Ophthalmology – Iritis-Uveitis in Children

Basics

Description

Uveitis refers to intraocular inflammation. In children, it can involve different parts of the eye and may be classified anatomically.

Anterior uveitis involves the iris and ciliary body and includes iritis and iridocyclitis. Intermediate uveitis mainly involves the pars plana and vitreous, as in pars planitis. Posterior uveitis involves the retina and/or choroid and may also affect the optic nerve and vitreous. Panuveitis refers to inflammation involving multiple segments of the eye.

Childhood uveitis is less common than adult uveitis but may be particularly dangerous because some forms are asymptomatic despite active inflammation.

Epidemiology

Childhood uveitis is uncommon.

Reported incidence is approximately 4–7 cases per 100,000 children, with prevalence around 30 per 100,000.

A large proportion of cases are idiopathic, but juvenile idiopathic arthritis (JIA) is the most important systemic association with noninfectious anterior uveitis in children.

Risk Factors

Important risk factors include:

• Juvenile idiopathic arthritis
• Autoimmune disease
• HLA-B27-associated disease
• Congenital or acquired infections
• Ocular trauma
• Immunosuppression
• Exposure to infectious agents

JIA-Related Risk Factors

Children at particularly high risk for JIA-associated uveitis include those with:

• Oligoarticular JIA
• Young age at arthritis onset
• Positive ANA
• Negative rheumatoid factor
• Female sex

The ocular inflammation may occur independently of joint activity.

Genetics

Genetic predisposition contributes to several causes of childhood uveitis.

HLA-B27 is associated with acute anterior uveitis and with systemic disorders such as:

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

Genetic susceptibility often interacts with environmental or infectious triggers.

General Prevention

The most important preventive measure is regular ophthalmologic screening of children at risk, especially those with JIA.

Because JIA-associated uveitis may occur in a completely white, quiet, asymptomatic eye, relying on symptoms can lead to delayed diagnosis and irreversible complications.

Prevention also includes appropriate treatment of systemic disease and avoidance or early treatment of infections when possible.

Pathophysiology

The mechanism depends on the underlying cause.

In autoimmune disease, inflammation is thought to result from dysregulated immune responses directed against ocular tissues.

The exact mechanism of JIA-associated uveitis remains incompletely understood.

Chronic inflammation can damage:

• Cornea
• Iris
• Trabecular meshwork
• Lens
• Vitreous
• Retina
• Optic nerve

This explains the broad range of potential complications.

Etiology

Anterior Uveitis

Important causes include:

• Juvenile idiopathic arthritis
• Idiopathic anterior uveitis
• HLA-B27-associated disease
• Trauma
• Behçet disease
• Sarcoidosis
• Kawasaki disease
• Tubulointerstitial nephritis and uveitis syndrome
• HSV or VZV
• Syphilis
• Tuberculosis
• Lyme disease
• Toxoplasmosis and other infections

Masquerade syndromes must also be considered, including:

• Retinoblastoma
• Leukemia
• Lymphoma
• Juvenile xanthogranuloma
• Coats disease
• Intraocular foreign body

JIA-Associated Uveitis

JIA is the most important cause of chronic noninfectious anterior uveitis in children.

The highest risk occurs with oligoarticular JIA.

The ocular disease may:

• Precede arthritis
• Occur during active arthritis
• Continue when joint disease is inactive

There is often no relationship between joint symptoms and ocular inflammatory activity.

The eye can appear externally normal despite significant inflammation.

A substantial proportion of affected children require prolonged treatment.

HLA-B27-Associated Uveitis

Children with enthesitis-related arthritis may develop HLA-B27-associated anterior uveitis.

Unlike classic JIA-associated uveitis, this form is more likely to be:

• Symptomatic
• Acute
• Painful
• Red
• Photophobic

Intermediate Uveitis

Possible causes include:

• Idiopathic intermediate uveitis
• Pars planitis
• Sarcoidosis
• Inflammatory bowel disease
• Multiple sclerosis
• Lyme disease

Intermediate uveitis is relatively uncommon in JIA.

Posterior Uveitis

Infectious causes are particularly important.

Toxoplasmosis is one of the most common infectious causes of posterior uveitis in children.

Other causes include:

• Toxocariasis
• Tuberculosis
• Syphilis
• Lyme disease
• Bartonella
• Fungal infection
• Bacterial infection
• HSV
• VZV
• CMV

Noninfectious causes include:

• Sarcoidosis
• Vogt-Koyanagi-Harada disease
• Sympathetic ophthalmia
• Masquerade syndromes

Panuveitis

Panuveitis may be caused by:

• Infection
• Systemic inflammatory disease
• Autoimmune disorders
• Masquerade syndromes

Because multiple ocular compartments are involved, extensive systemic evaluation may be necessary.

Commonly Associated Ocular Conditions

Childhood uveitis can be associated with:

• Band keratopathy
• Cataract
• Posterior synechiae
• Peripheral anterior synechiae
• Glaucoma
• Cystoid macular edema
• Chorioretinal scarring
• Retinal detachment
• Hypotony
• Vitreous hemorrhage
• Permanent vision loss

Diagnosis

History

History may provide the most important clues to the underlying cause.

Ask about:

• Eye redness
• Pain
• Photophobia
• Floaters
• Blurred vision
• Reduced vision
• Joint pain or swelling
• Skin rash
• Oral ulcers
• Fever
• Weight loss
• Recent infections
• Exposure to tuberculosis
• Tick exposure
• Travel
• Trauma
• Family history of autoimmune disease

Importantly, absence of ocular symptoms does not exclude active uveitis, particularly in JIA.

Physical Examination

A complete pediatric and ophthalmic examination should be performed.

Visual Acuity

Age-appropriate visual acuity testing is essential.

Young children may require:

• Fixation assessment
• Picture-based testing
• Matching symbols

Amblyopia may coexist and complicate interpretation.

Intraocular Pressure

IOP may be:

• Low during active ciliary body inflammation
• Elevated from chronic inflammation
• Elevated from steroid response
• Elevated from angle damage or synechiae

Both the disease and its treatment can therefore cause glaucoma.

Conjunctiva and Sclera

Possible findings include:

• Ciliary flush
• Episcleritis
• Scleritis
• Conjunctival nodules

The eye may nevertheless appear completely quiet in chronic JIA-associated uveitis.

Cornea

Possible findings include:

• Corneal edema
• Keratic precipitates
• Band keratopathy
• Interstitial keratitis
• Dendritic or geographic epithelial lesions in herpetic disease

Keratic precipitates may be small and nongranulomatous or larger and greasy in appearance, termed mutton-fat KPs.

Anterior Chamber

Slit-lamp examination may reveal:

• Cells
• Flare
• Fibrin
• Hypopyon

Anterior chamber cells are graded according to the number seen in a standardized slit beam.

Flare represents leakage of protein into the aqueous because of breakdown of the blood-aqueous barrier.

A true hypopyon contains inflammatory white blood cells. A pseudohypopyon can occur with tumor cells and should raise concern for a masquerade syndrome.

Iris

Important findings include:

• Posterior synechiae
• Peripheral anterior synechiae
• Iris nodules
• Iris neovascularization
• Irregular pupil

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

Lens

Chronic inflammation and corticosteroid treatment may both lead to cataract formation.

Gonioscopy

Gonioscopy can identify:

• Peripheral anterior synechiae
• Angle closure
• Neovascularization
• Inflammatory debris

It is particularly important in children with elevated IOP.

Vitreous

The vitreous may contain:

• Inflammatory cells
• Haze
• Hemorrhage
• Membranes

These findings indicate intermediate or posterior segment involvement.

Retina

Possible retinal findings include:

• Cystoid macular edema
• Cotton-wool spots
• Retinal hemorrhages
• Vascular sheathing
• Neovascularization
• Retinal detachment

Choroid

Choroidal inflammatory lesions may occur in systemic inflammatory and infectious disease.

Certain inflammatory disorders may produce small yellow-white lesions at the level of the retinal pigment epithelium and choroid.

Pars Plana

Intermediate uveitis may produce:

• Snowballs
• Snowbanking
• Peripheral neovascularization

Snowbanking refers to white inflammatory exudates over the pars plana.

Optic Nerve

Possible findings include:

• Optic disc edema
• Optic atrophy
• Neovascularization
• Infiltration

Optic nerve involvement may substantially worsen the visual prognosis.

Diagnostic Tests and Interpretation

The workup should be directed by the history and examination, rather than using a broad laboratory panel in every child.

Laboratory Testing

Possible tests include:

• CBC with differential
• ESR and/or CRP
• ANA
• ACE
• Serum calcium
• Syphilis serology
• Tuberculosis testing
• Lyme serology when epidemiologically appropriate
• HLA-B27 when clinically indicated
• Urinalysis

Additional targeted studies may be appropriate based on the suspected diagnosis.

Urinalysis and TINU

Urinalysis can be particularly useful when tubulointerstitial nephritis and uveitis syndrome is suspected.

Renal abnormalities may precede, accompany, or follow the ocular disease.

Chest Imaging

Chest radiography may be considered when evaluating for:

• Sarcoidosis
• Tuberculosis

Further chest imaging may be needed when suspicion remains high.

Ocular Ultrasound

B-scan ultrasonography can be useful when media opacity prevents adequate visualization of the posterior segment.

It can identify:

• Retinal detachment
• Vitreous abnormalities
• Mass lesions

OCT

Optical coherence tomography is especially useful for detecting and monitoring:

• Cystoid macular edema
• Epiretinal membrane
• Structural macular damage

Fluorescein Angiography

Fluorescein angiography may demonstrate:

• Retinal vasculitis
• Macular edema
• Capillary leakage
• Neovascularization

Wide-field angiography may be particularly useful for detecting peripheral inflammation.

Other Investigations

Depending on the clinical context, additional evaluation may include:

• MRI of brain or orbits
• Sacroiliac or hand imaging
• Lumbar puncture
• ANCA
• HIV testing
• Stool testing for parasites
• Skin testing for tuberculosis
• ERG
• VEP
• Visual fields
• Aqueous or vitreous sampling
• Tissue biopsy

Differential Diagnosis

Important masquerade and alternative diagnoses include:

• Retinoblastoma
• Leukemia
• Lymphoma
• Trauma
• Retained intraocular foreign body
• Coats disease
• Juvenile xanthogranuloma
• Retinal dystrophies
• Infectious retinitis

Atypical inflammation, poor response to therapy, or pseudohypopyon should increase concern for a masquerade syndrome.

Treatment

Treatment depends on:

• Anatomic location
• Severity
• Underlying cause
• Presence of infection
• Risk of complications

The major goals are to suppress inflammation, prevent structural damage, treat the cause, and preserve visual development.

Topical Corticosteroids

Topical corticosteroids are first-line therapy for many forms of anterior noninfectious uveitis.

Frequency depends on severity and may range from several times daily to very frequent dosing in severe disease.

Treatment must be tapered according to clinical response.

Prolonged corticosteroid use can cause:

• Cataract
• Ocular hypertension
• Glaucoma

Cycloplegic Therapy

Cycloplegics are used to:

• Relieve pain from ciliary spasm
• Reduce photophobia
• Prevent or break posterior synechiae

The specific agent and frequency depend on the degree of inflammation.

Periocular Corticosteroids

Periocular steroid injections may be considered when:

• Topical treatment is insufficient
• Intermediate or posterior inflammation is present
• Macular edema is significant

Potential complications must be considered carefully in children.

Systemic Corticosteroids

Systemic corticosteroids may be required for:

• Severe bilateral disease
• Posterior uveitis
• Panuveitis
• Sight-threatening inflammation
• Disease inadequately controlled with local therapy

Long-term systemic corticosteroid exposure is undesirable in children because of effects on:

• Growth
• Bone health
• Metabolism
• Immune function

Therefore, steroid-sparing therapy should be considered early when chronic treatment is expected.

Immunomodulatory Therapy

Systemic immunomodulatory therapy should be managed by physicians experienced with these medications, usually in collaboration with pediatric rheumatology.

Methotrexate

Methotrexate is a common first-line steroid-sparing agent for chronic JIA-associated uveitis when topical therapy is inadequate or prolonged steroid exposure would be required.

Biologic Therapy

Biologic agents, particularly anti-TNF therapy, may be used for refractory disease.

Adalimumab is an important treatment for JIA-associated uveitis when conventional immunomodulation is inadequate.

Other agents may be considered in selected cases.

Additional Immunosuppressive Agents

Options may include:

• Mycophenolate mofetil
• Azathioprine
• Cyclosporine
• Tacrolimus
• Rituximab in selected refractory cases
• Alkylating agents for severe resistant disease

Therapy is individualized according to diagnosis and response.

Infectious Uveitis

Infectious causes require specific antimicrobial treatment.

Corticosteroids should not be used as stand-alone therapy when active infection is present.

Depending on the infection, treatment may involve:

• Antivirals
• Antibiotics
• Antituberculous therapy
• Antiparasitic medication
• Antifungal therapy

Infectious disease consultation may be appropriate.

Referral

Children without an obvious isolated traumatic cause generally benefit from multidisciplinary evaluation.

Referral may include:

• Pediatric rheumatology
• Infectious disease
• Oncology
• Neurology
• Nephrology
• Genetics

depending on the suspected etiology.

Surgical Treatment

Band Keratopathy

Visually significant band keratopathy may be treated with EDTA chelation after inflammation is adequately controlled.

Cataract Surgery

Cataract surgery may be required when lens opacity significantly limits vision.

Ideally, inflammation should be well controlled before surgery.

These children are at increased risk for:

• Postoperative inflammation
• Posterior synechiae
• Glaucoma
• Posterior capsule opacification

Glaucoma Surgery

Glaucoma that cannot be controlled medically may require surgery.

Retinal Procedures

Retinal laser or retinal detachment repair may be necessary for posterior segment complications.

Drug-Delivery Implants

Local sustained-release drug-delivery systems may be considered in carefully selected refractory cases.

Inpatient Considerations

Most childhood uveitis is managed as an outpatient.

Hospital admission may be required when:

• Severe systemic disease is present
• Intravenous antimicrobial therapy is needed
• High-dose intravenous corticosteroids are required
• A serious masquerade or systemic inflammatory disorder is being evaluated

Ongoing Care

Follow-Up

Children require frequent ophthalmologic examinations, particularly when inflammation is active.

Follow-up should monitor:

• Visual acuity
• Amblyopia
• Anterior chamber cells and flare
• IOP
• Cataract
• Synechiae
• Band keratopathy
• Macular edema
• Retinal disease
• Medication toxicity

Systemic Monitoring

Children receiving systemic immunosuppression require regular monitoring appropriate to the medication.

Because children grow, weight-based drug doses must be reassessed periodically.

Coordination among ophthalmology, rheumatology, primary care, and other specialists is essential.

Amblyopia

Amblyopia deserves special attention in pediatric uveitis.

Vision may be reduced not only by inflammation but also by:

• Cataract
• Corneal opacity
• Refractive error
• Strabismus

These factors can interfere with visual development even after the inflammation has been controlled.

Patient and Family Education

Parents should understand that:

• Uveitis may be present without symptoms
• Regular eye examinations are essential
• Treatment may need to continue for years
• Medications must not be stopped abruptly without medical advice
• Glaucoma and cataract can result from both the disease and its treatment

Families should be encouraged to maintain close follow-up even when the child’s eyes appear normal.

Prognosis

Early recognition and aggressive control of inflammation can substantially reduce the risk of permanent visual loss.

Prognosis depends on:

• Underlying etiology
• Duration before diagnosis
• Location of inflammation
• Presence of complications
• Response to treatment
• Adherence to follow-up

Children with chronic asymptomatic anterior uveitis may already have complications at the time of diagnosis if screening has been inadequate.

Complications

Major complications include:

• Band keratopathy
• Cataract
• Posterior synechiae
• Secondary glaucoma
• Cystoid macular edema
• Hypotony
• Optic disc edema
• Vitreous hemorrhage
• Epiretinal or vitreoretinal membranes
• Retinal detachment
• Phthisis bulbi
• Amblyopia
• Permanent visual loss

The most important clinical pearl is that JIA-associated uveitis can be severe despite a completely white, painless eye, making scheduled slit-lamp screening essential for children at risk.