Nongranulomatous Iritis (Anterior Uveitis) 

Updated: Aug 04, 2017
Author: Andrew A Dahl, MD, FACS; Chief Editor: Hampton Roy, Sr, MD 

Overview

Background

Iritis, or anterior uveitis, is the most common form of intraocular inflammation. It is a common cause of a painful red eye. Inflammation of the iris may appropriately be termed iritis, whereas inflammation of the iris and the ciliary body is called iridocyclitis. Iritis may be subdivided into 2 broad categories: granulomatous and nongranulomatous.

This article discusses nongranulomatous iritis, although iritis due to a granulomatous disease process may have a nongranulomatous appearance. For information about granulomatous disease, see Uveitis, Anterior, Granulomatous. The most common form of nongranulomatous anterior uveitis is acute anterior uveitis (AAU), which is associated with the human leukocyte antigen (HLA)–B27 allele in one half to two thirds of cases. However, only 1% of people who carry the HLA-B27 allele develop acute anterior uveitis.[1]

Pathophysiology

The exact pathophysiology is not known. Inflammation of the iris and the ciliary body causes a breakdown of the blood-ocular barrier. This condition allows both protein and WBCs to extravasate into the aqueous, resulting in the typical iritis signs of cell and flare. Frequently, the cause is idiopathic, but certain ocular and systemic diseases may be the underlying cause of the iritis.[2]

In the case of HLA-B27–associated acute anterior uveitis, speculation about molecular mimicry has yet to be substantiated in humans. Certainly, recent interest in the microbiome (gut and other resident micro-organisms) in disease, as well as the observation that rats transgenic for HLA-B27 do not form ankylosis and other evidence of disease until the gut is colonized, suggest a possible connection to disease. A close relationship between asymptomatic (subclinical) ileocolitis has been demonstrated in patients with recurrent uveitis.[3]

Epidemiology

Frequency

United States

Iritis is the most frequent form of uveitis encountered by ophthalmologists. In one community-based study, anterior uveitis accounted for more than 90% of all cases of uveitis. The annual incidence rate is approximately 8 cases per 100,000 population.[4]

International

No particular geographic distribution for iritis has been noted.

Mortality/Morbidity

Morbidity arises from iritis and any associated disease process, if present.

Episodes of acute anterior uveitis are often associated with pain, photophobia, decreased vision, and the need for follow-up visits, all of which affect quality of life.

Patients may develop posterior synechiae, and, if severe, a secluded pupil and subsequent angle-closure glaucoma may result.

Associated ocular complications (eg, cataract, glaucoma, macular edema, hypotony) may result in severe vision loss.

Race

No significant racial differences exist. HLA-B27–associated anterior uveitis is more common in whites.

Sex

No significant sexual differences exist. However, the male-to-female ratio of ankylosing spondylitis, which is a common cause of iritis, is 3:1.[5]

Age

Iritis may develop in persons of any age but most commonly in the fourth and fifth decades of life.

 

Presentation

History

Inquire about the patient's complete medical history, including all medical conditions, surgeries, medications, and ocular history (eg, history of iritis, trauma, surgery). 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 recent ocular trauma, back stiffness, arthritis, rashes, shortness of breath, urethral discharge or dysuria, swollen lymph nodes, diarrhea, blood in stools, recent insect bites, sexually transmitted diseases (STDs), and tuberculosis (TB) exposure.

Inquire about the onset of the symptoms. Most cases of acute anterior uveitis begin with the sudden onset of redness, pain, and photophobia.

Family history is also important. Inquire about a family history of uveitis or other symptoms in family members that might suggest associated diseases, such as a spondyloarthropathy or other HLA-B27 processes.[6]

A dull, aching eye pain may occur and may worsen when one touches the eye through the eyelid. Pain may be referred to the temple or periorbital region. The pain is usually abrupt in onset. Photosensitivity to light, especially sunlight, may worsen the patient’s discomfort.

Redness with no mucopurulent discharge is seen. Patients rarely have a watery discharge or tearing. Some forms of iritis, such as Fuchs iridocyclitis, may have no symptoms other than loss of vision or glare from associated cataract.

Decreased vision may be noted.

Most cases of acute anterior uveitis are unilateral, although the same eye is not always involved in different episodes. Tubulointerstitial nephritis is a rare syndrome that is often associated with a bilateral anterior uveitis of sudden onset.

Physical

Vision

Visual acuity is usually normal or only slightly decreased, although, in severe episodes, the acuity can be very low.

Intraocular pressure

Intraocular pressure (IOP) is often lower in the eye with iritis when compared to the fellow eye. This is secondary to a decrease in aqueous production by the inflamed ciliary body. However, in some cases, the IOP may be elevated as a result of altered aqueous outflow; this may be more common in viral anterior uveitis.

Conjunctiva

Typically, the eye has a perilimbal injection termed ciliary flush. Less commonly, generalized redness of the bulbar conjunctiva may be present. This is not found in Fuchs heterochromic iridocyclitis or the anterior uveitis associated with juvenile idiopathic arthritis.

Cornea

Keratic precipitates (KPs) may be present. These clusters of WBCs collect on the endothelium. In nongranulomatous iritis, they tend to be small and are usually located over the inferior half of the cornea. Keratic precipitates in acute anterior uveitis associated with ankylosing spondylitis are shown below.

Fine keratic precipitates in a patient with ankylo Fine keratic precipitates in a patient with ankylosing spondylitis–associated acute anterior uveitis.

Stellate-shaped KPs, uniformly spread over the endothelium, are typical of Fuchs heterochromic iridocyclitis, as shown in the image below, and may also be seen in herpetic viral anterior uveitis.

Small stellate keratic precipitates with fine fila Small stellate keratic precipitates with fine filaments in a patient with Fuchs heterochromic iridocyclitis.

Calcific band keratopathy can occur in chronic uveitides as in the uveitis associated with juvenile idiopathic arthritis. Corneal stromal edema may be present secondary to viral endotheliitis or endothelial dysfunction due to uveitic glaucoma or extensive anterior chamber inflammation. Cytomegalovirus (CMV) infection in nonimmunosuppressed patients can cause corneal edema that may even recur in corneal grafts.[7]

Anterior chamber

Flare, cells, and/or hypopyon may be present.

Anterior chamber flare, resulting from extra protein in the aqueous, is usually present and can be graded using the SUN Working Group Grading Scheme for Anterior Chamber Flare, as follows:[8]

  • 0 = None

  • 1+ = Faint

  • 2+ = Moderate (iris and lens detail clear)

  • 3+ = Marked (iris and lens detail hazy)

  • 4+ = Intense (fibrin or plastic aqueous)

Cells, the hallmark of iritis, are present in the aqueous. They should be graded by severity under high-magnification slit lamp examination in a 1 X 3-mm field of light, as described by the SUN Working Group Grading Scheme for Anterior Chamber Cells, as follows:

  • 0 < 1

  • 0.5 = 1-5 cells

  • 1+ = 6-15 cells

  • 2+ = 16-25 cells

  • 3+ = 26-50 cells

  • 4+ = More than 50 cells

Hypopyon, if present, is highly suggestive of diseases associated with HLA-B27; with Behçet disease; or, less commonly, with an infection-associated iritis. Hypopyon is shown in the image below.

Acute anterior uveitis with plasmoid aqueous and h Acute anterior uveitis with plasmoid aqueous and hypopyon in a patient with ulcerative colitis.

Iris

Posterior synechiae may be present. Inflammatory nodules are usually not present in nongranulomatous iritis, although Koeppe nodules can be present in Fuchs heterochromic iridocyclitis. Sector atrophy of the iris, if present, suggests herpes zoster as the etiology of the inflammation, while patchy or generalized iris atrophy suggests herpes simplex uveitis. Iris changes may also be seen in CMV anterior uveitis. Iris atrophy is shown in the image below.

Iris atrophy in a patient with herpes simplex viru Iris atrophy in a patient with herpes simplex virus–associated anterior uveitis.

Heterochromia and loss of iris stromal detail suggest Fuchs heterochromic iridocyclitis. An example is shown in the image below.

Fuchs heterochromic iridocyclitis with cataract an Fuchs heterochromic iridocyclitis with cataract and iris heterochromia.

Lens and anterior vitreous

Lenticular precipitates may be present on the anterior lens capsule. Posterior subcapsular cataracts may be present if the patient has had repeated episodes of iritis.

Cells are commonly seen in the anterior vitreous. They represent either an iridocyclitis or a spillover of cells from the anterior chamber into the retrolental space. This may happen even in Fuchs iridocyclitis.

Occasionally, patients with HLA-B27 disease have an intense vitritis, papillitis, and cystoid macular edema.

Posterior segment

Carefully examine the posterior segment through a dilated pupil for evidence of optic nerve edema, for vasculitis, and for focal retinal and/or choroidal lesions. All patients with acute anterior uveitis must undergo dilated fundus examination to ascertain that the diagnosis is confined to the anterior segment. A patient with a granulomatous-appearing iritis is likely to have a more extensive uveitis.

Causes

It is important to ascertain whether the uveitis is unilateral or bilateral, symptomatic (pain and photophobia), and acute (lasting less than 3 months) or chronic.

Unilateral, sudden onset, acute

Causes of acute anterior uveitis may include the following:

  • Idiopathic

  • Diseases associated with HLA-B27 (eg, ankylosing spondylitis, reactive arthritis, inflammatory bowel disease, psoriasis) may manifest as unilateral acute anterior uveitis; they have a high tendency to recur at some later time in the same eye or contralateral eye; 50% of HLA-B27–positive patients with acute anterior uveitis will develop an associated seronegative spondyloarthropathy; 25% of patients with HLA-B27–associated systemic illness will develop acute anterior uveitis[1]

  • Behçet's disease

  • Sarcoidosis

  • Trauma

  • Infections (herpes zoster, herpes simplex, CMV, syphilis, postoperative or metastatic endophthalmitis)

Unilateral, chronic

Infectious causes may include the following:

  • Herpes zoster, herpes simplex, acute retinal necrosis, CMV

  • Syphilis

  • Fuchs heterochromic iridocyclitis (which may be due to rubella, at least in some cases)

The following are other potential causes:

  • Sarcoidosis

  • Chronic postoperative endophthalmitis

Bilateral

Causes of bilateral disease may include the following:[9]

  • Sarcoidosis

  • Lyme disease

  • Fuchs heterochromic iridocyclitis (rare cause)

  • Juvenile idiopathic arthritis[10]

  • Acute retinal necrosis

  • Tuberculosis

  • Tubulointerstitial nephritis and uveitis syndrome (a small group of patients with interstitial nephritis has tubulointerstitial nephritis and uveitis)

 

DDx

Differential Diagnoses

 

Workup

Laboratory Studies

A comprehensive review of the patient's past medical history and a review of systems should guide the laboratory evaluation, and the workup should be tailored accordingly.

If a patient presents with a first episode of nongranulomatous iritis and if the medical history and the review of systems are unremarkable, laboratory studies may not be indicated. Some uveitis specialists recommend specific antitreponemal serologies on all patients with uveitis.

Iritis that is recurrent, unusual in severity, unresponsive to medical therapy, unusually persistent, or bilateral should be thoroughly evaluated.

The following list of laboratory studies may be requested. At minimum, chest radiography (see Imaging Studies) and a rapid plasma reagin (RPR) test with a specific treponemal serology, such as the fluorescent treponemal antibody absorption (FTA-ABS) test, should be ordered.

The RPR test and the FTA-ABS test, or serologic tests for syphilis, should be ordered for each patient who undergoes a laboratory evaluation for uveitis.

The erythrocyte sedimentation rate (ESR), serum lysozyme level, and angiotensin-converting enzyme (ACE) test may help in evaluating the patient for sarcoidosis. However, these are not very sensitive or specific.

HLA-B27 typing: 1% of people who are HLA-B27–positive develop acute anterior uveitis. About 55% of cases of acute anterior uveitis are associated with an HLA-B27–positive serotype, rising to about 70% in patients with recurrent episodes of acute iritis.[1]

Antinuclear antibody (ANA) and, possibly, rheumatoid factor (RF) may be indicated if juvenile idiopathic arthritis is suspected.

Lyme serologic testing should be ordered if Lyme disease is suspected (although if no history otherwise consistent with Lyme disease or exposure, the predictive positivity of a positive test is very low).

Serum creatinine and urinalysis, including urinary beta-2 microglobulin levels, should be obtained if tubulointerstitial nephritis and uveitis are suspected.

A paracentesis for polymerase chain reaction (PCR) or culture may be considered if there is a question of viral anterior uveitis or other infectious uveitis.

Imaging Studies

Chest radiography helps to rule out sarcoidosis and tuberculosis. However, it is not very sensitive or specific.

High-resolution chest CT scanning is more sensitive for sarcoidosis than plain radiography and should be ordered if the radiographs are negative and if sarcoidosis is highly suspected as the etiology of the ocular inflammation.

Sacroiliac, lumbar, or thoracolumbar spine radiographs may be ordered if ankylosing spondylitis is suspected.

Procedures

If a patient presents with a secluded pupil from extensive posterior synechiae, iris bombe with angle-closure glaucoma may be present. In this case, an iridotomy may be necessary.

 

Treatment

Medical Care

A long-acting cycloplegic agent, such as cyclopentolate, homatropine, scopolamine, or even atropine, should be used to help relieve both pain and photophobia and to prevent the formation of posterior synechiae in acute symptomatic anterior uveitis. However, prolonged use of strong cycloplegic drops is often unnecessary; in fact, letting the pupil move a little may prevent posterior synechiae from forming in the dilated position.

Topical corticosteroids are the mainstays of therapy and should be used aggressively during the initial phases of therapy. For the most common acute anterior uveitis (eg, associated with HLA-B27), topical corticosteroids such as prednisolone acetate 1% are usually started at every hour initially, rarely more frequently for very severe episodes.

Difluprednate (Durezol) can be used at a less-frequent dose schedule than prednisolone acetate 1% and may be useful when increased effect or improved compliance is needed.

A subconjunctival injection of depot-steroids (eg, Celestone) may be used if the patient poorly complies with topical therapy or if the iritis is not responding to topical corticosteroids alone. A sub-tenon injection with a longer-acting corticosteroid, such as triamcinolone acetate, is reserved for more prolonged episodes, especially if there is cystoid macular edema that is not resolving with topical therapy.

In severe cases of acute anterior uveitis, the addition of oral corticosteroids to the treatment regimen may be necessary.

Therapy for increased IOP is as indicated.

In viral anterior uveitis, antiviral therapy (including valganciclovir for CMV) may be useful, but this is not well established.

Fuchs heterochromic anterior uveitis does not usually require corticosteroid treatment.

In chronic cases, such as in the anterior uveitis associated with juvenile rheumatoid arthritis, systemic immunomodulatory corticosteroid-sparing agents may be required. If cystoid macular edema is unresponsive to corticosteroid therapy, treatment with methotrexate and anti–tumor necrosis factor alpha (TNF-alpha) agents should be considered.[11]

Consultations

Consultations with other subspecialists should be arranged, as warranted by the patient's history or based on the results of laboratory or radiographic investigations.

 

Medication

Medication Summary

In acute anterior uveitis, topical corticosteroids and a cycloplegic agent should be started immediately, unless an infectious etiology is suspected. If the eye is not adequately responding to topical therapy within a week to 10 days or if the disease is very severe, the addition of either oral corticosteroids or a periocular injection of corticosteroids to the treatment regimen may be necessary as long as no systemic contraindications or evidence of infection is present. The injection of steroids may be contraindicated in a known steroid responder or in a patient with an already elevated IOP.

Tapering of steroid therapy is guided by the clinical response on follow-up examination. Topical nonsteroidal anti-inflammatory drugs (NSAIDs) tend to be of little or no benefit in the treatment of 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 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.

TNF-alpha inhibitors may be useful in patients with the seronegative spondyloarthropathies, including AS. TNF-alpha inhibitors that are available include infliximab, etanercept, and adalimumab. Reports suggest that infliximab is effective in reducing the number of flares of anterior uveitis in patients with ankylosing spondylitis. Adalimumab may also be effective, but there is evidence that etanercept is not.[12]

An internist or a rheumatologist should be involved in the management of patients treated with immunomodulatory agents.

Corticosteroids

Class Summary

These are the mainstays of therapy for iritis and help to stabilize the blood-aqueous barrier.

Prednisolone acetate 1% (Pred Forte, Econopred)

Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and by reversing increased capillary permeability.

Prednisone (Deltasone)

Can be used if topical therapy inadequate to treat iritis. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and by reversing increased capillary permeability.

Cycloplegics

Class Summary

These agents help prevent or break posterior synechiae and reduce ciliary body–induced pain.

Cyclopentolate HCl 1% (Cyclogyl)

Prevents spasm of ciliary muscle and iris sphincter. Induces mydriasis in 30-60 min and cycloplegia in 25-75 min.

 

Follow-up

Further Outpatient Care

Patients require close follow-up care, with steroids tapered as the inflammation resolves.

Patients should be reexamined 2-3 weeks after all medications have been tapered to ensure that no residual inflammation is present.

Complications

Recurrent episodes of iritis and the subsequent therapy may lead to cataract formation and to glaucoma.

Prognosis

Most patients can expect to have a recurrence of iritis.

Overall, the visual prognosis for patients with recurrent iritis is good in the absence of either cataract formation or glaucoma.

Patient Education

If the patient has known or newly diagnosed HLA-B27 disease, he or she should be instructed to always keep a bottle of steroids handy. The patient should instill the steroid at the first sign of an iritis flare. The patient should come into the office as soon as possible to confirm the presence or absence of the iritis.

For patient education resources, see the Eye and Vision Center, as well as Anatomy of the Eye and Iritis.