• Nonspecific term describing intraocular granulomatous inflammation.
• Symptoms may include painful red eye, photophobia and decreased vision.
• Classically presents with large keratic precipitates (KPs) on the corneal endothelium (mutton-fat KPs).
• Inflammation can involve only the anterior eye (iritis), vitreous (intermediate uveitis), retina and/or choroid (posterior uveitis), or the entire eye (panuveitis).
• More commonly associated with systemic disease or underlying ocular syndrome than nongranulomatous uveitis.
• Can be unilateral or bilateral
• Can be acute or chronic
• May occur at any age
• Geographic location (e.g., endemic areas for Lyme disease)
• Exposure to animals (e.g., cats for toxoplasmosis)
• Ethnicity (e.g., sarcoidosis more prevalent in African Americans and Scandinavians)
• Prior injury to fellow eye for sympathetic ophthalmia
• Disruption of lens capsule (traumatic or surgical) for lens associated uveitis
Associated diseases may have genetic markers (e.g., HLA-DR1 and HLA-DR4 for VKH).
• Exact pathophysiology unknown
• May result from an autoimmune reaction
• May depend on the host’s immune response to a systemic infectious process
• Idiopathic in 50% of cases
• May be associated with a number of systemic conditions or infectious processes
COMMONLY ASSOCIATED CONDITIONS
• Herpes zoster virus
• Herpes simplex virus
• Lens associated uveitis
• Lyme disease
• Vogt–Koyanagi–Harada (VKH) disease
• Sympathetic ophthalmia
• Tuberculosis (TB)
• Wegener granulomatosis
• Review all medical conditions, surgeries, and ocular history.
• Obtain a complete and detailed review of systems (joint pain, rashes, shortness of breath, swollen lymph nodes, recent headaches, hearing difficulties, hair loss, pigmentary skin changes, history of ocular trauma, recent insect bites, sexually transmitted diseases, tuberculosis exposure, pet or animal exposure, and recent travel).
• Vision: May be unchanged or decreased depending on amount of inflammation.
• Intraocular pressure (IOP): Usually decreased because inflammation of the ciliary body causes decreased production of aqueous humor. Increased IOP may suggest a viral etiology or secondary glaucoma from chronic disease.
• External findings: Enlarged lacrimal glands, enlarged parotid glands, and cranial nerve seven palsy may suggest sarcoidosis.
• Conjunctiva: Generalized redness of the bulbar conjunctiva may be present. The eye may have a perilimbal injection termed ciliary flush. Perilimbal vitiligo (Sugiura sign) is a sign of VKH disease, occurring within a month of disease onset.
• Cornea: KPs are found on the endothelium and are clusters of white blood cells (WBCs) usually located in the lower half of the cornea. Classic mutton-fat KPs are large and greasy in appearance.
• Anterior chamber: Cells and flare are usually present.
• Cells floating in the anterior chamber are found with anterior segment inflammation. They can be graded under high-magnification slit lamp examination in a 1 × 1 mm field of light, as described by The SUN Working Group Grading Scheme (1)[A].
– 0 < 1
– 0.5 = 1–5 cells
– 1+ = 6–15 cells
– 2+ = 16–25 cells
– 3+ = 26–50 cells
– 4+ = More than 50 cells
• Flare is the result of extra protein in the aqueous. It can be graded using the SUN Working Group Grading Scheme:
– 0 = None
– 1+ = Faint
– 2+ = Moderate (iris and lens details clear)
– 3+ = Marked (iris and lens details hazy)
– 4+ = Intense (fibrin or plastic aqueous)
• Iris: Peripheral anterior synechiae and posterior synechiae may be present. Inflammatory nodules on the iris represent accumulations of inflammatory cells. They can be present in the pupillary border, the iris surface or the anterior chamber angle.
• Lens: Lenticular precipitates may be visible on the anterior lens capsule. Posterior subcapsular cataracts may be present if the patient has had repeated episodes of iritis or ongoing chronic inflammation.
• Vitreous: Inflammatory cells in the vitreous imply involvement of the posterior segment. Aggregation of cells in the vitreous are called snowballs.
• Posterior segment: Optic nerve edema, sheathing of venules or arterioles, focal retinal and choroidal lesions, and exudative retinal detachment may be present.
DIAGNOSTIC TESTS & INTERPRETATION
• The patient’s medical history, review of systems and physical examination should guide the laboratory evaluation.
• All patients who present with granulomatous uveitis should receive a diagnostic evaluation even if it is their first episode.
• As a minimum, CBC with differential and fluorescent treponemal antibody absorption (FTA-ABS) or other specific antitreponemal syphilis serology should be ordered.
• The following tests should be considered based in the history:
– Purified protein derivative (PPD) test or gold quantiferon testing for TB.
– ACE and lysozyme can be obtained if sarcoidosis is suspected.
– Lyme serology
– Toxoplasmosis IgG and IgM by ELISA
– Antineutrophil cytoplasmic autoantibodies (ANCA): c-ANCA is found in 80–95% of active cases of Wegener granulomatosis.
– PCR may be obtained for HSV 1, HSV 2, VZV, CMV, and toxoplasma.
• If media opacity blocks the view of the posterior segment, B-scan ultrasonography may identify exudative detachment, subretinal granulomas, and optic nerve edema.
• Fluorescein angiography may identify vasculitis, papillitis, and choroiditis.
• Indocyanine green angiography may demonstrate defects of the choroid with greater detail than fluorescein angiography.
• Chest radiography may identify hilar adenopathy associated with sarcoidosis and tuberculosis.
Follow-up & special considerations
If chest radiography is equivocal, a chest CT or gallium scan can be considered if sarcoidosis is strongly suspected.
Lacrimal gland or conjunctival nodule biopsy is highly specific for sarcoidosis if positive.
Histopathology classically shows epithelioid and giant cells.
• Intraocular lymphoma
• Chronic retinal detachment
• Phacoanaphylactic glaucoma
• Topical corticosteroids (e.g., prednisolone acetate), should be used aggressively initially and tapered with response to treatment.
• Cycloplegic agents (e.g., cyclopentolate or homatropine) should be used to treat pain and photophobia and to prevent iris synechiae.
• Patients with a known etiology for their inflammation (e.g., tuberculosis or toxoplasmosis) should be treated for the underlying cause in addition to steroids and cycloplegic agents.
• After excluding infectious etiologies, oral, or periocular steroid may be required if inflammation does not adequately respond to topical steroids.
• Mid- to long-term oral steroids use should be accompanied by supplementary calcium and vitamin D to reduce the risk of osteoporosis.
• Prophylaxis against peptic ulcers should be considered using H2 blockers or proton pump inhibitors when systemic steroids are administered.
• Immunomodulatory and immunosuppressive agents may be considered in patients unresponsive to steroids or in patients needing long-term immunosuppressive (>3 mths) treatment (2)[A].
• Intravitreal steroid (e.g., triamcinolone acetonide 4 mg in 0.1 cm3) may be administered for severe cases. Risk of cataract and ocular hypertension must be discussed. Infectious etiologies must be ruled out prior to administration of intraocular steroid.
Patients may develop increased intraocular pressure which should be treated with topical IOP lowering drops.
Issues for Referral
• All patients who need long-term treatment with oral steroids should be followed by a primary care provider to monitor blood sugars, blood pressure, and bone densitometry.
• All patients who require immunomodulatory or immunosuppressive agents may be referred to a rheumatologist for initiation and management of therapy.
• If an underlying etiology for inflammation is identified, an appropriate consultation should be made to treat the systemic condition (e.g., pulmonology for sarcoidosis, infectious disease for TB).
• Elevated intraocular pressure may necessitate a referral to glaucoma specialist.
• Development of cystoid macular edema (CME) may necessitate a referral to a vitreoretinal specialist.
• Uncontrolled or persistent inflammation requires referral to a uveitis specialist.
• Patients with chronic or recurrent episodes of uveitis may be candidates for a fluocinolone (Retisert) implant (3)[B].
• Treatment with steroids may cause a cataract resulting in the need for cataract extraction and intraocular lens implantation.
• Ocular hypertension unresponsive to topical medications may require a trabeculectomy or valve implantation.
• Pars plana vitrectomy may reduce the severity of posterior uveitis in some cases.
• Usually not required if inflammation only affects the eye.
• Rarely may be indicated for treatment of systemic infections such as neurosyphilis, or for administration of IV medication, such as ganciclovir or acyclovir for viral retinitis.
Patients should be followed closely, and steroids should be tapered slowly as inflammation resolves.
Once inflammation has resolved patients should be seen at regular intervals to monitor for recurrences.
• Patients should be educated about signs and symptoms of flare ups of inflammation so they can return for prompt treatment.
• The often chronic or recurrent nature of granulomatous uveitis should be explained to the patient.
• The possibility of irreversible vision loss and even loss of the globe in the setting of untreated disease should be explained to the patient.
• Many patients will have recurrent episodes of inflammation.
• Visual prognosis is good in the absence of cataract, glaucoma or CME.
• Cystoid macular edema
• Exudative retinal detachment
• RPE atrophy
• Band keratopathy
1. Jabs DA, Nussenblatt RB, Rosenbaum JT. Standardization of uveitis nomenclature for reporting clinical data: Results of the First International Workshop; Standardization of Uveitis Nomenclature (SUN) Working Group. Am J Ophthalmol 2005;140:509–516.
2. Jabs DA, Rosenbaum JT, Foster CS, et al. Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: Recommendations of an expert panel. Am J Ophthalmol 2000;130(4):492–513.
3. Jaffe GJ, Martin D, Callanan D, et al. Fluocinolone acetonide implant (Retisert) for noninfectious posterior uveitis: Thirty-four-week results of a multicenter randomized clinical study. Ophthalmology 2006;113(6):1020–1027.