Zeroing in on Pediatric Uveitis

Pediatric uveitis can present challenges to the eye care professional, the patient, and their family. The classification of both adult and pediatric uveitis starts by determining whether the etiology is infectious or noninfectious and localizing the anatomic location. It is also helpful in the pediatric patient with uveitis to note age delineations: infancy = 0 to 2 years of age, toddler/school age = 2 to 10 years of age, and adolescence = 10 to 20 years of age.

Although adult uveitis is more common than pediatric uveitis, a higher percentage of posterior uveitis occurs in the pediatric population (40% vs 20%). Smith et al showed that anatomically, pediatric uveitis presents 40% to 50% posteriorly, 30% to 40% anteriorly, 10% to 20% intermediately, and 5% to 10% as panuveitis.¹ Because of the higher prevalence of posterior uveitis in the pediatric population, the overall visual consequences, complications, and vision loss can be more severe. Uveitis in children, as in the adult population, tends to have a female predominance.¹ A thorough and comprehensive patient history, examination, review of systems, and laboratory workup is needed to achieve a proper differential diagnosis and treatment plan.

Uveitis is uveal (iris, ciliary body, and choroid) inflammation that can be classified by the Standardization of Uveitis Nomenclature based on anatomical involvement.¹ Anterior uveitis is inflammation of the iris and/or anterior ciliary body, intermediate uveitis is inflammation of the vitreous body and posterior ciliary body, and posterior uveitis is inflammation of the retina and/or choroid with possible optic nerve involvement (Figures 1-5).² Panuveitis presents as full uveal inflammation, including the anterior chamber, vitreous, choroid, and/or retina.²

Although uveitis in the pediatric population is less common than in the adult population, early detection and treatment in children remain especially crucial due to the possibility of vision loss at an early age. Delay in diagnosis and insufficient treatment can put the pediatric uveitis patient at significant risk for amblyopia, cataracts, band keratopathy, synechiae, and cystoid macular edema.³

ETIOLOGY

The etiologies of pediatric uveitis include infectious diseases, autoimmune and inflammatory disorders, and conditions that masquerade as uveitis (Table 1). These masquerading conditions include malignancies such as retinoblastoma and leukemia, juvenile xanthogranuloma, inherited or congenital retinal diseases such as retinitis pigmentosa and Coats disease, trauma, and intraocular foreign body.^4,5 Leukemia, the most common masquerader, presents as retinal hemorrhages, cotton wool spots, perivascular exudates, and vascular sheathing. Juvenile xanthogranuloma presents with diffuse yellow or white iris lesions, hyphema, and an anterior chamber reaction.^4,5 All masqueraders need to be considered when a child presents with uveitis, especially when there is a poor response to standard antiinflammatory treatment.

Infectious Uveitis

The most common causes of infectious uveitis are toxoplasmosis and toxocariasis. These cases of pediatric uveitis are much more common in developing countries, where the Toxoplasma gondii parasitic protozoan, transmitted most commonly through exposure to cat feces or ingestion of undercooked meat or contaminated water, is prevalent.¹

Viral etiologies, including herpetic, are another prominent etiology of infectious uveitis. Herpes-associated uveitis is often nongranulomatous in acute cases and granulomatous in chronic cases.⁶

Other infectious etiologies of granulomatous uveitis include tuberculosis, cytomegalovirus, syphilis, Lyme disease, and fungal infections, while infectious etiologies of nongranulomatous uveitis include Rubella virus, cat scratch disease, and Ebola.⁶

Noninfectious Uveitis

Noninfectious etiologies compromise approximately 70% to 90% of pediatric uveitis cases, of which 45% to 57% are anterior uveitis presentations.⁷ Juvenile idiopathic arthritis is the most common noninfectious etiology of pediatric uveitis. It often presents as bilateral, nongranulomatous, chronic anterior uveitis in asymptomatic patients.² Sarcoidosis, an inflammatory disease that causes granuloma formation throughout the body, affects the eye in 30% to 60% of cases and presents as nongranulomatous in about one in five cases.²

In addition to the classic ocular symptoms associated with uveitis, patients may experience nonocular symptoms, such as shortness of breath, coughing, fatigue, and/or fever. Tubulointerstitial nephritis and uveitis is a disease of unknown etiology that affects the eyes and kidneys and results in systemic symptoms including flank pain, weight loss, and fever.² Tubulointerstitial nephritis and uveitis typically presents as nongranulomatous inflammation and is bilateral (77%) and anterior (80%) in the majority of cases.⁸

Pars planitis is an idiopathic disease that presents as intermediate uveitis, with diagnostic features including cells, haze, snowbanks, and snowballs in the vitreous humor.² Blau syndrome presents clinically as a triad of inflammation including uveitis, arthritis, and dermatitis. A skin rash during early childhood is often the first sign to appear.² Uveitis often appears in patients with Blau syndrome between 1 and 5 years of age in a bilateral presentation and can progress to panuveitis over time. Other causes of noninfectious uveitis include Beçhet disease, Vogt-Koyanagi-Harada disease, and irritable bowel syndrome.

INVESTIGATION

Each case of pediatric uveitis warrants thorough investigation into a possible systemic etiology. A diagnosis of idiopathic uveitis can only be made after an unremarkable systemic workup. In addition to reviewing medication and vaccine history, a complete review of systems is required. The optometrist should inquire about joint pain or stiffness, breathing difficulty, chest pain, flank pain, skin rashes, hearing loss, and gastrointestinal symptoms. The possibility of an infectious etiology in an immunocompromised child is especially important to rule out.

Although the eye care practitioner is primarily responsible for treating uveitis, a collaborative approach to treating noninfectious uveitis is often necessary. It includes treating the underlying etiology, preventing associated complications and/or loss of vision, and minimizing the risk of future flare-ups. This often requires involvement of the pediatrician, rheumatologist, and/or gastroenterologist. The optometrist must work with the patient’s other health care providers to initiate a systemic investigation to rule out underlying systemic etiology.

As suggested by Shivpuri et al, a summary of recommended systemic investigations for infectious and noninfectious etiologies are outlined in Tables 2 and 3.⁶ Although delayed diagnosis and treatment can have detrimental visual outcomes in both pediatric and adult patients, it is important to note that the sequelae for children can be especially problematic. Ocular complications such as strabismus and amblyopia can develop in children and present more of a threat to this vulnerable patient population, which is also more susceptible to adverse reactions to required treatments.

TREATMENT

Treatment for uveitis in pediatric patients is aimed at controlling active intraocular inflammation, reducing the chance of secondary complications, and managing the underlying etiology. Topical corticosteroids, most often prednisone acetate 1% suspension, are the first-line treatment for anterior uveitis.² Recalcitrant anterior uveitis and/or posterior uveitis may require periocular, intraocular, or systemic corticosteroids, which should be followed by immunomodulatory therapy, if insufficient (Table 4). Methotrexate is the most common immunomodulator used to treat chronic, noninfectious cases of pediatric uveitis due to its safety profile and efficacy, but other options include cyclosporine A, azathioprine, mycophenolate mofetil, and monoclonal antibodies.^2,4

Due to the possible adverse reactions of long-term corticosteroid therapy, it is preferred that the child be treated with immunosuppressive medications when long-term management is indicated. In the case of unsuccessful immunomodulator therapy, biologic response modifiers, which aim to inhibit immune system molecules involved in ocular inflammation, should be initiated.⁴ These agents include anti-tumor necrosis factor alpha inhibitors, anti-interleukin 1 inhibitors, anti-B-cell inhibitors, and anti-T-cell inhibitors.⁴

The pediatric patient with uveitis must be monitored until resolution, at which point the time between follow-up visits can increase to approximately every 8 to 12 weeks.⁴ Visual acuity, IOP, anterior segment, and posterior segment must be assessed at each visit. As per the American College of Rheumatology guidelines, children with juvenile idiopathic arthritis should be consistently examined for signs of uveitis every 3 months.⁹

In addition to diligent monitoring and management, it is important to consider the effect of the diagnosis and management plan on the child. Fear of vision loss, medication adverse reactions, and regular doctor’s appointments can negatively affect their quality of life.

As such, in combination with routine examinations, quality-of-life surveys can help assess and monitor a child’s vision-related functioning and quality of life.¹⁰ The Effects of Youngsters’ Eyesight on Quality of Life survey, a 25-question survey for patients between 5 and 18 years of age, is a useful tool to monitor a patient’s well-being. It also helps to determine whether additional psychosocial therapies may be beneficial for the patient and their family during what can be a challenging time in their lives.¹⁰

A TEAM EFFORT

The diagnosis and treatment of pediatric uveitis patients presents a unique set of challenges, including poor patient cooperation during the examination and patient inability to recognize and communicate their symptoms or visual changes as they present and, sometimes, progress.

An interdisciplinary approach must be taken when treating and managing pediatric patients with uveitis. Although the optometrist makes the initial uveitis diagnosis, holistic and collaborative care with a team approach will ultimately provide the most favorable outcome for these patients and their families.