> Table of Contents > Uveitis
Uveitis
Shailendra K. Saxena, MD, PhD
Mikayla Spangler, PharmD
Laura K. Klug, PharmD
image BASICS
DESCRIPTION
  • A nonspecific term used to describe any intraocular inflammatory disorder
  • Symptoms vary depending on depth of involvement and associated conditions.
  • The uvea is the middle layer of the eye between the sclera and retina. The anterior part of the uvea includes the iris and ciliary body. The posterior part of the uvea is the choroid.
    • Anterior uveitis: refers to ocular inflammation limited to the iris (iritis) alone or iris and ciliary body (iridocyclitis)
    • Intermediate uveitis: refers to inflammation of the structures just posterior to the lens (pars planitis or peripheral uveitis)
    • Posterior uveitis: refers to inflammation of the choroid (choroiditis), retina (retinitis), or vitreous near the optic nerve and macula
  • System(s) affected: nervous
  • Synonym(s): iritis; iridocyclitis; choroiditis; retinochoroiditis; chorioretinitis; anterior uveitis; posterior uveitis; pars planitis; panuveitis. Synonyms are anatomic descriptions of the focus of the uveal inflammation.
Geriatric Considerations
The inflammatory response to systemic disease may be suppressed.
Pediatric Considerations
  • Infection should be the primary consideration.
  • Allergies and psychological factors (depression, stress) may serve as a trigger.
  • Trauma is also a common cause in this population.
Pregnancy Considerations
May be of importance in the selection of medications
EPIDEMIOLOGY
  • Predominant age: all ages
  • Predominant sex: male = female, except for human leukocyte antigen B27 (HLA-B27) anterior uveitis: male > female, autoimmune etiology: female > male
Incidence
  • Overall prevalence is 38 to 714 cases/100,000 annual incidence.
  • Anterior uveitis is the most common.
Prevalence
Iritis is 4 times more prevalent than posterior uveitis.
ETIOLOGY AND PATHOPHYSIOLOGY
  • Infectious: may result from viral, bacterial, parasitic, or fungal etiologies
  • Suspected immune-mediated: possible autoimmune or immune-complex-mediated mechanism postulated in association with systemic (especially rheumatologic) disorders
    • Autoimmune uveitis (AIU) patients should be referred to an ophthalmologist for local treatment.
  • Isolated eye disease
  • Idiopathic (˜25%)
  • Some medications may cause uveitis. The most causative medications include rifabutin, bisphosphonates, sulfonamides, metipranolol, topical corticosteroids, brimonidine, prostaglandin analogs, anti-vascular endothelial growth factor (VEGF) agents, bacillus Calmette-Guerin (BCG) vaccination, and systemic and intraocular cidofovir.
  • Masquerade syndromes: diseases such as malignancies that may be mistaken for primary inflammation of the eye
Genetics
  • No specific pattern for uveitis in general
  • Iritis: 50-70% are HLA-B27-positive.
  • Predisposing gene for posterior uveitis associated with Behçet disease may include HLA-B51.
RISK FACTORS
  • No specific risk factors
  • Higher incidence is seen with specific associated conditions.
COMMONLY ASSOCIATED CONDITIONS
  • Viral infections: herpes simplex, herpes zoster, HIV, cytomegalovirus
  • Bacterial infections: brucellosis, leprosy, leptospirosis, Lyme disease, propionibacterium infection, syphilis, tuberculosis (TB), Whipple disease
  • Parasitic infections: acanthamebiasis, cysticercosis, onchocerciasis, toxocariasis, toxoplasmosis
  • Fungal infections: aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, cryptococcosis, histoplasmosis, sporotrichosis
  • Suspected immune-mediated: ankylosing spondylitis, Behçet disease, Crohn disease, drug or hypersensitivity reaction, interstitial nephritis, juvenile rheumatoid arthritis, Kawasaki disease, multiple sclerosis, psoriatic arthritis, Reiter syndrome, relapsing polychondritis, sarcoidosis, Sjögren syndrome, systemic lupus erythematosus, ulcerative colitis, vasculitis, vitiligo, Vogt-Koyanagi (Harada) syndrome
  • Isolated eye disease: acute multifocal placoid pigmentary epitheliopathy, acute retinal necrosis, bird-shot choroidopathy, Fuchs heterochromatic cyclitis, glaucomatocyclitic crisis, lens-induced uveitis, multifocal choroiditis, pars planitis, serpiginous choroiditis, sympathetic ophthalmia, trauma
  • Masquerade syndromes: leukemia, lymphoma, retinitis pigmentosa, retinoblastoma
image DIAGNOSIS
PHYSICAL EXAM
Slit-lamp exam and indirect ophthalmoscopy are necessary for precise diagnosis (1)[C].
  • Anterior uveitis (˜80% of patients with uveitis)
    • Conjunctival vessel dilation
    • Perilimbal (circumcorneal) dilation of episcleral and scleral vessels (ciliary flush)
    • Small pupillary size of affected eye
    • Hypopyon or hyphema (WBCs or RBCs pooled in the anterior chamber)
    • Frequently unilateral (95% of HLA-B27-associated cases); if first occurrence and otherwise asymptomatic, no further diagnostic testing is needed (1)[C].
    • Bilateral involvement and systemic symptoms (fever, fatigue, abdominal pain) may be associated with interstitial nephritis (1)[C].
    • Systemic disease is most likely to be associated with anterior uveitis (in one study, 53% of patients were found to have systemic disease) (1)[C].
  • Intermediate and posterior uveitis
    • More commonly bilateral
    • Posterior inflammation will generally cause minimal pain or redness unless associated with an iritis.
DIFFERENTIAL DIAGNOSIS
  • Acute angle-closure glaucoma
  • Conjunctivitis
  • Episcleritis
  • Keratitis
  • Scleritis
DIAGNOSTIC TESTS & INTERPRETATION
No specific test for the diagnosis of uveitis. Tests for etiologic factors or associated conditions should be based on history and physical exam (1)[C].
Initial Tests (lab, imaging)
  • CBC, BUN, creatinine (interstitial nephritis) (1)[C]
  • HLA-B27 typing (ankylosing spondylitis, Reiter syndrome) (1)[C]
  • Antinuclear antibody, ESR (systemic lupus erythematosus, Sjögren syndrome) (1)[C]
  • Venereal disease research laboratory (VDRL) test, fluorescent titer antibody (syphilis) (1)[C]
  • Fluorescent treponemal antibody absorption (FTA-ABS) or microhemagglutination assay for antibodies to Treponema pallidum (MHA-TP) (1)[C]
  • Purified protein derivative (PPD) tuberculin skin test (TB) (1)[C]
  • Lyme serology (Lyme disease) (1)[C]
  • Disorders that may alter lab results: immunodeficiency
  • Chest x-ray (sarcoidosis, histoplasmosis, TB, lymphoma) (1)[C]
  • Sacroiliac radiograph (ankylosing spondylitis) (1)[C]
Diagnostic Procedures/Other
Slit-lamp exam (1)[C]
Test Interpretation
  • Keratic precipitates
  • Inflammatory cells in anterior chamber or vitreous
  • Synechiae (fibrous tissue scarring between iris and lens)
  • Macular edema
  • Perivasculitis of retinal vessels
image TREATMENT
GENERAL MEASURES
  • Outpatient care with urgent ophthalmologic consultation
  • Medical therapy is best initiated following full ophthalmologic evaluation.
  • P.1097

  • Treatment of underlying cause, if identified
  • Anti-inflammatory therapy
MEDICATION
First Line
  • The treatment depends on the etiology, location, and severity of the inflammation.
  • Prednisolone acetate 1% ophthalmic suspension: 2 drops to the affected eye q1h initially, tapering to once a day with improvement
    • Contraindications
      • Hypersensitivity to the medication or component of the preparation
      • Topical corticosteroid therapy is contraindicated in uveitis secondary to infectious etiologies, unless used in conjunction with appropriate anti-infectious agents.
    • Precautions
      • Topical corticosteroids may increase intraocular pressure, increase susceptibility to infections, impair corneal or scleral wound healing, or cause corneal epithelial toxicity or crystalline keratopathy. Prolonged use may cause cataract formation and exacerbate existing herpetic keratitis, which may masquerade as iritis.
    • Significant possible interactions
  • Systemic corticosteroids are useful for maintenance therapy for patients with noninfectious uveitis. These should always be used with other immunosuppressive medications for steroid-sparing effects; prednisone 5 to 10 mg daily (3,4)[B].
  • Cycloplegic agents may be used to dilate the eye and relieve pain. Agents include scopolamine hydrobromide 0.25% (Isopto Hyoscine) or atropine 1% 1 to 2 drops up to QID or homatropine hydrobromide (Isopto) 2% or 5% 1 to 2 drops BID or as often as q3h if necessary (1)[C].
    • Contraindications
      • Cycloplegia is contraindicated in patients known to have, or be predisposed to, glaucoma.
    • Precautions
      • Use extreme caution in infants, young children, and elderly because of increased susceptibility to systemic effects.
Second Line
  • Anti-inflammatory: prednisolone sodium phosphate 1%, dexamethasone sodium phosphate 0.1%, dexamethasone suspension, rimexolone 1% (Vexol), and loteprednol etabonate 0.5% (Lotemax), difluprednate (Durezol) 0.05% (1,4)[C]
    • Rimexolone 1% (Vexol) may be equally effective as prednisolone acetate 1% for short-term treatment of anterior uveitis (1)[C].
    • Loteprednol etabonate (Lotemax) may not be as effective as prednisolone acetate 1% but may be less likely to increase intraocular pressure in cases of acute anterior uveitis.
  • Periocular corticosteroids may be injected with triamcinolone acetonide being most commonly used; 40 mg/1 mL (5)[C].
  • Intravitreous corticosteroid deposits may also be used for long-term maintenance. Fluocinolone acetonide (Retisert) 590 &mgr;g released >30 months, dexamethasone (Ozurdex) 0.7 mg released slowly >3 to 6 months (4,5)[B].
    • Retisert has caused all patients to develop cataracts and significant increases in intraocular pressure in about 2/3 of patients, whereas Ozurdex had only 1/4 of patients require medication for increased intraocular pressure and 15% develop cataracts (5)[C].
  • Intravitreal corticosteroid injections are used only in severe cases of recurrence; triamcinolone acetonide 4 to 20 mg/0.1 mL, dexamethasone phosphate 0.4 mg/0.1 mL, dexamethasone implant (Ozurdex)
    • Ozurdex has a longer effect than triamcinolone acetonide.
  • Immunosuppressive agents including antimetabolites (methotrexate, azathioprine, and mycophenolate mofetil), T-cell inhibitors (cyclosporine, tacrolimus, and sirolimus), and alkylating agents (cyclophosphamide, chlorambucil) may be employed in cases resistant to initial treatment but close monitoring is required (4,5)[C].
  • Although biologic therapy has been used for refractory uveitis, the sparsity of randomized clinical trials as well as high cost and adverse effect potential of these agents limit their use (3,4)[C].
  • Systemic and ophthalmic preparations of NSAIDs may provide some symptom relief (1)[C].
ISSUES FOR REFERRAL
Caution should be used when using empiric treatment; referral to an ophthalmologist is recommended in most cases.
SURGERY/OTHER PROCEDURES
Various surgical procedures may be used therapeutically for visual rehabilitation, diagnostically, or to manage complications associated with uveitis (6).
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
  • Complete history and physical to evaluate for associated systemic disease
  • Ophthalmologic follow-up as recommended by consultant
PATIENT EDUCATION
  • Instruct on proper method for instilling eye drops.
  • Wear dark glasses if photophobia is a problem.
PROGNOSIS
  • Depends on the presence of causal diseases or associated conditions
  • Uveitis resulting from infections (systemic or local) tends to resolve with eradication of the underlying infection.
  • Uveitis associated with seronegative arthropathies tends to be acute (lasting <3 months) and frequently recurrent.
REFERENCES
1. American Optometric Association. Optometric clinical practice guideline: care of the patient with anterior uveitis. http://www.aoa.org/documents/CPG-7.pdf. Accessed 2015.
2. Selmi C. Diagnosis and classification of autoimmune uveitis. Autoimmun Rev. 2014;13(4-5): 591-594.
3. de Smet MD, Taylor SR, Bodaghi B, et al. Understanding uveitis: the impact of research on visual outcomes. Prog Retin Eye Res. 2011;30(6): 452-470.
4. Babu K, Mahendradas P. Medical management of uveitis—current trends. Indian J Ophthalmol. 2013;61(6):277-283.
5. Gallego-Pinazo R, Dolz-Marco R, Martínez-Castillo S, et al. Update on the principles and novel local and systemic therapies for the treatment of noninfectious uveitis. Inflamm Allergy Drug Targets. 2013;12(1):38-45.
6. Murthy SI, Pappuru RR, Latha KM, et al. Surgical management in patient with uveitis. Indian J Ophthalmol. 2013;61(6):284-290.
Additional Reading
&NA;
  • Levy RA, de Andrade FA, Foeldvari I. Cutting-edge issues in autoimmune uveitis. Clin Rev Allergy Immunol. 2011;41(2):214-223.
  • Majumder PD, Biswas J. Pediatric uveitis: an update. Oman J Ophthalmol. 2013;6(3):140-150.
  • Pan J, Kapur M, McCallum R. Noninfectious immune-mediated uveitis and ocular inflammation. Curr Allergy Asthma Rep. 2014;14(1):409.
  • Yang MM, Lai TY, Luk FO, et al. The roles of genetic factors in uveitis and their clinical significance. Retina. 2014;34(1):1-11.
See Also
&NA;
Conjunctivitis, Acute; Glaucoma, Primary Closed-Angle; Scleritis
Codes
&NA;
ICD10
  • H20.9 Unspecified iridocyclitis
  • H30.90 Unspecified chorioretinal inflammation, unspecified eye
  • H20.019 Primary iridocyclitis, unspecified eye
Clinical Pearls
&NA;
  • Symptoms vary depending on depth of involvement and associated conditions but should be suspected when eye pain is associated with visual changes.
  • Severe or unresponsive uveitis may require therapy, including periocular injection of corticosteroids, sustained-release corticosteroid implants, systemic corticosteroids, cytotoxic agents, immunosuppressive agents, immunomodulatory agents, or tumor necrosis factor inhibitors.