Iritis, also known as anterior uveitis, is the most common form of intra-ocular inflammation and often causes a painful red eye. The term uveitis is synonymous with inflammation of the uveal tract, which consists of the iris, ciliary body, and choroid.
Inflammation of the iris appropriately may be termed iritis. Inflammation of the iris and the ciliary body is called iridocyclitis. Iritis may be subdivided into 2 broad categories: granulomatous and nongranulomatous.
A granulomatous iritis has an increased likelihood of being part of a systemic disease process or a component of certain ocular syndromes. However, the diagnosis of granulomatous iritis does not definitively indicate that an underlying systemic granulomatous process is present.
Patients with a granulomatous iritis may present with an acutely painful eye or with chronic subclinical inflammation that is discovered only during a routine ocular examination.
The exact pathophysiology of granulomatous iritis is unknown. It may result from an autoimmune reaction or from the host's immune response to a systemic infectious process, such as syphilis, Lyme disease, tuberculosis (TB), or local reactivation of herpetic viral infection.
Not all cases classified as granulomatous are necessarily granulomatous upon histologic examination. Granulomas are found in certain infectious and autoimmune processes and even in inflammation secondary to foreign bodies; they represent an inflammatory response that implies chronic inflammation.
Iritis, granulomatous and nongranulomatous, is the most frequent form of uveitis that ophthalmologists encounter. In one community-based study, anterior uveitis accounted for more than 90% of all cases of uveitis seen. The annual incidence is about 8 cases per 100,000 population. However, these cases were predominantly nongranulomatous anterior uveitis.
No particular geographic distribution has been noted for granulomatous iritis. Although certain etiologies may be more common in certain parts of the world (eg, TB in endemic areas).
Morbidity may arise from both the iritis and any associated systemic disease if present.
Patients may have anterior and posterior synechiae. Extensive posterior synechiae can lead to a secluded pupil that can result in angle-closure glaucoma. In addition, trabecular obstruction, due to either cellular debris or peripheral anterior synechiae, can lead to secondary glaucoma.
The eye with a granulomatous iritis is likely to have uveitis involving other structures of the eye, including the posterior segment. This may result in an increased risk of substantial visual impairment.
Associated ocular complications (eg, cataracts, corneal decompensation, glaucoma, chronic cystoid macular edema, hypotony) may result in severe vision loss.
Racial differences may exist, depending on the underlying cause of the iritis. For example, sarcoidosis is more likely to be diagnosed in the African American population than in other groups. Vogt-Koyanagi-Harada disease, although a rare cause of uveitis in the United States, is much more prevalent in persons of Mestizo, Asian, or American Indian ancestry.
No significant sex differences are reported.
Granulomatous iritis may develop in individuals of any age.
Inquire about the patient's complete medical history, to include all medical conditions, surgeries, medications, and ocular history (eg, history of iritis). Perform a detailed review of systems. This is critical, as the history and the review of systems in many cases will suggest a diagnosis.
Critical review questions include, but are not limited to, asking about arthritis, rashes, shortness of breath, swollen lymph nodes, recent headaches, hearing difficulties, hair loss, pigment changes in the skin, a history of ocular trauma, recent insect bites, sexually transmitted diseases (STDs), TB exposure, blood in stools, and recent travel.[2, 3, 4]
Inquire about the following symptoms:
A complete ocular examination is indicated, including dilation of the pupil and careful examination of the retinal periphery.
Granulomatous anterior uveitis with mutton-fat keratic precipitates on posterior corneal surface and Koeppe and Busacca nodules of the iris.
Granulomatous anterior uveitis with numerous Busacca nodules on the iris surface and a few mutton-fat keratic precipitates on the inferior aspect of t....
Not all patients with a granulomatous-appearing iritis have a systemic granulomatous disease process. A differential for a patient who has either bilateral granulomatous iritis or unilateral granulomatous iritis is outlined below. Many of these are more likely to be associated with intermediate or panuveitis and not isolated anterior uveitis. Alternatively, as in Vogt-Koyanagi-Harada disease, the chronic anterior uveitis may occur as the main clinical feature later in the course of the disease, with little active posterior segment inflammation.
Findings from the physical examination, a comprehensive review of the patient's medical history, and the review of systems should guide the laboratory evaluation. The workup should be tailored accordingly.
All patients who present with a granulomatous iritis should receive a diagnostic evaluation, even if it is their first episode of uveitis.
Laboratory tests that may be requested are outlined below. At the least, chest radiography and fluorescent treponemal antibody absorption (FTA-ABS) or other specific antitreponemal syphilis serology should be ordered.
MRI of the head may help in suspected cases of intraocular (CNS) lymphoma or in cases of multiple sclerosis; however, this is a rare cause of granulomatous anterior uveitis (multiple sclerosis is more commonly associated with intermediate uveitis and lymphoma with vitritis or subretinal lesions).
In patients in whom sarcoidosis is suspected and in whom chest radiographs are negative for disease, consider chest CT to look for hilar adenopathy. Up to 10% of patients with sarcoidosis who have negative chest radiographs may exhibit hilar pathology on chest CT.
Ultrasonography (B scan) of the eye if the posterior segment cannot be seen
Biopsy of any conjunctival nodules or the lacrimal gland may help in diagnosing sarcoidosis.
Vitreous biopsy may be indicated if a diagnostic dilemma exists and infection or masquerade syndrome is suspected; a specific tissue diagnosis, culture findings, or polymerase chain reaction results may alter or direct therapy.
Lumbar puncture may be required to help rule out intraocular (CNS) lymphoma.
If the patient presents with a secluded pupil from extensive posterior synechiae, iris bombe with angle-closure glaucoma may be present. Perform iridotomy as soon as possible (after quieting the eye with anti-inflammatory medications).
Mutton fat KPs: These consist of accumulation of macrophages but are not necessarily true granulomas.
Iris nodules: Histopathologic examination of the iris nodule has revealed abundant lymphocytes and plasma cells with areas of chronic granulomatous inflammation. However, not all iris nodules, including those that may be associated with granulomatous disease in some cases (eg, Koeppe nodules), are necessarily granulomas.
Treatment of inflammation of the anterior segment is discussed below.
Use a long-acting cycloplegic agent, such as cyclopentolate or homatropine, to relieve both pain and photophobia (if present) and to prevent the formation of posterior synechiae. However, this may not always be necessary in chronic disease, especially if the inflammation is well controlled. In any case, allowing for some pupil movement is helpful to prevent posterior synechiae formation in the dilated position.
Topical corticosteroids are the mainstay of therapy and should be used aggressively during the initial phases of therapy.
If the patient poorly complies with topical therapy or if the iritis is not responding to topical corticosteroids, a subconjunctival injection of shorter-acting or depot steroids may be used. Betamethasone (Celestone) is short and intermediate acting and can be used for exacerbations, whereas triamcinolone acetate is longer acting and is used more often for associated cystoid macular edema or vitritis.
Depot steroids should be avoided in cases of uveitis secondary to any suspected infectious process because of their potentially severe adverse effects.
In severe cases of iritis, oral corticosteroids may be added to the treatment regimen (after ruling out the infectious etiology or after under coverage of medication, which treats the infectious etiology).
Prolonged use of systemic corticosteroids is to be avoided. The goal is less than 10 mg of prednisone per day by 6 months. In severe disease or if prolonged corticosteroids are being used, systemic corticosteroid-sparing immunomodulatory agents are used in chronic noninfectious uveitis. If evidence shows involvement of the posterior uvea by noninfectious uveitis, intravitreal steroids can be used via intravitreal injection or insertion of a steroid-eluting delivery system (eg, Retisert, Iluvien, Ozurdex).
Treat increased intraocular pressure as indicated.
Systemic immunomodulating agents may be used in patients in whom regional or systemic corticosteroids are not responding or in patients who have the potential for steroid side effects. Systemic immunomodulating agents work by selectively blocking steps in the inflammatory and immune cascades. For example, abatacept and alefacept dampen the immune response by interfering with the activation of T cells, while adalimumab, etanercept, and infliximab target the inflammatory mediator TNF-alpha.
Glaucoma surgery can be performed if medical treatment fails to control the intraocular pressure and after quieting the eye from inflammation. In case of cataract, the eye must be free of inflammation at least 3 months before the surgery. A peripheral iridectomy may be indicated for iris bombe; however, if the pupil is not entirely occluded or secluded, an iridectomy can precipitate iris bombe by diverting flow from the small area of the pupil that is not occluded. In that case, if there is an exacerbation of inflammation, the pupil can close as there is no flow and the iridectomy may become occluded as well.
If a specific systemic diagnosis is suspected or is confirmed on the basis of laboratory and/or radiographic investigation, consultation with a subspecialist may be indicated.
Topical corticosteroids and a cycloplegic agent should be started. If the eye does not adequately respond to topical therapy within 1 week or so, or if very severe, oral corticosteroids or a periocular injection of corticosteroids may be added to the treatment regimen.
Oral corticosteroids may be particularly useful in cases of bilateral noninfectious granulomatous iritis. Routine use of depot steroids in infectious uveitis in known steroid responders or in patients with glaucoma or already elevated IOP should be considered carefully because of potential for severe or sight-threatening adverse effects.
In cases of severe granulomatous iritis, the treating clinician may elect to begin therapy with topical and oral corticosteroids. The tapering of steroid therapy is guided by the clinical response on follow-up examination. Topical or systemic nonsteroidal anti-inflammatory drugs (NSAIDs) are of little or no benefit in the treatment of granulomatous iritis.
Immunomodulatory and immunosuppressive medications may be useful in patients who are unresponsive to corticosteroids, in patients with chronic uveitis, or in patients who develop adverse effects of corticosteroid therapy.
A number of other agents have been used, including methotrexate, azathioprine, cyclosporin A, mycophenolate mofetil, cyclophosphamide, and chlorambucil. Myelosuppression and secondary infection are among the most common adverse effects of these agents.
Tumor necrosis factor alpha (TNF-alpha) inhibitors may be useful in some cases of granulomatous anterior uveitis. They are effective in reducing the number of flares of anterior uveitis in patients with sarcoidosis.
An internist or a rheumatologist should be involved in the management of patients treated with immunomodulatory agents.
Clinical Context: Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and by reversing increased capillary permeability.
Clinical Context: Can be used if topical therapy inadequate to treat iritis (especially if bilateral). Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and by reversing increased capillary permeability.
These agents are the mainstays of therapy for iritis, and they help to stabilize blood-aqueous barrier.
Clinical Context: Prevents muscle of ciliary body, and sphincter muscle of iris, from responding to cholinergic stimulation. Induces mydriasis in 15-30 min and cycloplegia in 25-45 min.
These agents are used to help prevent or break posterior synechiae and to reduce ciliary body–induced pain.
Patients should be observed closely, and steroids should be tapered as the inflammation resolves. It is prudent to reexamine the patient 2-3 weeks after all medications have been tapered to ensure that no residual inflammation is present and that no recurrence is beginning.
In chronic granulomatous iritis, it may not be possible to taper corticosteroids completely, especially without corticosteroid-sparing agents. These are often continued for 2-3 years before discontinuation if there is good control, and often they need to be used much longer. Some diseases are chronic and require very long-term treatment. When stopping immunomodulatory agents, it may take several months before disease recurs, so long-term vigilance is needed.
Consultations with other subspecialists should be arranged, if warranted by the patient's history and laboratory workup. Consultation with a uveitis subspecialist should be considered in unusual or difficult cases, cases not responding or progressing despite appropriate maximal therapy, or cases at risk for significant visual loss.
Recurrent episodes of iritis and subsequent therapy may lead to cataract formation and to the development of glaucoma (or secondary to medication use). Long-term hypotony due to ciliary body dysfunction (atrophy or detachment) is particularly ominous.
Most patients will more than likely have a recurrence of their inflammatory process.
The overall visual prognosis for patients with recurrent iritis is good in the absence of cataracts, glaucoma, or posterior uveitis.
For patient education resources, see the Eye and Vision Center, as well as Anatomy of the Eye and Iritis.