Pediatrics

Uveitis

OVERVIEW: What every practitioner needs to know

Are you sure your patient has uveitis?

Uveitis is a group of disorders characterized by the presence of intraocular inflammation. There are many causes of uveitis with numerous clinical manifestations. Referral to an ophthalmologist is always necessary to confirm the presence of intraocular inflammation. If uveitis is suspected, the patient should be evaluated by an ophthalmologist within 72 hours.

The diagnosis and management of uveitis in children can be difficult. Compared with adults, history-taking and examination can be challenging, delayed diagnosis occurs frequently, there is potential for long-term disability, and young children can develop amblyopia. For these reasons, it is important to refer these patients to ophthalmologists who are familiar with the evaluation and management of children with uveitis.

Anatomic Location

The location of the inflammation within the eye will often determine the clinical manifestations in a given patient. In addition, the location helps establish a focused differential diagnosis, aids in the choice of therapy, and may predict overall prognosis. A complete ophthalmic evaluation with dilated fundus examination is required to determine the location of the inflammation. The terminology used to describe the location of the inflammation is listed below:

  1. Anterior uveitis: inflammation confined to the anterior chamber. Mild inflammation may be present in the anterior vitreous. Older terms include iritis and iridocyclitis.

  2. Intermediate uveitis: inflammation primarily of the vitreous and peripheral retina. Spillover anterior uveitis is not uncommon but typically mild. Previously used terms include vitritis, pars planitis, and cyclitis.

  3. Posterior uveitis: inflammation primarily of the retina, choroid, or both. Terms include retinitis, choroiditis, retinochoroiditis, and chorioretinitis.

  4. Panuveitis: inflammation involving all three compartments--anterior chamber, vitreous, and retina and/or choroid.

Symptoms and Signs

Symptoms and signs of uveitis differ based upon several factors. The location and severity of the inflammation are major determinants of clinical manifestations in most patients. Clinical manifestations may also be different in patients with acute onset compared to those with chronic uveitis. Juvenile idiopathic arthritis (JIA) associated uveitis is an exception since it often has few if any symptoms and signs even when there is active inflammation.

  1. Anterior uveitis

  • Pain, decreased vision possible, photophobia

  • Redness

  • Intermediate uveitis

  • Floaters, decreased vision

  • Photophobia and pain (less common)

  • Posterior uveitis

  • Decreased vision, floaters

  • Scotomata

  • Panuveitis

  • Any or all of the above symptoms for other forms of uveitis

Etiology

Uveitis is often categorized into one of several groups based upon the etiology of the disease. Three broad categories include noninfectious uveitis, infectious uveitis, and masquerade syndromes.

  1. Noninfectious uveitis

  • Idiopathic

  • Juvenile idiopathic uveitis (JIA)

  • HLA-B27 associated uveitis

  • Reiter's syndrome

  • Inflammatory bowel disease

  • Ankylosing spondylitis

  • Sarcoidosis

  • Traumatic iritis

  • Tubulointerstitial nephritis and uveitis (TINU) syndrome

  • Vogt-Koyanagi-Harada (VKH) disease

  • Sympathetic ophthalmia

  • Kawasaki disease

  • Multiple sclerosis

  • Behçet's disease

  • Blau syndrome

  • Chronic infantile neurological cutaneous and articular/neonatal onset multisystem inflammatory syndrome (CINCA/NOMID)

  • Infectious uveitis

  • Toxoplasmosis

  • Toxocariasis

  • Diffuse unilateral subacute neuroretinitis (DUSN)

  • Herpes simplex

  • Varicella zoster

  • Cytomegalovirus

  • West Nile virus

  • Post-viral (measles, mumps, mononucleosis)

  • Rubella

  • Post-streptococcal syndrome

  • Cat-scratch disease

  • Lyme disease

  • Syphilis

  • Tuberculosis

  • Endogenous endophthalmitis

  • Masquerade syndromes

  • Leukemia

  • Lymphoma

  • Retinoblastoma

  • Juvenile xanthogranuloma (JXG)

  • Occult intraocular foreign body

  • Coat's disease

  • Retinitis pigmentosa

What other disease/condition shares some of these symptoms?

Infectious conjunctivitis

Allergic conjunctivitis

Corneal abrasion

Corneal foreign body

Conjunctival foreign body

Blepharoconjunctivitis

Keratitis

Cellulitis

What caused this disease to develop at this time?

Infectious forms of uveitis result from infection with the specific organism. In patients with some forms of infectious uveitis, such as toxoplasmosis, herpes simplex, and varicella zoster, recurrent episodes can occur despite prior treatment with antimicrobials.

Noninfectious forms of uveitis may develop as an isolated ocular disease or be associated with an underlying systemic disease.

Mechanisms for initiation of inflammation in these forms of uveitis likely involve one or more factors including:

  • Microbial infection resulting in molecular mimicry or activation of innate immunity

  • Trauma

  • Genetic factors

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

The treating ophthalmologist may obtain laboratory tests based upon the likely diagnosis and their experience with uveitis in children. In some cases, the ophthalmologist may request that the pediatric specialist assist in the work-up of the child with uveitis. As such, it is important for pediatric specialist to have a working knowledge of the spectrum of diseases associated with uveitis in children.

If the pediatric specialist is consulted to evaluate for an underlying etiology, it is important for the ophthalmologist to indicate the anatomic location of the uveitis and/or the possible etiologies. This communication will greatly improve the evaluation provided since the pediatric specialist will focus his/her efforts on a limited group of likely disorders. Table I outlines the laboratory studies that may aid in the evaluation of children with uveitis. Selection of specific tests should be based upon the likelihood of a specific disease using information gained from the detailed medical history and review of systems.

Table I.

Laboratory studies for the evaluation of children with uveitis
Type of Uveitis Laboratory Tests
Anterior uveitis CBC with differential, ANA, HLA-B27, FTA-ABS, ESR, urinalysis, urine beta-2 microglobulin, antistreptococcal lysin O serology, TB testing
Intermediate uveitis CBC with differential, FTA-ABS, serum angiotensin converting enzyme, ESR, urinalysis, urine beta-2 microglobulin, toxoplasma serology, toxocara serology, TB testing, cerebrospinal fluid analysis (if suspicious for multiple sclerosis)
Posterior uveitis CBC with differential, serum angiotensin converting enzyme, toxoplasma serology, toxocara serology, FTA-ABS, B. henselae serology, B.burgdorferi serology, West nile virus serology
Suspected masquerade (leukemia or lymphoma) CBC with differential, additional testing as indicated

Would imaging studies be helpful? If so, which ones?

Imaging studies have limited utility in the evaluation of children with uveitis. If the following diseases are suspected, imaging may be useful.

  • Sarcoidosis: chest x-ray. if not diagnostic and high index of suspicion exists, consider high resolution CT of chest

  • Toxoplasmosis: if child is immunosuppressed with evidence of ocular toxoplasmosis, consider MRI of the brain

  • Retinoblastoma: ultrasound of the eye, CT and MRI of the head and orbits

  • Pediatric onset multiple sclerosis: MRI of the brain

  • Occult intraocular foreign body: CT of the orbits with 0.5 mm cuts (helical scan may be best technique if available)

If you are able to confirm that the patient has uveitis, what treatment should be initiated?

Treatment of children with uveitis typically depends upon the etiology of the inflammation. Treatment recommendations are similar for many noninfectious forms of uveitis, while infectious uveitis requires specific therapy based upon the microbial pathogen.

Treatment of Noninfectious Uveitis

Most children with noninfectious forms of anterior uveitis are managed primarily by the ophthalmologist. The one exception is children with juvenile idiopathic uveitis (JIA). All of these patients are best managed using a team approach with an ophthalmologist and pediatrician or pediatric rheumatologist.

Children with the following forms of uveitis will likely require management using a team approach with an ophthalmologist and pediatrician or pediatric rheumatologist since most will require systemic therapy:

  • Intermediate uveitis not controlled with periocular corticosteroids

  • Noninfectious posterior uveitis

  • Noninfectious panuveitis

Several systemic medications have been used for children with uveitis. If systemic corticosteroids are utilized, the duration of treatment should be minimized to avoid significant side effects. The choice of specific medication often depends upon the underlying disease, comorbid conditions, anticipated compliance, and side effect profile. Systemic agents used in children include:ss

  • Prednisone--short-term only

  • Methotrexate

  • Azathioprine

  • Mycophenolate mofetil

  • Cyclosporine

  • Infliximab

  • Adalimumab

  • A general outline for treating children with noninfectious uveitis is shown in Table II.

Table II.

Therapy for children with noninfectious uveitis
Type of Uveitis Topical Therapy Periocular Therapy Systemic Therapy
Anterior Typically initial treatment; corticosteroids, cycloplegics For severe cases not controlled with topical therapy For severe chronic anterior uveitis not controlled with topical and/or periocular therapy. All children with JIA should receive systemic therapy.
Intermediate Corticosteroids, cycloplegics if anterior inflammation present Often used as initial therapy For cases not controlled with periocular therapy, or those with persistent inflammation despite laser or cryotherapy
Posterior Corticosteroids, cycloplegics if anterior inflammation present May be useful for noninfectious forms of uveitis Many/most will require systemic therapy to control the inflammation
Panuveitis Corticosteroids, cycloplegics if anterior inflammation present May be useful for noninfectious forms of uveitis Many/most will require systemic therapy to control the inflammation
Masquerade Treatment of the underlying disease once diagnosis established.

Treatment of Infectious Uveitis

Treatment of children with infectious forms of uveitis typically requires systemic antimicrobial therapy. Most cases of infectious uveitis are treated in an outpatient setting. The treating ophthalmologist will usually consult the pediatric specialist to aid in the treatment of some forms of infectious uveitis such as those with systemic manifestations (e.g. syphilis, tuberculosis, Lyme disease, etc.).

Anti-inflammatory therapy is often required in addition to antimicrobial therapy in many patients. Depending upon the specific pathogen, local therapy may include the following:

  • Topical corticosteroids

  • Topical cycloplegics

  • Periocular corticosteroids (should never be used for toxoplasmosis)

  • Oral corticosteroids

Treatment recommendations for specific infections are outlined in Table III.

Table III.

Treatment for children with infectious uveitis
Infection Treatment Other Treatment Options
Toxoplasmosis Classic "triple therapy" includes pyrimethamine, sulfadiazine, and prednisone for 6 weeks Several emerging treatment options are used increasingly:Trimethoprim (80 mg)/sulfamethoxazole (400mg) twice daily for 6 weeksAzithromycin with pyrimethamine daily for 4 weeksAzithryomycin daily for 5 weeksAtovaquone qid for 1-3 monthsIntravitreal clindamycin with dexamethasone
Toxocariasis Systemic and/or periocular corticosteroids Pars plana vitrectomy in some cases
Diffuse unilateral subacute neuroretinitis (DUSN) Laser photocoagulation of nematode If nematode cannot be located, treatment with oral albendazole 200 mg for one month may result in immobilization of the nematode
Herpes simplex (anterior uveitis) Topical corticosteroids Long-term (12-18 months) low dose antiviral agents may be useful in preventing recurrences. Oral acyclovir 400 mg bid, orOral valacyclovir 500 mg daily
Varicella zoster (anterior uveitis) Topical corticosteroids Oral acyclovir 5 times daily for 10 days orFamciclovir daily for 10 days (but no controlled studies for this drug in uveitis)
Acute retinal necrosis (herpes simplex or varicella zoster) Intravenous acyclovir 10 mg/kg daily (3 divided doses) until cessation of active retinitis (typically 10-21 days) followed by oral acyclovir for 3 months Patients who do not respond to intravenous acyclovir may benefit from intravitreal ganciclovir plus foscarnet with oral valacyclovirOral famciclovir or valacylovir has been used in a limited number of patients, but guidelines for using oral therapy only have not been established
Cytomegalovirus Treatment decisions typically based upon immune status of child. If treatment is necessary, specific drug and dosage determined by pediatric specialist.
West Nile virus Topical corticosteroids for anterior uveitis No clear indications for treatment of posterior uveitis
Post-viral Most require no therapy. If child is symptomatic, may require topical corticosteroids.
Rubella None for congenital infection. May benefit from topical corticosteroids in acquired disease.
Post-streptococcal syndrome Topical and/or systemic corticosteroids Systemic penicillins have been used, but no consensus regarding indications for use
Cat-scratch disease Topical corticosteroids for anterior uveitis No clear guidelines regarding use of antibiotics for vitritis, chorioretinitis, or neuroretinitis. If severe, consult pediatric infectious disease specialist.
Lyme disease Topical corticosteroids for anterior uveitis The presence of uveitis should prompt a systemic evaluation by a pediatric specialist and include lumbar puncture. Specific antibiotic treatment is based upon results of this evaluation.
Syphilis Topical corticosteroids for anterior uveitis Patients with syphilitic uveitis require a systemic evaluation by a pediatric specialist to determine the stage of the disease and appropriate antibiotic therapy.
Tuberculosis Topical corticosteroids for anterior uveitis Systemic therapy is required for all patients with uveitis associated with tuberculosis. Evaluation and selection of appropriate antibiotic therapy is determined by the pediatric specialist.
Endogenous endophthalmitis Systemic antifungal or antibiotic therapy based upon the specific organism Most patients have an underlying infection and are already receiving antimicrobial therapy. In severe cases, intravitreal antifungal agents may be useful.

What are the adverse effects associated with each treatment option?

Topical corticosteroids

  • Increased intraocular pressure

  • Glaucoma

  • Cataract formation

Periocular corticosteroids

  • Increased intraocular pressure

  • Glaucoma

  • Cataract formation

  • Ptosis

  • Hypopigmentation of eyelid skin at site of injection

Topical cycloplegics

  • Tachycardia

  • Skin flushing

  • Dry mouth

  • Fever

  • Irritability

  • Drowsiness

  • Mental status changes

  • Delirium

  • Blurred vision

Prednisone

  • Growth suppression

  • Cushingoid habitus

  • Hyperglycemia

  • Diabetes mellitus

  • Hypertension

  • Adrenocortical insufficiency

  • Myopathy

  • Delayed wound healing

  • Avascular necrosis of bone

  • Osteoporosis

  • Irritability

  • Depression

  • Euphoria

  • Increased risk for infections

  • Increased intraocular pressure

  • Glaucoma

  • Cataract formation

Methotrexate

  • Nausea/vomiting

  • Diarrhea

  • Hepatoxicity

  • Pneumonitis

  • Pulmonary fibrosis

AzathioprineAzathioprine

  • Leukopenia

  • Thrombocytopenia

  • Nausea/vomiting

  • Diarrhea

  • Hepatotoxicity

  • Pancreatitis

  • Interstitial pneumonitis

  • Secondary infections

Mycophenolate mofetil

  • Neutropenia

  • Pure red cell aplasia (PRCA)

  • Nephrotoxicity

  • Hepatotoxicity

  • Nausea

  • Increased risk for infections

  • Progressive multifocal leukoencephalopathy (PML)

  • Increased risk for lymphoproliferative disease or lymphoma

CyclosporineCyclosporine

  • Nephrotoxicity

  • Hypertension

  • Anemia

  • Nausea

  • Diarrhea

  • Gingival hyperplasia

  • Hirsutism

  • Paresthesias

  • Increased risk for opportunistic infections

Infliximab Infliximab

  • Infusion reactions

  • Headache

  • Nausea

  • Diarrhea

  • Abdominal pain

  • Upper respiratory infections

  • Increased ALT

  • Development of antinuclear antibodies

  • Development of antibodies to double-stranded DNA

Adalimumab

  • Injection site reactions

  • Headache

  • Rash

  • Antibodies to adalimumab

  • Development of antinuclear antibodies

  • Upper respiratory tract infections

  • Nausea

  • Abdominal pain

What are the possible outcomes of uveitis?

The prognosis for children likely differs by anatomic location of the uveitis, etiology, duration, treatment, chronicity, complications, and length of time between diagnosis and referral to a uveitis specialist. Complications occur in up to 76% of children. Up to 36% of children will develop moderate visual loss (visual acuity 20/50 or worse). Approximately 19% of children with uveitis will become legally blind in one eye.

Risk factors for poor visual outcome:

  • Posterior uveitis

  • Infectious uveitis; especially toxoplasmosis

Risks and benefits of the available treatment options

  • Topical corticosteroids: Highly beneficial; minimal risk in most cases.

  • Topical cycloplegics: Beneficial; minimal risk in most cases

  • Oral prednisone: Highly beneficial in severe cases; significant risk to children, especially if used for more than 3 months

  • Immunosuppressive therapy: Highly beneficial in severe or recalcitrant uveitis; significant risk that varies with specific drug

  • Biologic therapy: Long-term outcomes have not been described. Short-term outcomes indicate these agents may be highly beneficial in children who fail or have little response with traditional immunosuppressive therapy. Risk is probably less than other immunosuppressive agents. At present, cost is a major limiting factor.

What causes this disease and how frequent is it?

Estimates of the incidence of uveitis in children in North America and Europe are 4.3-6/100,000 population. The prevalence of childhood uveitis is approximately 30/100,000 population. All ages of children are affected. In a multicenter study, approximately 2/3 of cases were diagnosed between 6 and 15 years of age. Predisposing exposures include a limited number of microbial pathogens.

How do these pathogens/genes/exposures cause the disease?

N/A

Other clinical manifestations that might help with diagnosis and management

Risk factors for endogenous endophthalmitis include the following:

  • Premature infant

  • Immunosuppressed children

  • Sepsis

  • Diabetes mellitus

  • Hyperalimentation

  • Indwelling catheters

  • Post-organ transplantation

  • Recent abdominal surgery

  • Intravenous drug use

What complications might you expect from the disease or treatment of the disease?

Children less than 8 years of age are at risk for amblyopia if vision is impaired by the disease or its complications.

The complications of uveitis vary by anatomic location and etiology of the disease. Common complications are outlined in Table IV.

Table IV.

Common complications of uveitis
Type of Uveitis Common Complications
Anterior uveitis Posterior synechiae, cataract, increased intraocular pressure, glaucoma, band keratopathy, cystoid macular edema
Intermediate uveitis Cataract, band keratopathy, increased intraocular pressure, glaucoma, cystoid macular edema, vitreous hemorrhage, retinal detachment
Posterior uveitis Cataract, increased intraocular pressure, glaucoma, cystoid macular edema, retinal or chorioretinal scars, choroidal neovascularization, permanent scotomata, retinal detachment.
Panuveitis Posterior synechiae, cataract, increased intraocular pressure, glaucoma, band keratopathy, cystoid macular edema, retinal or chorioretinal scars, choroidal neovascularization, permanent scotomata, retinal detachment.

Are additional laboratory studies available; even some that are not widely available?

In cases suspicious for an infectious etiology and negative laboratory testing, polymerase chain reaction (PCR) of intraocular fluids may identify the organism. In most of these cases, vitreous biopsy or, less commonly, aqueous humor paracentesis is performed to obtain specimens for analysis. Currently there are a limited number of laboratories certified to perform PCR analysis of intraocular fluids.

How can uveitis be prevented?

In most cases, uveitis cannot be prevented. For some forms of infectious uveitis, avoiding possible exposures may be helpful (e.g., precautions to avoid tick bites if located in endemic regions for Lyme disease).

What is the evidence?

Smith, JA, Mackensen, F, Sen, HN. "Epidemiology and course of disease in childhood uveitis". Ophthalmology. vol. 116. 2009. pp. 1544-51.

(Large retrospective study from four centers in the United States.)

Kump, LI, Cervantes-Castañda, RA, Androudi, SN. "Analysis of pediatric uveitis cases at a tertiary referral center". Ophthalmology. vol. 112. 2005. pp. 1287-92.

(Large retrospective study from a single U.S. tertiary referral center.)

de Boer, J, Wulffraat, N, Rothova, A. "Visual loss in uveitis of childhood". Br J Ophthalmol. vol. 87. 2003. pp. 879-84.

(Large retrospective study from a single university hospital in the Netherlands.)

Cunningham, ET. "Uveitis in children". Ocul Immunol Inflamm. vol. 8. 2000. pp. 251-61.

(Review article describing the prevalence of uveitis in children.)

Holland, GN, Stiehm, ER. "Special considerations in the evaluation and management of uveitis in children". Am J Ophthalmol. vol. 135. 2003. pp. 867-78.

(Literature review and discussion from an international workshop regarding diagnosis and management of children with uveitis.)

Habot-Wilner, Z, Sallam, A, Roufas, A. "Periocular corticosteroid injection in the management of uveitis in children". Acta Ophthalmol. vol. 88. 2010. pp. e299-304.

(Retrospective series of 15 children demonstrating efficacy of periocular corticosteroids in controlling uveitis.)

Zierhut, M, Doycheva, D, Biester, S. "Therapy of uveitis in children". Int Ophthalmol Clin. vol. 48. 2008. pp. 131-52.

(Review article of therapeutic options with several algorithms used by the authors.)

Saurenmann, RK, Levin, AV, Rose, JB. "Tumour necrosis factor alpha inhibitors in the treatment of childhood uveitis". Rheumatology (Oxford). vol. 45. 2006. pp. 982-9.

(Small retrospective series of children treated with TNF alpha inhibitors after failing standard immunosuppressive therapy.)

Ardoin, SP, Kredich, D, Rabinovich, E. "Infliximab to treat chronic noninfectious uveitis in children: retrospective case series with long-term follow-up". Am J Ophthalmol. vol. 144. 2007. pp. 844-9.

(Small retrospective series of children treated with infliximab.)

Schatz, CS, Uzel, JL, Leininger, L. "Immunosuppressants used in a steroid-sparing strategy for childhood uveitis". J Pediatr Ophthalmol Strabismus. vol. 44. 2007. pp. 28-34.

(Retrospective series of 40 children treated with systemic corticosteroids combined with either azathioprine or mycophenolate mofetil.)

Sobrin, L, Kim, EC, Christen, W. "Infliximab therapy for the treatment of refractory ocular inflammatory disease". Arch Ophthalmol. vol. 125. 2007. pp. 895-900.

(Retrospective series of 27 children treated with infliximab following failure of conventional immunosuppressive therapy.)

Rosenberg, KD, Feuer, WJ, Davis, JL. "Ocular complications of pediatric uveitis". Ophthalmology. vol. 111. 2004. pp. 2299-306.

(Retrospective series of 148 children describing ocular complications of uveitis)

Soheilian, M, Rmezani, A, Azimzadeh, A. "Randomized trial of intravitreal clindamycin and dexamethasone versus pyrimethamine, sulfadiazine, and prednisolone in the treatment of ocular toxoplasmosis". Ophthalmology. vol. 118. 2011. pp. 134-41.

(Prospective, randomized trial of adults with active toxoplasmosis; no significant difference between intravitreal therapy and classic therapy)

Bosch-Driessen, LH, Verbraak, FD, Suttorp-Schulten, MS. "A prospective, randomized trial of pyrimethamine and azithromycin vs pyrimethamine and sulfadiazine for the treatment of ocular toxoplasmosis". Am J Ophthalmol. vol. 134. 2002. pp. 34-40.

(Prospective multicenter randomized open-label trial showing equivalent efficacy in treating ocular toxoplasmosis)

Rothova, A, Bosch-Driessen, LH, vanLoon, NH, Treffers, W. "Azithromycin for ocular toxoplasmosis". Br J Ophthalmol. vol. 82. 1998. pp. 1306-8.

(Small interventional case series describing effectiveness of azithromycin as single drug therapy.)

Pearson, PA, Piracha, AR, Sen Ha, Jaffe, GJ. "Atovaquone for the treatment of toxoplasma retinochoroiditis in immunocompetent patients". Ophthalmology. vol. 106. 1999. pp. 148-53.

(Prospective, randomized open-label trial of 17 patients demonstrating favorable response to therapy with limited side effects.)

Souza, EC, Casella, AM, Nakashima, Y, Monteiro, ML. "Clinical features and outcomes of patients with diffuse unilateral subacute neuroretinitis treated with oral albendazole". Am J Ophthalmol. vol. 140. 2005. pp. 437-45.

(Interventional case series of 12 children and adults demonstrating safety and benefit of albendazole.)

"A controlled trial of oral acyclovir for the prevention of stromal keratitis or iritis in patients with herpes simplex virus epithelial keratitis. The epithelial keratitis trial. The Herpetic Eye Disease Study Group ". Arch Ophthalmol. vol. 115. 1997. pp. 703-12.

(Randomized, masked, placebo controlled trial of oral acyclovir in patients age 12 or older; results suggest acyclovir may be beneficial in reducing recurrences of uveitis.)

Aizman, A, Johnson, MW, Elner, SG. "Treatment of acute retinal necrosis syndrome with oral antiviral medication". Ophthalmology. vol. 114. 2007. pp. 307-12.

(Small, nonrandomized interventional series of adults and one child treated with famciclovir or valacyclovir for acute retinal necrosis.)

Wormser, GP, Dattwyler, RJ, Shapiro, ED. "The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the infectious diseases society of America". Clin Infect Dis. vol. 43. 2006. pp. 1089-134.

(2006 guidelines for both children and adults with Lyme disease.)

Aldave, AJ, King, JA, Cunningham, ET. "Ocular syphilis". Curr Opin Ophthalmol. vol. 12. 2001. pp. 433-41.

(Review article describing ocular manifestations of congenital and acquired syphilis)

Woods, CR. "Syphilis in children: congenital and acquired". Semin Pediatr Infect Dis. vol. 6. 2005. pp. 245-57.

(Review of congenital and acquired syphilis in children.)

Lerman, MS, Burnham, JM, Change, PY. "Response of pediatric uveitis to tumor necrosis factor-α inhibitors". J Rheumatol. vol. 40. 2011. pp. 1394-403.

(Retrospective review of children with uveitis treated with anti-TNF therapy at five uveitis centers.)

Slabaugh, MA, Herligh, E, Ongchin, S, vanGelder, RN. "Efficacy and potential complications of difluprednate use for pediatric uveitis". Am J Ophthalmol. vol. 153. 2012. pp. 932-8.

(Case series of children treated with difluprednate with high rate of elevated intraocular pressure and cataract formation.)

Lerman, MS, Burnham, JM, Change, PY. "Response of pediatric uveitis to tumor necrosis factor-α inhibitors". J Rheumatol. vol. 40. 2011. pp. 1394-403.

(Retrospective review of children with uveitis treated with anti-TNF therapy at five uveitis centers.)

Slabaugh, MA, Herligh, E, Ongchin, S, vanGelder, RN. "Efficacy and potential complications of difluprednate use for pediatric uveitis". Am J Ophthalmol. vol. 153. 2012. pp. 932-8.

(Case series of children treated with difluprednate with high rate of elevated intraocular pressure and cataract formation.)

Ongoing controversies regarding etiology, diagnosis, treatment

N/A

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