An approach to pediatric uveitis

Uveitis is less common in children than In adults, accounts for fewer than 10% of reported cases of uveitis, but its diagnosis and management can be particularly challenging. Young children are often asymptomatic either because of inability to express complaints or because of the truly asymptomatic nature of their disease. Even in advanced cases, parents may not be aware of severe visual impairment until the development of externally visible changes such as band keratopathy, strabismus, or

leukocoria.

When diagnosing uveitis in children, as with adults, it is important first to localize

the disease. When it is limited to the anterior segment, the two most common

causes are juvenile idiopathic arthritis and chronic idiopathic anterior uveitis. If

the disease affects the posterior segment, infectious causes such as

TORCH (toxoplasmosis, rubella, cytomegalovirus, herpes) and

toxocariasis must be considered.

In panuveitis, conditions such as sarcoidosis, syphilis, and masquerade syndromes like leukemia may be involved.

patients diagnosed with juvenile idiopathic arthritis, sarcoidosis, and other conditions must be routinely evaluated for ocular inflammationConnection between specialists .

DIAGNOSTIC ENTITIES

Classification There is no universally accepted

technique for classifying uveitis. Many authors choose to classify uveitis based on causative factor. Those texts generally group uveitis into inflammatory or infective categories. Classification can also be based on time course of the disease, with acute, subacute, and chronic types as the major subclassifications.

Many ophthalmic texts also classify uveitis in terms of white cell types using granulomatous and nongranulomatous as the major subclassificatin.The pediatrician find it easier to classify uveitis based on the anatomical structures involved, uveitis will be classified into four categories: anterior uveitis, intermediate uveitis, posterior uveitis, and masquerade syndromes

Common causes of pediatric uveitis

Anterior uveitisJIA-associated iritisJuvenile spondyloarthropathiesHSV/HZVFuchs heterochromic iridocyclitis SarcoidosisBehçet syndromeSyphilisTuberculosisTraumatic iritisIdiopathic

Intermediate uveitis

Pars planitisSarcoidosis

Chronic cyclitisLyme disease

Behçet syndromeMultiple sclerosis

Idiopathic

Posterior uveitisToxoplasmosisToxocariasisVogt–Kayanag– Harada syndromeSympathetic ophthalmiaSarcoidosis TuberculosisCMV retinitisAcute retinal necrosisCysticercosisOnchocerciasisHistoplasmosis

Masquerade syndromesRetinoblastomaRetinitis pigmentosaChronic retinal detachmentLeukemiaLymphomaJuvenile xanthogranuloma

JIA-associated Anterior UveitisJIA is the most common systemic

association of pediatric uveitis. It is defined as arthritis of at least 6 weeks’ duration without any other identifiable cause in children younger than 16 years of age. The International League of Associations for Rheumatology (ILAR) has classified JIA into seven subtype

Patients with systemic-onset JIA have extraocular manifestations Uveitis is extremely rare in this subtype.

the oligoarticular subtype is diagnosed when fewer than 5 joints are involved during the first 6 months of the disease. Chronic anterior uveitis is most commonly associated with oligoarticular JIA.

Polyarticular JIA is diagnosed when 5 or more joints are affected during the first 6 months of the disease. Polyarticular JIA may be rheumatoid factor (RF) positive or negative. Uveitis is rare in the RF-positive group, however approximately 10% of patients with RF-negative polyarticular JIA develop uveitis.

Psoriatic arthritis is a less common subtype of JIA which may be associated with chronic anterior uveitis in 10–20% of cases. Patients with arthritis who do not fulfill any of these categories are classified as the “other” JIA subgroup.

Risk factors for ocular involvement in patients with JIA include female sex, oligoarticular arthritis, young age at onset of arthritis, antinuclear antibody (ANA) seropositivity and RF seronegativity

TREATMENTThe first line of treatment is topical corticosteroids, and mydriatic,Topical corticosteroids are used frequently during exacerbations and tapered as the inflammation subsides. If topical steroids are insufficient to control the inflammation, depot steroid injections or even systemic steroids are used. In cases of uveitis where significant doses of steroids are needed to control the inflammation, and they cannot be easily tapered, immunosuppressive agents are often used as an adjunct therapy.

PROGNOSISband keratopathy develop in More than 50% of patients

These are usually not visually significant unless they central

Cataracts can develop in up to one-third of patients recently a diagnosis of JIA has been acontraindication to lens implantation however, some ophthalmologists are attempting lens implantation with newer (less inflammatory) lenses.

Glaucoma occurs in about 20% of these patients and does not respond well to medical therapy

Early detection and treatment of JIA associated uveitis are of most importance to preserve vision in these children.

Juvenile spondyloarthropathies

This category of disease accounts for about

15% of pediatric anterior uveitis cases. It includes

juvenile ankylosing spondylitis,juvenile Reiter’s syndrome, juvenile psoriatic arthritis,

ulcerative colitis, Crohn’s disease.

CLINICAL PRESENTATIONBoys are more commonly affected, Usually >8 years of age, These patients often present with acute

recurrent uveitis that is bilateral and asymmetric.

A large majority of these patients are positive HLA-B27 ,most are RF negative.

Some juvenile ankylosing spondylitis patients can present with a severe acute anterior uveitis and hypopyon formation.

Treatment and prognosissimilar to JIA including topical

corticosteroids and mydriatic agents.

The acute recurring bouts of inflammation tend to taper off as these children age.

The first episode of uveitis is often the most severe, and if treated early, the visual prognosis is very good.

SarcoidosisThere are two distinct subgroups of

sarcoidosis that present with ocular inflammation.

Childhood sarcoidosis is seen in children< 5 years old, is more common in girls,

andis characterized by arthritis with a skin

rash.There is a striking predominance of

Caucasianchildren affected by this early-onset

sarcoidosis.

adult-type sarcoidosisIs also seen in children, most commonly

between the ages of 8 and 15 years, and is three times more common in African–American children than in Caucasians. This form is seen with equal frequency in boys and girls. These children have pulmonary findings, and may have hepatosplenomegaly and lymphadenopathy.

anterior uveitis is the most common presentation, granulomatous in nature sarcoidosis can present with intermediate, posterior, or pan uveitis.

Ocular signs

Laboratory investigationsAngiotensin-converting enzyme (ACE)

levels, ACE levels must be age-matched because children have higher ACE levels than adults

Serum lysozyme levels, Chest X-ray, and galliumScanning of the lungs and lacrimal

glands. Definitive diagnosis is made by biopsy of a

nodule showing non caseating granulomas

TREATMENT AND PROGNOSISTreatment of the anterior uveitis consists of

topical corticosteroids and mydriatic agents. Often systemic corticosteroids that are used to treat pulmonary complications can control the ocular disease. While dramatic improvement is seen clinically with systemic and topical steroids, the chronic nature of the uveitis associated with sarcoidosis often leads to the development of both cataracts and glaucoma. Both of these complications can be treated surgically with good results

Herpetic iridocyclitisCLINICAL PRESENTATION AND DIAGNOSIS

Both (HSV) and (HZV) can cause anterior uveitis.The inflammation is generally unilateral, can beeither acute or chronic, and is often associatedwith an increase in IOP. Herpetic uveitis typicallyoccurs in conjunction with significant cornealinvolvement. Children typically present withphotophobia and decreased vision. HSV andHZV uveitis can also present with concomitanthyphema

Sector iris atrophy as a result of HZV iritis

.

Gonioscopic photograph of a layeredhyphema in a patient with HZV iritis

TREATMENT AND PROGNOSISDiagnosis is usually confirmed by corneal

culturetopical or systemic antiviral agents,

corticosteroids, and mydriatics. Corticosteroids should be administered later in

the course of the disease as they can prevent corneal epithelial wound healing.

Prognosis is good, with the good visual outcome depending on the level of corneal scarring. Glaucoma can occur with active inflammation and is usually well treated with medical management. In cases of HZV uveitis, sector iris atrophy can be seen

Idiopathic Intermediate Uveitis (Pars Planitis)

According to the anatomic classification of uveitis by the Standardization of Uveitis Nomenclature (SUN) Working Group, the term “intermediate uveitis” defines a subset of uveitis where the vitreous is the primary site of inflammation.

Pars planitis is a diagnostic term that defines a subset of idiopathic intermediate uveitis where there is snowbank or snowball formation. This disease typically affects children and adolescents. the association of intermediate uveitis with a systemic disease is very rare in children. Associations between idiopathic intermediate uveitis and HLA-DR2 and HLA-DR15 have been reported suggesting an immunogenetic predisposition.

Typical clinical findings include mild to moderate anterior segment inflammation, diffuse vitreous cells and haze, and snowballs(accumulations of white blood cells in the anterior vitreous ) and snowbanks (exudates over the pars Plana) located inferiorly .

Band keratopathy and posterior synechiae may be seen in childhood pars planitis but are very rare in adults.

Optic disc edema and cystoid macular edema are the most frequent complications

.

snow ball opacities and vitreous haze in a child with pars planitis

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Behçet UveitisThe peak age of onset for Behçet

disease is in the third or fourth decade of life. Although the onset of recurrent oral ulcers in childhood is not uncommon, patients typically fulfill the diagnostic criteria after the age of 16 years. There are no internationally accepted diagnostic criteria for childhood-onset Behçet disease.

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In a recent international registry of patients suspected of pediatric Behçet disease, the presenting symptom was isolated recurrent oral ulcers in 83%, and the diagnosis was confirmed by an expert committee in 62% of registered cases.From an ophthalmological point of view, pediatric Behçet uveitis is defined as onset of uveitis at 16 years of age or younger irrespective of the age for fulfilling the diagnostic criteria.

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Mean age at onset is in late childhood (10–15 years).

a male predominance in the pediatric age group, similar to adult-onset Behçet uveitis.

A positive family history has been reported in 20–47% of pediatric cases from endemic areas, implying the role of genetic factor.bilateral involvement and recurrent panuveitis with retinal vasculitis (occlusive in nature , both arteries and veins are affected

Don’t forget shifting hypopyon

Diagnostic criteria1-painful oral aphthus ulcer recurrent

at least 3 times/year+ at least one of the following

-recurrent genital ulcers-uveitis-skin lesion(erythema nodosum or

papulovesicular lesion)-+ve pethargy test

Complications and prognosis

Cataract, macular edema or maculopathy, and optic atrophy are the most common complications.

While visual prognosis has been reported to be better than adults in some series.

posterior segment complications of Behçet's disease. branch retinal vein occlusion caused by periphlebitis; retinal infiltrates; massive retinal exudation; atrophy and vascular sheathing: posterior segment manifestation

ToxoplasmosisCLINICAL PRESENTATION/DIAGNOSIS

The most common cause of pediatric posterior uveitis

at least 50% of cases.

The infective agent is the intracellular protozoan Toxoplasma gondii.

Cats are the definitive host, with human infection a result of ingestion of the encysted organism in undercooked meats. but ingestion of encysted protozoans in immuno competent individuals usually does not cause infection

Congenital systemic toxoplasmosisTrancplacental when a pregnant woman

contracts the acute form. If the mother is infected before the pregnancy, the fetus will be unaffected.

infection during early pregnancy may result in stillbirth

infection during late pregnancy may cause generalized convulsions, paralysis, fever and visceral involvement. Intracranial calcification may be seen on plain skull radiographs

intracranial calcification in congenital toxoplasma

Macular scar in congenital toxoplasmosis

Acquired toxoplasmosis

Unilateral ,sudden onset visual loss and photophobia

Spillover anterior uveitis (granulomatous )Solitary inflammatory focus near old

pigmented scar(satellite lesion)Multiple foci un commonSever vitritis obscuring the fundus

picture ,however the active focus still visible (headlight in the frog appearance)

Toxoplasmic retinochoroiditis .

Active retinochoroiditis intoxoplasmosis.

ToxocariasisCLINICAL PRESENTATION/DIAGNOSISOcular toxocariasis is caused by the canine

roundworm Toxocara canis. Infection commonly occurs after ingestion of soilcontaminated by the roundworm eggs. Ocular toxocariasis is more common in boys and

usually there is a history of geophagia. Ocular involvement is usually unilateral and

presentseither as endophthalmitis or as a granuloma(peripheral or central).

posterior pole granuloma; optic nerve head granuloma; peripheral granuloma; severe fibrosis and tractional retinal detachmen

Retinal traction to the optic nerve head and macular scarring in toxocariasis.

Anterior traction on the optic nerve head from toxocariasis peripheral granuloma

Vogt–Koyanagi–Harada syndromeCLINICAL PRESENTATION AND

DIAGNOSISmore in darker pigmented individuals, three stages. The first stage is commonly

mistaken for a viral infection, with flu-like symptoms, headache, and tinnitus or hearing loss.

Stage 2 is the ophthalmic stage where patients develop bilateral panuveitis, hyperemia of the optic disc, and serous retinal detachments.

This stage is often when the patient presents with pain, photophobia, and decreased vision.

Stage 3, the convalescent stagedermatologic manifestations appear.

These include poliosis (whitening/graying of a patch of hair), vitiligo and alopecia in Stage 3 ophthalmic disease is characterized by retinal depigmentation, proliferation of retinal pigment epithelium, which can cause a puckering of the macula and development of peripheral yellow/white deposits under the retina (Dalen–Fuchs nodules).

Multiple serous retinal detachments in VKH.

Vitiligo

Diagnosis is made based on clinical findings

since the exact cause of VKH is unknown.Systemic autoimmune response to retinal,uveal, and cutaneous melanocytes.

Laboratory studies are usually not helpful in making the diagnosis, but a lumbar puncture with pleocytosis is supportive. Ophthalmic ultrasound during active inflammation shows findings consistent with panuvei tis

Sympathetic ophthalmiauncommonbilateral panuveitis seen after penetrating

ocular traum the injured eye (exciting eye) often develop inflammation first, and the uninjured eye (sympathizing eye) followingweeks to months later .

It develops within 3 months (70%) of the original injury; however, it may develop in as short as 5 days and as long as 42 years.

Sympathetic ophthalmia, can be prevented with early removal of the injured eye if there is no visual potential. Because of the rarity of sympathetic ophthalmia, if there is any potential vision, removal is not always recommended.

High-dose systemic steroids, along with topical and periocular injections, are recommended.

Cyclosporine can help in unremitting cases

Once inflammation has started ,some studies recommend removal of the exiting eye. This is controversial, and other studies have shown no benefit of removal.

Visual prognosis is good with up to 75% of patients retaining good vision (>20/50). Many of those patients require long-term steroids to retain that vision.

Masquerade syndromesRetinoblastoma

The most common pediatric malignant ocular tumor Retinoblastoma presents most commonly as either leukocoria , strabismus, or with signs of ocular inflammation.

The inflammation from retinoblastoma often causes a red, painful eye that is photophobic. A hypopyon may be as well as a ‘pseudohypopyon’, which actually represents a layering of the tumor cells in the anterior chamber.

U/S

LeukemiaThe most common ocular presentation of

systemic leukemia is retinal hemorrhages on fundus examination.

Leukemic infiltrates within the uvea may lead to pseudoanterior iritis, which can layer out in the anterior chamber forming a hypopyon .

Choroidal involvement generally presents as serous retinal detachments and optic nerve involvement presents as papilledema.

Definitive diagnosis is made with bone marrow biopsy and smear. Aqueous tap maybe be performed for cytology

Leukemic pseudohypopyon

CONCLUSION

Pediatric uveitis is a complex, chronic, and challenging condition for the patient, parent, and physician. Close monitoring, cooperation with other specialists, aggressive treatment, and consideration of amblyopia are all key to prevent complications from this disease.