetil
• Azathioprine
• Cyclosporine
• Tacrolimus
• Biologic therapy

These are usually managed with rheumatology or a uveitis specialist.

Biologic Therapy

Biologic agents, especially TNF-alpha inhibitors, may be particularly useful in:

• JIA-associated uveitis
• Behçet disease
• Spondyloarthropathy-associated uveitis
• Refractory noninfectious uveitis

Systemic infection screening is essential before biologic therapy.

Monitoring During Immunosuppression

Depending on the medication, monitoring may include:

• CBC
• Liver function
• Renal function
• Blood pressure
• Infection screening

Monitoring intervals depend on the specific drug and specialist protocol.

Glaucoma Management

Glaucoma may result from:

• Inflammatory trabeculitis
• Peripheral anterior synechiae
• Pupillary block
• Steroid response

Treatment may require:

• IOP-lowering drops
• Glaucoma specialist referral
• Surgery if uncontrolled

Cataract

Posterior subcapsular cataract may result from:

• Chronic inflammation
• Corticosteroid exposure

Cataract surgery is usually planned when inflammation has been well controlled.

Cystoid Macular Edema

CME is a major cause of reduced vision.

Treatment may include:

• Topical steroids
• Periocular steroid
• Intravitreal steroid
• Systemic anti-inflammatory treatment
• Steroid-sparing immunomodulation

Surgery

Possible procedures include:

• Cataract extraction
• Glaucoma surgery
• Vitrectomy in selected cases

Surgery is ideally performed when inflammation is well controlled.

Referral

Consider referral to:

• Uveitis specialist for recurrent or atypical disease
• Rheumatology for HLA-B27/JIA/systemic inflammatory disease
• Gastroenterology for IBD
• Pulmonology for sarcoidosis
• Retina specialist for CME or posterior involvement
• Glaucoma specialist for uncontrolled IOP

Follow-Up

During active inflammation, follow-up may initially be:

• Weekly
• Every 1–2 weeks

depending on severity.

Once the anterior chamber reaction improves and steroid dosing decreases, visits may be spaced out.

Patient Monitoring

Monitor:

• Visual acuity
• Anterior chamber cells
• Flare
• IOP
• Posterior synechiae
• Cataract
• CME
• Response to steroid taper

Prognosis

Prognosis depends on:

• Etiology
• Severity
• Recurrence
• Chronicity
• Treatment response
• Development of complications

Many acute unilateral cases have an excellent prognosis with appropriate treatment.

Chronic or recurrent disease may lead to permanent visual impairment.

Complications

Important complications include:

• Posterior synechiae
• Seclusio pupillae
• Iris bombe
• Secondary angle closure
• Steroid-induced glaucoma
• Chronic inflammatory glaucoma
• Posterior subcapsular cataract
• Cystoid macular edema
• Band keratopathy
• Hypotony in severe chronic disease

Ophthalmology Pearls

• NGAU = pain + photophobia + ciliary flush + anterior chamber cells/flare.
• Fine or stellate KPs favor a non-granulomatous pattern.
• HLA-B27 uveitis is typically acute, unilateral, recurrent, and can be severe with hypopyon.
• Anterior uveitis with high IOP should raise suspicion for herpetic disease, Fuchs uveitis syndrome, or Posner-Schlossman syndrome.
• Cycloplegics relieve pain and help prevent posterior synechiae.
• Always perform a dilated fundus examination to exclude posterior involvement.
• Laboratory testing should be targeted to the clinical picture, not ordered indiscriminately.
• Do not suppress presumed infectious uveitis with corticosteroids alone.
• CME, cataract, and glaucoma are major causes of long-term visual loss.
• Recurrent or steroid-dependent disease should prompt consideration of systemic immunomodulatory therapy.